Spectrum Of Chronic Liver Disease Research Articles

Genetic Heterogeneity of Hepatitis Viruses and its Clinical Significance

The genetic heterogeneity of hepatitis B virus (HBV) (8 genotypes A-H) has been applied for tracing the route of HBV transmission and the geographical migration of HBV carriers but it also appeared to have clinical implications. The secondary structure of e encapsidation signal could explain why the precore mutant virus prevails in Mediterranean countries, where genotype D is most prevalent, while the wild type virus is frequent in Western countries, where genotype A is most prevalent. There is increasing evidence that patients infected with genotype C have more severe outcome of chronic liver disease than those infected with genotype B. Genotype B was associated with fulminant hepatitis and more severe episodes of acute exacerbation of chronic HBV infection. Patients infected with genotype B appeared to seroconvert earlier than those infected with genotype C. The hepatitis delta virus (HDV) has 3 genotypes (I, II, III) which are associated with different disease patterns. Genotype III is the most distantly related HDV genotype and is associated with the most severe outcome while genotype II with relatively mild liver disease. The most geographically widespread genotype is I and is associated with a broad spectrum of chronic liver disease. The hepatitis C virus (HCV) displays high genetic heterogeneity with six genotypes (1-6), multiple subtypes and quasispecies. This viral diversity has epidemiological and clinical implications and has been associated with the severity of liver disease, prognosis, response to treatment and failure to generate an effective protective vaccine. HCV genotype 1 is the predominant genotype in Western countries and has been associated with a low response rate to interferon-alpha (IFN-alpha) or to the combination of ribavirin and IFN-alpha. Consequently the duration of treatment has been tailored according to HCV genotype.

Determination of hepatitis B virus genotype G by polymerase chain reaction with hemi-nested primers

Hepatitis B virus (HBV) has been classified into six genotypes designated A–F by sequence divergence in the entire genome exceeding 8%. Very recently, the seventh genotype was reported and named genotype G. HBV genotype G is distinct from genomes of the other six genotypes in that it possesses an insertion of 36 nucleotides in the core gene, and has been found so far in France and the United States. A method for determining HBV genotype G was developed by polymerase chain reaction (PCR) with primers deduced from the 36-nucleotide (nt) insertion in five isolates of HBV genotype G the sequences of which have been deposited in DNA databases. The validity of this method, for specifically detecting HBV genotype G, was verified on a panel consisting of 142 HBV isolates of six major genotypes and four of genotype G. A total of 540 sera containing HBV in Japan covering symptom free carriers and patients with a spectrum of chronic liver disease were tested by this method, but not a single HBV genotype G sample was found. A possible method for serological determination of hepatitis B surface antigen of genotype G is suggested, without amplification or sequencing nucleotides, which would expand epidemiological and clinical researches on HBV genotype G.

Spectrum of chronic liver disease due to hepatitis “C” virus infection

Spectrum of chronic liver disease due to hepatitis “C” virus infection

Role of hepatitis viruses in multistep hepatocarcinogenesis

K. Koike Worldwide, hepatitis B virus (HBV) and hepatitis C virus (HCV) infect hundreds of millions of people persistently and induce a spectrum of chronic liver diseases. Hence, they have an impact on society in a number of domains including medical, sociologic and economic. Hepatocellular carcinoma (HCC) has become the most frequent cause of death in individuals persistently infected with HBV or HCV. In particular, HCV has gained increasing attention because of its wide and deep penetration into the community, coupled with a very high incidence of HCC in the persistent infection. Once liver cirrhosis is established in hosts infected with HCV HCC develops at a yearly rate of 5 7% ‘. Knowledge on the mechanism by which HCC develops in chronic HCV infection is, therefore, urgently required for the prevention of HCC.

Value of liver biopsy in the evaluation and management of chronic liver disease in renal transplant recipients

purpose: Liver disease is a frequent complication in renal transplant recipients. To understand the nature and progression of hepatic disease in these patients, we performed percutaneous biopsies in 77 subjects who had chronic liver dysfunction in the posttransplant period. The purpose of the present investigation is to delineate the morphologic spectrum of chronic liver disease in the renal allograft recipients and to characterize the clinical and histologie progression of each of the different morphologic forms. patients and methods: Between 1971 and 1990, 915 patients received renal transplants at the Hennepin County Medical Center, Minneapolis, Minnesota. One hundred nineteen (13%) of them had abnormal liver function that persisted for longer than 6 months. Percutaneous liver biopsies were performed in 77 of these patients, but adequate tissue for histologie evaluation was available in only 72. After the biopsy, the clinical and histologie course of each subject was monitored in relation to the baseline hepatic morphology. To assess the predictive value of serum enzymes in diagnosing the histologie lesions, the level of serum enzymes at the time of the biopsy was correlated with the morphologic diagnosis. In addition, several clinical, biochemical, etiologie, and histologie variables were screened for their association with histologie progression to liver cirrhosis. results: The morphologic diagnosis in the 72 specimens evaluated at baseline was as follows: fat metamorphosis in 8 (11%), chronic persistent hepatitis in 20 (28%), early chronic active hepatitis in 20 (28%), advanced chronic active hepatitis in 15 (21%), and hemosiderosis in 9 (12%). There was no statistical correlation between the serum enzyme levels and the histologie diagnosis. During a mean follow-up of 5.7 ± 3.9 years, clinical progression to hepatic failure and death occurred in 35% of patients with early chronic active hepatitis, 55% with hemosiderosis, and 60% with advanced chronic active hepatitis. None of the patients with the morphologic diagnosis of fat metamorphosis or chronic persistent hepatitis died as a consequence of hepatic failure. Follow-up liver specimens were obtained in 34 (47%) of the original 72 subjects after a mean interval of 4.5 ± 4.3 years. Of the 15 patients with the initial diagnosis of early chronic active hepatitis, 9 (60%) showed morphologic transition to advanced chronic active hepatitis, and in 1 of the 5 patients with hemosiderosis (20%), the lesion had resolved after successive phlebotomies. During the follow-up, 60% with early chronic active hepatitis (9 of 14), 66% with hemosiderosis (2 of 3), and 100% with advanced chronic active hepatitis (4 of 4) showed histologie progression to liver cirrhosis. On the contrary, no morphologic alterations were observed in the follow-up specimens of patients with fat metamorphosis or chronic persistent hepatitis. Of the different variables screened for their association with histologie progression, older age at transplant, female sex, and morphologic diagnosis of advanced chronic active hepatitis were found to be significant. conclusion: Histologie diagnosis can be a useful marker in predicting the course of chronic liver disease after renal transplantation. Liver biopsy should be incorporated into the evaluation and management of chronic liver disease in renal transplant recipients.

The Spectrum of Chronic Liver Disease in Renal Transplant Recipients

Chronic liver disease has been reported to be an important cause of late morbidity and mortality in renal transplant recipients. We have examined the prevalence and nature of chronic liver disease among 538 patients with functioning renal allografts managed at the Western Infirmary, Glasgow, between 1980 and 1989. Thirty-seven patients (7 per cent) satisfied biochemical criteria for chronic liver dysfunction. Liver biopsies were obtained from 24 of these, and autopsy tissue was available from three other patients. Chronic hepatitis of variable severity was present in 15 patients, haemosiderosis in 12 patients and nodular regenerative hyperplasia in five patients. Nineteen patients (51 per cent) had serological evidence of infection with the hepatitis C virus, and one of these developed chronic hepatitis B and D infection as well. Although a variety of chronic liver diseases occurred in our transplant population, the frequency of serious sequelae from liver dysfunction was much lower than that reported from transplant centres in other countries.

Role of Hepatitis C Virus in Non-B Chronic Liver Disease

To assess the contribution of the recently identified hepatitis C virus to chronic liver diseases of unknown cause and chronic hepatitis attributed by exclusion to non-A, non-B hepatitis, we tested for antibody to hepatitis C in hepatitis B surface antigen-negative patients with a spectrum of chronic liver diseases. Antibody to hepatitis C virus, a marker of hepatitis C infection, was detected with a first-generation radioimmunoassay at the following frequencies in the following patient groups: 69% of transfusion-associated non-A, non-B hepatitis; 53% of non-transfusion-associated non-A, non-B hepatitis; 26% of hepatitis B surface antigen-negative hepatocellular carcinoma; 8% of cryptogenic cirrhosis; 5% to 7% of autoimmune chronic liver diseases; 19% of patients with miscellaneous types of chronic liver disease; and 0.67% of healthy controls. Among non-transfusion-associated cases, 81% with a history of intravenous drug use but only 18% with occupational exposure as health workers had antibody to hepatitis C virus. Among cases of hepatocellular carcinoma, 63% of Japanese patients but only 11% of American patients had evidence of hepatitis C infection. Comparison in a subgroup of 79 serum samples of a second-generation radioimmunoassay with the first-generation assay demonstrated a 12% increase in antibody frequency from 30% to 42%. We conclude that hepatitis C plays a substantial role in transfusion-associated and non-transfusion-associated non-A, non-B hepatitis as well as in hepatocellular carcinoma, especially in Japan, a limited role in cryptogenic cirrhosis, and essentially no role in autoimmune chronic liver diseases. Application of more sensitive immunoassays will increase the frequency of antibody seropositivity in all subgroups, but relative distinctions among risk groups are likely to remain.

PERCUTANEOUS LIVER BIOPSY AND CHRONIC LIVER DISEASE IN HÆMOPHILIACS

Systematic screening of forty-seven hæmophiliacs in Sheffield revealed abnormal liver-function tests in thirty-six (77%), with a tendency for these abnormalities to persist. To assess the importance of these abnormalities, percutaneous liver biopsy was carried out on eight symptom-free patients under factor-VIII cover. A wide spectrum of chronic liver disease was demonstrated, including chronic aggressive hepatitis and cirrhosis. The liver pathology bore no relation to clinical history or to biochemical findings. Hepatitis-B-virus markers were common, but evidence suggests that this is not the only factor contributing to the development of liver disease. The high incidence of chronic liver disease seems to be a recent development and is probably related to factor-concentrate replacement therapy.

Serum complement in chronic liver disease.

Total serum haemolytic complement activity (CH(50)) and the serum concentrations of both the third and fourth components of the complement system (C3 and C4) have been measured in 29 control subjects, 92 patients with chronic hepatocellular disease, and eight patients with large duct biliary tract obstruction. The mean C4 concentration was reduced in all types of chronic liver disease studied. However, the mean CH(50) and C3 values were increased in compensated primary biliary cirrhosis, were relatively normal in non-cirrhotic chronic active hepatitis, and were decreased in cryptogenic cirrhosis, particularly when ascites was present. There was a significant correlation between CH(50) and C3 in patients with chronic liver disease but no correlation between CH(50) and C4 or between C3 and C4. Raised values for CH(50) and C3 in primary biliary cirrhosis may be due at least in part to concomitant cholestasis since these values tend to be raised in patients with large duct biliary tract obstruction. Although primary biliary cirrhosis, chronic active hepatitis, and cryptogenic cirrhosis are considered to be part of a spectrum of chronic liver disease associated with disturbed immunity, the results of this study emphasize that there are clearly definable differences between these diseases in terms of the pattern of changes in serum complement.