Susceptibility to hepatitis A virus infection among chronic liver disease patients and healthy blood donors in Thailand.

Due to improvements in socio-economic and sanitation conditions, Thailand has undergone a change from hyperendemicity to intermediate endemicity for hepatitis A virus infection, leaving a large part of the adult population without immunity. At the same time, the country is still highly endemic for hepatitis B and especially in the northeast, hepatitis C virus infection both of which when acquired during infancy or early childhood exhibit a strong tendency to turn towards chronic liver disease, although in particular with hepatitis B virus the asymptomatic carrier state is also rather common. As no cross-immunity exists between any of these viruses, double or triple infections do occur, a situation where previously acquired immunity to HAV becomes crucial as double infections have been shown to take a more severe or even fatal course. In the present study, we investigated 820 HBV- and/or HCV-related chronic liver disease (CLD) patients and 195 blood donors, both groups divided by 10-year age intervals, for the prevalence of anti-HAV. The results showed the same age dependence of immunity for all groups tested as can be expected for an area of intermediate endemicity, in that approximately 50% of those between 21 and 30 years of age had acquired anti-HAV. These findings indicate the immune response to HAV infection not to be altered by chronic infection with either HBV or HCV. Hence, vaccination against HAV should be considered, particularly in anti-HAV-negative patients with CLD.

Hepatitis G infection and therapeutic response to interferon in HCV-related chronic liver disease.

Circulating HGV-RNA was determined in 117 patients with HCV-related chronic liver disease and in 200 healthy blood donors. The patients, aged 50.8+/-13.8 years, were classified as chronic hepatitis (CH; n = 82), liver cirrhosis (n = 25) and hepatocellular carcinoma (HCC; n = 10). HGV-RNA was detected in 5 (4.3%) patients, all with CH and in 10 (5%) of blood donors. The majority of all groups (52% to 70%) were infected with HCV genotype II/1b, including 4/5 patients with HGV co-infection. Of 5 patients with HGV co-infection, 4 were positive for anti-HBs and anti-HBc and none exhibited jaundice. A 24-week course of interferon treatment with 12-month follow-up was achieved in 27 patients with chronic active hepatitis, including 3 with HGV co-infection. Of these, 55.6% responded to the therapy, but only 6/27 (22.2%) patients were sustained responders. The majority of sustained responders were HCV genotype III/2a (4/6) while genotype II/1b was found in the majority of patients with relapse (7/9) and non-responders (9/12). At the 48- month follow up, 2/6 sustained responders (one with HGV co-infection) became HCV RNA positive. These results show that the prevalence of HGV infection in HCV-related chronic liver disease is low, as in the general population, and is found in younger patients with chronic hepatitis. HGV coinfection does not interfere with clinical severity, disease progression or response to interferon in patients with HCV-related chronic liver disease. The favorable factors ofinterferon treatment for HCV infection are young age, low HCV-RNA levels and HCV genotype III/2a.

Haemostatic abnormalities in patients with liver disease associated with viral hepatitis.

Clinical and laboratory findings were studied in 56 patients with liver disease (10 acute hepatitis, 10 fulminant hepatitis and 36 cirrhosis). Spontaneous bleeding occurred in 19 patients (8 fulminant hepatitis, 11 cirrhosis) and another 8 cirrhotic patients had variceal bleeding. There were 22 deaths (36%), 12 of these patients had spontaneous bleeding. Depletion of antithrombin III (AT III) occurred in fulminant hepatitis (mean +/- S.D. = 27 +/- 16%) and cirrhosis (49 +/- 23%) but thrombin-antithrombin III complexes (TAT) were significantly higher in the former (45 +/- 22 vs 8.6 +/- 7.0 ng/ml; p = 0.006). Within subgroups of cirrhosis (with or without spontaneous bleeding or with variceal bleeding), there were no significant differences in levels of AT III or TAT. Of all patients, those with spontaneous bleeding had persistently lower AT III levels but had variable changes of other coagulation parameters (PT, PTT, TT, FDP, fibrinogen and platelet counts). This study showed that coagulopathic consumption is an important cause of AT III deficiency in fulminant hepatitis but not in cirrhosis. Serial changes in AT III levels correlated with bleeding risk in patients with liver disease.

Prevalence and outcomes of HBV and anti-HCV seropositive patients with chronic liver disease and hepatocellular carcinoma.

The prevalences of serological markers of hepatitis B virus (HBV) and antibody to hepatitis C virus (anti-HCV) were determined in 168 patients (135 males and 33 females), aged 19-79 years (mean = 50.8) in Thailand. Of these, 33 had chronic persistent hepatitis, 35 chronic active hepatitis, 50 cirrhosis and 50 hepatocellular carcinoma (HCC). Seromarkers for either HBV or anti-HCV or both were detected in 140 (83.3%), 3 (1.8%) and 18 (10.7%) patients, respectively, but 7 (4.2%) were sero-negative for both viruses. The overall prevalence of anti-HCV was 12.5% but was significantly lower in HCC (2%) compared to the other 3 groups of liver disease (12-21.5%, p less than or equal to 0.05) and in HBsAg positive (5%) compared to HBsAg negative (30%) patients (p less than 0.001). After 0.5-9 years follow-up of all anti-HCV positive patients, 2 died and another 6 had progressive liver disease. The prevalence of coexistent HBV seromarkers was similar in patients with a progressive (87.5%) and a stable clinical course (92.3%) (p = 0.62). A higher proportion of the anti-HCV-positive patients with a progressive course had a history of blood transfusion [75.0% vs 46.1% (p = 0.20)]. These findings suggest that HBV is the most important etiologic virus associated with chronic liver disease and HCC in Thailand, but HCV may play a role particularly in HBsAg-negative patients.