Hepatitis: Leung KW

Hui CK, Zhang HY, Bowden S, Locarnini S, Luk JM, Leung KW, Yueng YH, Wong A, Rousseau F, Yuen KY, Naoumov NN, Lau GK. · Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China. · J Hepatol. · Pubmed #18207280 No free full text.

Abstract: BACKGROUND/AIMS: In order to prevent the occurrence of drug-resistant mutants associated with treatment for chronic hepatitis B virus (HBV) infection, combination therapy is being developed. To determine the efficacy of adefovir dipivoxil (ADV) plus emtricitabine (FTC) combination therapy in chronic HBV infection. METHODS: Thirty treatment-nai ve, HBeAg-positive patients were randomized to combination ADV plus FTC (n=14) or ADV plus placebo monotherapy (n=16) for 96 weeks. HBV DNA was measured by polymerase chain reaction. Treatment was stopped in those with HBeAg seroconversion. RESULTS: The median decrease in HBV DNA at week 96 was higher in the combination group (-5.30 vs. -3.98 log(10)copies/ml, p=0.05). More patients in the combination group had normalization of alanine aminotransaminase and HBV DNA<300 copies/ml at week 96 when compared with the monotherapy group [11 of the 14 patients (78.6%) vs. 6 of the 16 patients (37.5%), p=0.03]. However, HBeAg seroconversion at week 96 was similar in the 2 groups [2/14 (14.3%) vs. 4/16 (25.0%), p=NS]. No ADV or FTC resistance was detected at week 96. In those with HBeAg seroconversion, 50.0% had post-treatment relapse. CONCLUSIONS: Combination ADV plus FTC resulted in more potent suppression of HBV DNA over 96 weeks of therapy.

Hui CK, Leung N, Yuen ST, Zhang HY, Leung KW, Lu L, Cheung SK, Wong WM, Lau GK, Anonymous00074. · Department of Medicine, University of Hong Kong, Hong Kong Special Administrative Region (SAR), China. · Hepatology. · Pubmed #17628874 No free full text.

Abstract: In view of the findings that high hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is associated with increased risk of chronic hepatitis B (CHB)-related complications, disease progression in CHB patients in the immune-tolerant phase is uncertain. We evaluated disease progression in 57 immune-tolerant CHB patients with high HBV DNA. Each subject underwent an initial liver biopsy. In those who remained in the immune-tolerant phase, a follow-up liver biopsy was performed after 5 years of follow-up. Patients who developed elevated serum alanine aminotransferase (ALT) levels were discontinued from the study after a follow-up liver biopsy. Disease progression was defined as a 1-point increase in fibrosis stage. Initial liver biopsies showed the median fibrosis stage of the study patients was 1 (range 0-1). By the end of follow-up, 9 of the 57 patients (15.8%) had developed elevated serum ALT. In those who remained in the immune-tolerant phase, follow-up fibrosis stage was comparable with the initial fibrosis stage (P = 0.58). However, disease progression was greater in patients who developed elevated serum ALT when compared with those who remained in the immune-tolerant phase (5 of 9 vs. 3 of 48, respectively, P = 0.001). The median rate of fibrosis progression of patients who remained in the immune-tolerant phase was lower than that of patients with high serum ALT (0 U/year [range -0.40-0.20 U/year] versus 0.21 U/year [range 0-1.11 U/year], respectively, P = 0.04). CONCLUSION: CHB patients in the immune-tolerant phase have mild disease. In those who remained in the immune-tolerant phase in the present study, disease progression was minimal. However, immune-tolerant patients who progressed to the immune clearance phase often faced disease progression.

Hui CK, Zhang HY, Shek T, Yao H, Yueng YH, Leung KW, Lai ST, Lai JY, Leung N, Lau GK. · Department of Medicine, Queen Mary Hospital, and Research Centre of Infection and Immunity, The University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China. · Aliment Pharmacol Ther. · Pubmed #17509096 No free full text.

Abstract: BACKGROUND: Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. AIM: To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. METHODS: Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. RESULTS: At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). CONCLUSION: Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.

Hui CK, Zhang HY, Lee NP, Chan W, Yueng YH, Leung KW, Lu L, Leung N, Lo CM, Fan ST, Luk JM, Xu A, Lam KS, Kwong YL, Lau GK, Anonymous00381. · Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China. · J Hepatol. · Pubmed #17462782 No free full text.

Abstract: BACKGROUND/AIMS: Despite the possible role of adiponectin in the pathogenesis of liver cirrhosis, few data have been collected from patients in different stages of liver fibrosis. We studied the role of adiponectin in 2 chronic hepatitis B (CHB)-patient cohorts. METHODS: Serum adiponectin was quantified by enzyme-linked immunosorbent assay. One-hundred liver biopsy specimens from CHB patients with different stages of fibrosis and 38 paired liver biopsies from hepatitis B e antigen-positive patients randomized to lamivudine (n=15), pegylated interferon alfa-2a (n=15) or pegylated interferon alfa-2a plus lamivudine (n=8) therapy for 48 weeks were assessed. RESULTS: Serum adiponectin was detected at levels ranging over fourfold magnitude with advancing fibrosis stage and correlated positively with fibrosis stage [r=0.45, p<0.001]. CHB patients with stage 0-1 fibrosis had higher composition of high molecular weight (HMW) form of adiponectin when compared with CHB patients with liver cirrhosis [mean+/-SEM 51.2+/-2.1% vs. 40.9+/-1.7%, respectively, p=0.001]. After antiviral therapy, patients with fibrosis reduction had marked decline in serum adiponectin level and increase in HMW form of adiponectin [mean+/-SEM 43.5+/-1.2% vs. 37.0+/-3.0%, respectively, p=0.04]. CONCLUSIONS: Serum adiponectin may have a role in fibrosis progression in CHB infection. A marked decline in serum adiponectin after antiviral therapy is associated with fibrosis reduction.

Hui CK, Cheung WW, Leung KW, Cheng VC, Tang BS, Li IW, Luk JM, Lee NP, Kwong YL, Au WY, Yuen KY, Lau GK, Liang R. · Department of Microbiology, University of Hong Kong, Queen Mary Hospital, Hong Kong, Special Administrative Region, China. · Hepatology. · Pubmed #18452145 No free full text.

Abstract: Whether preemptive anti- hepatitis B virus (HBV) therapy should be considered in all hepatitis B surface antigen (HBsAg)-negative patients with occult HBV infection receiving alemtuzumab containing chemotherapy is uncertain. We determined the outcome and effect on HBV-specific immunity of an alemtuzumab-containing chemotherapy regimen in occult HBV-infected patients. Twenty-one consecutive occult HBV-infected patients treated with an alemtuzumab containing chemotherapy regimen were studied. T cell reactivity to HBV antigens and -peptides were quantified by ELISpot and the T cell subset by flow cytometry. Six of the 21 patients (28.6%) developed HBsAg seroreversion. The median (range) time to development of HBsAg seroreversion after the end of chemotherapy was 1.8 months (0.2-2.3 months). Direct sequencing showed that the occult HBV infection of all six patients (100%) was reactivated. These six patients developed severe HBV-related hepatitis. At the end of follow-up, four of these six patients (66.7%) had become negative for HBsAg again. Recovery of CD4+ T cell count and CD4+T cell reactivity against hepatitis B core antigen (HBcAg) occurred 9 months after the end of chemotherapy. Loss of HBsAg occurred after recovery of the CD4+T cell count and increased CD4+T cell reactivity against HBcAg 9 months after the end of chemotherapy. CONCLUSION: An alemtuzumab-containing chemotherapy regimen is associated with a high risk of reactivation of occult HBV infection. Suppression of HBV immunity by an alemtuzumab-containing chemotherapy regimen would persist until 9 months after the end of chemotherapy. In occult HBV-infected patients receiving an alemtuzumab-containing chemotherapy regimen, preemptive anti-HBV therapy should be continued until 9 months after the end of chemotherapy, when recovery of HBV immunity has occurred.