Ming-Yang Lai

Purpose Adiponectin possesses anti-inflammatory and insulin-sensitizing properties. Little is known about the role of adiponectin in hepatitis B-related liver disease. Methods Serum adiponectin and hepatitis B viral factors were cross-sectionally assayed in 280 patients with chronic hepatitis B virus (HBV) infection including 120 patients with chronic HBV infection, 40 patients with cirrhosis, and 120 patients with hepatocellular carcinoma (HCC); 116 healthy adults were used as controls. The dynamics of serum adiponectin level was also studied longitudinally in 25 patients with hepatitis B e antigen (HBeAg) seroconversion (SC). Results We found that serum adiponectin level in patients with chronic HBV infection was similar to that in healthy controls and was significantly lower than patients with cirrhosis and HCC. In univariate analysis, high serum adiponectin level significantly correlated with the presence of HBV-related cirrhosis or HCC, abnormal serum ALT level, and HBV genotype C. Multivariate analysis revealed that high serum adiponectin level significantly correlated with the development of HCC. Serum adiponectin levels remained stationary in patients experiencing HBeAg SC. Conclusions Our findings suggest that HBV infection itself does not affect adiponectin levels. Serum adiponectin level correlates with the progression of HBV-related liver diseases but not with the development of HBeAg SC.

The correlation of HBV genotype with clinical outcome has been recognized in chronic hepatitis B patients. However, there are few reports on the distribution and clinical significance of HBV genotypes in acute hepatitis B patients. Nineteen acute hepatitis B patients were identified and their HBV genotypes were determined. The serological and clinical data were thus compared between patients with different HBV genotypes. Two HBV genotypes (B and C) were found in the patients. Genotype B was more predominant than genotype C (12 vs. 7). The age, serum alanine aminotransferase level, serum alpha-fetoprotein level, and serum HBV DNA level were not significantly different between patients infected with genotype B or C. None of them had persistent HBsAg for longer than 6 months. Genotype B predominates in acute hepatitis B patients in Taiwan; however, the clinical features between genotype B and genotype C patients are comparable.

Background The clinical implications of metabolic profiles in patients with chronic hepatitis C remain controversial. To study the association of metabolic abnormalities with chronic hepatitis C, we conducted a case–control study with special emphasis on serum lipid pattern, fasting blood glucose, and adiponectin. Methods We enrolled 500 patients with chronic hepatitis C and 536 sex and age-matched controls. Unadjusted and adjusted associations of demographic and metabolic variables were estimated. Results Chronic hepatitis C patients had higher alanine aminotransferase (ALT) and high-density lipoprotein-cholesterol levels, but lower total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol levels than controls. Stratifying ALT level according to its upper limit of normal, HCV infection was associated with younger age, female gender, and higher TC levels in chronic hepatitis C patients with normal ALT levels, but with lower TC and lower TG levels in those with abnormal ALT levels. By using multiple linear regression analyses for subjects with available adiponectin data, presence of HCV infection was independently associated with higher serum adiponectin levels. Conclusions Metabolic profiles of chronic hepatitis C patients are affected by age, gender, serum adiponectin, and ALT levels. Further longitudinal studies are needed to clarify the complex interplay between HCV infection and metabolic profiles.

Background. Ribavirin’s mechanism of action in the treatment of chronic hepatitis C remains to be clarified. Double-stranded RNA-activated protein kinase (PKR) plays a role in cell defense against virus infection. This study investigated whether PKR is a mediator of the effectiveness of ribavirin, used either alone or in combination with interferon (IFN)—α, against hepatitis C virus (HCV) infection.

Allelic loss of chromosome 4q is one of the most frequent genetic aberrations found in human hepatocellular carcinoma (HCC) and suggests the presence of putative tumor suppressor genes within this region. To precisely define the region containing these tumor suppressor genes for further positional cloning, we tried a detailed deletion mapping strategy in 149 HCCs by using 49 microsatellite markers covering 4q12 approximately 25. A common region with allelic loss has been identified based on the interstitial deletions occurring within it; this region is found between D4S1534 and D4S1572 (a 17.5-cM genetic interval). When we included all cases with limited aberration regions for comparison, 2 smaller regions were derived: 1 between D4S1534 and D4S2460 (3.52 cM) and 1 between D4S2433 and D4S1572 (8.44 cM). A few candidate genes were found to be down-regulated in HCCs, but without sequence mutations. In these HCCs, 4q alleleic loss was associated with hepatitis B virus infection status and the elevation of serum alpha-fetoprotein (>/=400 ng/mL). In conclusion, the current study not only mapped a common allelic loss region on chromosome 4q, but it also revealed that its loss may be involved in hepatitis B virus-related hepatocarcinogenesis and the elevation of serum alpha-fetoprotein.

Hepatitis B virus (HBV) is classified into eight genotypes (A–H), and genotype C is associated with more aggressive liver disease compared to genotype B. However, the mechanisms responsible for the clinical differences remain unclear. To test whether genotype C patients had with lower rates of spontaneous hepatitis B ge antigen (HBeAg) seroconversion than genotype B patients, stored serum samples from 146 Taiwanese adult HBeAg-positive hepatitis B carriers followed-up for a mean of 52 months (range, 12–120 months) were tested for HBV genotype by a molecular method. Genotype C patients were significantly older than genotype B patients (mean age, 37 ± 12 vs. 29 ± 10 years, P < 0.001). During the follow-up period, genotype C patients had a significantly lower rate of spontaneous HBeAg seroconversion than genotype B patients (27 vs. 47%, P < 0.025). Spontaneous HBeAg seroconversion occurred one decade later in genotype C patients compared with genotype B patients. Multivariate analyses identified age ≤35 years (odds ratio: 2.08; 95% confidence interval [CI], 1.07–4.0; P < 0.05), high baseline serum alanine aminotransferase level (odds ratio: 2.34; 95%CI, 1.39–4.09; P < 0.005), and HBV genotype B (odds ratio: 1.94; 95%CI, 1.03–3.63; P < 0.05) as independent factors associated with spontaneous HBeAg seroconversion. In conclusion, genotype C patients, compared to genotype B patients, have a delayed HBeAg seroconversion in the immune clearance phase of chronic HBV infection, which may contribute to a more progressive liver disease and more refractory to antiviral therapy. J. Med. Virol. 72:363–369, 2004.

Background: Reactivation of hepatitis B after organ transplantation in hepatitis B surface antigen (HBsAg) carriers may be fatal. In this study, we reported our experience of lamivudine treatment in HBsAg carriers who had post-transplant reactivation of hepatitis B. Methods: The patients were 15 men and one woman. Nine received kidney transplants, six received heart transplants, and one received a lung transplant. They developed a reactivation of hepatitis B 1–101 months (median, 14 months) after transplantation. They received lamivudine 100 mg daily on a compassionate-use basis, and had regular follow ups. The median pretreatment total serum bilirubin level was 3.0 mg/dL, and the alanine aminotransferase level was 357 U/L. Four of the 16 patients were positive for HBeAg. The serum hepatitis B virus (HBV) DNA levels were > 3000 pg/mL in 13 (81%) patients. Three were coinfected with hepatitis C virus. Results: The overall survival rate was 75%. All four fatal cases had a pretreatment total serum bilirubin level of ≥ 3 mg/dL. Serum HBV-DNA soon became undetectable in 12 survivors. Of the 12 survivors, after a median treatment period of 101 weeks, a lamivudine-resistant strain with variation in the YMDD motif of the HBV polymerase gene developed in three (25%). None had significant adverse reactions to lamivudine treatment. Conclusions: These results indicated that lamivudine is effective in the treatment of post-transplant hepatitis B reactivation, including patients with dual chronic hepatitis B and C. Early recognition of HBV reactivation and prompt lamivudine treatment are important to prevent mortality.