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Hepatocellular carcinoma (HCC) represents the most common form of malignant tumor among males in Thailand, an area endemic for hepatitis B virus (HBV) infection. Various risk factors have been associated with the development of HCC, among them exposure to certain toxins, and infection with hepatitis viruses, in particular HBV, as well as HCV in areas non-endemic for HBV infection. To examine the association of hepatitis viruses with HCC, our group investigated 101 patients who had been clinically, mainly via alpha fetoprotein level, and/or histologically diagnosed with hepatocellular carcinoma. We also examined 200 voluntary blood donors as controls. All subjects underwent serological tests for the presence of hepatitis B surface antigen (HBsAg) and anti-HCV with polymerase chain reaction (PCR) used for the detection of HBV and TT virus (TTV) DNA, and reverse transcription (RT)-PCR for the detection of HCV RNA and HGV RNA. Besides showing a clear preponderance of HCC among males, with a peak incidence the age group 51-70 years, the results obtained in the HCC patients demonstrated that the prevalence of HBV was 65%, four times that of HCV (17%), ten times that of HGV (6%), and seven times that of TTV (9%). In the controls, the prevalence of HBV was 0.5%; that of HCV, 0.5%: that of HGV, 5%; and that of TTV, 7%. These findings confirmed that hepatitis B virus was associated with the development of hepatocellular carcinoma among the Thai population, among whom case histories of chronic hepatitis and cirrhosis have also been encountered quite frequently.

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The novel hepatitis TT virus first described by a Japanese group has been reported to be parenterally transmitted and furthermore, to have been detected in patients with hepatitis of unknown etiology. Hence, in the present study its prevalence was investigated within groups at high risk for contracting blood-borne viruses, such as individuals with chronic liver disease, intravenous drug users and recipients of blood and blood products, as compared to voluntary blood donors and pregnant women. To that end, DNA was extracted from sera obtained from the respective patients and subjected to PCR using semi-nested primers. The frequency of TTV DNA detected within high risk groups, such as nine out of 50 patients with chronic non-A-to-G liver disease (18%), nine out of 98 hepatocellular carcinoma cases (9.2%), 17 out of 52 intravenous drug users (32.7%), 15 out of 80 thalassemia patients with multiple blood transfusions (18.8%) and three out of 31 prostitutes (9.7%) exceeded that among voluntary blood donors and pregnant women, which amounted to 14 out of 200 (7%) and seven out of 103 (6.8%), respectively. Additional molecular research should be performed in order to determine its short-, as well as long-term clinical significance.

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In order to further elucidate the tropism of the novel hepatitis TT virus (TTV) we investigated 22 intravenous drug users (IVDU) for the presence of viral DNA in their peripheral blood mononuclear cells (PBMC) by means of seminested polymerase chain reaction using a set of primers specific for the conserved region of its genome. We detected TTV DNA in 63% of those individuals who had previously been found positive for the agent in their serum, whereas the three remaining ones not displaying TTV DNA in their serum and hence, serving as controls also proved negative in their PBMC. The results presented here further support earlier findings by other authors and their conclusion as to the virus employing a parenteral route of transmission. Further investigation will be required in order to clarify the mechanism of viral infection.

The impact of acute super-infection with hepatitis A virus (HAV) was determined in 20 asymptomatic carriers of the surface antigen (HBsAg) of hepatitis B virus (HBV), eight patients with HBV-related chronic liver disease (CLD), and four patients with CLD related to hepatitis C virus (HCV). For comparison, 100 patients with isolated HAV infection were also studied. The HBsAg carriers and patients with CLD related to HBV or HCV were significantly older than the patients with isolated HAV infection, with mean (S.D.) ages of 43.9 (14.1), 46.4 (16.0), 52.5 (8.6) and 28.4 (10.7) years, respectively (P < or = 0.02). There were no significant between-group differences in the baseline serum concentrations of alanine aminotransferase. All the patients with isolated HAV infection fully recovered. Fulminant or submassive hepatitis occurred in 11 (55%) of the HBsAg carriers and four (33%) of the 12 patients with CLD related to either HBV or HCV. Nine of the 15 patients with severe hepatitis died and the mortality rate among the HBsAg carriers was not significantly different from that among the CLD patients (25% v. 33%; P = 0.15). These fatal cases were all aged > 50 years and were significantly older [59.0 (2.1) years] than the six severe cases who recovered [43.2 (10.7) years] as well as the remaining 17 uncomplicated cases with CLD or HBsAg [40.3 (13.0) years] (P < or = 0.001). The results indicate that acute HAV is rarely fatal in young adults but may be severe and potentially fatal in patients with underlying chronic HBV or HCV infection, especially among the elderly. Vaccination against HAV should be considered for the patients at high risk who are negative for anti-HAV.