Etiology Of Chronic Liver Disease Research Articles

Aetiology and Pathophysiology of Chronic Liver Disorders

The aetiology of chronic liver disease covers a wide range of congenital or acquired abnormalities of the hepatocellular biochemical network. Although our knowledge has considerably increased in recent years, the aetiology of chronic liver disease often remains obscure. Acquired irreversible disturbances of normal liver function can be mediated by hepatotrophic viruses, chemicals, chronic oxygen depletion, or interference with the immune system. Considerable progress has been made in the detection and characterisation of hepatitis B, C, and D viruses as causative agents of chronic active hepatitis. Alcohol abuse remains the predominant cause of chronic liver disease in the Western world. The targets of autoantibodies used to diagnose autoimmune diseases of the liver and primary biliary cirrhosis continue to be biochemically defined. Their significance for the aetiology of the disease, however, remains to be established. Nonparenchymal cells play an important role in the sequence of events following hepatocellular injury and ultimately leading to liver cirrhosis. They release vasoactive compounds, cytokines, and other important mediators, and participate in the modulation of the extracellular matrix that is characteristic of liver fibrosis and cirrhosis. The biochemical basis of liver cell necrosis remains poorly defined. In spite of recent progress, and the detection of some new pathogenic principles that help in the understanding of the complications of chronic liver disease such as portal hypertension, oesophagogastric variceal bleeding, portosystemic encephalopathy, ascites, and other metabolic disturbances, many questions concerning the aetiology and pathophysiology of chronic liver disease and its complications remain to be answered.

Development of a second generation monoclonal immunoradiometric assay increased sensitivity leads to enhanced detection of hepatitis B viral infection

We have developed and employed a second generation monoclonal immunoradiometric assay (M2-IRMA) using antibodies of high affinity for epitopes that reside on hepatitis B surface antigen (HBsAg). This assay is capable of detecting as little as 15 pg/ml of HBsAg in serum. Improvements in sensitivity over a first generation immunoradiometric assay (MI-IRMA) was achieved by increasing the sample volume and time of incubation, and subjecting the reaction to a mechanical rotary devise. We then studied 164 subjects with chronic hepatitis, 105 with cirrhosis, 67 with hepatocellular carcinoma, six with acute hepatitis A, seven with acute hepatitis B, 167 chronic carriers of hepatitis B virus (HBV) and 235 healthy individuals from Japan and compared the results of the M2-IRMA to a conventional polyclonal radioimmunoassay (P-RIA). By using a more sensitive assay design (M2-IRMA), a significant number of additional cases of HBV infection heretofore unsuspected in the etiology of chronic liver disease were identified. We conclude that improvement in assay sensitivity for HBsAg is important in the serologic diagnosis of HBV in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma.

Liver Disease in Recipients of Long-Functioning Renal Allografts

Liver disease in recipients of long-functioning renal allografts. After noting that hepatic failure was the leading cause of death in our transplant recipients whose renal allografts had functioned for more than five years, we reviewed retrospectively the post-transplant course of these patients to assess the long-term effect of liver disease in this population. Sufficient data was available to evaluate 184 of 217 longterm survivors (85%). Twenty-six patients (14%) experienced a doubling of SGOT and/or SGPT of greater than six months' duration and were defined as having chronic liver disease. The etiology of chronic liver disease was identified in 14 patients (54%), of whom 11 were HB5Ag positive. Evidence of chronic hepatitis developed in only six of 26 patients (22%) during the first four years post transplant. Once enzyme abnormalities occurred, they were unremitting until death or end of the study in 73% of patients, Actuarial survival of patients with chronic liver disease was markedly decreased compared to longsurviving transplanted controls. Ten of the 12 deaths in patients with hepatocellular abnormalities were due to hepatic failure, of which eight occurred in the setting of extrahepatic sepsis. Chronic liver disease is a late complication of transplantation and is associated with significant mortality due to an increased susceptibility to overwhelming sepsis.

Liver disease in recipients of long-functioning renalallografts

After noting that hepatic failure was the leading cause of death in our transplant recipients whose renal allografts had functioned for more than five years, we reviewed retrospectively the post-transplant course of these patients to assess the long-term effect of liver disease in this population. Sufficient data was available to evaluate 184 of 217 long-term survivors (85%). Twenty-six patients (14%) experienced a doubling of SGOT and/or SGPT of greater than six months' duration and were defined as having chronic liver disease. The etiology of chronic liver disease was identified in 14 patients (54%), of whom 11 were HBsAg positive. Evidence of chronic hepatitis developed in only six of 26 patients (22%) during the first four years post transplant. Once enzyme abnormalities occurred, they were unremitting until death or end of the study in 73% of patients. Actuarial survival of patients with chronic liver disease was markedly decreased compared to long-surviving transplanted controls. Ten of the 12 deaths in patients with hepatocellular abnormalities were due to hepatic failure, of which eight occurred in the setting of extrahepatic sepsis. Chronic liver disease is a late complication of transplantation and is associated with significant mortality due to an increased susceptibility to overwhelming sepsis.

Emerging Patterns off Hepatitis B Chronic Liver Disease in Australia

Until now, the hepatitis B virus has been thought to play a minor role in the aetiology of chronic liver disease in Australia. This is a report of 21 patients with cirrhosis and/or primary hepatocellular carcinoma with hepatitis B antigenaemia. Primary hepatocellular carcinoma occurred in six patients, five of whom had underlying cirrhosis. The disease occurred mainly in non-Australian born males, and was not often associated with a previous history of hepatitis. The death of 16 patients within 12 months of presentation is in contrast to previous concepts of the benign nature of hepatitis B associated cirrhosis.