Chun Kyon Lee

Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg-positive chronic hepatitis B.

The reported durability of virologic response after successful lamivudine monotherapy is variable, and the question remains as to whether virologic responses can be maintained over an extended follow‐up period. The aim of this study was to investigate posttreatment durability, the optimal duration of additional treatment after HBeAg clearance or seroconversion, and determinants for sustained virologic response (SVR) following lamivudine monotherapy in patients with HBeAg‐positive chronic hepatitis B (CHB). From January 1999 to August 2004, 178 Korean patients with HBeAg‐positive CHB were treated with lamivudine and achieved complete responses, defined as a loss of serum HBeAg and hepatitis B virus DNA, and alanine aminotransferase normalization. The mean duration of lamivudine monotherapy was 26 months (range, 12‐77). SVR was maintained in 138 patients (77.5%). Host and viral factors were compared between 138 patients with SVR and 40 patients whose response was not sustained. The cumulative relapse rates increased from 15.9% at 1 year to 30.2% at 5 years, with a mean time to relapse after cessation of lamivudine of 12 months (range, 7‐42). Most relapses occurred within 2 years after discontinuation of lamivudine (33/40, 82.5%). On multivariate analysis, age ≤40 years and additional treatment for more than 12 months after HBeAg clearance or seroconversion were independent factors for SVR. Conclusion: The lamivudine‐induced virologic response was durable in patients under 40 years old and those receiving lamivudine for more than 12 months after HBeAg clearance or seroconversion. Age and additional treatment were major predictive factors for SVR. (HEPATOLOGY 2010.)

Ascitic fluid infection in patients with hepatitis B virus‐related liver cirrhosis: Culture‐negative neutrocytic ascites versus spontaneous bacterial peritonitis

Background and Aim:  Ascitic fluid infection (AFI) consists of culture‐negative neutrocytic ascites (CNNA) and spontaneous bacterial peritonitis (SBP). The present study compared the clinical characteristics and prognosis of CNNA and SBP in hepatitis B virus (HBV)‐related cirrhotic patients.

Discrimination of Nonalcoholic Steatohepatitis Using Transient Elastography in Patients with Nonalcoholic Fatty Liver Disease

Background/aims The accuracy of noninvasive markers to discriminate nonalcoholic steatohepatitis (NASH) is unsatisfactory. We investigated whether transient elastography (TE) could discriminate patients with NASH from those with nonalcoholic fatty liver disease (NAFLD). Methods The patients suspected of NAFLD who underwent liver biopsy and concomitant TE were recruited from five tertiary centers between November 2011 and December 2013. Results The study population (n = 183) exhibited a mean age of 40.6 years and male predominance (n = 111, 60.7%). Of the study participants, 89 (48.6%) had non-NASH and 94 (51.4%) had NASH. The controlled attenuation parameter (CAP) and liver stiffness (LS) were significantly correlated with the degrees of steatosis (r = 0.656, P<0.001) and fibrosis (r = 0.714, P<0.001), respectively. The optimal cut-off values for steatosis were 247 dB/m for S1, 280 dB/m for S2, and 300 dB/m for S3. Based on the independent predictors derived from multivariate analysis [P = 0.044, odds ratio (OR) 4.133, 95% confidence interval (CI) 1.037–16.470 for CAP>250 dB/m; P = 0.013, OR 3.399, 95% CI 1.295–8.291 for LS>7.0 kPa; and P<0.001, OR 7.557, 95% CI 2.997–19.059 for Alanine aminotransferase>60 IU/L], we developed a novel CLA model for discriminating patients with NASH. The CLA model showed good discriminatory capability, with an area under the receiver operating characteristic curve (AUROC) of 0.812 (95% CI 0.724–0.880). To assess discriminatory power, the AUROCs, as determined by the bootstrap method, remained largely unchanged between iterations, with an average value of 0.833 (95% CI 0.740–0.893). Conclusion This novel TE-based CLA model showed acceptable accuracy in discriminating NASH from simple steatosis. However, further studies are required for external validation.

Partial virological response to entecavir in treatment-naive patients with chronic hepatitis B.

BACKGROUND The proposed definition of a partial virological response (PVR) to nucleos(t)ide analogue therapy in the 2009 European Association for the Study of the Liver (EASL) guidelines is based on limited evidence, especially in terms of the cutoff HBV DNA level and the time point at which to judge it. This study assessed optimal PVR criteria for predicting virological response (VR) at week 96 in treatment-naive patients with chronic hepatitis B (CHB) receiving entecavir (ETV). METHODS A total of 175 patients (126 men, 49 women) who completed 96 weeks of first-line ETV therapy were prospectively recruited. For predicting VR at week 96, the area under the receiver operating characteristic curve (AUC) was used to find the optimal time point and the Youden index was used to calculate the optimal cutoff HBV DNA level. RESULTS After 96 weeks of ETV therapy, 139 (79.4%) patients achieved VR. The AUC at week 48 was significantly better than that at week 24 for predicting VR at week 96 (P=0.023). The optimal cutoff HBV DNA level at week 48 was 35 IU/ml. Forty-one (23.4%) patients met this PVR criteria of ETV (HBV DNA level >35 IU/ml at week 48). CONCLUSIONS An HBV DNA level >35 IU/ml at week 48 is the optimal PVR criteria for predicting non-VR at week 96 in treatment-naive patients with CHB who are receiving ETV. This study supports the proposed EASL PVR for ETV based on scientific evidence.

Multicenter comparison of PEG-IFN α2a or α2b plus ribavirin for treatment-naïve HCV patient in Korean population

BackgroundTwo recent Italian studies suggested that Pegylated-interferon (PEG-IFN) alfa-2a achieves a higher sustained virological response (SVR) rate than PEG-IFN alfa-2b. We intended to compare the efficacy and safety of PEG-IFN alfa-2a with those of PEG-IFN alfa-2b in Korean patients with chronic hepatitis C virus (HCV).MethodsThis retrospective, multi-center trial was conducted on 661 treatment-naïve chronic HCV patients. Patients received PEG-IFN alfa-2a (180 μg/week; n=402) or PEG-IFN alfa-2b (1.5 μg/kg/week; n=259) with ribavirin (800–1200 mg/day) for 24 or 48 weeks according to HCV genotypes.ResultsEarly virologic response and sustained virologic response (SVR) rates were not significantly different between two PEG-IFN groups both in patients with HCV genotype 1 (all P-values>0.05) and 2/3 (all P-values>0.05). SVR rates were not different between two groups in each categorized baseline characteristics: age (years) (≤50 and >50), HCV viral load (IU/mL) (≤7×105 and >7×105), and hepatic fibrosis (F0-2 and F3-4) (all P-values >0.05). In additional analysis for 480 patients who sufficiently complied with treatment doses and duration (80/80/80 rule) and propensity-score matched analysis, SVR rates were not different between two groups both in patients with HCV genotype 1 and 2/3 (all P-values >0.05). Adverse event rates were similar between two groups.ConclusionsUnlike the Western data, efficacy and safety of PEG-IFN alfa-2a were similar to those of PEG-IFN alfa-2b in chronically HCV-infected Korean patients regardless of age, HCV viral load, and hepatic fibrosis.

Efficacy of adefovir dipivoxil in the treatment of lamivudine-resistant hepatitis B virus genotype C infection.

Background and Aims: Adefovir dipivoxil (ADV) is a nucleotide analogue that is known to be effective for lamivudine‐resistant hepatitis B virus (HBV) mutants as well as wild‐type HBV. The aim of this study is to assess the efficacy of ADV against lamivudine‐resistant genotype C HBV mutants.

Maintaining remission in lamivudine-resistant patients with a virological response to adefovir add-on lamivudine after stopping lamivudine therapy.

We examined the durability of the virological response after discontinuing lamivudine (LVD) in chronic hepatitis B (CHB) patients with LVD‐resistant hepatitis B virus (HBV), who responded to LVD plus adefovir (ADV) combination therapy, and the outcome of switching to ADV monotherapy compared to maintaining combination therapy.

Spontaneous Bacterial Peritonitis in Patients with Hepatitis B Virus-Related Liver Cirrhosis: Community-Acquired versus Nosocomial

Purpose Spontaneous bacterial peritonitis (SBP) frequently develops in patients with liver cirrhosis; however, there is little data to suggest whether the acquisition site of infection influences the prognosis. This study compared the bacteriology, clinical characteristics and treatment outcomes of community-acquired SBP (CA-SBP) and nosocomial SBP (N-SBP). Materials and Methods The medical records of 130 patients with hepatitis B virus (HBV)-related liver cirrhosis, who had experienced a first episode of SBP between January 1999 and December 2008, were reviewed. Results The study population included 111 (85.4%) patients with CA-SBP and 19 (14.6%) patients with N-SBP. Baseline and microbiological characteristics as well as clinical course, including in-hospital mortality, did not differ between patients with CA-SBP and those with N-SBP (all p>0.05). The median survival time was 6.5 months, and 117 (90.0%) patients died during the follow-up period. Patients with CA-SBP and N-SBP survived for median periods of 6.6 and 6.2 months, respectively, without significant difference (p=0.569). Time to recurrence did not differ between patients with CA-SBP and N-SBP (4.7 vs. 3.6 months, p=0.925). Conclusion The acquisition site of infection did not affect clinical outcomes for patients with HBV-related liver cirrhosis who had experienced their first episode of SBP. Third-generation cephalosporins may be effective in empirically treating these patients, regardless of the acquisition site of the infection.

Individual prediction model for lamivudine treatment response in hepatitis B virus e antigen-positive chronic hepatitis B patients

Although prolonged lamivudine (LAM) therapy is associated with the emergence of LAM‐resistant mutations, it is still a commonly used therapy in many Asian countries because of its established long‐term safety and low cost. The aim of our study was to assess the predictors of long‐term LAM treatment response and to establish an individual prediction model (IPM) for hepatitis B virus e antigen (HBeAg) seroconversion in HBeAg‐positive chronic hepatitis B (CHB) patients.

Rescue therapy with adefovir in decompensated liver cirrhosis patients with lamivudine-resistant hepatitis B virus

Background/Aims Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV. Methods In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study. Results Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16±5 to 14±10 (mean ± SD, P<0.001) during the follow-up period. With ADV treatment, 67 patients (56.3%) had undetectable serum HBV DNA (detection limit, 0.5 pg/mL). Virologic breakthrough occurred in 38 patients (36.1%) and 9 patients had a suboptimal ADV response. The overall survival rate was 89.9% (107/119), and a suboptimal response to ADV treatment was associated with both no improvement in Child-Pugh score (≥2 points; P=0.001) and high mortality following ADV rescue therapy (P=0.012). Conclusions Three years of ADV treatment was effective and safe in decompensated patients with lamivudine-resistant HBV.