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This case–control study was aimed to assess the effect of genetic variants of tumor necrosis factor (TNF) α−308 and lymphotoxin (LT) α+252 on development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Their gene–gene interaction was also investigated. We enrolled 200 pairs of age- and sex-matched patients with cirrhotic HBV-HCC and unrelated patients with HBV-cirrhosis alone. Polymorphisms of TNFα −308 and LTα +252 were genotyped. Synergy index was used to calculate interaction between the variant genotypes. The results indicated that the frequency distribution of the variant genotypes ( TNFα −308 G/A and LTα +252 G/G) in patients with HCC were significantly higher than those in patients with cirrhosis alone. Multivariate analysis indicated that TNFα −308 G/A (odds ratio [OR], 2.34) and LTα +252 G/G (OR, 2.04) were independent risk factors for HCC. By the clinical characteristics of study population, multivariate analysis demonstrated that independent factors associated with harboring the variant genotypes included cirrhosis with Child-Pugh C (OR = 6.47 in cases and OR = 11.56 in controls) and thrombocytopenia (OR = 8.86 in cases and OR = 7.74 in controls). Calculation of synergy index (SI) indicated that there are additive interaction between TNFα −308 G/A and LTα +252 G/G on risk of HCC (SI = 1.29). In conclusion: There are independent and additive interactions between TNFα −308 G/A and LTα +252 G/G on risk for HBV-HCC. They correlated with advanced hepatic fibrosis and severe liver damage, which might contribute to a higher risk for HCC.

This case–control study aimed to assess the interactive effect between polymorphisms of lymphotoxin (LT) α +252 and habitual substance use on risk of hepatocellular carcinoma (HCC). We enrolled 150 pairs of sex- and age-matched HCC patients and unrelated healthy controls. LTα genotypes were detected with polymerase-chain reaction and restrictive fragment length polymorphisms. Information about habits of substance use was obtained through personal interview. Multivariate analysis indicated that LTα +252 G/G genotypes [odds ratio (OR) = 3.36], Hepatitis B surface antigen (OR = 16.68), antibodies to hepatitis C virus (OR = 34.88) and having at least two habits of substance use (OR = 2.50) were independent risk factors for HCC. There were additive interactions among LTα +252 G/G genotype, chronic viral hepatitis, and habit of each substance use. In conclusion: There are independent and additive interactions between LTα +252 G/G genotype, chronic viral hepatitis, and habits of substance use on risk of HCC.

TT virus (TTV) is a newly isolated DNA virus from the serum of a patient with posttransfusion hepatitis of unknown etiology in 1997. To evaluate the clinical and molecular characteristics of TT virus (TTV) in a hepatitis C virus (HCV) and B (HBV) hyperendemic area (Masago), 200 residents were enrolled in the study. The sera were tested for alanine aminotransferase (ALT), HCV RNA and GB virus C/Hepatitis G virus (HGV) RNA, TTV DNA, HBsAg, anti-HCV and antibodies to HGV E2-protein (anti-E2). TTV DNA was positive in 99 of the 200 sera with a prevalence rate of 49.5%. The prevalence of HBsAg, anti-HCV, HCV RNA, HGV RNA, anti-E2 and HGV exposure (defined as positive for serum HGV RNA and/or anti-E2) was 38.9%, 69.5%, 64.5%, 17.0%, 25.5% and 39.5%, respectively. Neither clinical nor virological factors were associated with TTV viremia. The rate of ALT abnormality was significantly elevated in HCV RNA-positive (34.9%) than -negative (7.0%) residents (p0.001). HCV viremia was the only factor significantly associated with ALT elevation by multiple logistic regression (odds ratio: 6.96; 95% C.I.: 2.60-18.7). We concluded that in this HCV/HBV hyperendemic area, the prevalence of TTV DNA was high. No significant clinical factor was observed to be associated with TTV infection. TTV infection is not related to abnormal ALT levels and ALT abnormality was mainly attributable to HCV but not TTV, HBV or HGV infection.

To investigate the genotype distribution of hepatitis C virus (HCV) in southern Taiwan, the sera from 56 patients with chronic HCV infection were studied. Twenty-nine patients were men and 27 were women. Age ranged from 22 to 65 years (mean, 47.3 +/- 11.4). Eighteen of them had chronic persistent hepatitis, 27 had chronic active hepatitis, and 11 had liver cirrhosis. HCV RNA was detected by reverse transcription-nested polymerase chain reaction using primers derived from the 5'-noncoding region. The genotypes of HCV were determined by amplification of the core region with the type-specific primers as described by Okamoto et al.. All sera were positive for HCV RNA. The prevalence rates of genotypes were as follows: 1b/II, 44.6%(25/56); 2a/III, 41.1%(23/56); 2b/IV, 3.6%(2/56); mixed 1b/I + 2a/III, 5.4%(3/56): mixed 1b/II + 2b/IV, 1.8%(1/56) and type unclassified 3.6%(2/56). The distribution of genotypes was not related to the patients' age, sex, and histological changes. Nevertheless, patients having past history of blood transfusion had a significantly higher rate of HCV type 2a/III infection (72.2% versus 34.2%, p.05, chi-square test). We concluded that both of the HCV genotypes 1 b/II and 2a/III are predominant types in southern Taiwan and regional HCV genotype distribution may differ even within this island. Selective transmission of specific genotypes may pass along different infectious routes.

Interferon alpha (IFN-alpha) has been indicated to be dramatically effective in some but not all patients with chronic hepatitis C virus (HCV) infection. We investigated prospectively 27 patients of chronic hepatitis C, 12 females and 15 males, treated with IFN-alpha for a better regimen of the therapy and for any effective predictor of response to the treatment. All patients were treated with 3 to 6 million units (MU) of recombinant IFN-alpha 2b (n = 15) or lymphoblastoid IFN-alpha (n = 12) given 3 times weekly for 12 to 36 weeks. Patients with normal alanine aminotransferase (ALT) value during therapy, who sustained this response throughout 6 months follow-up after treatment was completed, were grouped into the complete responders. Patients with normal ALT value during therapy but who relapsed after treatment completed, were grouped as partial responders. Non-responders were defined as patients without normal ALT value during therapy. The rates of complete response, partial response, and non-response were 29.6%, 40.8%, and 29.6%, respectively. The degree of response to IFN-alpha therapy was not related to age, sex, type of IFN-alpha, history of blood transfusion, the state of liver pathology, or pretreatment level of ALT value. The complete responsive rate to IFN-alpha was higher in patients treated with total dose above 215 MU [38.1% (8/21) vs. 0% (0/6), p = 0.06], in patients treated for at least 24 weeks [40% (8/20) vs. 0% (0/7), p0.05], and in patients with non-genotype 1b/II HCV infection [40% (8/20) vs. 0% (0/7), p0.05]. We concluded that IFN-alpha was effective in the treatment of chronic HCV infection, particularly in those other than HCV genotype 1b/II. A high-dose, and long-duration regimen may be recommended for better response of chronic hepatitis C to IFN-alpha therapy.

To elucidate the status of serum hepatitis B virus (HBV) DNA in HBsAg-positive hepatocellular carcinoma (HCC), 100 type B chronic liver disease (CLD) patients and 19 HCC patients were studied. The positive rate of serum HBV DNA in HBeAg-positive CLD patients was significantly higher than that in HBeAg-negative CLD patients, and the correlation between the presence of serum HBV DNA and patients' age showed a negative trend. In contrast, the positive rates of serum HBV DNA in HCC patients were not related to the status of HBeAg and age, and the positive rate of serum HBV DNA in HBeAg-negative HCC patients was significantly higher than that in HBeAg-negative CLD patients. Nevertheless, the serum concentrations of HBV DNA in HCC patients were significantly lower than those in CLD patients. These results suggest that replication of HBV in HCC patients might differ from that in CLD patients, and that persistent low-level HBV replication might be related to the presence of HCC.

Necrotizing fasciitis is a rare and rapid progression soft tissue infection. The only identifiable feature is tissue necrosis along a single fascia plane. Because the skin is initially spared, it is difficult for early recognition prior to extensive tissue destruction. Ultrasonography was used for early diagnosis of this infection in five cases. All 5 patients presented with severe cellulitis. Under the suspicion of necrotizing fasciitis, ultrasonography was performed before surgical debridement. Tissue biopsy was done for histological confirmation of the diagnosis. Three patients were proven to have necrotizing fasciitis and two cellulitis only. The ultrasonographic findings of necrotizing fasciitis included: 1) irregularity of the fascia; 2) abnormal fluid collections along the fascia plane; and 3) diffuse thickening of the fascia when compared with the control site in the normal limb. However, in severe infectious cellulitis, the above mentioned findings were not observed. Our results indicate the usefulness of the ultrasonography for early diagnosis of necrotizing fasciitis.