Byung Hoon Han

Twenty‐four‐week clevudine therapy showed potent and sustained antiviral activity in HBeAg‐positive chronic hepatitis B

Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n = 182) or placebo (n = 61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log10 copies/mL in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log10 reduction at week 34 and 2.02 log10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P < 0.0001). ALT normalization in the clevudine group was well maintained during post‐treatment follow‐up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. Conclusion: A 24‐week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg‐positive chronic hepatitis B. (HEPATOLOGY 2007;45:1172–1178.)

Clevudine is highly efficacious in hepatitis B e antigen‐negative chronic hepatitis B with durable off‐therapy viral suppression

Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B (e‐CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were −4.25 and −0.48 log10 copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log10 reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well‐maintained during the post‐treatment follow‐up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment. Conclusion: A 24‐week clevudine therapy was well‐tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e‐CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission. (HEPATOLOGY 2007.)

Hepatitis C virus (HCV) genotypes and the influence of HCV subtype 1b on the progression of chronic hepatitis C in Korea: a single center experience

Background/Aims There is some controversy regarding whether or not hepatitis C virus (HCV) subtype 1b is more influential than non-1b subtypes on the progression of chronic hepatitis (CH) C to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Methods We retrospectively analyzed 823 patients with chronic HCV infection, including 443 CH patients, 264 LC patients, and 116 HCC patients, who were HCV RNA positive and HBsAg negative. These patients had not received any prior treatment with either interferon alone or a combination of interferon and ribavirin. Results HCV subtypes 1b (51.6%) and 2a/2c (39.5%) were the two most common genotypes. The proportions of genotypes 2 (2a/2c, 2b, and 2) and 3 were 45.8% and 1.1%, respectively. One case of genotype 4 was found. HCV subtype 1b (47.3%) was less common than the non-1b subtypes (52.7%) in non-LC patients, but its proportion (56.9%) was higher than that of non-1b subtypes (43.1%) in LC patients (P=0.006). The proportions of patients with HCV subtype 1b did not differ significantly between the LC (55.3%) and HCC (60.3%) groups. Older age, male gender, and the relative progression of liver damage (non-LC vs. compensated LC vs. decompensated LC) were significant risk factors for HCC, with odds ratios of 1.081 (95% confidence interval [CI], 1.056-1.106), 5.749 (95% CI, 3.329-9.930), and 2.895 (95% CI, 2.183-3.840), respectively. HCV subtype 1b was not a significant risk factor for HCC (odds ratio, 1.423; 95% CI, 0.895-2.262). Conclusions HCV subtypes 1b and 2a/2c were the two most common HCV genotypes. HCV subtype 1b seemed to be more influential than non-1b subtypes on the progression of CH to LC, but not on the development of HCC from LC.

Prevalence of hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma in Korea

Summary. To investigate the contribution of hepatitis C virus (HCV) to chronic liver disease and hepatocellular carcinoma (HCC) in Korea, antibodies to HCV (anti‐HCV) were tested by enzyme immunoassay in 1759 patients with chronic liver disease and HCC, and in 808 healthy adults. The prevalence of anti‐HCV was 1.6% in 808 controls. Anti‐HCV was present in 32 (7.7%) of 418 hepatitis B surface antigen (HBsAg)‐positive and 128 (53.1%) of 241 HBsAg‐negative patients with chronic hepatitis, 16 (6.0%) of 265 HBsAg‐positive and 90 (30.5%) of 295 HBsAg‐negative patients with liver cirrhosis, and 16 (4.8%) of 330 HBsAg‐positive and 61 (29.0%) of 210 HBsAg‐negative patients with HCC. Antibodies to hepatitis B core antigen (anti‐HBc) were present in 80–88% of patients who were seropositive for anti‐HCV and seronegative for HBsAg. Among the sera from 114 patients with HBsAg‐negative and anti‐HCV‐positive chronic liver diseases, HBV DNA and HCV RNA were detected by polymerase chain reaction (PCR) in 54 (47.4%) and 61 (53.3%), respectively. Both HBV DNA and HCV RNA were detected in 4 (4.4%) samples. The mean age of the patients with both HBsAg and anti‐HCV was not different from that of patients who were seropositive for HBsAg alone. These findings indicate that current and/or past HBV infection is still the main cause of chronic liver disease in Korea. Although multivariate analysis showed that anti‐HCV is a risk factor for chronic hepatitis, cirrhosis of the liver and HCC, PCR data for HBV DNA and HCV RNA indicate that HCV infection plays only a minor role in HBsAg‐positive as well as in HBsAg‐negative liver disease and does not accelerate the development of HCC in HBV carriers.

Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition

Background & Aim To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions. Methods We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea. Results Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001). Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192). Patients with previous acute decompensation (AD) within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001). Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391). Conclusions The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF.

Percutaneous transluminal forceps biopsy in patients suspected of having malignant biliary obstruction: factors influencing the outcomes of 271 patients

ObjectivesTo evaluate predictive factors for false-negative diagnosis of percutaneous forceps biopsies in patients suspected of having a malignant biliary obstructionMethodsTwo hundred seventy one consecutive patients with obstructive jaundice underwent percutaneous forceps biopsy. In each patient, three to five specimens (mean, 3.5 specimens) were collected from the lesion. The final diagnosis for each patient was confirmed with pathologic findings at surgery, additional histocytologic data, or clinical and radiologic follow-up. Univariate and multivariate logistic regression analysis was used to identify risk factors associated with false-negative diagnosis.ResultsOne hundred ninety four of 271 biopsies resulted in correct diagnoses of malignancy, while 20 biopsy diagnoses were proved to be true-negative. There were 57 false-negative diagnoses and no false-positive diagnoses. The diagnostic performance of transluminal forceps biopsy in malignant biliary obstructions was as follows: sensitivity, 77.2%; specificity, 100%; and accuracy, 78.9%; positive predictive value, 100%, negative predictive value; 25.9%. Periampullary segment of common bile duct, intrahepatic bile duct and metastatic disease were the significant risk factors of false-negative diagnosis.ConclusionsPercutaneous forceps biopsy provides relatively high accuracy in the diagnosis of malignant biliary obstructions. The predictive factors of false-negative biopsy were determined to be biopsy site and origin of primary tumour.Key Points• Percutaneous forceps biopsy provides relatively high accuracy in diagnosis of malignant biliary obstructions.• The predictive factors of false-negative biopsy were biopsy site and origin of primary tumour.• The procedure-related complications were low.

Barriers to treatment of failed or interferon ineligible patients in the era of DAA: single center study

Background/Aims Interferon-based treatment is not appropriate for a large number of patients with chronic hepatitis C for various medical and social reasons. Newly developed directly acting antivirals (DAAs) have been used to treat chronic hepatitis C without severe adverse effects and have achieved a sustained viral response (SVR) rate of 80-90% with short treatment duration. We were interested to determine whether all patients who failed to respond to or were ineligible for interferon-based therapy could be treated with DAAs. Methods Medical records of patients with positive serum anti-hepatitis C virus (HCV) or HCV RNA between January 2009 and December 2013 were reviewed. Demographic, clinical, and treatment data were collected for analysis. Results A total of 876 patients were positive for both anti-HCV and HCV RNA. Of these, 244 patients were eligible for interferon, although this was associated with relapse in 39 (16%) of patients. In total, 130 patients stopped interferon therapy (67% adverse effects, 28% non-adherent, 4% malignancy, 1% alcohol abuse) and 502 patients were ineligible (66% medical contraindications, 25% non-adherent, 5% socioeconomic problems). Among 671 patients who were ineligible for or failed to respond to interferon therapy, more than 186 (27.7%) could not be treated with DAA due to financial, social, or cancer-related conditions. Conclusions Newly developed DAAs are a promising treatment for patients with chronic hepatitis C who are ineligible for or failed to respond to interferon-based therapy. Nevertheless, not all chronic hepatitis C patients can be treated with DAAs due to various reasons.

Mucinous cystadenoma of the liver with ovarian-like stroma: the need for complete resection

Cystadenoma of the liver is a rare neoplasm. Although many cystadenomas are asymptomatic, symptoms can include abdominal pain, postprandial epigastric discomfort, and nausea. Dramatic changes in hepatic imaging techniques have been helpful for diagnosing cystic lesions of the liver, such as simple cyst, hydatid cyst, cystadenoma, cystadenocarcinoma, and metastatic neuroendocrine tumors. However, it remains difficult to differentiate cystadenoma from cystadenocarcinoma for multiseptated cystic hepatic lesions with papillary projection on computed tomography (CT) and magnetic resonance imaging (MRI). Here we report the case of a 47-year-old woman with several months of postprandial discomfort and abdominal fullness. CT and MRI revealed multiseptated cystic lesions with papillary excrescences. A left hemihepatectomy was performed. Histology showed a benign mucinous cystic tumor with ovarian-like stroma.

Percutaneous Transcholecystic Removal of Common Bile Duct Stones: Case Series in 114 Patients

Purpose To evaluate the safety and effectiveness of percutaneous transcholecystic removal of common bile duct (CBD) stones in 114 patients. Materials and Methods This retrospective study was approved by the institutional review board. From September 2011 through February 2017, 114 consecutive patients (68 men, 46 women; mean age, 73 years) underwent percutaneous transcholecystic removal of CBD stones. All patients had acute cholangitis or cholecystitis. Stones were extracted through a 12-F sheath by using a Wittich nitinol stone basket uder fluoroscopic guidance. Technical success rates, complications, and long-term follow-up were evaluated. Results Technical success was achieved in 96 of 114 (84.2%) patients. In 18 patients, stone removal was unsuccessful due to failure of cystic duct cannulation (n = 11), proximal migration of the CBD stone (n = 3), multiple CBD stones (n = 3), and low insertion of the cystic duct (n = 1). No major procedure-related complications were seen. During the mean follow-up of 644 days (range, 11-2206 days), CBD stones recurred in 12 patients after a mean of 884 days (range, 439-1799 days) after the procedure. Conclusion Percutaneous transcholecystic removal of common bile duct stones seems to be a safe and effective method.

Baracle ® vs Baraclude ® for 48 weeks in patients with treatment-naïve chronic hepatitis B: a comparison of efficacy and safety

Background and objective Entecavir (ETV) is a standard of care for chronic hepatitis B (CHB). In a bioequivalence study, ETV from Dong-A ST (Baracle®) was found to have a pharmacokinetic profile equivalent to ETV from Bristol-Myers Squibb (BMS) (Baraclude®). The present study was conducted to evaluate the antiviral activity and safety of ETV from Dong-A ST in comparison to ETV from BMS in patients with CHB. Methods In this multicenter, double-blind, active-controlled, stratified-randomized, parallel group, comparative trial, 118 treatment-naïve patients with CHB were randomly assigned to receive either 0.5 mg of ETV from Dong-A ST or ETV from BMS once daily for 48 weeks. The primary efficacy endpoint was virologic improvement (a mean reduction from baseline in serum HBV DNA levels) at 24 weeks. Secondary efficacy endpoints included a mean reduction in serum HBV DNA levels at 48 weeks, proportion of patients with undetectable levels of serum HBV DNA, rates of hepatitis B e antigen (HBeAg) loss and seroconversion, rates of HBsAg loss and seroconversion, and rates of normalization of alanine aminotransferase (ALT) levels. Results From baseline to week 24, HBV DNA levels (log10) decreased by 4.81 and 4.63 with ETV from Dong-A ST and with ETV from BMS, respectively. The upper limit of two-sided 95% confidence intervals (CI) (equivalent to one-sided 97.5% CIs) for the difference between the treatment groups was 0.208, which was below the noninferiority margin of 1, thus supporting the noninferiority of ETV from Dong-A ST in comparison to ETV from BMS. No statistically significant differences were noted between the treatment groups in all secondary and tertiary efficacy endpoints. Safety profiles were also similar between the two groups. Conclusion In patients with previously untreated HBeAg-positive or negative HBV infection, the efficacy of ETV from Dong-A ST was noninferior to that of ETV from BMS, and there were no significant differences in efficacy or safety between two groups.