Ribavirin in acute viral hepatitis.

Sixty-four patients suffering from acute viral hepatitis (excluding those suffering from hepatitis B) were selected for the double blind clinical trial. They were randomly allocated to either ribavirin therapy (200 mg four times a day) or placebo. Four patients were lost to follow up and therefore final analysis was carried out on 60 patients (thirty had received ribavirin and the rest placebo). Patients receiving ribavirin showed significant rapid improvement, with the disappearance of annoying symptoms (e.g., nausea, vomiting, etc) and return of good appetite; moreover, the abnormal blood parameters showed significant rapid changes towards normal values in ribavirin treated patients as compared to those observed in placebo group. Ribavirin was well tolerated and there were no side effects. Since acute viral hepatitis is endemic with outbreaks of epidemics in many areas at various times and as yet there is no effective anti-viral drug available with the physicians in India, ribavirin is indeed a most welcome drug for its therapy.     

Immune reactions in acute viral hepatitis.

Serial studies of PHA-induced lymphocyte transformation, serum autoantibodies, immunoglobulins and complement were performed in seventeen patients with hepatitis A and nine patients with hepatitis B. In both types of hepatitis PHA-induced transformation was markedly impaired during the 1st week after the onset of jaundice and there was less marked but prolonged impairment for a further period of 6-10 weeks. A group of eleven subjects with a previous history of hepatitis had values which were similar to those of healthy persons. Serum from patients with hepatitis A and hepatitis B contains an inhibitor of lymphocyte response to PHA. The inhibitor depresses the function of both patients' and normal lymphocytes and is only detectable during the acute phase of the illness. Washing lymphocytes free from autologous serum did not restore the PHA response to normal but the markedly impaired response present during the first 2 weeks of the illness was improved. A serum factor or factors may therefore be responsible for at least part of the impaired response of lymphocytes to PHA during the acute phase of hepatitis but does not appear to account for the more prolonged impairment of the PHA response. The protracted lymphocyte defect is possibly induced by hepatitis virus. The incidence of autoantibodies and the changes in immunoglobulin levels were similar to those reported by other workers.     

Immunological studies in children with acute viral hepatitis.

Sera from 116 consecutive unselected cases of sporadic acute viral hepatitis in children were examined for hepatitis B antigen (HBAg), smooth-muscle autoantibodies (SMA), other autoantibodies and immunoglobulins, and skin tests were performed with dinitrochlorobenzene (DNCB). HBAg was detected in twenty-one and SMA in ninety-eight out of 116 sera that had been obtained during the 1st or 2nd week from the onset of jaundice. Hepatitis B antigen was present in seventeen out of the eighteen SMA negative patients (94-4%) and in only four out of the ninety-eight SMA-positive patients (4-1%). The presence of SMA was not related to the sex and age of the patients or to the serum bilirubin and transaminase levels. SMA did not persist for more than 6 weeks from the onset of jaundice in most of the cases. In twenty-eight out of forty-one sera which were tested the IgM level was found to be elevated during the acute phase of illness and within normal limits during the recovery stage. A negative correlation between the presence of SMA and the elevated serum IgM level and the presence of HB Ag in the same patients was observed. The DNCB skin test was found to be positive in all fifty-two patients who did not have HBAg in their serum and in twenty out of the twenty-one patients who had circulating HbAg. From these findings there appears to be no gross impairment of cell-mediated immunity in acute viral hepatitis, and hepatitis A is associated with SMA production and an increase in serum IgM levels, when compared to hepatitis associated with HBAg.     

Natural killer activity in patients with acute viral hepatitis.

Using the natural killer (NK) sensitive K562 cell line, enhanced NK cell cytotoxicity was demonstrable early in the course of acute hepatitis B while normal values were obtained in patients studied during convalescence. No evidence of enhanced NK activity was instead obtained in the course of acute non-A, non-B hepatitis. Serum levels of alpha-interferon, as determined by radioimmunoassay (RIA), were significantly increased in patients with acute hepatitis B showing enhanced NK cell activity but not in those with acute non-A, non-B hepatitis and normal NK cell activity. These results suggest that natural cytotoxicity may play a role early in the course of acute hepatitis type B, before antigen-specific T lymphocytes become fully operative.     

A new hepatitis B virus variant in a chronic carrier with multiple episodes of viral reactivation and acute hepatitis

To examine whether there are HBV variants not yet described which cannot express HBe due to a mutation in the pre-C region, and, if they exist, whether they cause a particular course of infection and disease, we analyzed the HBV genomes of a HBs/anti-HBe positive chronic carrier who had several episodes of acute reexacerbations of chronic hepatitis with at least two viremic phases. Direct sequencing of the precore/core and the pre-S regions of the HBV sequences of both viremic phases amplified by the polymerase chain reaction revealed that they were very similar to each other but substantially divergent from published HBV genomes. Both virus populations contained a mutation in the first nucleotide of the pre-C translation initiation codon (AUG/CUG) which prevents HBeAg expression. These data demonstrate the existence of a new HBV variant which can enter a latent phase from which it can be reactivated with acute reexacerbation of liver inflammation.     

Immune response to rabbit liver-specific lipoprotein in acute viral hepatitis.

A serial prospective study of cell-mediated immunity to rabbit liver-specific lipoprotein (RLSP) has been done in 26 patients with acute viral hepatitis (AH) (18 HBsAg+ and eight HBsAg-) using a lymphocyte transformation test. An increased stimulation index was recorded in 56% of HBsAg+ cases and in 63% of the HBsAg- group at the first determination within 2 weeks of presentation. A progressive return to normal values was observed during the course of the disease. In one patient, however, the stimulation index remained high at 6 months after presentation and liver biopsy showed the appearance of chronic active hepatitis. Results within the normal range of values were observed when a macromolecular kidney protein fraction was used as antigen: further evidence of an organ-specific component in RLSP preparation to which the immune response seems to be directed. These findings demonstrate the existence of a common and time-limited sensitization to RLSP in acute viral hepatitis irrespective of HBsAg status. It is suggested that RLSP may be a useful alternative to human LSP in evaluating immune reactions in liver diseases.     

Morphological characteristics of acute viral hepatitis]

From the literature and their own observations the authors present morphological criteria of acute viral hepatitis which may be used for differential diagnosis from hepatites of other etiology (toxic, drug). Examinations of liver biopsies from patients with viral hepatitis permit to establish the stage of the disease and to predict its possible outcomes.     

Outbreak of acute viral hepatitis due to hepatitis E virus in Hyderabad

PURPOSE: A waterborne outbreak of viral hepatitis occurred in the old city of Hyderabad from March through August 2005. An attempt was made to study the outbreak clinically, serologically, and etiologically. METHODS: Five hundred and forty-six clinically and biochemically documented cases were screened for the hepatotropic viral markers, hepatitis A, B, C, and E by the ELISA method. Their demographic characteristics and outcomes were analyzed. Point source contamination of the water supply with sewerage was identified. RESULT: Our data confirms hepatitis E as the major cause of the outbreak (78.57%). Occasionally, mixed infection of HEV-HAV (5.31%) or HEV-HBV (0.91%) was detected in the present series of acute viral hepatitis. CONCLUSIONS: HEV was confirmed as the major etiological agent in this outbreak that was transmitted by contaminated drinking water. The study highlights the importance of screening for both enterically transmitted hepatotropic viral markers as well as the parenterally transmitted hepatotropic viral markers during outbreaks of acute viral hepatitis.     

Developments in viral hepatitis.

Viral hepatitis is a major public health problem occurring endemically in all parts of the world. The general term viral hepatitis refers to infections caused by hepatitis virus type A, type B and a more recently identified infection referred to as "non-A: non-B" hepatitis. These clinically and pathologically similar forms of hepatitis have been studied intensively following the discovery of a specific antigen, Australia antigen, one of the markers of infection with hepatitis B virus.     

Liver morphology in acute viral hepatitis related to the hepatitis B antigen

The liver histology in infectious hepatitis or hepatitis A (HA) and serum hepatitis or hepatitis B (HB) is generally described as identical. However, the clinical separation of the two types has been a problem. Today a serological reaction based on the well documented association between hepatitis antigen and HB is of great assistance in the differential diagnosis. The present study of 165 hepatitis cases separated into hepatitis A and B by this test method indicates quantitative differences in the liver histology of the two types. Thus HB was associated with more prominent parenchymal cell damage and Kupffer cell reaction, while intrahepatic cholestasis was found in a significantly higher frequency in cases presumed to represent HA.The presence of intrahepatic cholestasis was associated with higher levels of serum bilirubin but otherwise no correlation was found between liver morphology and biochemical liver tests.The patients included a group of young intravenous amphetamine addicts with HB. No differences of importance were found histologically in addicts and other patients with hepatitis B.     

Pathogenesis of an acute viral hepatitis: inclusion body hepatitis in the chicken

Summary The pathogenesis of inclusion body hepatitis was studied following the oral administration of a serotype 8 strain of avian adenovirus into 2-day-old specific pathogen free chickens. Viral antigens were detected in tissues at various times post inoculation (pi) by enzyme-linked immunosorbent assay and by immunocytochemistry. Viral antigens were detected in intestinal epithelium from 12 h to 13 days pi and in the plasma fraction of blood by 24 h pi. A biphasic, cell-free viremia with peaks at 2 and 7 days pi was recorded. Antigens were first detected in the liver from 2 days and reached peak levels at 6 days pi. The second peak of viral antigens in blood plasma was probably due to release of virus from damaged hepatic cells. Initially, viral antigens in the liver were restricted to cells lining the sinusoids but increasing involvement of hepatocytes occurred with time. Small amounts of viral antigens were detected in other tissues. Following the appearance of neutralizing antibodies in serum from 7 days pi, the levels of viral antigens in all tissues decreased and were undetectable by 15 days pi. This viral hepatitis of chickens is possibly a useful model for other viral infections where a cell-free viremic phase is important for spread of virus from primary sites to target organs, such as the liver.     

Naturally occurring anti-interferon-alpha 2a antibodies in patients with acute viral hepatitis.

The occurrence of antibodies against recombinant human interferon-alpha 2a (IFN-alpha 2a) in patients with acute viral hepatitis (AVH) was examined by ELISA. Naturally occurring IgG anti-IFN-alpha 2a were found in 50% of patients with type A, 50% of those with type B and in 8.3% of those with non-A, non-B AVH. The corresponding frequencies of IgM antibodies were 80%, 30% and 33.3%, respectively. IgM anti-IFN-alpha 2a were found more frequently in patients with AVH type A than in normal control subjects (P less than 0.01). Anti-IFN-alpha 2a were detectable at the highest frequency 3 weeks after acute onset and then became negative. An absorption experiment revealed that IgM anti-IFN-alpha 2a did not cross-react with recombinant human IFN-alpha 2b. Immunoblotting analysis confirmed the binding of antibodies to IFN-alpha 2a. Sera positive for IgG and/or IgM anti-IFN-alpha 2a were unable to neutralize IFN-alpha 2a. The appearance of anti-IFN-alpha 2a was not correlated with disease severity. There was no evidence to suggest that anti-IFN-alpha 2a impaired the elimination of hepatitis virus. This is the first study to demonstrate the occurrence of anti-IFN-alpha 2a in patients with AVH. Detection of anti-IFN-alpha 2a may be useful for clarifying any underlying immune events in various diseases.