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Notes: Background : Non-alcoholic fatty liver disease is an important cause of chronic hepatitis and cryptogenic cirrhosis. The natural history of non-alcoholic fatty liver disease is not well understood especially in Asian populations.Aim : To investigate the histological progression in Chinese patients with biopsy-proven non-alcoholic fatty liver disease.Methods : Chinese patients who had liver biopsy at least 3 years ago and confirmed to have non-alcoholic fatty liver disease were invited for a second liver biopsy. Clinical and laboratory parameters related to their liver function and metabolic syndrome were recorded and analysed. Liver biopsies were scored for the degree of steatosis, necroinflammation and fibrosis. Correlation coefficients were calculated to assess the association between changes in histological scores and metabolic parameters.Results : Seventeen patients who had been followed up for a median period of 6.1 (range: 3.8–8.0) years underwent a second liver biopsy. Nine (53%) patients had progressive disease with worsening of fibrosis score. No statistically significant correlation was found between the changes in histological scores and metabolic parameters. Seven patients developed hypertension or diabetes mellitus during the period of follow-up.Conclusions : Non-alcoholic fatty liver disease is a progressive disease in Chinese patients as in their Caucasian counterparts. Diagnosis of non-alcoholic fatty liver disease may predate development of new components of metabolic syndrome.

Notes: Cyclooxygenase-2 may play a role in the development of hepatocellular carcinoma, but the relationship between cyclooxygenase-2 and chronic hepatitis B is unknown.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To investigate the expression and cellular localization of cyclooxygenase-2 in chronic hepatitis B patients and the effects of anti-viral therapy.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Using immunohistochemistry, in situ hybridization, Western blot and reverse transcription polymerase chain reaction, protein and messenger RNA expression and cellular localization of cyclooxygenase-2 in 35 chronic hepatitis B patients were assessed. Fourteen histologically normal and non-viral-infected livers were used as controls. The cyclooxygenase-2 immunoreactivities of paired liver biopsies from 12 patients receiving anti-viral therapy were compared.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Immunohistochemistry and in situ hybridization revealed that cyclooxygenase-2 expression was confined to hepatocytes. Patients with chronic hepatitis B had significantly higher cyclooxygenase-2 expression compared with controls. The cyclooxygenase-2 expression of hepatitis B e antigen-positive and -negative chronic hepatitis B patients was not significantly different, although the necro-inflammatory activity of the latter group was significantly lower. Over-expression of cyclooxygenase-2 in patients with chronic hepatitis B was further confirmed by Western blot and reverse transcription polymerase chain reaction. Twelve hepatitis B e antigen-positive chronic hepatitis B patients received anti-viral therapy: lamivudine in seven and interferon in five. Despite hepatitis B e antigen seroconversion, disappearance of hepatitis B virus DNA in serum, normalization of liver enzymes and a significant reduction in necro-inflammatory activity in all 12 patients, no significant change in cyclooxygenase-2 expression was found.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Chronic hepatitis B is associated with elevated cyclooxygenase-2 levels in hepatocytes, and the over-expression of this enzyme does not reflect inflammatory activity. Up-regulation of cyclooxygenase-2 persists after successful anti-viral therapy.

Notes: Background : Previous studies suggested that Phyllanthus species have an anti-viral effect on hepatitis B, but methodologies have been inadequate.Aims : This study aimed to investigate the anti-viral effect of Phyllanthus urinaris.Methods : Chronic hepatitis B patients with positive hepatitis B e-antigen (HBeAg), hepatitis B virus (HBV) DNA 〉 500 000 copies/mL and elevated alanine transaminase (ALT) were recruited. Patients were randomized into groups of 12 receiving P. urinaris 1, 2 and 3 g three times daily for 6 months or placebo (six cases). The primary endpoint was HBV DNA reduction, and secondary endpoints were HBeAg seroconversion and ALT normalization.Results : On an intention-to-treat analysis there was no difference in log10[HBV DNA] reduction of the Phyllanthus 1-g (0.18 ± 1.42), 2-g (0.33 ± 1.08) and 3-g (0.85 ± 1.30) groups vs. placebo (0.28 ± 0.85) (P = 0.90, 0.92 and 0.38, respectively) at the end of treatment. The percentage of patients among the placebo, Phyllanthus 1-g, 2-g and 3-g groups undergoing HBeAg seroconversion (0%, 9.1%, 8.3% and 16.7%, respectively) and ALT normalization (0%, 0%, 8.3% and 33.3%) were not significantly different at the end of treatment. No delayed virological or biochemical response was documented at 24 weeks after the cessation of treatment. No serious adverse event was reported.Conclusion : P. urinaris treatment for 6 months has no demonstrable anti-viral effect in chronic hepatitis B.

Notes: Exacerbation of chronic hepatitis B infection can lead to fulminant hepatic failure with a mortality of up to 90%.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To evaluate the efficacy of lamivudine in the treatment of this subgroup of patients.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Twenty-four patients with exacerbation of chronic hepatitis B infection and fulminant hepatic failure were treated with lamivudine, 100 mg daily. Hepatitis A, C, D and human immunodeficiency virus co-infections and hepatocellular carcinoma were excluded.〈section xml:id="abs1-4"〉〈title type="main"〉Results:The median age was 53 years (range, 24–77 years) with a male predominance of 20:4. Seventeen patients were hepatitis B e antigen positive. Mean hepatitis B virus DNA was 2079 Meq/mL. Eight patients (33%) survived (group A). Thirteen patients died and three patients received liver transplantation (67%) (group B). Baseline laboratory results were comparable between the two groups, including serum albumin, bilirubin, alanine aminotransferase, prothrombin time and creatinine. Group B patients had significantly more comorbid illnesses at baseline and more complications, including sepsis and renal failure, compared with group A patients. Six out of eight survivors (75%) had full hepatitis B e antigen seroconversion, but this was not sustained in four patients.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Lamivudine may be useful in treating patients with fulminant hepatic failure due to exacerbation of chronic hepatitis B. Hepatitis B e antigen seroconversion was less durable in this subgroup of patients and long-term therapy may be required.

Notes: Trials of thymosin treatment in chronic hepatitis B virus infection have been small and the results have been inconsistent.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To conduct a meta-analysis to evaluate the efficacy of thymosin treatment in chronic hepatitis B virus infection.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Randomized controlled trials comparing thymosin for over 24 weeks vs. placebo (or usual care) in the treatment of chronic hepatitis B virus infection were identified through MEDLINE, EMBASE and the Cochrane Register of Clinical Trials. Biochemical (normalization of transaminases) and virological (loss of hepatitis B virus DNA and hepatitis B e antigen) responses were analysed using the intention-to-treat method. The odds ratio was used to measure the magnitude of the efficacy.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Five trials (353 patients) were identified. The odds ratio (95% confidence interval) of the virological response of thymosin over placebo at the end of treatment, 6 months post-treatment and 12 months post-treatment were 0.56 (0.2–1.52), 1.67 (0.83–3.37) and 2.67 (1.25–5.68), respectively. There was an increasing trend of the virological response with time since the cessation of thymosin treatment (P=0.02). There was no difference in the biochemical response between the thymosin and placebo groups at the end of treatment, 6 months post-treatment and 12 months post-treatment.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Thymosin is effective in suppressing viral replication in chronic hepatitis B virus infection, but the effect is delayed until 12 months after the cessation of treatment.

Notes: Background:  Pegylated interferon-α has been shown to be more efficacious than conventional interferon in treating chronic hepatitis C. The use of peginterferon in chronic hepatitis B virus infection with positive hepatitis B e antigen has also been tested in a number of trials since 2003.Aim:  To systematically summarize and compare the results of these studies.Methods:  Four studies were identified from PubMed, Medline and reference lists. Data from the trials were extracted and analysed. Where appropriate, combined odds ratio of different trials was calculated. Safety data including serious adverse events and emergence of drug-resistant mutants were recorded.Results:  Three of the four trials contained predominantly Asian patients. Peginterferon is found to be superior to lamivudine monotherapy and induced sustained biochemical and virological responses in about one-thirds of patients after 12 months of therapy. Coadministration of lamivudine did not result in improvement in viral suppression. Peginterferon appears to reduce the emergence of YMDD mutation in the combination treatment groups. It was well tolerated with serious adverse events reported in 〈10% of patients in most trials.Conclusions:  Peginterferon-α treatment of at least 6 months should be considered as one of the first-line therapeutic options for hepatitis B virus infection.

Notes: Background : Non-alcoholic fatty liver disease is prevalent in affluent countries and is a cause of cirrhosis and possibly hepatocellular carcinoma.Aim : To examine the clinical and histological features of biopsy-proven non-alcoholic fatty liver disease and investigate the predictors of severe histological disease in Chinese patients.Methods : Electronic records of all patients (n = 247) who underwent liver biopsy between 1996 and 2003 in our hospital were retrieved. Patients who had histological features of non-alcoholic fatty liver disease were identified. The demographic, clinical, laboratory and histological (Brunt's criteria) parameters of these patients were analysed.Results : Forty-two patients had histology-proven non-alcoholic fatty liver disease. The median age was 47 years (range 23–69). All except one patient had features of metabolic syndrome. The median alanine aminotransferase was 93 (range 24–270) IU/L. Thirty-six (85.7%) patients had steatohepatitis and 11 (26.1%) also had fibrosis. Only one patient had stage 3 fibrosis. The presence of diabetes mellitus predicted higher grade steatohepatitis and fibrosis (P = 0.019) whereas alanine aminotransferase level had no correlation with histological severity of steatohepatitis. After a median follow-up of 42 months, no patient developed hepatic decompensation.Conclusions : Most Chinese patients with non-alcoholic fatty liver disease had features of the metabolic syndrome. Histological activity was generally mild. Diabetes mellitus was the most important predictor of severe histological disease.

Notes: Background : The efficacy of lamivudine therapy in chronic hepatitis B is well established. However, drug-resistant YMDD mutants emerge with extended therapy. This may result in the resurgence of viral replication, the return of hepatitis and histological deterioration.Aim : To study the safety of stopping lamivudine when the drug is no longer effective.Methods : In the 5-year Asian Lamivudine Study, 34 patients from a single centre were included in this study. They had harboured YMDD mutants for at least 2 years. Lamivudine was discontinued and they were followed up at regular intervals. Clinical symptoms, liver biochemistry and viral serology were monitored.Results : In a median follow-up of 20 months after stopping lamivudine (range, 7–39 months), 20 of the 34 patients (58.8%) had elevated alanine aminotransferase (ALT), 13 patients (38.2%) had elevated ALT one to five times the upper limit of normal and seven patients (20.6%) had an ALT flare (ALT more than five times the upper limit of normal with detectable hepatitis B virus DNA). There was no liver decompensation. ALT flare could be predicted by ALT over twice the upper limit of normal at the time of stopping lamivudine (P = 0.037).Conclusions : It is relatively safe to stop lamivudine after YMDD mutants have emerged. ALT levels greater than or equal to twice the upper limit of normal at the time of stopping lamivudine have a higher risk for ALT flare.