Prevalence, incidence, and outcomes of hepatitis E virus coinfection in patients with chronic hepatitis C.

This study aimed to elucidate the anti-hepatitis E virus (HEV) immunoglobulin G (IgG) prevalence and incidence of seroconversion and seroreversion as well as its risk factors and to analyze the clinical outcomes of HEV and hepatitis C virus (HCV) coinfected patients compared to those of HCV-monoinfected patients. We prospectively enrolled 502 viremic HCV patients with paired plasma samples (at intervals of ≥ 12 months) from 5 tertiary hospitals. Anti-HEV IgG positivity was tested using the Wantai ELISA kit in all paired samples. Mean age was 58.2 ± 11.5 years old, 48.2% were male, 29.9% of patients had liver cirrhosis, and 9.4% of patients were diagnosed with hepatocellular carcinoma (HCC). The overall prevalence of anti-HEV IgG positivity at enrollment was 33.3%, with a higher prevalence in males and increasing prevalence according to the subject's age. During the 916.4 person-year, the HEV incidence rate was 0.98/100 person-years (9/335, 2.7%). Hepatic decompensation or liver-related mortality was not observed. There were six seroreversion cases among 172 anti-HEV-positive patients (1.22/100 person-years). In conclusion, approximately one-third of the adult Korean chronic HCV patients were anti-HEV IgG positive. The HEV incidence rate was 1 in 100 persons per year, without adverse hepatic outcomes or mortality.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study.

BACKGROUND: Prospective studies of the long-term outcomes of patients with hepatitis C virus (HCV) infection after treatment with interferon-based therapy (IBT) or direct-acting antivirals (DAA) are limited in many Asian countries. AIM: To elucidate the incidences of hepatocellular carcinoma (HCC) and death/transplantation based on treatment with IBT or DAA, to compare the outcomes of the sustained virologic response (SVR) to IBT and DAA, and to investigate outcome-determining factors after SVR. METHODS: This cohort included 2054 viremic patients (mean age, 57 years; 46.5% male; 27.4% with cirrhosis) prospectively enrolled at seven hospitals between 2007 and 2019. They were classified as the untreated group (n = 619), IBT group (n = 578), and DAA group (n = 857). Outcomes included the incidences of HCC and death/transplantation. The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution. A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation, followed by propensity score matching to confirm the results. RESULTS: During a median of 4.1 years of follow-up, HCC and death/transplantation occurred in 113 and 206 patients, respectively, in the entire cohort. Compared with the untreated group, the incidences of HCC and death/transplantation were significantly lower in the IBT group [adjusted hazard ratio (aHR) 0.47, 95%CI: 0.28-0.80 and aHR 0.28, 95%CI: 0.18-0.43, respectively] and the DAA group (aHR 0.58, 95%CI: 0.35-0.96, and aHR 0.19, 95%CI: 0.20-0.68, respectively). Among 1268 patients who attained SVR with IBT (n = 451) or DAA (n = 816), the multivariable-adjusted analysis showed no differences in the risks of HCC (HR 2.03; 95%CI: 0.76-5.43) and death/transplantation (HR 1.38; 95%CI: 0.55-3.49) between the two groups. This was confirmed by a propensity score-matching analysis. Independent factors for HCC after SVR were age, genotype 1, and the presence of cirrhosis. CONCLUSION: Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection. The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.

Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose.

Background/Aims: Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to investigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection. Methods: From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecutively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by intention- to-treat (ITT) and per-protocol (PP) analyses. Results: The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/ mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber's discretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were observed in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea. Conclusions: SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.

Epidemiological and Clinical Characteristics of Hepatitis C Virus Infection in South Korea from 2007 to 2017: A Prospective Multicenter Cohort Study.

Background/Aims: This study aimed to elucidate the epidemiological and clinical characteristics of chronic hepatitis C (CHC) patients in South Korea from 2007 to 2017 and to compare the treatment patterns between two periods before and after the first approval of direct-acting antivirals (DAA) in South Korea in 2015. Methods: This prospective, multicenter cohort enrolled 2,758 patients with hepatitis C virus (HCV) viremia at seven tertiary centers, and clinical data were prospectively collected with questionnaire surveys focused on lifetime risk factors related to HCV infection. Results: The HCV patients had a mean age of 57.3 years (50.8% male). Among them, 14.3% showed a positive history of transfusion before HCV screening and 5.6% reported intravenous drug use (IVDU), with significant differences in these risk factors between men and women. The proportions of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) were 69.5%, 18.9%, and 11.5%, respectively. The mean alanine aminotransaminase level was within the upper normal limit at 49.9%, and the major genotypes were 1b (48.2%) and 2 (46.4%). The overall treatment rate was 53.8%, showing a rapid transition from interferon-based therapy to DAA therapy. In the post-DAA-approval era, the untreated group was older, had a higher prevalence of HCC, and had less education than the treated group. Conclusions: More than 90% of CHC patients were over 40 years old, the major genotypes were 1b and 2, and IVDU was observed in less than 6% of CHC patients. Approximately half of the patients underwent antiviral therapy even in the DAA era, showing an unmet need with regard to HCV elimination.

Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial.

BACKGROUND & AIMS: Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC. METHODS: In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS). RESULTS: For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006). CONCLUSION: Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC. LAY SUMMARY: For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.

Factors Associated with Health-Related Quality of Life in Korean Patients with Chronic Hepatitis C Infection Using the SF-36 and EQ-5D.

Background/Aims: This study aimed to describe the health-related quality of life (HRQoL) outcomes for Korean chronic hepatitis C patients and to investigate the impact of patient and virus-related factors on HRQoL. Methods: HRQoL was assessed in 235 hepatitis C virus (HCV)-infected patients from seven nationwide tertiary hospital, including those with liver cirrhosis and hepatocellular carcinoma (HCC), using the Shor-Form 36 (SF-36) version 2 and the European quality of life questionnaire-5 dimensions (EQ-5D-3L). Results: The SF-36 physical (48.8±8.3) and mental (46.2±11.7) component summary scores of the HCV-infected patients were below normal limits. Of the eight domains, general health, vitality, and mental health tended to show low scores. Patients with decompensated cirrhosis had the lowest HRQoL, while HCC and chronic hepatitis patients had similar HRQoL results. The EQ-5D index was low (0.848±0.145) in the HCV infected patients. Multivariable analysis showed age ≤65 years, high monthly family income (＞$2,641), low comorbidity score, and sustained virologic response (SVR) were independently associated with favorable HRQoL. Conclusions: HRQoL in Korean patients with chronic HCV infection was low and was affected by cirrhosis severity, SVR, and comorbidity as well as income, which had the strongest effect. Therefore, HRQoL may be improved by antiviral therapy with reasonable costs to prevent cirrhosis progression.

Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study.

BACKGROUND: Orantinib is an oral multi-kinase inhibitor. This study was done to evaluate the efficacy of orantinib combined with conventional transcatheter arterial chemoembolisation (cTACE) in patients with unresectable hepatocellular carcinoma. METHODS: This randomised, double-blind, placebo-controlled, phase 3 study was done at 75 sites in Japan, South Korea, and Taiwan. Patients with unresectable hepatocellular carcinoma, no extra-hepatic tumour spread, and Child-Pugh score of 6 or less were randomly assigned (1:1) by interactive web response system using a computer-generated sequence to receive orantinib or placebo, within 28 days of cTACE. Randomisation was stratified by region, Child-Pugh score (5 vs 6), alpha fetoprotein concentrations (<400 ng/mL vs ≥400 ng/mL), and size of the largest lesion (≤50 mm vs >50 mm). Orantinib at 200 mg, twice per day, or placebo was given orally until TACE failure or unacceptable toxicity. The patients, investigators, and study personnel were masked to treatment assignment. The primary endpoint was overall survival, analysed in the full analysis set (patients who had received at least one dose of study drug). This study is registered at ClinicalTrials.gov, number NCT01465464, and has been terminated. FINDINGS: Between Dec 10, 2010, and Nov 21, 2013, 889 patients were randomly assigned to receive either orantinib (445 patients; 444 treated) or placebo (444 patients; all treated). The study was ended at interim analysis for futility evaluation. Median follow-up was 17·3 months (IQR 11·3-26·4). There was no improvement in overall survival with orantinib compared with placebo (median 31·1 months [95% CI 26·5-34·5] vs 32·3 months [28·4-not reached]; hazard ratio 1·090, 95% CI 0·878-1·352; p=0·435). The main adverse events in the orantinib group were oedema, ascites, and elevation of aspartate and alanine aminotransferases. The most frequent adverse events of grade 3 or worse in the orantinib group included elevated aspartate aminotransferase (189 [43%] patients in the oratinib group, 161 [36%] patients in the placebo group), elevated alanine aminotransferase (150 [34%] patients in the oratinib group, 132 (30%) patients in the placebo group), and hypertension (47 [11%] patients in the oratinib group, 39 [9%] patients in the placebo group). Serious adverse events were reported in 200 (45%) patients in the orantinib group and 134 (30%) patients in the placebo group. INTERPRETATION: Orantinib combined with cTACE did not improve overall survival in patients with unresectable hepatocellular carcinoma. FUNDING: Taiho Pharmaceutical.

The clinical outcomes of chronic hepatitis C in South Korea: A prospective, multicenter cohort study.

This prospective cohort study aimed to elucidate the clinical outcome and its related factors of chronic hepatitis C in a hepatitis B-dominant Asian region.From January 2007 to October 2012, 382 patients with chronic hepatitis C without liver cirrhosis were prospectively enrolled at 6 university hospitals, and regularly followed until Apr 2014 to identify the development of liver cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC), and overall survival.During the median follow-up of 39.0 months (range 18.0-81.0 months), liver cirrhosis, hepatic decompensation, and HCC developed in 42 patients (11.0%), 4 patients (1.0%), and 12 patients (3.1%), respectively. The cumulative probability of development of cirrhosis at 3 years and at 5 years was 9.6% and 16.7%, respectively. That of HCC at 3 and 5 years was 1.6% and 4.5%, respectively. The 3-year and 5-year overall survival rate was 99.7% and 96.0%, respectively. Pegylated interferon-based antiviral therapy was undertaken in 237 patients (62.0%) with a sustained virologic response (SVR) rate of 74.3%. The factors related to the overall clinical outcomes were age ≥55 years (HR 2.924, P = 0.016), platelet counts <150  × 10/L (HR 3.195, P = 0.007), and the achievement of SVR (HR 0.254, P = 0.002).The clinical outcomes of this Korean chronic hepatitis C cohort were modest with minimal mortality, but significant disease progression occurred in the patients with old age, low platelet, and non-SVR after interferon-based antiviral treatment or no treatment, suggesting priority for direct acting antiviral therapy.

Treatment rate and factors related to interferon-based treatment initiation for chronic hepatitis C in South Korea.

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.

Pre-stimulation of CD81 expression by resting B cells increases proliferation following EBV infection, but the overexpression of CD81 induces the apoptosis of EBV-transformed B cells.

Hepatitis C virus (HCV) E2 protein binds to CD81, which is a component of the B cell co-stimulatory complex. The E2-CD81 interaction leads to B cell proliferation, protein tyrosine phosphorylation and to the hypermutation of immunoglobulin genes. Epidemiological studies have reported a high prevalence of B cell non-Hodgkin lymphoma (NHL) in HCV-positive patients, suggesting a potential association between HCV and Epstein-Barr virus (EBV) in the genesis of B lymphocyte proliferative disorders. In the present study, in order to investigate the association between EBV and HCV in B cells, we created an in vitro EBV-induced B cell transformation model. CD81 was gradually overexpressed during transformation by EBV. B cells isolated from HCV-positive patients grew more rapidly and clumped together earlier than B cells isolated from healthy donors following EBV infection. Pre-stimulation of CD81 expressed by resting B cells with anti-CD81 monoclonal antibody (mAb) or HCV E2 accelerated the generation of lymphoblastoid cell lines (LCLs) by EBV infection. These cells proliferated prominently through the early expression of interleukin-10 and intracellular latent membrane protein (LMP)-l. By contrast, the overexpression of CD81 on EBV-transformed B cells by anti-CD81 mAb or HCV E2 protein induced apoptosis through reactive oxygen species (ROS)-mediated mitochondrial dysfunction. These results suggest that the engagement of CD81 expressed by B cells has differential effects on B cell fate (proliferation or apoptosis) according to EBV infection and the expression level of CD81.

A review of the burden of hepatitis C virus infection in China, Japan, South Korea and Taiwan.

Hepatitis C virus (HCV) infection is associated with substantial clinical and economic burden and is an important public health issue in Asia. The objective of this review was to characterize HCV epidemiology and related complications in China, Japan, South Korea and Taiwan. A search of electronic databases and conference abstracts identified 71 potentially relevant articles. Of those, 55 were included in the epidemiology review and 9 in the review of HCV-related complications. HCV prevalence in the general population was 1.6% in China, 0.6-0.9% in Japan, 0.6-1.1% in South Korea and 1.8-5.5% in Taiwan. Prevalence was higher for injecting drug users (48-90%) and those with human immunodeficiency virus coinfection (32-85%) and was lower for blood donors (<1%). Annual incidence of HCV in China was 6.01 per 100,000. HCV genotype 1b was associated with the highest incidence of hepatocellular carcinoma (HCC). Five-year survival for patients with liver cirrhosis was 73.8%, decreasing to 39.2% following liver transplantation; the majority of deaths were attributable to HCC. Limitations were that the majority of studies included in the epidemiology review were small, regional studies conducted in specific populations, and there was an absence of large population-based studies. Thus, estimates may not be representative of the epidemiology of HCV for each country. The prevalence HCV in China and HCV incidence in the Asian region remain largely unknown, and they are likely underestimated. Further epidemiologic and clinical data are needed to provide more precise estimates for use by public health agencies.

Prospective cohort study on the outcomes of hepatitis C virus-related cirrhosis in South Korea.

BACKGROUND AND AIMS: The 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. METHODS: From 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. RESULTS: During 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 < 3.8 g/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 < 3.8 g/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). CONCLUSION: The 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.

Accuracy of transient elastography in assessing liver fibrosis in chronic viral hepatitis: A multicentre, retrospective study.

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.

Geographic differences in the epidemiological features of HCV infection in Korea.

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.

Role of interleukin-28B genetic polymorphisms in Korean patients with hepatitis C virus infection.

BACKGROUND/AIMS: This study investigated the role of single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene with respect to clinical outcomes and the antiviral response in hepatitis C virus (HCV) infection to suggest the practical utility of IL28B genotyping in Korea. METHODS: Two SNPs near IL28B, rs12979860 and rs8099917, were analyzed using an allelic discrimination assay in a total of 454 individuals, including 147 health-check examinees and 307 patients with HCV infection. RESULTS: The CC genotype frequency was significantly higher in the spontaneous recovery group than in the chronic infection group and was higher in the chronic hepatitis group than in the liver cirrhosis or hepatocellular carcinoma group, suggesting its favorable role in the clinical outcome. Multivariate analysis revealed that the rs12979860 CC genotype was an independent predictor of sustained virologic response (SVR) in genotype 1 HCV infection. During the currently used response-guided therapy, IL28B genotyping was most helpful for the patients who exhibit early virologic responses without rapid virologic responses, as those patients exhibiting the non-CC type did not achieve SVR, although they represented approximately one-third of the total patients. CONCLUSIONS: The IL28B SNP is an independent predictor of SVR. Our results may be helpful if the findings are carefully applied to select patients in Korea.

Clinical and epidemiological features of hepatitis C virus infection in South Korea: a prospective, multicenter cohort study.

The epidemiological and clinical features of hepatitis C virus (HCV) infection in South Korea were examined in a prospective, multicenter cohort study that included 1,173 adult patients with positive results for anti-HCV antibody who completed a questionnaire survey on the risk factors for HCV infection from January 2007 to December 2011 at five university hospitals. The HCV cohort had a mean age of 55.4 years with 48.3% men, and diagnostic categories of acute hepatitis (n = 63, 5.3%), past infection (n = 37, 3.2%), chronic hepatitis (n = 777, 66.2%), cirrhosis of the liver (n = 179, 15.3%), and hepatocellular carcinoma (n = 117, 10.0%). The major HCV genotypes were genotype 1 (52.7%) and genotype 2 (45.3%). Liver biopsy was performed in 301 patients (25.7%), and 42.8% of the subjects received antiviral therapy against HCV. The behavioral risk factors possibly related to HCV infection were intravenous drug use (5%), needle stick injury (7%), blood transfusion before 1995 (19%), sexual relationship with more than three partners (28%), piercings (35%), tattoos (36%), surgery (43%), acupuncture (83%), diagnostic endoscopy (85%), and dental procedures (93%). Age, intravenous drug use, needle stick injury, transfusion before 1995, and tattoos were the independent risk factors of HCV infection.

A practical scoring system for predicting cirrhosis in patients with chronic viral hepatitis.

BACKGROUND/AIMS: The purpose of the current study was to develop a simple model for predicting cirrhosis in chronic viral hepatitis patients and to evaluate the usefulness of decision tree algorithms. METHODOLOGY: Serum markers of fibrosis were compared with the stage of fibrosis in liver biopsy specimens prospectively obtained from 526 subjects with chronic HBV and HCV infections (estimation set, 367; validation set, 159). RESULTS: Univariate analysis revealed that age, bilirubin, platelet count, APRI, ALP, hyaluronic acid (HA), α2-macroglobulin, MMP-2, TIMP-1, and procollagen III N-terminal peptide (PIIINP) were significantly different between patients with (F4) and without cirrhosis (F0123). Multivariate logistic regression analysis identified platelet count, HA and PIIINP as independent predictors of cirrhosis. We categorized the individual variable into the most appropriate cut-off value by calculating the likelihood ratio for predicting cirrhosis and constructed a score system expressed by the following simple formula: PHP index = platelet score + HA score + PIIINP score. For predicting cirrhosis, the area under the receiver operating characteristic curve (AUROC) was 0.824 and 0.759 in the estimation and validation set, respectively. Using a cut-off score of 4, the presence of cirrhosis was predicted with high accuracy. The diagnostic performance of the PHP index was similar to decision tree algorithms (AUROC=0.819) for predicting liver cirrhosis, but more useful in clinical situations. CONCLUSIONS: Compared to a decision tree model, a simple score system using a categorized value based on a combination of platelet count, HA and PIIINP identified patients with liver cirrhosis with a higher clinical usability.

Durability of a sustained virological response in chronic hepatitis C patients treated with pegylated interferon alfa and ribavirin.

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.

Usefulness of multiple biomarkers for the prediction of significant fibrosis in chronic hepatitis B.

BACKGROUND/AIMS: It has not been explicitly addressed whether new biomarkers, in addition to readily available clinical data, make a contribution to the prediction of liver fibrosis. METHODS: A total of 209 patients with chronic hepatitis B who underwent liver biopsy were recruited. The Clinical Score (CS) model using only routine clinical data and the Biomarker Score (BS) model using 7 putative biomarkers were derived from the derivation set (n=105), and these models were applied to a separate patients group (n=104) to investigate whether the addition of BS improved the diagnostic accuracy in predicting significant fibrosis beyond an assessment based solely on CS. RESULTS: The most informative biomarkers for predicting significant fibrosis were hyaluronic acid and matrix metalloproteinase-2. The BS was an independent predictive factor for significant fibrosis even after accounting for CS in both sets. Among the derivation set, the incorporation of the BS into the CS model did not significantly increase the receiver operating characteristic area, with only a small improvement of about 2% (P=0.11). Similarly, in the validation set, a combined model with CS and BS showed no superior diagnostic accuracy over the CS model alone, with an improvement of approximately 2% [0.83 (0.75 to 0.92) vs. 0.81 (0.70 to 0.91); P=0.16]. CONCLUSIONS: The simultaneous addition of several biomarkers adds only modestly to clinical predictive factors for risk assessment of individual patients. These results highlight the need for the models to be validated in another cohort with a broader distribution of fibrosis severity.