Hepatitis Ebook

Alternative Hepatitis C Treatments


Alternative Hepatitis C Treatments Overview


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Hepatitis B Virus Hbv History

Jaundice (from jaune) is a disease of the liver that has been known for centuries. Its most notable characteristic is an orange--yellow discoloration of the skin and con-junctivae, caused by deposition of elevated levels of bilirubin produced from damaged hepatocytes. Viral hepatitis, a general term for infections of the liver, can be caused by a number of hepatitis viruses, only one of which, HBV, is classified as a DNA virus. HBV is an unusual DNA virus in that it has, as a component of its life cycle, an RNA reverse transcriptase activity, a function normally associated with RNA retroviruses. The mechanism of HBV replication is unique for a DNA virus, in that it involves an RNA intermediate. HBV has a striking tropism for hepatocytes, but also can be detected in PBMCs. Although viral hepatitis is a major public health problem, the identification of its viral association(s) and of HBV as one of the infectious agents of the disease was long in coming. Prior to its ultimate discovery,...

Is there a vaccine which can prevent hepatitis B

For several years a vaccine has been available which is very effective in preventing, although not in treating, hepatitis B. In the U.S., women who receive prenatal care are screened for hepatitis B infection. For women infected with hepatitis B, transmission to their newborns can be prevented by administering hepatitis B vaccine and immune globulin to their infants immediately after birth and continuing the series of three immunizations over the next six months. In infants born to uninfected women, the hepatitis B series is routinely started within the first two months of life. Adults at risk for exposure to hepatitis B may also receive the hepatitis B vaccine series. Once completed, the vaccine provides highly effective, long-term protection that is, direct exposure of a vaccinated individual to the virus through sex or blood will not result in infection. In the past, recipients of blood products were at high risk. Blood donations in this country and other developed countries are...

Are there other causes of hepatitis

Hepatitis can be caused by many different types of hepatitis viruses. Currently vaccines are only available for hepatitis A and B, the most common forms. Hepatitis C is common among injecting drug users but can probably be transmitted less efficiently through sexual contact. Blood donors are screened for hepatitis C, but there is no vaccine to prevent infection. In addition to viruses, chemicals may also damage the liver. Alcohol ingestion is the most common cause of non-viral hepatitis. Drinking excessively can lead to cirrhosis or liver cancer.

Transfusion Acquired Chronic Hepatitis

Childhood cancer survivors transfused before the introduction of effective screening measures for hepatitis-B and -C represent a significant population at risk for transfusion-acquired hepatitis. Hepatitis-B screening was implemented in 1971 in the United States. Hepatitis-C screening by the first generation enzyme immunoassay (EIA) was initiated in 1990 a more sensitive, second generation EIA became available in 1992. Hence, transfusion-acquired viral hepatitis should be considered in long-term survivors presenting with chronic hepatic dysfunction who received transfusions before donor screening was available. Hepatitis-B is characterized by a more aggressive acute clinical course and a lower rate of chronic infection (< 10 ). In contrast, acute infection with hepatitis-C is often mild or asymptomatic, but the rate of chronic infection is high (approximately 80 ). Regardless of the etiology, survivors with chronic hepatitis experience significant morbidity and mortality related to...

Hepatitis C Virus HCV

HCV is a single-stranded RNA virus which shows marked genetic heterogeneity and at least six major subtypes are known, of which Ib is thought to be the most likely to lead to chronic liver disease. Whilst it is associated with only about one-sixth of all cases of hepatocellular carcinoma world-wide, this proportion is higher and rising in some areas, notably Japan and, to a lesser extent, Spain, Italy and the Middle East (Idilman et al., 1998 Bosch et al., 1999 Colombo, 1999). The infection is usually acquired in adult life via transfusion of blood and blood products or by the use of contaminated instruments and syringes by intravenous drug abusers. Perinatal and sexual transmission are unimportant. The onset of malignancy is preceded by cirrhosis in 90 of cases. The course is long, 20-40 years from infection to tumour, and patients are affected in late middle to old age. Table 3 shows that HCV is definitely associated with hepatocellular carcinoma in case-control and follow-up...

Hepatitis B Virus HBV

HBV is one of a group of viruses known as Hepadnaviruses which affect humans (HBV) and certain animals such as the woodchuck (WHV), ground squirrel (GSHV) and duck (DHV). All of these cause liver disease acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma, in their respective hosts. In humans, transmission is mainly via blood or blood products, contaminated instruments, male homosexual contact and, most important, from mother to infant at birth. HBV is a partly double-stranded DNA virus possessing a genome consisting of four open reading frames which encode for four different proteins, surface HCV (HBsAg) and core (HBcAg) antigens, DNA polymerase and the X protein. The 'e' antigen (HBeAg) is closely associated with HBcAg. Replication takes place through reverse transcriptase and the virus is capable of integration into the host cell's genome. Most of the antigens and antibodies directed against them are demonstrable in the serum at one time or another during acute and...

How can I protect myself from contracting hepatitis B

Not having sex is the most effective way to prevent getting an infection. Monogamy is also safe two people who only have sex with each other are safe if neither partner is infected. People who choose to have sex outside a monogamous relationship but don't know whether their partners carry this virus can protect themselves by receiving the vaccine series. Condoms may also be effective in preventing hepatitis B transmission. Washing the genitals, urinating, or douching after sex does not prevent STDs. For more detailed information on strategies to reduce your risk of acquiring STD HIV see SHARP FafChoosing Safer Options Reduces Risk at

IoTb management of hepatitis

Most anti-TB drugs can damage the liver. Isoniazid and pyrazinamide are most commonly responsible. Ethambutol is rarely responsible. When a patient develops hepatitis during anti-TB treatment, the cause may be the anti-TB treatment or something else. It is often difficult to find out. Try to rule out other possible causes before deciding that the hepatitis is drug-induced. Hepatitis presents with anorexia, jaundice and often liver enlargement. If you diagnose drug-induced hepatitis, stop the anti-TB drugs.Wait until the jaundice or hepatic symptoms have resolved and the liver enzymes have returned to baseline. If liver enzymes cannot be measured, then it is advisable to wait two weeks after the jaundice has disappeared before recommencing anti-TB treatment. It is strange, but fortunate, that in most cases the patient can restart the same anti-TB drugs without hepatitis returning.This can be done either gradually or all at once (if the hepatitis was mild). If the hepatitis has been...

Hepatitis B

Hepatitis B is one of the commonest and most widespread viral infections of humans. Furthermore, it is the major viral cause of cancer (hepatocellular FIGURE 1.5 Worldwide distribution of hepatitis B carriers. FIGURE 1.5 Worldwide distribution of hepatitis B carriers. carcinoma), and also of cirrhosis, particularly in Asia and Africa. Infectious hepatitis B virions are found in almost all biological fluids, at high concentrations in the blood, menstrual fluid, semen, vaginal secretions and saliva at low concentrations in the urine, but usually not in feces unless contaminated by blood. Therefore, the methods of transmission of hepatitis B virus are via the blood (including all forms of parenteral contact, such as injecting drug use and nosocomial transmission in hospitals), vertically (usually at parturition), and sexually. Hepatitis B surface antigen (HBsAg) has been found in breast milk, but there is no convincing evidence for transmission by this route (Alter et al., 1986...

Hepatitis Delta

Hepatitis delta is a virus whose transmission depends upon the superinfection of hepatitis B carriers or coinfection of susceptible persons with hepatitis B and delta viruses. In Western countries the most common mode of transmission is injecting drug use, but it can also be transmitted sexually, although much less efficiently than hepatitis B. The hepatitis delta antibody prevalence among homosexual men is higher than in control populations and is not attributable to other risk behaviors such as injecting drug use (DeCock et al., 1998 Solomon et al., 1988). The distribution of hepatitis delta throughout the world is not uniform. Regions of high seroprevalence include the Mediterranean, the Middle East, West Africa, the Amazon basin of South America, Central Asia and some Pacific Islands. The modes of transmission that maintain such high seroprevalence are not clear (Torres et al., 1996).

Hepatitis C

In the past decade there has been considerable debate in the literature as to whether hepatitis C is sexually transmitted. In support of sexual transmission, higher seroprevalences of hepatitis C have been reported in STD clinic attendees, those with a higher number of lifetime sexual partners or other sexually transmitted diseases, prostitutes and homosexual men (Melbye et al., 1990 Rail and Dienstag, 1995 Dienstag, 1997). However, alternative risk factors, including injecting drug use, can account for many of these apparent cases of sexual transmission (Bresters et al., 1993 Brettler et al., 1992 Conry-Cantilena et al., 1996 Osmond et al 1993). Anecdotal cases of sexual transmission have been reported, and sequence homology of a common hepatitis C viral strain in sexual partners without other risk factors has been demonstrated (Thomas et al., 1995 Peano et al., 1992). However, studies of stable monogamous sexual partners of patients with chronic hepatitis C usually failed to...

Hepatitis A

Like hepatitis B and delta, hepatitis A shows a non-uniform distribution of infection throughout the world, as measured by age-specific acquisition and seroprevalence. Although transmitted mainly by the fecal-oral route in food and water, and under other conditions of poor hygiene, it has recently been shown to be an important sexually transmitted disease among homosexual men. Since 1980, periodic epidemics of hepatitis A among homosexual men have occurred, especially as seroprevalence fell and the number of those susceptible increased (Christenson et al., 1982 Coutinho et al., 1983 Leentvaar-Kuijpers et al., 1995). In 1991 a large epidemic occurred simultaneously in large US, Canadian, European and Australian cities (CDC, 1992 Mulhall et al., 1995). The risk of infection has been clearly related to oroanal and digital-anal intercourse in case control studies. Some of these epidemics have spread to the rest of the community (Henning et al., 1995 Katz et al., 1997). In addition,...

What is Hepatitis B

Hepatitis means inflammation of the liver. Chronic infection can lead to liver cirrhosis and the destruction of liver cells. Hepatitis B is caused by a virus transmitted through exposure to infected blood, semen, and vaginal fluids. Many people still do not understand that it can be transmitted sexually. In developing countries hepatitis B infection frequently occurs in infancy and childhood due to perinatal transmission and the use of contaminated needles. In developed countries, hepatitis B is more common in certain subgroups of the population, to include intravenous drug abusers, heterosexuals with multiple sex partners, gay men, staff of hemodialysis centers and others who are routinely exposed to infected blood. Individual responses to infection can vary greatly. Persons infected with hepatitis B may not experience any adverse symptoms or may require hospitalization for severe liver disease, where treatment is basically supportive (no cure). The person's immune system responds to...

Hepatitis B Virus

The role of chronic infection with hepatitis B virus (HBV) in the aetiology of primary liver cancer, specifically hepatocellular carcinoma, is well established (IARC, 1994a). Hepatitis B is one of the most common infectious Figure 1 The geographical distribution of hepatitis B infection. Black, > 8 , high grey, 2-7.9 , intermediate white, < 2 , low (from WHO). Figure 1 The geographical distribution of hepatitis B infection. Black, > 8 , high grey, 2-7.9 , intermediate white, < 2 , low (from WHO). diseases worldwide, with between 300 and 350 million chronic carriers up to 10 of the population in high prevalence areas two-thirds of whom will develop chronic hepatitis. Of those, 20 25 will eventually die from primary liver cancer or cirrhosis. As a result, primary liver cancer is one of the most common cancers, particularly in parts of sub-Saharan Africa, China and South-east Asia, where the virus is prevalent (Figure 1). The hepatitis B virus is responsible for causing up to a...

Donna E Goldman Graham M Woolf

In the United States, there are approximately 2000 cases year of acute hepatic failure (AHF) in adults and children.1 The term fulminant hepatitis was introduced by Lucke and Mallory in 1948 to describe posttransfusion hepatitis in soldiers dying within 9 days of the onset of their illness.2 Since that time, the criteria for defining fulminant hepatic failure (FHF) have evolved due to improved understanding of the etiology, prognosis and complications of the disease. However, in spite of our improved understanding of the disease process, the definition and classification of FHF continue to remain confusing and often controversial.

Fulminant and Subfulminant Hepatic Failure

FHF is associated with a mortality rate greater than 80 with medical management alone 6 the rate is higher in comatose compared to noncomatose patients.3 FHF is more commonly associated with cerebral edema and a hepatitis A or B viral etiology than SFHF. The latter is less frequently associated with cerebral edema and more frequently associated with non-A and non-B hepatitis (NANBH) and drug toxicity. Survivors of FHF can recover fully and do not develop chronic liver disease.

How can a pregnant womans baby become infected

STDs can be transmitted from a pregnant woman to the fetus, newborn, or infant before, during, or after birth. Some STDs (like syphilis) cross the placenta and infect the fetus during its development. Other STDs (like gonorrhea, chlamydia, hepatitis B, and genital herpes) are transmitted from the mother to the infant as the infant passes through the birth canal. HIV infection can cross the placenta during pregnancy, infect the newborn during the birth process, and, infect an infant as a result of breast-feeding.

Hepatic Failure in Infants and Children

FHF in infants is usually caused by an inborn error of metabolism such as galactosemia, hereditary fructose intolerance or tyrosemia.143 Prognosis is better for children than adults, perhaps due to the greater regenerative capacity of the liver at a younger age. Other causes of FHF include herpes virus, echo virus, Epstein-Barr virus infections and hepatitis B.27 In childhood, encephalopathy is the major complication and cause of death. In one series, 9 out of 31 (28 ) patients survived. Mortality correlated well with the severity of encephalopathy but not with patient age or underlying etiology. Most cases were of indeterminate etiology, but five were due to paracetamol overdose, halothane and amanita mushroom poisoning.144

Associated Neurological Findings

Decreased position, vibratory, temperature, and pain appreciation occurs in several neuropathies associated with hyposmia. These include diabetes, the neuropathy of renal and hepatic failures, and a large variety of toxic neuropathies. In patients with pernicious anemia, the large myelinated central fibers carrying position and vibration senses are preferentially affected. In the context of hepatitis, the acquired immune deficiency syndrome (AIDS), and other virus-related illnesses, hyposmia can occur along with an ascending polyneuropathy of the Guillain-Barre type. In seizure patients with uncal or temporal lobe foci that induce dysosmic auras, altered sensations in a hemibody distribution can occur as part of the seizure or as a postictal transient sequela.

Genome Structure Replication and Antigens

The 2.4- and 2.1-kb transcripts produce the large, middle and small envelope proteins, which share common carboxy termini. The small, but major, transcript encodes the hepatitis B surface antigen (HBsAg). The middle and large transcripts which encode preS-2 and preS-1 antigens, respectively have amino acid extensions. The envelope proteins are cotranslationally inserted into ER membranes, where they aggregate, bud into the lumen and then are secreted by the cell as 22 nm subviral particles (Figures 12 and 13) or, if they have enveloped nucleocapsids before budding, become 42 nm infectious virions. The filamentous particles are generated when the large envelope protein is overexpressed. These are not usually secreted, but rather give an histologically distinct appearance (like 'ground glass') to cells, and hypersensitize them to the cytopathic effects of interferon-7.

HBV and Immunoprophylaxis

The host--cell interactions that allow for the persistence of a virus, and the failure of the immune system to eliminate it in an immunocompetent individual, is a topic of considerable relevance for the DNA tumour virus field. For largely noncytopathic viruses, such as HPV, EBV, KSHV and HBV, they must either overwhelm an effective immune response or adopt mechanisms that allow for avoidance, as suggested by one or more of the hypothesized routes for progression from infection to generation of hepatocellular carcinoma (Figure 18). One approach for EBV therapy, as discussed elsewhere, assumes that the immune system may need to, and can, be stimulated specifically to recognize viral genes that might be expressed in its associated tumours, with beneficial effects. As noted, however, realistically such an approach is aimed at reducing morbidity, rather than effecting cure (Khanna et al., 1999). Such an approach may be even more valid for HBV, which can infect virtually all the hepatocytes...

SBP in Acute Liver Disease

SBP has almost always been reported in patients with cirrhosis, i.e., in patients with chronic long-standing liver disease. It was reported in acute liver disease as early as 1982 and occasionally since (74). Recently, Chu and coworkers reported that SBP is very common in severe acute hepatitis in Taiwan (75). SBP was observed in 26 of 82 consecutive patients with acute, viral hepatitis (32 ). Why was SBP so common in this group of patients Usually SBP occurs in patients with cirrhosis and severe portal hypertension with well-developed portal-systemic shunting. The SBP was monobacterial as in the cirrhotic type, and the infecting bacteria were largely aerobic, gram-negative rods. Were these Taiwanese patients different in some fundamental way Indeed, they were The hepatitis in these patients was very severe. Prothrombin times were > 5 sec prolonged in > 90 of them. In fact, they were so prolonged that it was too dangerous to perform liver biopsies in these patients, and so the...

Production of Homogeneous RNA by In Vitro Transcription

Terminal heterogeneity can be removed from transcripts using ribozymes in cis and trans geometries. When included as part of an RNA transcript, hammerhead, hairpin, and hepatitis delta virus ribozyme sequences will self-cleave during or after transcription to produce RNA with defined termini. This method has been used by several groups to obtain RNA samples suitable for structure determination.3,4

Chronic Liver Disease

Liver diseases impose a heavy burden and affect approximately 17 of the population. Cirrhosis, the end result of long-term liver damage, has long been an important cause of death in the UK and showed a large increase in death rates over the past 20 years.1 Cirrhosis is a progressive liver disease and is marked by the gradual destruction of liver tissue over a period of time. Several liver diseases fall under this category, including fibrosis of the liver, and hepatitis B and C viral infections. At the cir-rhotic stage, liver disease is considered irreversible and the only alternative is orthotopic liver transplantation. While orthotopic liver transplantation cures chronic liver disease and a variety of metabolic and genetic deficiency disorders, the increasing shortage of donor organs restricts liver transplantation. The number of patients waiting for orthotopic liver transplantation is far greater than the organ supply, and there is obviously a demand for new strategies to supplement...

David B Wolfson and Cyr Emile MLan 1 Introduction

If you were to peruse a volume of say, The Archives of Surgery, you would almost surely encounter terms such as Kaplan-Meier estimates, log rank tests, and Cox's proportional hazards model. For example Vol 131, Jan.-June 1996, of The Annals of Surgery contains articles on Multimodel-Therapy Breast Salvage in the Urban Poor with Locally Advanced Cancer (Boddie et al), Patient Selection for Hepatic Resection of Colorectal Metastases (Wanebo et al), Hepatitis C Viral Infection in Liver Transplantation (Johnson et al), and Surgical Aspects of Patients with Adenocarcinoma of the Stomach Operated on for Cure (Soreide et al), whose statistical analyses include methods of survival analysis.

How Do Tumours Begin In Humans

We often say that tumours arise from a single cell, and therefore form clonal populations. 'If a proliferation is clonal it is a neoplasm' is a statement often heard. Tumour clonality is an important concept in our attempts to understand malignant transformation, and it is worthwhile reminding ourselves of the experimental basis of this proposal. Why do we believe that epithelial tumours, such as the early adenoma in the colonic mucosa, are clonal proliferations The main methods which have been used for the analysis of clonality in human tumours have been based on X-chromosome inactivation analysis and the detection of somatic mutations. Viral integration, e.g. by Southern blotting in Epstein-Barr virus (EBV)-associated tumours or in hepatitis B- or C-associated liver tumours, are also useful there is excellent agreement between X-inactivation and EBV integration in nasophayrngeal carcinoma, for example.

Personal Characteristics

Many cancers are more common among men than among women. This has been attributed, in many instances, to the higher past exposure of men to tobacco smoking and alcohol drinking. However, some intriguing gender differences remain unexplained. The incidence of hepatitis B-positive hepatocellular carcinoma is three times higher among men, even though the prevalence of chronic hepatitis B virus infection is only two times higher among them.

Definitions and Patient Selection

Over the past twenty years, several prognostic criteria have been proposed to assess the outcome of acute hepatic failure based on retrospective analyses of data from a relatively small number of patients. Christensen analyzed 21 variables in 33 patients with FHF.14 Few variables were found to be predictive of outcome, including age, male sex, duration of history, hepatitis B, low serum glucose and albumin and prolonged prothrombin time. Discriminant score was calculated based on the predictive coefficient of each variable and survival rate was significantly better (p 0.000003) if the score was greater than 0.5 (86 ) compared to that of patients with a score less than 0.5 (5 ). Tygstrup and Ranek1 reviewed the literature on assessment of prognosis in FHF and examined the predictive value of several variables with a multivariant analysis. Despite the large number of prognostic variables studied in FHF, this retrospective analysis did not identify useful outcome predictors among...

When To Stop Antitb Drugs

Hepatitis peripheral neuropathy hepatitis if age > 40 sleepiness lethargy hepatitis joint pains hepatitis hepatitis, agranulocytosis The commonest reactions necessitating change in treatment include gastrointestinal disturbance and hepatitis.There may be an increased risk of rifampicin-associated anaphylactic shock and thrombocytopenia. vomiting and confusion (suspected drug-induced pre-icteric hepatitis)

Insulin Secreting Cells

In studies using an adenoviral vector capable of higher and more prolonged expression, in vivo Pdx-1 expression in the liver had a different effect. In this circumstance, insulin-producing cells were present, but cells exhibiting characteristics of exocrine cells, including expression of trypsin, were also present (44,45). Interestingly, insulin and trypsin were coexpressed by the same cells, and the latter induced a severe hepatitis (44,45). In contrast, use of this same adenoviral vector to express the transcription factor NeuroD1 Beta2 and betacellulin resulted in the formation of islet clusters capable of reversing streptozotocin-induced diabetes (44,45). The islet-like clusters were, in general, localized immediately underneath the liver capsule. Thus the cells from which islet-like structures were generated appeared to be distinct from those in the proximity of the central vein that differentiated into insulin-secreting cells following Pdx-1 expression. After expression of...

Where can I get more information

Your medical care provider should be consulted if you think you may have been exposed to any sexually transmitted disease, including hepatitis B. CDC provides information through their National STD Hotline at (800) 227-8922. For further information regarding your sexual health, visit the Sexual Health and Responsibility Program Home Page at http www-nehc.med.navy.mil hp sharp.

Hepatic Veno Occlusive Disease

Regenerative liver nodule and portal triad in hepatitis C disease. Narrow bands of connective tissue separate small nodules of regenerative liver which shows fatty metamorphosis of some individual hepato-cytes. The portal triad contains a dense lymphocytic infiltrate that in some cases may contain germinal centers. Hematoxylin & eosin stain 20x original magnification. (Courtesy of Dr. J. Jenkins)

Bone Marrow Transplant

And represents a major cause of transplant-related morbidity and mortality 95 .Approximately 80 of individuals with chronic GVHD have liver involvement 10, 96 . Drug toxicity from immunosuppres-sive agents, antibiotics, antifungal and antiviral drugs, sedatives, antiemetics and antipyretics may exacerbate chronic GVHD 22 . Chronic infections, most commonly hepatitis-C, may also accelerate the course of liver injury. Severe chronic liver disease with cirrhosis represents an important late complication of hematopoietic stem cell transplantation that, in most cases,is due to chronic hepatitis-C (Fig. 12.6) 16, 19, 20 . Reports documenting deaths from cirrhosis and hepatic failure suggest that chronic liver disease may predispose to early mortality in long-term survivors treated with allogeneic bone marrow transplantation 11, 16, 19 .

Can I get HIV from getting a tattoo or through body piercing

Personal service workers who do tattooing or body piercing should be educated about how HIV is transmitted and take precautions to prevent transmission of HIV and other blood-borne infections in their settings. If you are considering getting a tattoo or having your body pierced, ask the staff at the establishment about procedures they use to prevent the spread of HIV and other blood-borne infections, such as hepatitis B virus. You also may call the local health department to find out what sterilization procedures are in place in the local area for these types of establishments.

Table 1 Cancers attributable to infections these are conservative estimates adapted from Parkin et al 1999

Hepatitis B virus Epstein-Barr virus Epstein-Barr virus HIV Human herpesvirus-8 HIV Human T cell leukaemia virus Hepatitis C virus Helicobacter pylori The majority of infection attributable cancers (perhaps 1 million cases per year) occur in the developing world, reflecting the higher prevalence of the major causative agents, particularly hepatitis B, human papillomaviruses (HPV), H. pylori and human immunodeficiency virus (HIV). It is conservatively estimated that if these infectious diseases were controlled, up to one in four cancers in developing countries and one in 10 cancers in developed countries might be prevented. This chapter briefly reviews the association between certain infections and cancer, outlines the mechanism by which disease might be caused (if known) and presents comments on the potential for prevention of such tumours.

Transport into the Cell

Possible, as demonstrated by a number of infectious viruses, which use endocytosis for the efficient transfer of their genetic material into certain target cells. Such viruses have special capsid proteins that allow them to escape the early endosome. The signal for their escape is triggered by the drop in pH.21,22 As soon as the pH in the endosome starts to decrease, the capsid proteins undergo a conformational change that enables them to fuse with the membrane of the early endosome. The result is a disruption of the vesicle and the release of the virion into the cytoplasm. A synthetic peptide derived from the capsid of the hepatitis A virus has recently been shown to mimic this endosome escape induced by low pH.23 Another, less efficient, way to escape the lysosome consists in the utilization of lysosome blocking agents such as chloroquine24 or even simpler in an osmotic shock enforced by exposing the cells to nontoxic and nonionic compounds but osmotically active molecules such as...

Mechanisms Of Cell Engraftment And Proliferation In The Liver

Hepatic damage by a toxic transgene driven by the albumin promoter (59). Several additional animal models have verified these principles, including the FAH mutant mouse, in which accumulation of toxic intermediates in the tyrosine metabolic pathway provides the stimulus for proliferation of wild-type cells (13). Induction of apoptosis in mice susceptible to Fas ligand-mediated apoptosis (60) was also highly effective. The FAH mouse has been extraordinarily helpful in issues concerning the stem cell potential of hepatocytes and other liver or pancreatic cells, stem cell plasticity, and correction of tyrosinemia (13,21,32,35, 37,38,57). Similarly, Fas ligand-induced apoptosis has been effective in mouse studies of liver repopulation, stem cell biology, and therapeutic manipulations (61,62). The alb-uPA transgene-based mouse strains have been helpful in studies of xenotransplantation, including human hepatocytes to develop viral hepatitis models (63-65).

Liver Directed Cell Therapy for Inborn Errors of Metabolism

Several excellent animal models are available to establish the principles of liver cell therapy. These animal models include the Gunn rat model of Crigler-Najjar Syndrome type 1 (73), in which bilirubin-UDP-glucuronosyltransferase (UGT1A1) activity is deficient and unconjugated bilirubin accumulates producing neurotoxicity Nagase analbuminemic rats (NAR), which exhibit extremely low levels of serum albumin resulting from defective albumin mRNA processing the Watanabe heritable hyperlipidemic rabbit, which lack cell surface receptors for low-density lipoproteins and models familial hypercholesterolemia (74) the Long-Evans Cinnamon (LEC) rat, an animal model for Wilson's disease (75) the FAH mouse, which models hereditary tyrosinemia type-1 (13,21) and the mdr-2 knockout mice, which model progressive familial intrahepatic cholestasis (76). Mutant animals with diseases of the urea cycle, porphyria, lipidoses, and coagulation disorders are also available (77-80). Similarly, animal models...

Progressive Infantile Poliodystrophy Alpers Disease

A trial of pyridoxine, 50 mg twice a day orally can be done to rule out pyridoxine- dependent deficient seizures. If the serum and CSF glycine levels are elevated, the glycine cleavage enzyme activity should be assessed by liver biopsy in a laboratory qualified to do this test and treatment should be started with dextromethorphan, leucovorin, and sodium benzoate for nonketotic hyperglycinemia. In symptomatic treatment of the seizures, valproic acid should be avoided, because the risk of accelerating the course and a resultant fatal toxic hepatitis is very high. Other treatments of refractory, non- surgically treatable epilepsy at this age, such as adrenocorticotropic hormone or prednisone, ketogenic diet, and intravenous IgG, are unproven and may be harmful.

Stress Proteins in Inflammatory Liver Disease

The liver is not only involved as a bystander organ in many systemic diseases, it is also, more than most other organs, the focus of many chronic inflammatory diseases. Hepatitis B virus infection is the most prevalent infectious disease in the world, and chronic hepatitis C appears to be similarly common worldwide, although with a different geographical distribution. Alcoholic hepatitis as the inflammatory lesion in many patients with alcoholic liver disease is thought to be largely immune mediated. Although systemic autoimmune diseases like lupus erythematosus rarely affect the liver, the liver itself is the target organ of autoimmune attack in autoimmune hepatitis (which in itself is probably a heterogeneous group of diseases), primary biliary cirrhosis, amd primary sclerosing cholangitis. Expression of and immunity to hsp 60, as explained elsewhere in this book, has been thought to play a critical role in the immunopathogenesis and prepetuation of autoimmune diseases. In liver...

Human Model Systems For Oval Cell Activation

It is impossible, for obvious reasons, to treat human subjects with agents that induce oval cell proliferation. Consequently, studies of human liver have to rely on biopsy specimens excess tissue from tumor resections tissue from liver transplants or donated livers that, for logistical or immunological reasons, went unused. When taken together, results from a number of studies suggest that progenitor cells arise in the human liver under conditions similar to those that activate their rodent counterparts. As noted above, oval cell expansion is a consistent feature of liver tissue taken from patients infected with hepatitis C virus (HCV) or hepatitis B virus (HBV) (Hsia et al., 1992 Lowes et al., 1999 Dominguez-Malagon and Gaytan-Graham, 2001). Hepatic progenitor cells positive for C-kit and OV6 have been found in liver specimens from pediatric patients diagnosed with biliary atresia, a1 antitrypsin deficiency, or fulminant hepatic failure (Crosby et al., 1998 Baumann et al., 1999). As...

Protective Immune Response in Primary Q Fever

The control of the infection in patients with primary Q fever involves systemic cell-mediated immune response and granuloma formation. The granulomatous lesions have a central open space and a fibrin ring, and are referred to as doughnut granulomas. They consist of macrophages with epithelioid morphology and of multinucleated giant cells, and are pau-cibacillary (16-18). A systemic cell-mediated immune response, manifesting as a marked proliferative response to C. burnetii antigen, is observed in patients who have convalesced from acute Q fever and patients with acute Q fever hepatitis (19). The individuals vaccinated with It is likely that factors, such as the route of infection and the inoculum size, affects the expression of C. burnetii infection. Indeed, the respiratory route is associated with pneumonia, and the intraperitoneal route with hepatitis in mice and guinea pigs (22). High inocula are associated with myocarditis in guinea pigs (1). Gender and age also affect the...

P16INK4a induction with Ageing Telomere Independent

A particularly important question relates to the relationship of telomeres and p16INK4a. As discussed, some data suggest that sufficient telomere attrition occurs in human stem cells during normal ageing to activate an intrinsic DNA damage response with attendant compromise of stem cell replicative function. Humans who harbor short telomeres because of congenital deficiencies of the telomerase complex develop an age-related failure of bone marrow function and other self-renewing compartments (Mitchell et al. 1999, Vulliamy et al. 2001, Yamaguchi et al. 2005) (see also Du et al., this volume). Moreover, telomere shortening has been shown to precede the development in overt cirrhosis in patients with chronic hepatitis of various etiologies (Kitada et al. 1995, Miura et al. 1997, Urabe et al. 1996, Wiemann et al. 2002). Lastly, some studies have demonstrated a relationship between telomere length in peripheral blood lymphocytes (PBL) and the onset of certain diseases associated with...

Chronic Q Fever Endocarditis

Establishing a diagnosis of Q fever endocarditis is not very difficult. Patients without fever, or with sporadic or low-grade fever, are often misdiagnosed. Q fever should be systematically suspected in a patient with valvular abnormalities, presenting with evocative clinical signs (fever, hepatitis, tiredness, clubbed fingers, weight loss, renal failure), or laboratory findings (elevated ESR, elevated liver enzymes, thrombocytopenia). A Q- fever serology must be carried out in such patients, and the diagnosis can be assessed using modified Duke's criteria (26).

Variations in Q Fever Clinical Presentation

We had the opportunity to compare the two main presentations (189 hepatitis, 79 pneumonia) the patients with hepatitis were younger, less frequently immunocompromised, had more often fever, headaches, myalgia, thrombocytopenia, and elevated ESR. Those with pneumonia more often had EKG abnormalities. Also, patients who presented without hepatitis or pneumonia were more frequently females.

Function And Proliferation

Several animal models are now available to demonstrate survival of transplanted cells in the liver (see review by Gupta and Rogler, 1999). The essential approach concerns marking of transplanted cells with genetic reporters. The earliest models utilized inbred transgenic mice, in which unique foreign genes were expressed. In one system, mouse hepatocytes containing hepatitis B virus surface antigen (HBsAg) gene were transplanted into recipient congeneic mice (Gupta et al., 1990). In another system, transplanted cells contained either human al antitrypsin (hAAT) gene or Escherichia coli P-galactosidase (LacZ) gene (Ponder et al., 1991). Transplanted cells could then be identified in various organs by localizing transgene expression by molecular methods, including in situ hybridization (ISH), or by demonstrating transgene products by histochemistry in tissues or by various assays in the peripheral blood. The success of this approach for cell marking led to additional strategies, in...

Animal Models Available For Assessing Therapeutic Potential Of Stem Cells

These models should be similarly effective in defining the potential of stem cell transplantation. If the goal is to correct genetically determined metabolic disorders, transplantation of normal hepatocytes will be required. Alternatively, one could modify autologous stem cells in vitro and transplant corrected cells (ex vivo gene therapy). Treatment of acquired disorders, such as chronic viral hepatitis, requires transplantation of hepatocytes resistant to hepatitis virus infection. By contrast, patients with acute liver failure could be treated with healthy cells from any source.

Proinflammatory architecture of the host immune system

Analysis of molecular interaction networks of the host immune system indicates that it is fundamentally proinflammatory 58 , and requires active control to reduce inflammatory reactions once started 59-61 . There are many positive feedback loops that escalate secretion of cytokines and promote further inflammation. Hyper-activation of a cytokine network, often called 'cytokine storm', is one of the major factors that aggravates patient health and may results in death. For example, influenza infection causes a range of cytokine release as its acute response 62, 63 . However, the infection is generally localized to epithelial cells yet extensive cytokine release often takes place systemically. This systemic release of cytokines particularly IL-1a and IFN-f aggravates inflammation leading to fever and lung inflammation, and sometimes leads to fatality. Mice infected with influenza virus in which IL-1a and IFN-f are suppressed show substantial mitigation of such risks 64, 65 . Similarly,...

Preoperative Evaluation

Patients should be assessed for the presence of hepatitis or cirrhosis. The degree of hepatic reserve must be estimated. This is based on tests of liver function including prothrombin time, albumin, bilirubin, liver enzymes, and the presence of ascites, varices, or encephalopathy. For patients with colorectal hepatic metastases the colon should be assessed for the possibility of a second primary tumor.

Mechanical Debridement

Large ulcer in a young, drug addicted, patient affected by hepatitis C and cryoglobulinemia. (A) Ulcer covered by necrotic tissue, deeply infected (B) after removal of necrotic tissue by means of Versajet on the same day of admission to hospital (C) vacuum-assisted closure (VAC) is applied immediately after Versajet (D) after four days and two VAC applications. The ulcer bed is now completely debrided and is in the granulation phase. (See color insert.) Large ulcer in a young, drug addicted, patient affected by hepatitis C and cryoglobulinemia. (A) Ulcer covered by necrotic tissue, deeply infected (B) after removal of necrotic tissue by means of Versajet on the same day of admission to hospital (C) vacuum-assisted closure (VAC) is applied immediately after Versajet (D) after four days and two VAC applications. The ulcer bed is now completely debrided and is in the granulation phase. (See color insert.)

Disruption of the Interferon Activating Pathway

An important clue that interferon (INF) might contribute to lupus comes from a series of studies in patients who received INFa as a therapeutic agent for viral hepatitis or carcinoid tumors. Nearly a quarter of INFa-treated subjects (22 ) developed a positive antinuclear antibodies blood test (34), and one in five (19 ) developed overt autoimmunity, including a small number who developed SLE (35).

History of genetic and animal resources at the jackson laboratory

All mice that are imported into TJL are processed through an established importation program, designed to free incoming mouse strains of any pathogens they might carry. The importance of this procedure is demonstrated by the fact that 51 of the mice imported into TJL during the past three years carried pathogens. A large percentage of these infections are attributable to mouse hepatitis virus. All new strains are rederived by hysterectomy or embryo transfer to ensure a high health status and to avoid endangering existing strains. The process is described in the IMR section below.

Systematic review of economic evaluations

Taking examples of health care interventions from immunisation and neonatal intensive care, a group of economists investigated whether it might be fruitful to attempt systematic review of economic evaluation studies, with the aim of summing up the economic benefit of a particular health technology. We identified a range of problems. Economic studies of the same form of care often, quite legitimately, have a range of purposes and viewpoints and designs, apply to disparate populations, and refer to different baseline levels of health care. This applied strongly in the cases of immunisation against hepatitis B, and influenza, but less so in the case of giving exogenous surfactant in neonatal intensive care units to prevent neonatal respiratory distress, where the populations, risks and technologies were more homogeneous among studies. Even if the differences among the design of the studies were not a problem, the quality of the reported studies, or the evidence they used, has generally...

MiRNAs and Their Potential Involvement in Diseases

As for miR-122, which is highly and specifically expressed in the liver, its sequestration caused a marked loss of autonomous replicating hepatitis C viral RNAs (76). This miRNA was found to facilitate replication of hepatitis C viral by targeting the 5' NTR of its genome (76).

Risk Based Healthcare Definition and Rationale

Radiation therapy (breast, thyroid and skin), altered bone metabolism and osteoporosis, obesity-related health problems (dyslipidemia, hypertension, diabetes mellitus, cardiovascular disease), liver failure secondary to chronic hepatitis C following blood transfusion and endocrine dysfunction following chest mantle or cranial radiotherapy. Primary, secondary and tertiary prevention, including tobacco avoidance cessation, physical activity, low-fat diet and adequate calcium intake, can modify risk. Longitudinal care addressing other late effects, such as infertility, musculoskeletal problems, cognitive dysfunction and psychosocial issues, may also improve survivors' health outcomes and quality of life.

Drugs For Treating Amebiasis

Amebiasis is an infection of the body by the protozoa Entamoeba histolytica, which most often affects the large intestine, although they can also affect the lungs, liver, brain, and other organs. This disease can attack the gastrointestinal tract without any clinical symptoms, with moderately expressed clinical symptoms (diarrhea, cramps, meteorism), as well as with symptoms of acute ameba dysentery, which is accompanied by bloody diarrhea, vomiting, fever, and dehydration. The presence of the protozoan microorganisms E. his-tolytica in other organs can cause liver death, ameba hepatitis, and lung abscess. Cases of heart damage (causing pericarditis) and brain damage (leading to brain abscess) have been described.

Sbp And Sbprelated Complications As Possible Risk Factors Attending Liver Transplantation

Assessment of possible contraindications to liver transplantation is also mandatory in patients who are potential candidates for this therapy. Patients with SBP can present with noninfectious contraindications to liver transplantation that may preclude the transplant procedure. Such contraindications include (a) massive peritoneal adhesions (b) complete splenic-mesenteric-portal thrombosis (c) poor short-term prognosis because of extrahepatic malignancy or AIDS or (d) other severe extrahepatic diseases, advanced hepatocellular carcinoma, active alcoholism or high hepatitis B virus (HBV) replicative status (1-6,25,26). In addition, several specific circumstances capable of influencing the result of liver transplantation in patients with SBP deserve adequate discussion.

The Clinical Problems Hemophilia A

Hemophilia A is an X-linked hemorrhagic disease due to a mutation of the gene encoding for factor VIII. The incidence is 1 in 5000 males and 60 of patients with the mutant gene are severely affected with less than 1 of normal factor VIII activity. Those with 1-5 have moderate disease and over 5 the disorder is mild. Intravenous exogenous factor VIII is the accepted treatment that does not always prevent bleeding episodes and is expensive. Bleeding into joints leads to arthropathy which can be severely disabling and bleeding can occur at any site causing a multiplicity of symptoms. Plasma and blood transfusions have caused severe viral infections, notably HIV and hepatitis B and C.

Remediation Of Sewage Contamination

Basic principles of sewage remediation include (1) prompt physical removal of sewage (black) water, (2) thorough and often repeated disinfection of interior surfaces that came in contact with sewage water, and (3) prompt drying of interior surfaces following disinfection so as to remove conditions that promote mold growth. Specific actions recommended during sewage cleanup are described in IICRC Standard S50013 and by Berry et al.37 Prompt removal of sewage water and disinfection of affected surfaces are recommended because of the presence of pathogenic microorganisms and invertebrates (e.g., hepatitis A, Escherichia coli 0157 H7, Giardia lamblia, Ascaris lumbricoides see Ref. 38 for a description of sewage organisms).14

Congenital Abnormalities and Metabolic Disorders


Microscopic Features Histological Patterns and Cytological Variants Ultrastructure and Special Techniques

Brown Atrophy The Liver

Pathways of hepatitis B and C viruses and of aflatoxin have been discussed already. Both Tables 4 and Figure 7 are somewhat wishful and idealized since such evidence as we have is patchy. Broadly speaking, the genetic changes in carcinogenesis at any site are multiple and cumulative and their phenotypic expressions are not easily identified. What we have at present is an incomplete mosaic from which most of the pieces are missing. However, they can be broken down into alterations in cell cycle regulation, growth factors, oncogenes, tumour-suppressor genes and epigenetic changes, such as telomerase activity. All of these have been investigated in hepatocellular carcinoma and found to be acting abnormally in a varying proportion of cases (Feitelson and Duan, 1997 Geissler et al., 1997 Idilman et al., 1998 Chen and Chen, 1999 Hirohashi et al., 2000). This is a distinctive type of hepatocellular carcinoma that affects adolescents and young adults of either gender. It is not associated...

Epidemiology Of Q Fever In Humans

Dominant features are fever and hepatitis (10,11). In contrast, in the south of France both hepatitis and pneumonia are observed, but hepatitis is more frequent than pneumonia (12). It is noteworthy that in Canada, the features of an outbreak of Q fever in Newfoundland were confined to a self-limited febrile illness in Alberta, sporadic cases consist mostly of hepatitis or a self-limited febrile illness. Interestingly, in this province many of the patients with Q fever have an urticarial rash. Thus, one might ask why pneumonia is a dominant manifestation of Q fever in Nova Scotia and not elsewhere in Canada. Furthermore, Q fever in a geographic area may be endemic or epidemic and shift back and forth between these two entities.

Primary bacterial infections pyodermas

Body piercing has been frequently associated with localized staphylococcal infection and pseudomonas infection and rarely bacteremia and endocarditis. Tuberculosis, hepatitis C and B, and even HIV may have been transmitted in this way. Noninfectious complications are keloids and allergic dermatitis. This fad should not be recommended, especially in tongue, lips, navels, nipples, and genitalia.

Congenital triangular alopecia Brauer nevus temporally limited alopecia

Purpura, livedo reticularis, and ulcers, especially on lower extremities caused by a complex of proteins that precipitate on cooling in vitro. It can be primary or associated with underlying cancer, collagen vascular diseases, infection, and thromboembolic disease. Hepatitis C may be associated and interferon alpha may be therapeutic.

Hepatic Vascular and Lymph Systems

When liver parenchymal cells are destroyed, they are replaced with fibrous tissue that eventually contracts around the blood vessels, thereby greatly impeding the flow of portal blood through the liver. This disease process is known as cirrhosis of the liver. It results most commonly from alcoholism, but it can also follow ingestion of poisons such as carbon tetrachloride, viral diseases such as infectious hepatitis, obstruction of the bile ducts, and infectious processes in the bile ducts.

Antiproliferative Effect of SST Analogs on Gep Net

Somatostatin Analogues

The most common side-effects of somatostatin analog are generally mild and include nausea, transient abdominal cramps, flatulence, diarrhea and local reaction at the injection site. Most of these minor side-effects resolve with time. In 2-50 of patients gall stones are formed de novo, but these remain virtually always asymptomatic. Rare, more severe adverse events of octreotide therapy include hypocalcemia, bradycardia, acute pancreatitis, hepatitis, jaundice, transitory ischemic attacks, and a negative inotropic effect of the analogs.18,4

SHARP Fact Fact Sheets

- Chlamydia, Gonorrhea, Syphilis, Bacterial Vaginosis, Trichomoniasis, Genital Herpes, Human Papillomavirus, and Hepatitis B Bacterial Vaginosis pdf or html Chlamydia pdf or html Gonorrhea pdf or html Genital Herpes pdf or html Hepatitis B pdf or html Human Papillomavirus pdf or html Syphilis pdf or him Trichomoniasis pdf or htm

Effect Of Spirulina On Fatty Liver

Fatty liver is a common cause of chronic liver disease and refers to accumulation of excess fat in the liver. It is diagnosed that if fat exceeds 5 of the total weight of normal liver or when more than 30 of the hepatocytes in a liver lobule have lipid deposits, most of the fat that accumulates in the liver is triacylglycerols and fatty acids other forms of fat, such as cholesterol, cholesterol ester, and phospholipids, are also present. Fatty liver is often associated with alcoholic liver disease, hyperinsu-linemia, and insulin-resistance. Accordingly, it is most often observed in alcoholics, obese persons, and diabetic patients. It is also frequently caused by drugs,83 viral hepatitis,84 chemical intoxication,85 pregnancy,86 intestinal bypass surgery,87 and malnutrition.88 Histological findings reveal that fat deposits in the liver may vary in size and distribution. Hepatocytes may contain large fat droplets with an anomalously displaced nucleus (macrovesicular type) or multiple...

Spirulina Antiviral Studies In Vivo

Patients with chronic viral hepatitis treated for 1 month with Spirulina did not show any improvement in the aminotransferases levels or in their general state.25 This result could be explained because until now, there is not any in vitro study showing that Spirulina has an antiviral effect on hepatitis B or C viruses, which are the viruses involved in chronic hepatitis. On the other hand, even though Spirulina could enhance the immune response of the patients, it is known that viral chronic hepatitis are related to alterations on the immune response induced by the viral infections.

Porphyria Cutanea Tarda

The most common porphyria with cutaneous manifestations is symptomatic porphyria or porphyria cutanea tarda (PCT). Patients with this disorder usually are older than 40 years, drink heavily, and are unaware that they are sensitive to sunlight. Diabetes mellitus is found in 25 of cases of PCT 90 or more have hepatic siderosis. Nearly all untreated patients with PCT show abnormal bromsulfophthalien retention. PCT is relatively uncommon in women who are not taking estrogens. A PCT-like illness has been observed in patients undergoing hemodialysis for chronic renal failure. PCT also has been linked to several toxins ( e.g., hexachlorobenzene and dioxin). Hepatitis C infection has been implicated as a possible etiologic agent in some patients and may be related to some of the associated liver disease. HIV-positive patients have an increased incidence of PCT associated with hepatitis C infection.

Hepatobiliary Tree 1231 Pathophysiology 12311 Normal Anatomy and Physiology

The liver is the largest organ in the body and consists of right and left lobes joined posteroinferiorly at the porta hepatis. The gall bladder lies under the visceral surface of the liver. The hepatic lobule, which contains a central vein that is a tributary of the hepatic vein, is the basic ultrastructural unit of the liver. The central vein of each hepatic lobule drains into the inferior vena cava. Columns of hepatocytes radiate from the center of each lobule and are separated by sinusoids. Hepatic sinusoids are lined with reticu-loendothelial or Kupffer's cells. The hepatic lobule is divided into three functional zones that each receives blood of varying nutrient and oxygen content. Zone 3,which receives the least oxygen and nutrients,is the most vulnerable to injury. Hepatic arterioles, portal vein radicles, and branches of the left and right hepatic ducts are located in portal triads between the hepatic lobules. The left and right hepatic ducts fuse at the porta hepatitis to...

Protection against Irritants

Iodine and a substance that makes the iodine soluble in water insensitive to blood and organic substances active against hepatitis B viruses absorption and systemic toxicity possible under certain conditions incompatible with mercury compounds, metals and quaternaries can stain clothing and porous surfaces Coal tar derivatives, turn milky in water, strong odour toxic stable, not very sensitive to organic substances ineffective on hepatitis B virus phenols must not come into contact with strong oxidizing agents such as peracetic acid phenols modify rubber and synthetic materials

Selective Activation Of Rodent Liver Progenitor Cells

From a practical standpoint, protocols that avoid the use of liver carcinogens would be highly desirable, and several of these have been devised. Intraperitoneal injection of galactosamine induces extensive liver damage that results in marked oval cell proliferation beginning within 24 h post injection, peaking at 5 d (Lemire et al., 1991 Dabeva and Shafritz, 1993) and diminishing thereafter as oval cells undergo hepatocytic differentiation or apoptosis. In Long-Evans Cinnamon (LEC) rats, an inbred strain that carries a defect in the Wilson's disease gene, oval cell expansion occurs spontaneously in response to the acute hepatitis that occurs at 20-23 wk of age (Takahashi et al., 1988 Betto et al., 1996). Survivors of acute hepatitis (the end result of copper accumulation caused by the genetic defect) develop chronic hepatitis that ultimately leads to the generation of cholangiocarcinomas Although the rat has been the preferred animal model for studying oval cell activation, several...

OGrady Classification

The above definitions have attempted to clarify the relationship between prognosis and time of onset of encephalopathy. However, after a detailed review of their FHF patients, O'Grady et al proposed a new terminology (Table 2.1).8 Hyperacute liver failure was defined as the development of encephalopathy within 7 days of the appearance of jaundice. These patients had a fair prognosis with a survival rate of 36 , despite a 69 incidence of cerebral edema. Etiology in this group included all cases of paracetamol overdose and many hepatitis A and B virus infections. Patients with acute liver failure developed encephalopathy 8-28 days after the onset of liver dysfunction. Even though the incidence of cerebral edema (56 ) was similar to that seen in hyperacute liver failure, the survival rate was only 7 . Indeterminate etiology accounted for 46 of these cases. Subacute hepatic failure occurred when encephalopathy developed 5-12 weeks after the onset of jaundice. Although the incidence of...

Epidemiological Studies Evaluating Cancer Causation

Among cancer patients, the outcome under investigation (death, metastasis or recurrence) is a relatively frequent effect, and the corresponding study size can be manageable. Among healthy individuals, the frequency of occurrence of any particular cancer is low and the corresponding study size must be very large, making the follow-up and compliance problems exceedingly difficult. Nevertheless, a few such studies have been undertaken, either by investing large resources (e.g. the IARC study targetting the prevention of hepatocellular carcinoma in the Gambia through active immunization against hepatitis B virus) or by reducing the required sample size by focusing on preneoplastic conditions that identify high risk individuals. Epidemiological studies specifically designed to address a particular aetiological hypothesis are usually called analytical. The objective of analytical studies is to document causation between exposures and a certain disease. In analytical...

Lars Zender and Stefan Kubicka

RNA interference (RNAi) is a sequence-specific gene-silencing mechanism triggered by double-stranded RNA. RNAi was shown to allow transient or stable knockdown of gene expression in a broad range of species and has been used successfully for functional genomic screens in mammalian cells and Caenorhabditis elegans. Standard therapeutic use of RNAi in clinical settings in humans has been hampered by the lack of effective methods to deliver the small-interfering RNAs (siRNAs) or short-hairpin RNA expression vectors into the diseased organs. In mice, systemic delivery of siRNAs by hydrodynamic intravascular injection leads to highly efficient uptake of siRNAs into the liver. Several groups demonstrated therapeutic use of RNAi in mouse models of acute liver failure or hepatitis B virus replication. This chapter will focus on the technical background of hydrodynamic and portal vein delivery techniques in mice and will give practical guidance for using these techniques for siRNA delivery...

Stem Cells of the Liver and

The clonogenic ability of human hepatocytes in chronic hepatitis can be indirectly estimated. Using mathematical modelling of viral kinetics it has been estimated that in chronic HBV infection, between 0.3 and 3 of all hepatocytes are killed daily and therefore replaced to maintain a stable liver cell mass (this approximates to 109 of the liver's 2 x 1011 hepatocytes).12 This is in accordance with the hepatocyte proliferation levels in chronic hepatitis B and C, where proliferating cell nuclear antigen (PCNA) indices of 0.1 to 3.6 are found, and Ki-67 labelling indices in hepatitis C of 1 to 14 .13'14 In chronic hepatitis the parenchymal mass can therefore be maintained through prolonged hepatocyte self-replication, and such cells could be the target for DNA-damaging agents and thus initiation events. The hepatocyte proliferation rate increases in hepatitis C with increasing histological damage until cirrhosis is reached when the proliferation rate falls.15 This fall in hepatocyte...

Nonneoplastic and Preneoplastic Lesions

In the human liver opinion is divided concerning the clonality of lesions often regarded as preneoplastic some maintain that while lesions such as benign adenomatous hyperplasia and focal nodular hyperplasia are polyclonal, but hepatic adenomas and even small (< 25 mm) hepato-cellular carcinomas are clonal. Others, examining the integration patterns of hepatitis B virus, claim that atypical adenomatous hyperplasisa and focal nodular hyperplasias are clonal. Hepatocellular carcinoma is frequently multi-focal and whether these arise from a single clone or independently is controversial, but most authors agree that an independent origin is more likely. Thus, after liver damage, clonal selection occurs during regeneration, leading to the genesis of persistent benign focal proliferations, which may be themselves clonal. This is followed by the development of clonal hepatocellular cancer from one or more such nodules. There is also substantial evidence from hepatitis B and C virus...

Therapeutical Use of siRNA to Prevent and Treat Acute Liver Failure in Mice

ALF is defined as a dramatic clinical syndrome in which a previously normal liver fails within days or weeks. Three subgroups of ALF can be distinguished, hyperacute, acute, and subacute liver failure. Despite the frequent occurrence of cerebral edema and renal failure in patients with hyperacute liver failure, prognosis without transplantation is relatively good. Survival rates in patients with acute and subacute liver failure, however, are at best 15 (20,21). The etiology of ALF shows marked worldwide variation in underdeveloped countries viral causes predominate, whereas drug-induced hepatotoxicity and seronegative hepatitis predominate in most countries of the Western world (22). To this day, the management of these varying clinical scenarios is essentially supportive. It aims to identify and remove the insult that led to destruction of the liver, whereas preventing associated complications, such as acute renal and respiratory failure, bleeding diatheses, severe sepsis, cerebral...

Chance Confounding And Bias

Otherwise strongly related with it, is also independently related to the exposure under investigation (Figure 1). Thus, if one wishes to examine whether hepatitis C virus (HCV) causes liver cancer, hepatitis B virus (HBV) would be a likely confounder because HBV causes liver cancer and carriers of HBV are more likely to also be carriers of HCV (because these two viruses are largely transmitted by the same route). Hence, if the confounding influence of hepatitis B is not accounted for in the design (by limiting the study to hepatitits B-negative subjects) or in analyses of the data, then the strength of the association between hepatitis C and liver cancer would be overestimated.

Risk Assessment and Risk Reduction Counseling Guidance and Training for Health Care Providers

You can't tell if potential partners are high risk just by looking at them. People who may be at higher risk of having a sexually transmitted infection including those who trade sex for money or sex for drugs, because they may have sex with many other people. Other people who may be at higher risk are people who share needles, because this activity can result in HIV, Hepatitis B and C infections, which can then be spread sexually. Non-monogamous men who have sex with men are also at higher risk of being infected with HIV and Hepatitis B because the risk of transmitting these viruses is greater with anal intercourse than with vaginal or oral intercourse and because these men may have many sex partners.

Precancerous Changes in the Liver Screening and Prevention

Cirrhosis itself is a precancerous condition but the magnitude of the risk varies with aetiology, i.e. it is high with HBV and HCV but low with alcohol. Sustained proliferation of liver cells consequent upon chronic hepatitis B and C or the daily ingestion of a hepatoxic agent such as alcohol over many years seems to be the most likely mechanism of carcinogenesis as it predisposes the cell to accumulate DNA abnormalities. Proliferation prevents the repair of any damage to DNA and it is then 'fixed' and transmitted to the progeny. The 'right' combination of sites of damage that results in neoplastic transformation is a rare event, hence it takes time for the tumour to develop. The best preventive measure for hepatocellular carcinoma is elimination of the causative agent (primary prevention). Vaccination against HBV is highly effective in reducing chronic infection with this virus and has resulted in a reduction of tumour incidence in countries with nation-wide programmes such as...

Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College 1 Xian Nong Tan Street

The genus Salvia has a variety of more than one hundred species distributed in several regions in China. Thirty of them are used as traditional and folk medicines (Huang 1991). The dried root of Salvia miltiorrhiza, called Danshen, is one of the most well known traditional Chinese medicines among these species. It has the effect of promoting blood circulation and removing stasis, and is widely used for the treat ment of coronary heart diseases, cerebrovascular diseases, hepatitis, hepatocirrhosis, chronic renal failure, dysmenorrhea and neurasthenic insomnia. The chemical constituents of S. miltiorrhiza have been studied for more than fifty years. But the studies have mainly been focused on the lipophylic diterpenoid quinones. According to traditional Chinese medicinal prescriptions it is used as a decoction. Since the seventies injections of Danshen have been used for the treatment of angina pectoris, myocardial infarction and various types of hepatitis. So there should still be...

Changes Induced by Cytotoxic Therapy

Fibrosis,which is generally periportal and concentric (Fig. 12.4), is the most frequently described complication of antineoplastic therapy observed in the liver 63 . Hepatic fibrosis may be associated with fatty infiltration, focal necrosis and nodular regeneration of cirrhosis, as well as portal hypertension. Chronic hepatitis, regardless of its etiology, is characterized by portal-periportal lymphoplasmacytic infiltration with varying degrees of fibrosis and piecemeal necro sis. The histopathology of veno-occlusive disease demonstrates endothelial injury with fibrin deposition if progressive, fibrous obliteration of central veins ensues. GVHD is associated with hepatocellular necroinflammatory changes suggestive of chronic active hepatitis, a paucity of interlobular bile ducts and intrahepatic cholestasis (Fig. 12.5) 22, 64 . Cell-mediated immune dysregulation is implicated in the pathophysiology of chronic GVHD in most studies. However, findings of deposits of immuno-globulin and...

Cirrhosis In Liver Disease


Assessment Of Immune Response With Antigen Arrays

These data are encouraging in terms of the development of microarrays with a large panel of epitopes and mimotopes for the diagnosis of viral and perhaps bacterial infections that provoke levels of pathogenic agents in humans too low to be detected by convenient methods. In contrast, the generated antibodies are sufficient to provide a higher sensitivity for detection with arrayed antigens 67 . Antigen microarrays will also be useful to assess the antibody repertoire in patients infected by Epstein-Barr or hepatitis B and C viruses since acute, chronic, and convalescence forms of the corresponding infections are characterized by modulation of IgG and IgM immunoglobulin titer against particular viral antigens (reviewed in Neuman de Vegvar et al. 64 and Storch 68 ).

Therapeutic Interventions In The Prevention Of Vertical Hiv Transmission

Drug toxicity was observed in 29 (5 17) of patients randomized to the NVP arm compared with only 5 (1 21) of patients randomized to the nelfinavir arm (p 0.07). Severe reactions reported in the NVP group included one participant with fulminant hepatic failure who died, and a second participant who developed Stevens-Johnson syndrome. The single adverse reaction reported in the nelfinavir group was hepatitis. The authors caution that continuous NVP use may be associated with increased toxicity among HIV-infected women, particularly those with CD4 lymphocyte counts greater than 250 cells L. These findings are corroborated by observations in nonpregnant patients. There were no adverse events in either mothers or infants. There were no reports of hypersensitivity reaction associated with the use of abacavir. Additionally, there were no reports of birth defects in this cohort, and growth parameters at 6 mo of age were normal for all infants. The transmission rate in this group was 2.8 ,...

Decreased Prothrombin Factor VII Factor IX and Factor X Caused by Vitamin K Deficiency

With few exceptions, almost all the blood-clotting factors are formed by the liver. Therefore, diseases of the liver such as hepatitis, cirrhosis, and acute yellow atrophy can sometimes depress the clotting system so greatly that the patient develops a severe tendency to bleed.

Viral Causes of Liver Failure

Viral Hepatitis Hepatitis A (HAV) The incidence of fulminant and subfulminant HAV is very low and occurs in less than 0.01 of all HAV infections.3 Younger patients rarely develop hepatic failure. HAV accounted for less than 6 of FHF and SFHF cases due to viral hepatitis in the United States and France but 31 of the cases in Britain.14-16 HAV infection results in FHF more frequently than SFHF.17 Survival with medical therapy is relatively high, ranging between 40 and 60 .16,18 Relapse of HAV occurs in 10 of patients, usually within 2-3 months after clinical improvement from the initial illness.19 Relapse is recognized by an increase in transaminases and bilirubin, with reappearance of the virus in the stool. If encephalopathy occurs during this period, the outcome is usually fatal.20 Hepatitis B (HBV) Fulminant and subfulminant HBV accounts for less than 1 of HBV infections, but is the most common cause of fulminant viral hepatitis.21-23 In the United States and France, the prevalence...

Carcinogenesis Protocols Producing Progenitor Cellderived

Recent studies indicate that progenitor cell activation is a constant feature of viral hepatocarcinogenesis. Patients with chronic HCV and HBV infections often exhibit extensive oval cell proliferation, usually in close proximity to regenerating nodules and HCC (Hsia et al., 1992 Lowes et al., 1999). Approximately 50 of the HCCs found in HBV-positive individuals express both oval cell and hepatocyte markers, a percentage similar to CDE diet-induced carcinomas in the rat. These observations suggest that HCCs resulting from viral carcinogenesis arise from oval cell progenitors. Interestingly, in the woodchuck experimental model systems for viral hepatocarcinogenesis, oval cells are nonpermis-sive for virus infection (Hsia et al., 1992 Hixson et al., 1996). This suggests that, similar to other induction protocols, activation of progenitors in the woodchuck model results from the ability of the virus to compromise directly or indirectly the viability replicative capacity of hepatocytes....

Clinical Manifestations Of Mitochondrial Toxicity

Hepatitis C itself is associated with lipoperoxidation that can lead to mito-chondrial dysfunction and depletion in mtDNA (53). A recent study found significant mtDNA depletion as well as electron microscopic alterations of mitochondria in 92 of patients with hepatitis C, genotype 1 (54). In addition, ribavirin may enhance the risk of NRTI-associated mitochondrial dysfunction (55). Therefore, in subjects coinfected with HIV and hepatitis C, the potential for mitochondrial damage is significant these subjects deserve close observation and a low threshold to undergo lactate testing in case of any suggestive symptom(s).

Liver Directed Cell Therapy for Acute and Chronic Liver Failure

End-stage liver disease with complications, such as hepatic encephalopathy and coagulopathy, represents another challenging condition for cell therapy. Many patients with chronic liver failure are candidates for orthotopic liver transplantation. However, the current organ supply is insufficient and fourfold or greater disproportionality exists in the United States between people on waiting lists versus recipients of liver transplants. Many liver recipients develop recurrent disease in the transplanted organ (e.g., hepatitis C). These individuals often show rapid advancement toward liver failure and have no further therapeutic prospects. Moreover, in many parts of the world, liver transplantation is not available either because of prohibitive costs or lack of donor organs. Therefore, cell transplantation could have a potential role to play in this situation, especially if transplanted cells could be made to resist viral hepatitis or other ongoing

Using Foods To Convey Medication

There are many sound reasons why intramuscular injection is effective for conveying vaccine antigens to stimulate human immune systems. The Sabin oral vaccine for poliomyelitis is one exception. Now Charles J Arntzen and his colleagues want to produce edible vaccines in fruits, and a high priority has been suggested for hepatitis B vaccine in bananas.32 The justification offered is that local production of the fruit

Concluding Remarks and Potentials for Therapeutic Options

Heterotrimeric G proteins transduce signals in response to a number of hormones and neurotransmitters. Furthermore, about 50 of all drugs used in therapy act through GPCRs, thus emphasizing the importance of GPCR G protein signaling pathways in medical treatment. In addition to the role of G proteins in signaling mechanisms, the identification of their localization also intracellu-larly as well as the discovery of novel receptor-independent mechanisms for their activation, suggest that G proteins may have other important cellular functions than acting as signal transducers. In light of this, the growing body of evidence that connects heterotrimeric G proteins to various diseases, is not surprising. Added to the initial discoveries that toxin-mediated modifications of G proteins may cause infectious disease as well as the delineation of Gsa mutations as the cause of certain endocrine disorders, is an emerging understanding of a more complex role for G proteins in disease mechanisms....

Immunological Considerations

Carcinogenicity of this virus, in the causation of BL and other non-Hodgkin lymphomas, immunosuppression-related lymphomas, Hodgkin's disease (HD), sinonasal angiocentric T cell lymphoma and NPC, to allow them to conclude that EBV is a human carcinogen. Subsequent to this document, more information on the expression of EBV in breast cancer has been published, and the viral genome has also been identified on two occasions in carcinomas of the liver, previously a preserve of the hepatitis viruses. The future will undoubtedly bring more 'associations' for this ubiquitous virus, and hopefully, if suitable animal models

Other Viral Causes of Liver Failure

The herpes virus family rarely causes FHF or SFHF. There have been several reports of Herpes simplex virus types 1 and 2 producing massive hepatic necrosis, usually in patients who are pregnant or immunocompromised.68-71 Reports of FHF with cytomegalovirus and Epstein-Barr virus infections have been controversial due to lack of availability of serological confirmation and or exclusion of other etiologies.72,73 Disseminated adenovirus can occur in immunosuppressed patients and presents with fever, pneumonia and liver dysfunction.74 Syncytial giant cell hepatitis with intracytoplasmic structures resembling paramyxoviral nucleocapsids has also been reported to cause FHF.75 A recently discovered RNA virus, hepatitis G (HGV), has been evaluated as a potential cause of FHF. In two studies, 50 of Japanese (3 of 6) and German (11 of 22) patients with FHF tested positive for HGV RNA by PCR.76,77 Six of the 11 German patients had a primary diagnosis of fulminant hepatitis B, but their clinical...

Nucleoside Triphosphates

NTP-binding has also been observed in a number of RdRPs at sites other than the active site. In hepatitis C virus (HCV) and bovine viral diarrhea virus (BVDV) RdRPs, a regulatory guanosine triphosphate (GTP)-binding site has been localized (Bressanelli et al. 2002 Cai et al. 2005 Choi et al. 2006 Choi et al. 2004). In addition, a number of RdRP complexes have been obtained with NTPs in the absence of RNA (Ago et al. 1999 Bressanelli et al. 2002 O'Farrell et al. 2003 Thompson and Peersen 2004). Although the binding modes for NTPs that are observed in these complexes are sometimes similar to the productive mode expected for the phospho-transfer reaction, the absence of base-pairing with the template RNA strand usually leaves the base in a conformation that differs substantially from that expected in the productive mode.

Category C Severely Symptomatic

Initial laboratory studies should include CD4+ CD8+ counts (absolute cell counts and percentages) and, if possible, HIV-1 RNA levels. CBC with differential count, electrolyte and liver function panel, hepatitis screen, reactive protein reagin (RPR) or VDRL, anti-toxoplasma IgG antibodies purified protein derivative (PPD) with anergy panel, and chest x-ray should also be obtained. Ophthalmologics, dental, and gynecological examinations (including a PAP smear, chlamydia and gonorrhea studies) should be pursued. The stage of HIV-1 infection will then determine follow-up, prophylaxis, and therapeutic strategies.

Foetal Cell Microchimerism

Foetal cells may play a role both in the mother's peripheral circulation and in her tissues during gestation. During pregnancy, foetal cells have been shown to reflect the biology of pregnancy by being associated with dermato-logic disorders, such as polymorphic eruption of pregnancy56 and systemic disorders, such as pre-eclampsia.57 Foetal microchimeric cells were also present in higher numbers in women with some autoimmune diseases, such as systemic sclerosis, than in control groups58-62 and non-autoimmune disorders, such as hepatitis C63 and cervical cancer.64 Thus, foetal cells were associated with the maternal response to injury as opposed to causing disease. A non-invasive procedure based on the retrieval of microchimeric foetal cells circulating within the maternal blood for antenatal genetic analysis would enable foetal testing without risking the pregnancy. Male and female foetal cells cross the placenta in equal numbers. However, it is quicker and easier to detect the...

The Influence of Genetic Variations on Drug Effects in Other Diseases

Heterotrimeric G proteins might somehow be involved in the susceptibility to the combination treatment of hepatitis C infection using interferon-a and ribavirin. The C825T polymorphism of the GP3-subunit protein is reported to affect the response to this treatment in hepatitis C patients (52). It was found