H.L. Chan

Meta‐analysis: the efficacy of anti‐viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B‐related hepatocellular carcinoma

Aliment Pharmacol Ther 2011; 33: 1104–1112

Increased liver stiffness measurement by transient elastography in severe acute exacerbation of chronic hepatitis B.

Background and Aims:  The proposed cut‐off values for the degree of fibrosis as assessed by liver stiffness measurement (LSM) might not be applicable in severe acute exacerbation of chronic hepatitis B (CHB). We aimed to assess the effect of necroinflammatory activity on LSM in this condition.

Prediction of off-treatment response to lamivudine by serum hepatitis B surface antigen quantification in hepatitis B e antigen-negative patients.

BACKGROUND The timing of antiviral therapy cessation in hepatitis B e antigen (HBeAg)-negative patients is controversial. Here, we aimed to investigate the role of HBV DNA and hepatitis B surface antigen (HBsAg) monitoring to predict off-treatment sustained response. METHODS A total of 53 HBeAg-negative chronic hepatitis B patients who received lamivudine for 34 ±23 (range 12-76) months and had lamivudine stopped for 47 ±35 months were studied. Primary outcome was sustained response, defined as HBV DNA≤200 IU/ml, at 12 months post-treatment (SR-12). RESULTS A total of 9 (17%) patients achieved SR-12. HBV DNA at baseline, month 6 and end of treatment had no association with SR-12. HBsAg levels tended to decrease more significantly during treatment among SR-12 responders. At the end of treatment, both HBsAg ≤2 log IU/ml and reduction by >1 log from baseline had sensitivity, specificity, positive and negative predictive values for SR-12 of 78%, 96%, 78% and 96%, respectively. All 5 patients with HBsAg≤2 log IU/ml and reduction >1 log at the end of treatment achieved SR-12 and all 40 patients with HBsAg>2 log IU/ml and reduction ≤1 log did not have SR-12. The cumulative probability of sustained response and HBsAg clearance at 5 years among patients with HBsAg≤2 log IU/ml were 88% and 72%, respectively, that among patients with HBsAg reduction >1 log were 74% and 61%, respectively. CONCLUSIONS Monitoring of HBsAg level can guide the timing of stopping lamivudine in HBeAg-negative chronic hepatitis B.

Relationship of clinical and virological factors with hepatitis activity in hepatitis B e antigen-negative chronic hepatitis B virus-infected patients.

To investigate the factors associated with active disease among hepatitis B surface antigen (HBsAg) positive/hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B virus (HBV) infection we studied chronic HBV infected patients who had undetectable HBeAg at the first visit. HBV DNA was determined by the cross‐linking assay (NAXCOR) and polymerase chain reaction (PCR). Mutations in the core promoter and precore regions and viral genotypes were studied. Clinical outcome of these patients were followed and categorized as: (i) relapse (ALT > 200 IU/L or three times the previous levels); (ii) active hepatitis (elevated ALT < 200 IU/L with concomitant detectable HBV DNA); or (iii) remission. A total of eighty‐five patients were followed up for 5.5 ± 1.0 years. At first visit, 31 (36.5%) patients had elevated ALT levels, 12 (14.1%) had measurable HBV DNA by the cross‐linking assay and 26 (30.6%) by PCR. Sixteen (18.8%) patients had hepatitis relapse, 13 (15.3%) had active hepatitis, and 56 (65.9%) remained in remission. Core promoter and precore stop codon mutants were found in 27 and 12 patients, respectively. Eleven and 20 had genotype B and C HBV, respectively. Initial elevated ALT and detectable HBV DNA were associated with active liver disease. Patient demographics, viral mutants or genotypes failed to predict disease activity. Hence, serum ALT and HBV DNA levels offer the best prediction of natural course of HBeAg‐negative chronic HBV infection.

Hepatitis B virus reactivation associated with anti-neoplastic therapy

Reactivation of hepatitis B virus (HBV) infection is a known complication during and after anti‐cancer therapy. This condition can affect two patient populations: it is most commonly seen in patients who are seropositive for hepatitis B surface antigen (HBsAg), but it is also being increasingly reported among patients who are HBsAg‐negative but who have prior infection, as evident by seropositive status for antibody to hepatitis B core antigen (anti‐HBc), irrespective of their anti‐HBs (antibody to HBsAg) status. The clinical course can vary from asymptomatic hepatitis to fulminant hepatic failure that can be potentially fatal. With the increasing use of biological agents in addition to potent cytotoxic chemotherapy in the armamentarium of anti‐cancer treatments, reactivation of hepatitis B has become a common clinical situation that is faced by both oncologists and hepatologists especially in HBV endemic areas. In this review, we discuss the clinical course of reactivation in the two HBV‐infected sub‐populations, and the role of anti‐virals in the prevention and management of HBV reactivation in association with cytotoxic chemotherapy and biological therapies.

Controlled attenuation parameter for the diagnosis of steatosis in non-alcoholic fatty liver disease

Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan) is a recent method for non‐invasive assessment of steatosis. Its usefulness in non‐alcoholic fatty liver disease (NAFLD) is unknown. We prospectively investigated the performance of CAP for the diagnosis of steatosis in NAFLD, factors associated with discordances between CAP and steatosis grades, and relationships between CAP and clinical or biological parameters.

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

On‐treatment monitoring of serum hepatitis B virus (HBV) DNA to guide treatment strategy for patients on entecavir has received little attention.

Expression of cyclooxygenase‐2 in chronic hepatitis B and the effects of anti‐viral therapy

Cyclooxygenase‐2 may play a role in the development of hepatocellular carcinoma, but the relationship between cyclooxygenase‐2 and chronic hepatitis B is unknown.

Evaluation of Model for End Stage Liver Disease (MELD)-based systems as prognostic index for hepatocellular carcinoma.

Background:  The Cancer of Liver Italian Program (CLIP) and Japan Integrated Scoring System (JIS) used the Child‐Turcotte‐Pugh (CTP) score to evaluate the liver function.

Management options for lamivudine‐resistant chronic hepatitis B patients with suboptimal virological suppression by adefovir

Aliment Pharmacol Ther 2011; 34: 972–981