Meta-analysis: The association of hepatitis B virus genotypes and hepatocellular carcinoma.

BACKGROUND: A meta-analysis on the risk of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) genotypes is warranted as the current data are conflicting. AIM: To investigate the relative risk of HCC among the four major HBV genotypes (A-D). METHODS: A meta-analysis was performed based on literature search from electronic databases and bibliography between 1950 and 2012. All abstracts with keywords 'hepatitis B', 'hepatocellular carcinoma' and 'genotype' were screened. Studies were included if they reported HBV genotype as an exposure and HCC as an outcome. RESULTS: Nine hundred and eighty-eight abstracts were found through literature search, among them 43 studies were eligible for this meta-analysis. A total of 14,545 patients with an average age of 43 years were included; 71% were male patients and 17% had cirrhosis. In 33 studies, HCC was found in 1541/6060 (25%) genotype C vs. 550/4417 (12%) genotype B HBV-infected patients [odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.52-2.76, P < 0.001]. No difference in the risk of HCC was found among genotype A (71/517, 14%) vs. genotype D (170/1506, 11%) HBV-infected patients in 14 studies (OR = 0.94, 95% CI = 0.67-1.32). In 10 studies, the risk of HCC was also found higher among genotype C (498/1659, 30%) than genotype A&D (103/1403, 7%) HBV-infected patients (OR = 2.34, 95% CI = 1.63-3.34, P < 0.001). Subgenotype Ce and Cs HBV-infected patients had similar risk on HCC (OR = 1.13, 95% CI = 0.76-1.67, P = 0.54). On funnel plot analysis, there was no significant publication bias in all comparisons. CONCLUSION: Genotype C hepatitis B virus is associated with a higher risk of hepatocellular carcinoma than other major hepatitis B virus genotypes.

Undetectable HBV DNA at month 12 of entecavir treatment predicts maintained viral suppression and HBeAg-seroconversion in chronic hepatitis B patients at 3 years.

BACKGROUND: On-treatment monitoring of serum hepatitis B virus (HBV) DNA to guide treatment strategy for patients on entecavir has received little attention. AIM: To investigate the predictive value of on-treatment HBV DNA levels for responses to entecavir. METHODS: This was a retrospective cohort study among nucleos(t)ide analogue-naïve HBV-infected patients on entecavir with a minimum follow-up of 2 years. Maintained virological suppression was defined as undetectable HBV DNA (<20 IU/mL) until the last visit. Genotypic drug resistance was screened by using the INNO-LiPA DR assay. RESULTS: A total of 440 chronic hepatitis B patients (160 HBeAg-positive) followed for 34 ± 9 months were included. The cumulative probability of maintained virological suppression at year 1, 2 and 3 were 76.5%, 83.0% and 88.3% respectively. On multivariate analysis, lower baseline HBV DNA, undetectable HBV DNA at month 12 and negative HBeAg were the independent predictors of maintained virological suppression. M12 responders (who had undetectable HBV DNA at month 12) had higher probability of maintained virological suppression at 3 years (99.1%) as compared to non responders (57.5%; P < 0.001). The cumulative probability of HBeAg-seroconversion at year 1, 2 and 3 were 19.0%, 27.2% and 33.5% respectively. M12 responders had higher probability of HBeAg-seroconversion at 3 years (43.2%) than the non responders (19.0%; P = 0.003). M12 responders had lower probability of drug resistance at 3 years (0%) than the non responders (2.6%; P = 0.004). CONCLUSION: Month 12 HBV DNA responses could predict the probability of maintained virological suppression, HBeAg-seroconversion and risk of drug resistance among patients on entecavir treatment at 3 years.

Meta-analysis: reduction in hepatic events following interferon-alfa therapy of chronic hepatitis B.

BACKGROUND: The long-term benefit of interferon-alfa (IFN-α) treatment in preventing various hepatic complications is not certain. AIM: To study the effects of IFN-α on reducing the risk of developing overall hepatic events (hepatocellular carcinoma, cirrhotic complications and liver-related mortality) in chronic hepatitis B patients. METHODS: Randomized controlled trials, case-control studies and cohort studies were retrieved from electronic databases and conference abstracts. Relative risks (RRs) of different hepatic complications among patients treated by IFN-α vs. no treatment or placebo were studied. RESULTS: Eleven studies were identified totalling 975 patients treated by IFN-α vs. 1147 untreated controls for analysis. Patients were treated by IFN-α for 1-24 months with a post-treatment follow-up of 1-13 years. Treatment by IFN-α reduced the risk of overall hepatic events (RR 0.55, 95% confident interval or CI 0.43-0.70, P < 0.001) and cirrhotic complications (RR 0.46, 95% CI 0.32-0.67, P < 0.001) by 45% and 54% respectively. Patients who responded to IFN-α had more profound reduction in overall hepatic events (RR 0.20, 95% CI 0.05-0.87, P = 0.03) and cirrhotic complications (RR 0.19, 95% CI 0.09-0.38, P < 0.001) vs. the untreated controls. CONCLUSION: Interferon-alfa treatment reduces the risk of hepatic events particularly among responders to treatment.

Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B.

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.

Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B.

BACKGROUND: Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear. AIM: We aimed to study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB. METHODS: We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM. RESULTS: 1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively. CONCLUSION: Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.