Yuk-Fai Lam

Hepatitis B Reactivation in Patients With Previous Hepatitis B Virus Exposure Undergoing Rituximab-Containing Chemotherapy for Lymphoma: A Prospective Study

PURPOSE Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described. PATIENTS AND METHODS HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered. RESULTS Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients. CONCLUSION A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications.

Changes of HBsAg and HBV DNA levels in Chinese chronic hepatitis B patients after 5 years of entecavir treatment

Hepatitis B surface antigen (HBsAg) kinetics during long‐term entecavir therapy has not been well investigated.

Current Antiviral Therapy of Chronic Hepatitis B: Efficacy and Safety

The treatment of chronic hepatitis B is in constant evolution. Interferon, the first agent licensed for chronic hepatitis B treatment, has been superseded by the growing popularity of nucleoside/nucleotide analogues (NA). However, resistance to these agents is a major challenge. Newer NAs, such as entecavir and tenofovir dipivoxil fumarate, have very low resistance rates and favorable safety profiles. Long-term use of these agents can effectively suppress hepatitis B virus DNA, leading to decrease in incidence of hepatitic flares, as well as in the development of cirrhosis and hepatocellular carcinoma. The efficacy and safety of various antiviral agents is discussed in this review.

Association of Hepatitis B Core-Related Antigen With Hepatitis B Virus Reactivation in Occult Viral Carriers Undergoing High-Risk Immunosuppressive Therapy

OBJECTIVES:Hepatitis B core-related antigen (HBcrAg) is a novel serum marker that correlates with intrahepatic hepatitis B virus (HBV) activity. Its association with HBV reactivation in hepatitis B surface antigen (HBsAg)-negative antibody to hepatitis B core antigen (anti-HBc)-positive patients undergoing high-risk immunosuppressive therapy is undefined.METHODS:HBcrAg was measured in HBsAg-negative, anti-HBc-positive Asian patients with undetectable HBV DNA, who participated in two prospective studies investigating HBV reactivation during rituximab-containing chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Patients were monitored every 4 weeks for up to 2 years, with entecavir started when HBV reactivation, defined as HBV DNA ≥10 IU ml−1, developed.RESULTS:One hundred and twenty-four HBsAg-negative, anti-HBc-positive patients (rituximab, N=62; allogeneic HSCT, N=62) with a median follow-up of 64 weeks (range: 4–104 weeks) were studied. HBV reactivation occurred in 31 patients, with a 2-year cumulative reactivation rate of 40.4%. Serum HBcrAg was detected in 43 (34.7%) patients. Baseline HBcrAg positivity was significantly associated with HBV reactivation (P=0.004, hazard ratio (HR): 2.94, 95% confidence interval (95% CI): 1.43–6.07). HBcrAg-positive patients had a significantly higher 2-year HBV reactivation rate than HBcrAg-negative patients (71.8 vs. 31%, P=0.002). In the rituximab cohort, the HRs for positive HBcrAg and negative antibody to HBsAg for HBV reactivation were 3.65 and 2.84, respectively (P=0.011, 95% CI: 1.35–9.86 and P=0.032, 95% CI: 1.10–7.37, respectively).CONCLUSIONS:Serum HBcrAg positivity is a significant risk factor of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing high-risk immunosuppressive therapy and can potentially have a role in identifying patients who will best benefit from prophylactic nucleoside analogue treatment.

Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)–negative, antibody to hepatitis B core antigen (anti‐HBc)–positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg‐negative, anti‐HBc–positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg‐negative, anti‐HBc–positive, of whom 62 were recruited and monitored for a median of 48 (4‐104) weeks. The 2‐year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8‐100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft‐versus‐host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft‐versus‐host disease, compared with the remaining patient cohort, had a significantly lower 2‐year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. Conclusion: HBsAg‐negative, anti‐HBc–positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft‐versus‐host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451‐1461).

Seven-Year Treatment Outcome of Entecavir in a Real-World Cohort: Effects on Clinical Parameters, HBsAg and HBcrAg Levels

Objectives:We aimed to determine the levels of alanine aminotransferase (ALT), hepatitis B virus DNA (HBV DNA), HBsAg, and a novel viral marker (hepatitis B core-related antigen (HBcrAg)); hepatitis B e antigen (HBeAg) seroconversion and drug resistance rates after 7 years of entecavir treatment in chronic hepatitis B (CHB) patients.Methods:Two hundred and twenty-two Chinese CHB patients on continuous entecavir treatment were recruited. Serologic, virologic, biochemical outcomes, and the occurrence of entecavir signature mutations were determined.Results:The rates of ALT normalization, HBeAg seroconversion, and undetectable HBV DNA were 98.3%, 82.1%, and 98.7%, respectively, after 7 years of entecavir treatment. The genotypic resistance rate was 1.2%. Decline of HBsAg level was modest with a median decline rate of 0.107 log IU/ml/year. Among patients with baseline HBsAg <1,000 IU/ml and annual HBsAg decline rate of ≥0.166 log IU/ml, all have HBsAg of <200 IU/ml (a level highly predictive for HBsAg seroclearance) at year 7. In contrast, in patients with baseline HBsAg ≥1,000 IU/ml and annual HBsAg decline rate of <0.166 log IU/ml, 95.5% had HBsAg of ≥200 IU/ml at year 7. Decline of HBcrAg levels was moderate with a median decline rate of 0.244 log kU/ml/year. Forty-seven patients (32.0%) had undetectable HBcrAg level at year 7.Conclusions:Long-term entecavir therapy continued to have good responses with low drug resistance rate. However, the decline of HBsAg with treatment was suboptimal. HBcrAg level declined at a relatively better rate. Baseline HBsAg level of <1,000 IU/ml and annual decline of 0.166 log IU/ml could be used to predict HBsAg response.

HLA-DP and γ-interferon receptor-2 gene variants and their association with viral hepatitis activity in chronic hepatitis B infection.

Studies show that polymorphisms in human leukocyte antigen (HLA)‐DP loci and certain γ‐interferon (IFN‐γ) signaling pathway genes are related to persistence of hepatitis B virus (HBV) infection and viral load in chronic HBV (CHB) infection respectively. Our study aims to determine whether single‐nucleotide polymorphisms (SNPs) linked to HLA‐DP loci and IFN‐γ signaling pathway are associated with HBV activities.

A Territory-Wide Study on the Seroprevalence of Hepatitis B Virus in the General Population after Universal Hepatitis B Immunization ERA in Hong Kong, China

Poster Presentations: Viral hepatitis: Hepatitis A, B, D, E – clinical (except therapy): no. THU-162

Su1059 Findings on Surveillance Colonoscopy in Patients With Serrated Lesions of the Colon

G A A b st ra ct s Conclusion: Clinical characteristics between familial IBD and sporadic IBD patients do not seem to be significantly different. A family history of IBD does not seem to be an important predictive factor affecting clinical characteristics or disease course. The duration of disease might be more important factor predictive of disease course rather than the familial history of IBD. Further large scaled prospective studies are warranted to compare clinical characteristics and disease course of familial IBD with sporadic IBD patients.