Ming-Chao Tsai

Hepatocellular Carcinoma Surveillance at 4- vs. 12-Month Intervals for Patients With Chronic Viral Hepatitis: A Randomized Study in Community

OBJECTIVES:To compare the efficacy of hepatocellular carcinoma (HCC) surveillance at 4- and 12-month intervals in a community for patients with chronic viral hepatitis and thrombocytopenia.METHODS:In 10 townships, adults (≥40 years) with platelet ≤150 (×109)/l, positive hepatitis B surface antigen, or antibody to hepatitis C virus were invited to this study. These townships were randomized into 4- (group A) and 12-month (group B) interval surveillance groups. Seven hundred and eighty-five and 796 residents met the study criteria in groups A and B. Ultrasonography (US) was the surveillance method.RESULTS:A total of 744 residents (group A: 387; group B: 357) were enrolled. In the study period, HCC was diagnosed in 39 residents (group A: 24; group B: 15). There was no difference in cumulative 3-year HCC incidence between the two groups. The tumors were smaller in group A than in group B, though group A had more patients with tumor ≤2 cm (P=0.003) who were in Barcelona Clinic Liver Cancer (BCLC) very-early stage (P=0.017) and had undergone curative treatments (P=0.049). Male gender, cirrhosis, and platelet ≤100 (×109)/l were associated factors of HCC occurrence. There was no difference in 4-year overall survival between the two groups. Patients undergoing recommended treatments had better 4-year survival rates.CONCLUSIONS:Compared with 12-month interval, US surveillance at 4-month interval detected more patients with HCC≤ 2 cm who were in BCLC very-early stage and were fit for curative treatments. Up to 4-year follow-up, however, the overall survival was not different.

Clinical-guide risk prediction of hepatocellular carcinoma development in chronic hepatitis C patients after interferon-based therapy

Background:Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies.Methods:From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed.Results:Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13–2.65 for aged 60–69 and aHR=2.20, 95% CI=1.43–3.37 for aged ⩾70), Male gender (aHR=1.74, 95% CI=1.26–2.41), platelet count <150 × 109/l (HR=1.91, 95% CI=1.27–2.86), α-fetoprotein ⩾20 ng ml−1 (HR=2.23, 95% CI=1.58–3.14), high fibrotic stage (HR=3.32, 95% CI=2.10–5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10–2.14), and non SVR (HR=2.40, 95% CI=1.70–3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively.Conclusion:The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies.

A Polymorphism in Interferon L3 Is an Independent Risk Factor for Development of Hepatocellular Carcinoma After Treatment of Hepatitis C Virus Infection

BACKGROUND & AIMS Polymorphisms in interferon (IFN)L3 (encodes IFNλ3 or interleukin 28B) are associated with outcomes of treatment for hepatitis C virus (HCV) infection. However, there is controversy regarding how polymorphisms in IFNL3 affect the risk for development of hepatocellular carcinoma (HCC) in patients treated with pegylated interferon and ribavirin. METHODS In a retrospective study, we analyzed data from 1118 patients with HCV infection (589 men; median age, 60 y; 49.9% infected with genotype 1; 51.3% with advanced fibrosis) treated with pegylated interferon and ribavirin from March 2000 through October 2009 at the Chang Gung Memorial Hospital in Kaohsiung, Taiwan (71.64% achieved sustained virologic response [SVR]). Baseline samples were collected before therapy. Starting 24 weeks after treatment, clinical and biochemical features were assessed every 3 to 6 months and patients underwent ultrasound examinations. Lesions detected were examined by computed tomography, angiography, or fine-needle aspiration biopsy analyses. Patients were followed up from the initiation of HCV therapy until a diagnosis of HCC (based on published guidelines), death, or March 31, 2013 (median, 60 mo). DNA samples from each patient were analyzed for rs12979860 in IFNL3. Kaplan-Meier analysis was used to determine the risk for development of HCC. RESULTS The percentages of patients with the IFNL3 rs12979860 CC, CT, and TT genotypes were 86.4%, 13.2%, and 0.3%, respectively. A total of 108 patients (9.66%) developed HCC. The IFNL3 rs12979860 CT and TT genotypes correlated with high baseline levels of α-fetoprotein (AFP; ≥20 ng/mL), advanced stage of fibrosis, diabetes, or lack of an SVR (all P < .05). Based on multivariate Cox regression analysis, age 60 years and older, low platelet count (<15 × 10(9) cells/L), AFP level of 20 ng/mL or greater, advanced stage fibrosis, diabetes, lack of an SVR, and the IFNL3 rs12979860 CT and TT genotypes were significant risk factors for HCC (P < .05). Age 60 years and older, low numbers of platelets or high AFP level, and advanced fibrosis were risk factors for HCC among patients with a SVR. The IFNL3 rs12979860 genotype did not have a significant effect on risk for HCC among patients with SVRs, although some of these patients (with the CT or TT genotype) did develop HCC. Among patients without SVRs, only fibrosis stage and the IFNL3 rs12979860 CT and TT genotypes (hazard ratio, 1.80; 95% confidence interval, 1.06-3.07; P = .030) were independent risk factors for HCC. CONCLUSIONS Based on a retrospective study of patients treated for HCV infection, the IFNL3 rs12979860 CT and TT polymorphisms are associated with a risk for HCC, especially in patients without a SVR.

A comparison of telbivudine and entecavir for chronic hepatitis B in real-world clinical practice

OBJECTIVES To evaluate the efficacy of telbivudine and entecavir in chronic hepatitis B (CHB) patients over a 1 year period. METHODS Ninety-seven telbivudine-naive and 98 entecavir-naive CHB patients who had been treated for at least 1 year were enrolled. Serial serum hepatitis B virus (HBV) DNA levels were checked at baseline and at weeks 24 and 48 after treatment. RESULTS Entecavir and telbivudine groups had similar baseline HBV DNA levels (5.9 ± 1.7 versus 6.0 ± 1.5 log copies/mL, P=0.529). The undetectable rate of HBV DNA after 1 year of treatment was significantly higher in the entecavir group than the telbivudine group (94.9% versus 82.0%, P=0.009). Resistance developed in 6.7% of the telbivudine-naive patients after 1 year compared with none of the entecavir-naive patients (P=0.009). However, there was a significant difference between the telbivudine and entecavir groups in hepatitis B e antigen (HBeAg) seroconversion 24 weeks after treatment (40% versus 12.5%, P=0.007). Multiple logistic regression analysis revealed that baseline alanine aminotransferase (ALT) >200 IU/L (P=0.008) was independently associated with HBeAg seroconversion. Applying the roadmap concept with ALT >2× upper limit of normal at baseline, telbivudine and entecavir had favourable outcomes in PCR negativity, ALT normalization, HBeAg seroconversion and resistance. CONCLUSIONS In real-world clinical practice, telbivudine resulted in higher rates of HBeAg seroconversion and drug resistance at week 48 compared with entecavir. A combination with baseline ALT plus 24 week HBV DNA levels led to the lowest rates of resistance in HBeAg-positive telbivudine-naive patients and had the highest probability of HBeAg seroconversion in both entecavir- and telbivudine-naive patients.

Efficacy and Safety of Pegylated Interferon Alfa-2b and Ribavirin Combination Therapy Versus Pegylated Interferon Monotherapy in Hemodialysis Patients: A Comparison of 2 Sequentially Treated Cohorts

BACKGROUND Pegylated interferon (peginterferon; interferon with an attached polyethylene glycol molecule) monotherapy is the recommended treatment for chronic hepatitis C virus (HCV) infection in hemodialysis patients. Limited data concerning peginterferon alfa-2b and ribavirin treatment in this population are available. STUDY DESIGN 2 prospective observational cohort studies. SETTING & PARTICIPANTS From 2007-2009, a total of 26 patients received peginterferon alfa-2b monotherapy. From 2009-2012, an additional 26 patients were treated with peginterferon alfa-2b and ribavirin. PREDICTORS Peginterferon alfa-2b monotherapy, 1.0 μg/kg/wk, versus peginterferon alfa-2b, 1.0 μg/kg/wk, and ribavirin, 200 mg, 3 times per week. Treatment durations were 24 and 48 weeks for HCV genotypes non-1 and 1, respectively. OUTCOMES & MEASUREMENTS End-of-treatment virologic response and sustained virologic response (SVR) were undetectable HCV RNA at the end of treatment and 24 weeks after treatment ended, respectively. SVR and treatment-related withdrawal rate were evaluated by intention-to-treat (ITT) and per-protocol (PP) analyses. Severe anemia was defined as nadir hemoglobin level <8 g/dL. RESULTS Patients who received combination therapy had a higher end-of-treatment virologic response than patients who received monotherapy (85% vs 62% in ITT [P = 0.03] and 100% vs 80% in PP [P = 0.03]). The SVR rate was higher in the combination-treatment cohort than in the monotherapy cohort (62% vs 27% in ITT [P = 0.01] and 73% vs 35% in PP [P = 0.01]). Patients who received combination therapy had a significantly higher rate of severe anemia than those who received monotherapy (58% vs 27%; P = 0.03). However, treatment withdrawal rates were similar between the combination (15%) and monotherapy (23%) groups. LIMITATIONS Comparison of 2 sequential cohorts rather than a randomized control study. CONCLUSIONS Peginterferon alfa-2b and ribavirin combination therapy provided a higher SVR rate than peginterferon alfa-2b monotherapy for treatment-naive dialysis patients with chronic HCV infection through careful monitoring of hematologic parameters and ribavirin dose modification. Severe anemia was significantly higher in patients receiving combination therapy than patients treated with monotherapy.

Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience

This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.

Favorable α‐fetoprotein decrease as a prognostic surrogate in patients with hepatocellular carcinoma after radiofrequency ablation

Background and Aim:  To assess the significance of adequate α‐fetoprotein decrease in monitoring the treatment effects of radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients.

The Changes of Liver Stiffness and Its Associated Factors for Chronic Hepatitis B Patients with Entecavir Therapy

Liver stiffness measurement (LSM) using transient elastography has been proposed to assess liver fibrosis well in various liver diseases. This study was to determine the changes of LSM and its associated factors for chronic hepatitis B (CHB) patients undergoing Entecavir therapy. Consecutive CHB patients underwent Entecavir therapy with two LSMs were enrolled. Patients with aspartate transaminase (AST) and/or alanine transaminase ≧200 IU/L were excluded. The retrospective study enrolled 233 patients including 132 without cirrhosis (group 1) and 101 with cirrhosis (group 2). The mean values of initial liver stiffness were 7.9 and 16.6 kPa for patients in group 1 and group 2, respectively (p<0.001). In addition to the decline of transaminase levels, there was significant reduction of liver stiffness value in a mean interval of 52.8 and 61.9 weeks between the two LSMs for patients in group 1 and 2, respectively (p<0.001). Multivariate analysis showed that higher initial LSM value and presence of hepatitis B e-antigen were associated with a greater decline of LSM value, whereas follow-up AST≧40 IU/L with increased LSM value for group 1 patients. For group 2 patients, longer interval between the two LSMs, higher initial LSM value and AST≧40 IU/L were associated with a greater decline of LSM value, whereas presence of diabetes mellitus (DM) contributed to increased LSM value. In conclusion, CHB patients improved their LSM values after Entecavir therapy. Higher initial LSM value contributed to greater LSM reduction. However, in cirrhotic patients, DM was associated with an increased LSM value after therapy.

Surveillance cultures of samples obtained from biopsy channels and automated endoscope reprocessors after high-level disinfection of gastrointestinal endoscopes

BackgroundThe instrument channels of gastrointestinal (GI) endoscopes may be heavily contaminated with bacteria even after high-level disinfection (HLD). The British Society of Gastroenterology guidelines emphasize the benefits of manually brushing endoscope channels and using automated endoscope reprocessors (AERs) for disinfecting endoscopes. In this study, we aimed to assess the effectiveness of decontamination using reprocessors after HLD by comparing the cultured samples obtained from biopsy channels (BCs) of GI endoscopes and the internal surfaces of AERs.MethodsWe conducted a 5-year prospective study. Every month random consecutive sampling was carried out after a complete reprocessing cycle; 420 rinse and swabs samples were collected from BCs and internal surface of AERs, respectively. Of the 420 rinse samples collected from the BC of the GI endoscopes, 300 were obtained from the BCs of gastroscopes and 120 from BCs of colonoscopes. Samples were collected by flushing the BCs with sterile distilled water, and swabbing the residual water from the AERs after reprocessing. These samples were cultured to detect the presence of aerobic and anaerobic bacteria and mycobacteria.ResultsThe number of culture-positive samples obtained from BCs (13.6%, 57/420) was significantly higher than that obtained from AERs (1.7%, 7/420). In addition, the number of culture-positive samples obtained from the BCs of gastroscopes (10.7%, 32/300) and colonoscopes (20.8%, 25/120) were significantly higher than that obtained from AER reprocess to gastroscopes (2.0%, 6/300) and AER reprocess to colonoscopes (0.8%, 1/120).ConclusionsCulturing rinse samples obtained from BCs provides a better indication of the effectiveness of the decontamination of GI endoscopes after HLD than culturing the swab samples obtained from the inner surfaces of AERs as the swab samples only indicate whether the AERs are free from microbial contamination or not.

Tenofovir versus Entecavir in Treatment of Chronic Hepatitis B Virus with Severe Acute Exacerbation

ABSTRACT Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are effective antivirals recommended as first-line monotherapies for treatment of chronic hepatitis B (CHB) infection. This study aimed to compare the short-term efficacies of TDF and ETV in the treatment of CHB with severe acute exacerbation. From 2008 to 2013, 189 consecutive treatment-naive CHB patients receiving TDF (n = 41) or ETV (n = 148) for severe acute exacerbation were enrolled. The primary endpoint was overall mortality or receipt of liver transplantation by week 24. The baseline characteristics were comparable between these two groups. By week 24, 8 (19% [95% confidence interval {CI}, 7% to 32%]) patients in the TDF group and 26 (18% [95% CI, 11 to 24%]) patients in the ETV group died (n = 30) or received liver transplantation (n = 4) (P = 0.749). The two groups of patients developed similar rates of liver-related complications and achieved comparable biochemical and virological responses at week 24. Cox regression analysis showed that baseline viral DNA level (P = 0.002), hypertension (P = 0.002), model for end-stage liver disease (MELD) score (P = 0.01), platelet count (P = 0.005), early presence (within 4 weeks) of ascites (P = 0.005), hepatic encephalopathy (P = 0.002), and hepatorenal syndrome (P < 0.001) were independent factors for mortality or liver transplantation. Among the patients who survived by week 24, there was no difference between the two groups in the percentage of patients who had a serum creatinine increase of ≥0.5 mg/dl from baseline (6.7% [95% CI, 0% to 16%] versus 2.0% [95% CI, 0% to 4.8%] in the TDF and ETV groups, respectively; P = 0.231), whereas a significant reduction in the estimated glomerular filtration rate (eGFR) was found in the two groups (P = 0.001 for both). In conclusion, TDF and ETV produce a similar treatment response and clinical outcome in patients with severe acute exacerbation of CHB.