Background/AimsThe association between depression and chronic hepatitis C virus (HCV) infection or pegylated interferon α and ribavirin therapy (PR therapy) has not been extensively studied in Korea. We aimed to clarify the prevalence of depression and its incidence during PR therapy in chronic hepatitis C (CHC) patients.Methods : In this prospective, multicenter study, 114 CHC patients were screened for depression using two self-reported scales, the Beck Depression Inventory-I (BDI-I) and the Hospital Anxiety and Depression scale (HADS). The incidence of depression during PR therapy was evaluated in 62 patients who underwent PR therapy during the study period.Results : The prevalence of baseline depression was 17.5% according to the BDI-I score ≥10 criterion and 4.4% according to the HADS-D score ≥8 criterion in the 114 CHC patients, and it was significantly associated with an unmarried state. During PR therapy, depression developed in 34.6% according to the BDI-I scale and 29.5% according to the HADS-D, which negatively affected sustained virologic response (SVR).Conclusion : sThe prevalence of depression in Korean CHC patients appears to be low compared to that in Western patients; however, its incidence during PR therapy (approximately 30%) was similar to that of other populations, which led to a lower SVR rate. Active screening and multidisciplinary management of depression during PR therapy is warranted.

BACKGROUND/AIMS:Transient elastography (TE) has become an alternative to liver biopsy (LB). This study investigated the diagnostic performance of liver stiffness (LS) measurement using TE in Korean patients with chronic hepatitis B and C (CHB and CHC). METHODS:From April 2006 to June 2014, 916 patients (567 CHB and 349 CHC) who underwent LB and TE at 15 centres were analyzed. The Batts and Ludwig scoring system was used for histologic assessment. Aspartate aminotransferase (AST)-to-platelet ratio indexes (APRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used. RESULTS:The median age, LS value, and APRI score were 45 years, 8.8 kPa, and 0.61, respectively, in CHB patients vs. 51 years, 6.8 kPa and 0.55, respectively, in CHC patients. TE was significantly superior to APRI in CHB patients (AUROC 0.774 vs. 0.72 for ≥F2, 0.849 vs. 0.812 for ≥F3, and 0.902 vs. 0.707 for F4, respectively; all P < 0.05). Furthermore, TE was significantly superior for predicting ≥ F3 stage (AUROC 0.865 vs. 0.840, P = 0.009) whereas it was similar for predicting ≥ F2 and F4 stage (AUROC 0.822 vs. 0.796; 0.910 vs. 0.884; all P > 0.05) in CHC patients. In CHB patients, optimal cut-off LS values were 7.8 kPa for ≥F2, 8.2 kPa for ≥ F3, and 11.6 kPa for F4, vs. 6.8 kPa, 8.6 kPa, and 14.5 kPa, respectively, in CHC patients. CONCLUSIONS:TE can accurately assess the degree of liver fibrosis in Korean patients with CVH. TE was superior to APRI for predicting each fibrosis stage.

Under‐recognition and under‐treatment of chronic hepatitis C virus (HCV) infection is an important determinant of the disease outcome. The aim of this study was to investigate the treatment rate and factor of initiation of interferon‐based antiviral treatment for chronic hepatitis C patients in a prospective, multicenter Korean HCV cohort. Treatment‐naïve 759 patients with chronic HCV infection were prospectively followed from January 2007–2013 at six university hospitals during a median (interquartile range) follow‐up of 769 (76–1,427) days. The subjects consisted of patients with chronic hepatitis C (n = 553, 72.9%), liver cirrhosis (n = 127, 16.7%), and hepatocellular carcinoma (n = 79, 10.4%), and were treated usually using pegylated interferon alpha and ribavirin. Treatment initiation rate and its related factors were analysed. The initiation rate of antiviral treatment was 37.3% (n = 273), and the cumulative probability of treatment initiation over 5 years was 39.4%. Multivariate analysis showed that age <58 years (hazard ratio [HR] = 1.588, 95% CI = 1.151–2.193), job employment (HR = 1.737, 95% CI = 1.279–2.363), absence of HCC (chronic hepatitis, HR = 2.534, 95% CI = 1.003–6.400; liver cirrhosis, HR = 2.873, 95% CI = 1.101–7.494), alanine transaminase (ALT) >40 IU/L (HR = 1.682, 95% CI = 1.228–2.303), and genotype 2 (HR = 1.364, 95% CI = 1.034–1.798) were independent factors related to treatment initiation. Interferon‐based antiviral treatment was initiated in more than one third of chronic HCV infected patients visiting university hospitals, who were young, employed, HCV genotype 2, and with abnormal ALT without HCC, in Korea. J. Med. Virol. 88:275–281, 2016. © 2015 Wiley Periodicals, Inc.

Background and AimsThe outcomes of hepatitis C virus (HCV)-related liver cirrhosis was limitedly studied in a hepatitis B virus-endemic area. This multicenter, prospective cohort study was conducted to elucidate the incidence of hepatocellular carcinoma (HCC) and mortality in the Korean patients with HCV-related cirrhosis.MethodsFrom January 2007 through June 2012, 196 patients with HCV-related cirrhosis were prospectively enrolled and regularly followed at six university hospitals to determine HCC occurrence and mortality. A multivariable analysis using Cox proportional hazards regression was performed to clarify the related factors to the outcomes.ResultsDuring a mean follow-up period of 39.2 months, 31 (15.8%) patients developed HCC, and 33 (16.8%) patients died or underwent liver transplantation. The estimated HCC incidence was 5.8 per 100 person-years, and the independent factors for HCC were absence of anti-HBV surface antibody (HBs hazard ratio [HR], 5.018; 95% confidence interval [CI], 1.710-14.726; P=0.003) and serum albumin<3.8g/dL (HR, 3.051; 95% CI, 1.318-7.067; P=0.009). The overall mortality rate was 5.1 per 100 person-years, and the related independent factors were the presence of ascites (HR, 2.448; 95% CI, 1.142-5.210; P=0.022), serum albumin<3.8g/dL (HR, 3.067; 95% CI, 1.254-8.139, P=0.014), and nonachievement of sustained virologic response (SVR) (HR, 0.066; 95% CI, 0.001-0.484, P=0.002).ConclusionThe incidence of HCC in HCV-related cirrhosis seems to be high in Korea, and advanced liver disease and no achievement of SVR were associated with mortality. The absence of anti-HBs in hepatocarcinogenesis related to HCV warrants further study.

ABSTRACT Tenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated the antiviral efficacy and safety of TDF alone compared to those of TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (P = 0.562 and P = 0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has antiviral efficacy comparable to that of TDF plus LAM or LdT combination therapy, with a favorable safety profile in CHB patients with LAM-resistant HBV variants.

Background/Aims The prevalence of hepatitis C virus (HCV) infection in Korea exhibits significant geographic variation, with it being higher in Busan and Jeonam than in other areas. The reason for this intranational geographic difference was investigated in this study by conducting a comparative analysis of the risk factors related to HCV infection among three geographic areas: the capital (Seoul), Busan, and the province of Jeolla. Methods In total, 990 patients with chronic HCV infection were prospectively enrolled at 5 university hospitals located in Seoul (n=374), Busan (n=264), and Jeolla (n=352). A standardized questionnaire survey on the risk factors for HCV infection was administered to these three groups of patients, and a comparative analysis of the findings was performed. Results The analysis revealed significant regional differences in exposure to the risk factors of HCV infection. By comparison with patients in Seoul as a control group in the multivariate analysis, patients in Busan had significantly more experience of invasive medical procedures, acupuncture, cosmetic procedures, and multiple sex partners. In contrast, patients in Jeolla were significantly older, and they had a higher prevalence of hepatocellular carcinoma, a lower prevalence of multiple sex partners, and had experienced fewer invasive procedures. Conclusions There was a significant geographic difference in the exposure to potential risk factors of HCV infection between patients from the three studied regions. This may explain the regional variation of the prevalence of HCV infection in Korea, and should be taken into account when planning strategies for the prevention and management of HCV infection.

Residual stone after endoscopic treatment of common bile duct stone may evolve recurrent common bile duct stone or serve as a nidus for further common bile duct stone growth. The aim of this study was to identify risk factors of residual stone after endoscopic treatment of common bile duct stone.

BACKGROUND AND AIM:Liver fibrosis is associated with the deposition of the extracellular matrix, and hepatic stellate cells (HSCs) are the major source of these matrix proteins. Guggulsterone has recently been shown to induce apoptosis in several cell lines. Thus, the aim of this study was to evaluate whether guggulsterone has antifibrotic activities by reducing the activation and survival of HSCs. METHODS:Apoptotic and fibrosis-related signaling pathways and nuclear factor kappa B (NF-κB) activity were explored in LX-2 cells, an immortalized human HSC line, and in a mice model of liver fibrosis. RESULTS:Guggulsterone suppressed LX-2 cell growth in a dose- and activation-dependent manner. This growth suppression was due to the induction of HSC apoptosis, which was mediated by the activation of c-Jun N-terminal kinase and mitochondrial apoptotic signaling. Additionally, guggulsterone regulated phosphorylation of Akt and adenosine monophosphate-activated protein kinase, which were subsequently proven responsible for the guggulsterone-induced HSC growth suppression. Guggulsterone inhibited NF-κB activation in LX-2 cells, which is one of the major mediators in HSC activation. Indeed, guggulsterone decreased collagen α1 synthesis and α-smooth muscle actin expression in these cells. Compared with the control mice or mice treated with a low dose of guggulsterone, high dose of guggulsterone significantly decreased the extent of collagen deposition and the percentage of activated HSCs undergoing apoptosis. CONCLUSIONS:These results demonstrate that guggulsterone suppressed HSC activation and survival by inhibiting NF-κB activation and inducing apoptosis. Therefore, guggulsterone may be useful as an antifibrotic agent in chronic liver diseases.

Background and Aim: As a rare liver disease, little is known about autoimmune hepatitis (AIH). This study investigated the clinical features and compared two diagnostic criteria of AIH in Korea.Methods: A nationwide, multicenter, retrospective analysis was done of data of adult patients diagnosed with AIH from January 2005 to December 2009.Results: The enrolled patients (n = 343; mean age, 52.8 years; range, 19-87 years; 12% male, 88% female) met diagnostic criteria of AIH according to the revised original criteria (n = 311) or the simplified criteria (n = 250). At diagnosis, 30.6% were asymptomatic, 22.7% were cirrhotic, and 4.3% displayed hepatic decompensation. The positive results for anti-nuclear antibody, smooth muscle antibody, and anti-liver/kidney microsomal antibody were 94.2%, 23.0%, and 2.9%, respectively. Definite AIH and probable AIH according to the revised original criteria were 24.8% and 65.3%, respectively, while those according to the simplified criteria were 34.4% and 38.5%, respectively. The diagnostic sensitivity and positive predictive value of simplified criteria in comparison with the revised original criteria were 69.9% and 86.4%, respectively. As an initial therapy, corticosteroid (37.7%) or corticosteroid with azathioprine (36.8%) was administered. Remission, incomplete response, and treatment failure were noted with 85.7%, 10.5%, and 3.9% of patients, respectively.Conclusions: Autoimmune hepatitis in Korea is mostly type I, showing a mean age of 53 years with comparable clinical features to other countries. The concordant rate of the two diagnostic criteria was rather low with modest sensitivity of the simplified criteria. Further studies on the validation of the diagnostic criteria are warranted.

Background: Hepatitis C virus infection frequently causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC). There are few studies addressing the effi cacy of treatmenet with full-dose peginterferon-alpha plus weightadjusted RBV dose in a patient population with compensated cirrhosis. We compared long term outcomes and adverse event profiles between cirrhotic patients with or without antiviral treatments. Methods: This is a single centered, retrospective study of patients with HCV-related cirrhosis who, since 2002, had received treatment in a academic hospital in Busan, Korea. Diagnosis of cirrhosis was biopsy proven in 6 cases (5.66%) and the remaining 100 cases (94.34%) met at least one of the following criteria: platelet count 1 (P=0.022) was significantly lower in the anti-viral treatment group with SVR. But, The incidence of hepatocellular carcinoma(P=0.200) and variceal hemorrhage(P=1.000) were not statistically associated with anti-viral treatment. Conclusions: Treatment with full-dose peg interferon-alpha plus weight-adjusted RBV dose in a patient population with compensated cirrhosis reduces the likelihood of clinical decompensation and improves event free survival.

Epithelial colon polyps are largely divided into hyperplastic and adenomatous polyps. Adenomatous polyps are premalignant lesions, whereas hyperplastic polyps are regarded as benign lesions. However, this histological classification has been blurred, as cases of malignant changes in hyperplastic polyposis, mixed hyperplastic adenomatous polyps (MHAPs), and serrated adenomas in the colon have been reported. Rare cases of MHAP have been reported, and are mainly found at the proximal colon with a relatively large size. MHAPs seem to be an intermediate stage of the hyperplastic polyp-adenoma sequence or a collision tumor. Here, we report on a case of a single polyp in the rectum diagnosed with a MHAP combined with an invasive adenocarcinoma.

BACKGROUND/AIMS This study was designed to determine whether bile aspiration before contrast injection cholangiogram prevent of post-ERCP cholangitis, liver function worsening, cholecystitis and pancreatitis. METHODS One hundred and two patients in the bile aspiration group before contrast injection from December 1, 2008 to December 30, 2009 and 115 patients in the conventional control group from January 1, 2010 to June 30, 2010 were analyzed. The incidence of post-ERCP cholangitis, liver function worsening, cholecystitis, pancreatitis, and hyperamylasemia only were compared between these two groups. RESULTS In the 102 patients with the bile aspiration group, post-ERCP cholangitis in 3 patients (2.9%), liver function worsening in 4 patients (3.9%), cholecystitis and pancreatitis in none, and hyperamylasemia only in 6 patients (5.8%) occurred. In the 115 patients with control group, post-ERCP cholangitis in 1 patient (0.4%), liver function worsening in 9 patients (7.8%), cholecystitis in none, pancreatitis in 3 patients (2.6%), hyperamylasemia only in 10 patients (8.6%) developed. The two groups did not significantly differ in terms of the incidence of post-ERCP cholangitis, liver function worsening, pancreatitis, and hyperamylasemia only (p>0.05). CONCLUSIONS Initially bile juice aspiration just before contrast injection into the bile duct rarely prevented post-ERCP cholangitis, liver function worsening, and pancreatitis in patients with the extrahepatic bile duct obstruction.

Objective. Thymosin alpha-1 plus interferon alpha-2a offers superior efficacy over interferon alpha-2a alone in patients with chronic hepatitis B. The aim was to compare the antiviral efficacy of thymosin alpha-1 plus peginterferon alpha-2a and peginterferon alpha-2a alone in HBeAg-positive chronic hepatitis B patients. Materials and methods. HBeAg-positive CHB patients were enrolled in this prospective, randomized, open-label study. Fifty-one patients were assigned to either combination (26 patients; 180 mu g of peginterferon alpha-2a weekly for 48 weeks and 1.6 mg of thymosin alpha-1 twice a week for the first 12 weeks) or monotherapy (25 patients; 180 mu g of peginterferon alpha-2a weekly for 48 weeks) groups. Results. The rates of the combined response, defined as HBeAg seroconversion, HBV DNA suppression, and normalization of serum ALT, were 4/26 (15.4%) and 3/25 (12.0%) for the combination group and the monotherapy group at the end of treatment (p = 0.725), and 6/26 (23.1%) and 5/25 (20.0%) at the end of follow-up (p = 0.789), respectively. Based on multiple logistic regression analysis, a >2 log(10) IU/mL reduction of HBV DNA at week 12 was identified as an independent predictor for combined response (OR, 9.72; 95% CI, 1.33-71.06; p = 0.025) at the end of follow-up. A lower pretreatment HBV DNA level (<= 7 log(10) IU/mL) was another predictor for combined response (OR, 9.64; 95% CI, 1.23-75.32; p = 0.031). No significant differences in adverse events were observed. Conclusions. The short-term addition of thymosin alpha-1 was not superior to peginterferon alpha-2a alone in HBeAg-positive CHB patients on the basis of antiviral efficacy.

Background/Aims: The reappearance rates of hepatitis C virus (HCV) RNA after a sustained virological response (SVR) have been reported to be 1-2%. We investigated the reappearance rate of HCV RNA after SVR in chronic hepatitis C (CHC) patients treated with pegylated interferon (PEG-IFN) and ribavirin. Methods: In total, 292 CHC patients who achieved an SVR after PEG-IFN and ribavirin treatment were included. They were treated with subcutaneous injections of either PEG-IFN-α 2a or 2b plus ribavirin orally. Liver function tests and qualitative HCV RNA assays were performed every 6 months during the follow-up period after an SVR. Results: Among the 292 patients, 224 (genotype 1, 92; genotype non-1, 132) were followed up for more than 6 months after SVR. These 224 patients were aged 48.1±11.5 years (mean±SD), and 129 of them were male. The median follow-up duration was 18 months (range 6-60 months). The reappearance rate of HCV RNA during follow-up was 0%. Two patients who achieved an SVR developed hepatocellular carcinoma during the follow-up period. Conclusions: An SVR was maintained in all CHC patients treated with PEG-IFN plus ribavirin during a median follow-up of 18 months. However, a screening test for hepatocellular carcinoma is needed for patients with an SVR. (Korean J Hepatol 2011;17:183-188)

The importance of serum hepatitis B surface antigen (HBsAg) level as a surrogate marker for viral load and a predictor of treatment response remains unclear. The aim of this study was to investigate whether serum HBsAg correlates with serum hepatitis B virus (HBV) DNA during peginterferon (PEG-IFN) α-2a treatment (with or without thymosin α-1) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and whether it can predict treatment response. Sera from 37 HBeAg-positive chronic hepatitis B patients receiving 48-weeks PEG-IFN α-2a with (n = 20) or without (n = 17) an initial 12-weeks thymosin α-1 were obtained at baseline and at weeks 12, 24, 36, 48 (end of treatment), 56, 72, 84, and 96 (end of follow-up). Taqman HBV DNA tests (Roche) and Architect HBsAg QT (Abbott) were performed. There was a moderate correlation between the HBsAg and HBV DNA levels (r = 0.452, P < 0.001). Median HBsAg levels at baseline and at week 96 were 6,218 IU/ml and 4,038 IU/ml, respectively. The mean HBV DNA and alanine aminotransferase (ALT) levels were 7.48 log(10) IU/ml and 173 IU/L at baseline and 5.37 log(10) IU/ml and 102 IU/L at week 96, respectively. A decrease to <60% of baseline levels of HBsAg at week 12 was identified as an independent predictive factor for HBeAg seroconversion (OR = 45.7, P < 0.05) at week 96. Serum HBsAg levels may be helpful for predicting the response to PEG-IFN therapy in HBeAg-positive chronic hepatitis B patients.