Hsing-Tao Kuo

Sustained hepatitis C virus clearance and increased hepatitis B surface antigen seroclearance in patients with dual chronic hepatitis C and B during posttreatment follow-up†‡§

Patients dually infected with hepatitis C virus (HCV)/hepatitis B virus (HBV) have a higher risk of developing advanced liver disease or hepatocellular carcinoma compared with monoinfected patients. Yet, there is a similar rate of sustained virologic response (SVR) after peginterferon alfa‐2a and ribavirin combination therapy in these patients compared with HCV‐monoinfected patients and a high hepatitis B surface antigen (HBsAg) seroclearance rate. The durability of hepatitis C and B clearance in coinfected patients was investigated in a 5‐year follow‐up study. Patients with active HCV genotype 1, both HBV‐coinfected (n = 97) and HBV‐monoinfected (n = 110), underwent 48‐week combination therapy with peginterferon alfa‐2a plus ribavirin. In patients with active HCV genotype 2 or 3, both HBV‐coinfected (n = 64) and monoinfected (n = 50) patients underwent 24‐week combination therapy. A total of 295 (91.9%) patients completed treatment and 24 weeks posttreatment follow‐up; 264 (89.5%) patients agreed to receive additional follow‐up for up to 5 years after the end of treatment. After a median follow‐up of 4.6 ± 1.0 years, six of the 232 patients achieving SVR developed HCV RNA reappearance, including five HCV genotype 1/HBV‐coinfected patients and one HCV genotype 2/3‐monoinfected patient. Subgenomic analysis of the HCV core gene indicated that five patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI], 0.9%‐5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI, 21.5%‐42.0%); with 33.1% (95% CI, 21.8%‐50.1%) in the 48‐week combination therapy group and 24.3% (95% CI, 13.7%‐42.9%) in the 24‐week therapy group. Conclusion: Peginterferon alfa‐2a and ribavirin therapy provides good HCV SVR durability and a high accumulative HBsAg seroclearance rate in patients who are coinfected with HCV and HBV. (HEPATOLOGY 2013;)

HBsAg Profiles in Patients Receiving Peginterferon Alfa-2a plus Ribavirin for the Treatment of Dual Chronic Infection with Hepatitis B and C Viruses

BACKGROUND With use of peginterferon alfa-2a and ribavirin combination therapy in patients with dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, 11.2% of patients achieved clearance of hepatitis B surface antigen (HBsAg) at 6 months after treatment; however, reactivation of HBV DNA was observed in 36.3%. We investigated the predictive potential of HBsAg quantification. METHODS HBsAg quantification was performed in 120 e antigen-negative patients dually infected with HBV and hepatitis C virus and treated with peginterferon alfa-2a/ribavirin for 48 weeks (HCV genotype 1; n = 74) or 24 weeks (HCV genotype 2/3; n = 46). HBsAg was quantified at baseline, week 4, week 12, end of treatment, and 24 weeks after treatment. RESULTS The baseline median serum HBsAg level was 120 IU/mL and decreased gradually during treatment. Low baseline HBsAg was significantly associated with HBsAg clearance (40% for HBsAg level 20 IU/mL vs 2.2% for HBsAg level >20 IU/mL; P < .05). A decrease in HBsAg level from baseline to week 12 of 50% was associated with a reduced likelihood of HBV DNA reactivation in patients with baseline undetectable serum HBV DNA (positive predictive value, 89.5%). CONCLUSIONS HBsAg quantification appears to be a useful indicator of posttreatment outcome in patients dually infected with HBV and hepatitis C virus.

High hepatitis B virus surface antigen levels and favorable interleukin 28B genotype predict spontaneous hepatitis C virus clearance in uremic patients

BACKGROUND & AIMS Host and viral factors interplay in the spontaneous clearance of hepatitis C virus (HCV) infection. We aimed to explore the roles of IL28B genotypes and hepatitis B virus (HBV) infections in spontaneous HCV seroclearance. METHODS IL28B rs8099917 genotypes, HCV and HBV markers were determined in 290 patients who were seropositive for HCV antibodies from 1681 total uremic patients on maintenance hemodialysis. RESULTS Persistent HCV viremia was observed in 74.6% (214/287) of patients. Logistic regression revealed that the strongest factors associated with spontaneous HCV seroclearance were carriage of rs8099917 TT-type (odds ratio/95% confidence intervals [OR/CI]: 6.22/1.41-27.35, p=0.016), followed by concurrent hepatitis B surface antigen (HBsAg) seropositivity (OR/CI: 2.37/1.06-5.26, p=0.035). The clearance rate was highest among patients with both positive HBsAg/rs8099917 TT-type (44.8%, OR/CI: 20.88/3.5-402.5), followed by positive HBsAg/rs8099917 non-TT-type (28.6%, OR/CI: 8.86/1.8-160.8), and negative HBsAg/rs8099917 TT-type (26.7%, OR/CI: 12.75/1.0-319.4), compared to 4% of negative HBsAg/rs8099917 non-TT-type (trend p=0.0002). HBsAg levels, but not HBV DNA levels, were significantly associated with spontaneous HCV seroclearance. Spontaneous HCV seroclearance rate was 58.3% in patients with HBsAg>200IU/ml/rs8099917 TT-type (OR/CI: 42.54/5.7-908.4), 28.0% in patients with HBsAg<200IU/ml/rs8099917 TT-type or HBsAg>200IU/ml/rs8099917 non-TT-type (OR/CI: 11.12/2.3-201.0), compared to only 3.3% in those with HBsAg<200IU/ml/rs8099917 non-TT-type (trend p=0.0004). Five of 214 (2.3%) HCV viremic patients at enrollment had spontaneous HCV seroclearance during one-year follow-up, which was associated with baseline HCV RNA and HBsAg levels. CONCLUSIONS High HBsAg levels and favorable IL28B genotype were additively associated with spontaneous HCV seroclearance in uremic patients.

Discrepancy between Serological and Virological Analysis of Viral Hepatitis in Hemodialysis Patients

Background and Aim: Viral hepatitis is a health threat for hemodialysis (HD) patients and it may be transmitted during treatment. Some patients categorized to have viral hepatitis were found to be non-viremic. To clarify the discrepancy between the serological tests in HD patients, we conducted the study. Methods: A total of 1681 HD patients was included. Blood samples were analyzed for hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody (anti-HCV). Detection of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA were performed in either HBsAg (+) or anti-HCV (+) samples. HBV DNA/HCV RNA was also measured in a subset of HBsAg (-) and anti-HCV (-) patients. Liver function tests were analyzed and compared with the serological and virological tests. Results: The serological tests showed that 230 patients (13.7%) were HBsAg (+) and 290 (17.3%) were anti-HCV (+). We were unable to detect HBV DNA in 97 of 230 (42.2%) HBsAg (+) patients, and HCV RNA could not be found in 76 of 290 (26.2%) anti-HCV (+) patients. In 167 HBsAg (-) patients, only one showed a trace amount of HBV DNA. None of 151 anti-HCV (-) patients showed detectable HCV RNA. The prevalence rate of viral hepatitis remains high in Taiwanese HD patients: 13.7% for HBV and 17.3% for HCV. However, virological analysis showed 42.2% non-viremic rate for HBsAg and 26.2% non-viremic rate for anti-HCV. Conclusions: The findings might challenge the presently suggested principles of bed and machine dedication and the diagnosis of viral hepatitis in HD patients.

Post-treatment alpha fetoprotein and platelets predict hepatocellular carcinoma development in dual-infected hepatitis B and C patients after eradication of hepatitis C

We investigated the long-term risk of hepatocellular carcinoma (HCC) in dual-infected hepatitis B and C patients after eradication of hepatitis C virus (HCV). A total of 164 (62% male, median age, 50.5 years) hepatitis B and C dual-infected patients who achieved HCV sustained virological response were recruited. Half the patients were HCV genotype 1 with a median viral load of 5.5 log10 IU/mL, and 22.6%had an HBV DNA level ≥ 2000 IU/mL before therapy. HCC developed in 14 patients (8.5%), with an annual incidence of 1.38% per person-year. The 3-year, 5-year, 10-year, and 15-year cumulative probabilities were 2.5%, 5.1%, 12.6%, and 22.7%, respectively. Six months after treatment, a Cox regression hazard analysis revealed platelet level (HR: 0.98, 95% CI: 0.957–0.999, P = 0.038) and AFP level (HR: 1.20, 95% CI: 1.031–1.400, P = 0.019) to be independent factors in HCC. A higher 10-year cumulative risk of HCC was detected in patients with 6-month post-treatment AFP levels > 5.0 ng/mL and platelet levels < 130 x1000/µL (54.9%), compared to patients with neither (8.6%). Although the risk of HCC is low, surveillance of HCC is encouraged in dual-infected patients after eradication of HCV. Post-treatment AFP and platelet levels predict HCC development.

527 SUSTAINED HCV CLEARANCE AND INCREASED HBSAG SEROCLEARANCE IN PATIENTS WITH DUAL CHRONIC HEPATITIS C AND B POST-PEGINTERFERON ALFA-2A AND RIBAVIRIN TREATMENT: A 5-YEAR FOLLOW-UP

8 weeks than that of in placebo group, but there were no significant difference between lamivudine and entecavir group. The number of patients in lamivudine and entecavir group with undetectable HBV DNA was 30.5% and 36.6% at week 12 respectively, there was significant difference between two groups (P < 0.05). Among patients with HBeAg positive diseases, 45.3% patients in lamivudine group and 44.7% in entecavir group lost HBeAg at follow up week 12 respectively, whereas none in placebo group. 36.0% patients in lamivudine group and 34.2% in entecavir group had HBeAg seroconversion at week 12, while none of patient in placebo had HBeAg seroconversion at follow up period. Conclusion: Antiviral treatment therapy can significantly reduce the mortality of patients with chronic hepatitis B liver failure. Both lamivudine and entecavir can be prescribed as an initial treatment in patients with chronic hepatitis B liver failure to reduce the mortality.

PL-005 Profile of HBsAg levels in patients with dual hepatitis B virus and hepatitis C virus infection treated with peginterferon alfa-2a and ribavirin

for preventing Trichinella spiralis infection. We have previously reported that a recombinant Ts87 protein was considered as a potential candidate vaccine for Trichinella spiralis. In this study mucosal immune responses induced by SL7207/pvax1-Ts87 were assessed. Methods: We constructed a recombinant plasmid pvax1-Ts87, and evaluated safety, stability of SL7207/pvax1-Ts87, a DNA vaccine delivered in attenuated Salmonella typhimurium, and immune responses induced by immunizing BALB/c mice orally with SL7207/pvax1-Ts87 of 108 CFU dosage. After the final boost, mice were challenged orally with 500 Trichinella spiralis infective muscle larvae for per mouse. Results: Oral immunization of mice with SL7207/pvax1-Ts87 elicited significant elevation of intestinal secretory IgA and serum anti-Ts87 IgG. The immunized mice exhibited a high ratio of IgG1 to IgG2a. Splenocytes were isolated after the immunization to determine the antigen-specific T-cell response by the ELISPOT assay. The result showed that CD4+ T cells produced IFN-γ, IL-4, IL-5, IL-6 and IL-10. Immunofluorescent microscopy revealed that the recombinant Ts87 protein was expressed in the dendritic cells of mesenteric lymph nodes. Furthermore BALB/c mice vaccinated with SL7207/pvax1-Ts87 demonstrated 29.8% reduction in adult worm burden and muscle larval reduction (34.2%) following Trichinella spiralis larvae challenge. Conclusion: Our results demonstrated a SL7207/pvax1-Ts87 DNA vaccine delivered in attenuated Salmonella typhimurium can elicit specific immune response as well as provide effective protection against Trichinella spiralis infection in mice.

697 AN OPEN-LABEL, COMPARATIVE, MULTICENTRE STUDY OF PEGINTERFERON ALFA-2A (40KD) PLUS RIBAVIRIN IN THE TREATMENT OF PATIENTS CHRONICALLY INFECTED WITH HCV/HBV OR HCV ALONE

C.-J. Liu1, W.-L. Chuang2, C.-M. Lee3, S.-S. Wu4, L.-Y. Liao5, H.-T. Kuo6, Y.-C. Chao7, C.-L. Chen1, P.-J. Chen1, D.-S. Chen1. 1National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, 2Kaohsiung Medical University Hospital, Kaohsiung, 3Chang Gung Memorial Hospital, Kaohsiung, 4Changhua Christian Hospital, Changhua, 5Ren-Ai Branch, Taipei City Hospital, Taipei, 6Chi-Mei Medical Center, Tainan, 7Tri-Service General Hospital, Taipei, Taiwan E-mail: karensearle@elementscommunications.com