Po-Lin Tseng

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 ⩾20u2009ngu2009ml−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.

Neither Diabetes Mellitus nor Overweight Is a Risk Factor for Hepatocellular Carcinoma in a Dual HBV and HCV Endemic Area: Community Cross-Sectional and Case–Control Studies

OBJECTIVES:Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are well-known risk factors for hepatocellular carcinoma, and diabetes mellitus (DM) and overweight have also been reported as risk factors for hepatocellular carcinoma (HCC). We tried to elucidate the roles of DM and overweight in HCC development in a dual HBV and HCV endemic area of southern Taiwan.METHODS:In 2004, a community-based comprehensive screening program was conducted in Tainan County. Hepatitis B surface antigen (HBsAg), anti-HCV, α-fetoprotein, complete blood counts, triglyceride, cholesterol, and glucose levels were examined. DM was defined as fasting blood sugar >126u2009mg per 100u2009ml, and overweight was defined as a body mass index >24u2009kgu2009m−2. Subjects with thrombocytopenia (platelet count <150 × 109u2009l−1) and elevated α-fetoprotein (>20u2009ngu2009ml−1) underwent ultrasonographic screening for HCC. A total of 56,307 adults (>40 years old) participated, and 72 new HCC cases were detected and confirmed.RESULTS:In comparisons of all 72 HCC cases with the other 144 individual age-, sex-, residency-, HBsAg-, and anti-HCV-matched controls, only thrombocytopenia and high alanine transaminase (ALT) levels were shown to be independent risk factors. Neither DM nor overweight was shown to be significant in any of the analyses.CONCLUSIONS:On the basis of the community-based cross-sectional and case–controlled studies, neither DM nor overweight was a risk factor for HCC in a dual HBV and HCV endemic area. However, male gender, age (≧65 years), HBsAg, anti-HCV, thrombocytopenia, and high ALT levels were independent risk factors for HCC.

Determinants of early mortality and benefits of lamivudine therapy in patients with hepatitis B virus‐related decompensated liver cirrhosis

Summaryu2002 Chronic hepatitis B infection (HBV) is a major health problem worldwide. The prognosis is grave for patients with HBV‐related decompensated liver cirrhosis (LC). We evaluated the effectiveness and the determinants of early mortality of lamivudine treatment in patients with HBV‐related decompensated LC. Thirty patients with HBV‐related decompensated LC and active viral replication were treated with lamivudine 100u2003mg daily for a median duration of 9u2003months. Among these patients, five patients died within 3u2003months. Two patients were lost to follow‐up at week 8 and 9. One patient was treated for <6u2003months. Twenty‐two patients were treated over 6u2003months. Univariate analysis revealed that the total bilirubin (Pu2003=u20030.008), prothrombin time (Pu2003=u20030.004), Child–Turcotte–Pugh score (Pu2003=u20030.005), the model of efd‐stage liver disease score (Pu2003=u20030.004) and stage III hepatic encephalopathy (Pu2003=u20030.001) were predictive factors of early mortality. Multivariate analysis revealed that the independent factor associated with early mortality was stage III encephalopathy. Among 22 patients, liver function improved markedly after lamivudine therapy. Of the nine hepatitis B e antigen (HBeAg)‐positive patients, three had HBeAg seroconversion. Two patients had YMDD mutant and virological breakthrough at 41 and 46u2003weeks. One of the two had hepatocellular carcinoma and died of hepatic failure at week 125; the other received adefovir and is doing well. Lamivudine appeared to have benefits in viral suppression and significant improvement in liver function in patients with HBV‐related decompensated LC. As noted in prior studies, poor baseline liver function is associated with a poor prognosis in Asian patients with decompensated HBV cirrhosis treated with lamivudine.

Entecavir vs. lamivudine in chronic hepatitis B patients with severe acute exacerbation and hepatic decompensation

BACKGROUND & AIMSnWe compared the mortality and treatment response between lamivudine (LAM) and entecavir (ETV) in chronic hepatitis B (CHB) patients with severe acute exacerbation and hepatic decompensation.nnnMETHODSnFrom 2003 to 2010 (the LAM group) and 2008 to 2010 (the ETV group), 215 and 107 consecutive CHB naïve patients with severe acute exacerbation and hepatic decompensation treated with LAM and ETV respectively, were recruited.nnnRESULTSnAt baseline, the LAM group had higher AST levels and end-stage liver disease (MELD) scores, and lower albumin levels than the ETV group. Univariate analysis showed that the LAM group had a higher rate of overall (p=0.02) and liver-related mortality (p=0.052) at week 24 than the ETV group, including in patients with acute-on-chronic liver failure. Multivariate analysis showed that MELD scores, ascites, and hepatic encephalopathy were independent factors for overall and liver-related mortality at week 24. ETV or LAM treatment was not an independent factor for mortality in all patients or patients with acute-on-chronic liver failure. The best cut-off value of MELD scores were 24 for 24-week liver-related mortality. The ETV group achieved better virological response (HBV DNA <300 copies/ml) than the LAM group at week 24 (p=0.043) and 48 (p=0.007). The T1753C/A mutation was also an independent predictor associated with overall and liver-related mortality at week 24.nnnCONCLUSIONSnThe choice between ETV and LAM was not an independent factor for mortality in CHB patients with acute exacerbation and hepatic decompensation. Patients with ascites, hepatic encephalopathy, and MELD scores ⩾24 were associated with poor outcome and should be considered for liver transplantation.

A comparison of efficacy and safety of 2-year telbivudine and entecavir treatment in patients with chronic hepatitis B: a match–control study

There are limited data comparing the clinical outcomes between telbivudine and entecavir. We consecutively enrolled 115 telbivudine-naive and 115 entecavir-naive chronic hepatitis B patients, who were matched for age, sex, hepatitis B e antigen (HBeAg) status and cirrhosis, and treated for at least 2xa0years or less than 2xa0years but had developed resistance. Except for the rate of HBeAg seroconversion, which was similar, patients in the entecavir group had better clinical outcomes than those in the telbivudine group for alanine aminotransferase normalization (85.2% vs 78.4%, pxa0<0.048), undetectable HBV DNA (96.5% vs 74.8%, pxa0<0.001), and viral resistance (0.9% vs 21.7%, pxa0<0.001) after 2xa0years of treatment, After applying roadmap or super-responders concepts, entecavir still had better outcomes than telbivudine in undetectable HBV DNA and viral resistance. The cumulative incidence of hepatocellular carcinoma development was similar between telbivudine-naive and entecavir-naive patients (pxa00.565). In renal function analysis, there were significantly more patients with estimated glomerular filtration rate (eGFR) category improvement in both the telbivudine and entecavir groups at year 1 (pxa00.006 and pxa00.047, respectively). The rate of virological improvement was significantly higher with entecavir than with telbivudine after 2xa0years of treatment, whether applying the concepts of roadmap or super-responders. The incidence of hepatocellular carcinoma was similar between telbivudine and entecavir. Both telbivudine and entecavir were associated with eGFR improvement, especially in patients with renal insufficiency.

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.

Lower prevalence of hypercholesterolemia and hyperglyceridemia found in subjects with seropositivity for both Hepatitis B and C strains independently

Background and Aim:u2002 To evaluate the association of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with hypercholesterolemia and hypertriglyceridemia.

Community-based screening for hepatocellular carcinoma in elderly residents in a hepatitis B- and C-endemic area

Background and Aim:u2002 The aim of the present study was to elucidate a reasonable model and the efficacy of hepatocellular carcinoma (HCC) screening on an elderly population.

Comparing the efficacy and clinical outcome of telbivudine and entecavir naïve patients with hepatitis B virus-related compensated cirrhosis.

There is limited data on the efficacy and outcome of telbivudine (LdT) therapy in patients with chronic hepatitis B and compensated cirrhosis. We evaluated LdT as first‐line therapy in these patients and compared with those treated with entecavir (ETV).

Three-year efficacy and safety of tenofovir in nucleos(t)ide analog-naïve and nucleos(t)ide analog-experienced chronic hepatitis B patients

This study compared the efficacy and safety of tenofovir disoproxil fumarate (TDF) up to 3u2009years of innucleos(t)ide analog (NA)‐naïve and NA‐experienced chronic hepatitis B (CHB) patients.