Showing papers by "Kwang Hyub Han published in 2018"

Serotonin signals through a gut-liver axis to regulate hepatic steatosis

Abstract: Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement

Abstract: Background Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. Aim To determine how to use CAP in interpreting liver stiffness measurements. Methods This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. Results Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. Conclusions Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Sarcopenia is associated with the risk of significant liver fibrosis in metabolically unhealthy subjects with chronic hepatitis B.

Abstract: BACKGROUND Sarcopenia is significantly associated with the degree of liver fibrosis. This study investigated the influence of sarcopenia on liver fibrosis in individuals with chronic hepatitis B. METHODS Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analysed. The sarcopenia index (total appendicular skeletal muscle mass [kg]/body mass index [kg/m2 ]) was calculated using dual-energy X-ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cut-offs: 0.89 for men and 0.58 for women). The fibrotic burden was assessed using the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index. Significant fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile and a fibrosis-4 index ≥2.67. RESULTS Among the 506 respondents with chronic hepatitis B (258 men and 248 women), the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index identified sarcopenia and significant fibrosis in 126 (24.9%) and 217 (42.9%), respectively. Sarcopenia was significantly associated with significant fibrosis, regardless of the fibrosis prediction model used (all P < 0.05). When the study population was stratified according to metabolic factors, sarcopenia was specifically associated with an increased risk of significant fibrosis among subgroups with obesity, insulin resistance, metabolic syndrome and liver steatosis (odds ratio 2.37-3.57; all P < 0.05). An independent association between sarcopenia and significant fibrosis was identified after adjusting for other confounders (odds ratio 2.67-3.62 by the nonalcoholic fatty liver disease fibrosis score and 2.04-2.62 by the fibrosis-4 index; all P < 0.05). CONCLUSIONS Sarcopenia is associated with significant fibrosis in subjects with chronic hepatitis B, specifically those with obesity, insulin resistance, metabolic syndrome and liver steatosis.

Noncontrast magnetic resonance imaging versus ultrasonography for hepatocellular carcinoma surveillance (MIRACLE-HCC): study protocol for a prospective randomized trial

Abstract: Biannual ultrasound (US)—with or without alpha-fetoprotein (AFP)—is recommended by current guidelines for the surveillance of hepatocellular carcinoma (HCC). However, the inadequate sensitivity of US has been a concern. Magnetic resonance imaging (MRI) is known to have high sensitivity in detecting hepatic malignancies, even without contrast enhancement. The purpose of our study is to compare US with noncontrast (unenhanced) MRI for HCC surveillance of high-risk patients. MIRACLE-HCC (usefulness of noncontrast MagnetIc Resonance imAging versus nonContrast ultrasonography for surveiLlancE of HepatoCellular Carcinoma) is a prospective, single-center, nonblinded, balanced-randomized, parallel-group study. This study was approved by our institutional review board, and informed consent will be obtained from all participating patients. All patients with compensated liver cirrhosis will undergo noncontrast US or MRI, with serum AFP testing every 6 months. If a suspicious lesion is newly detected, or if the serum AFP level is elevated in an increasing trend for two consecutive tests, dynamic contrast-enhanced imaging will be performed to confirm the diagnosis. The primary endpoints are detection rates of very early or early stage HCC, stage distribution at the initial diagnosis, and false positive referral rates, which will be compared using Fisher’s exact or chi-square tests. The study will include 416 patients in a tertiary academic medical center in South Korea. MIRACLE-HCC is the first prospective randomized trial to compare the effectiveness of noncontrast MRI and noncontrast US in the surveillance of HCC in at-risk patients. The results of this trial will show whether noncontrast MRI surveillance is superior to noncontrast US surveillance in the early detection of HCC. The trial will also determine whether there are fewer false referrals with noncontrast MRI than with noncontrast US and, eventually, whether there is improvement in the overall survival of HCC patients. The date of trial registration (ClincalTrials.gov: NCT02514434 ) for this study is July 23, 2015. Enrollment of participants was finished in November 2017. No authors have relationships, conditions, or circumstances that present potential conflicts of interest.

Downstaging with Localized Concurrent Chemoradiotherapy Can Identify Optimal Surgical Candidates in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

Abstract: Locally advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has a poor oncological outcome. This study evaluated the oncological outcomes and prognostic factors of surgical resection after downstaging with localized concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC). From 2005 to 2014, 354 patients with locally advanced HCC underwent CCRT followed by HAIC. Among these patients, 149 patients with PVTT were analyzed. Exclusion criteria included a total bilirubin ≥ 2 mg/dL, platelet count 20%. During the same study period, 18 patients with PVTT underwent surgical resection as the first treatment. Clinicopathological characteristics and oncological outcomes between groups were compared. Among 98 patients in the CCRT group, 26 patients (26.5%) underwent subsequent curative resection. The median follow-up period was 13 months (range 1–131 months). Disease-specific survival differed significantly between the resection after localized CCRT group and the resection-first group {median 62 months (95% confidence interval [CI] 22.99–101.01) versus 15 months (95% CI 10.84–19.16), respectively; P = 0.006}. Multivariate analyses showed that achievement of radiologic response was an independently good prognostic factor for both disease-specific survival (P = 0.039) and disease-free survival (P = 0.001) Localized CCRT could be an effective tool for identifying optimal candidates for surgical treatment with favorable tumor biology. Furthermore, with a 26.5% resection rate and 100% response in PVTT for resection after CCRT, our localized CCRT protocol may be ideal for PVTT.

Reduced risk of hepatocellular carcinoma by achieving a subcirrhotic liver stiffness through antiviral agents in hepatitis B virus-related advanced fibrosis or cirrhosis.

Abstract: Background&Aims A subcirrhotic range of liver stiffness (sc-LS), assessed by transient elastography, is associated with better outcomes in patients with chronic hepatitis B (CHB). We investigated whether the achievement of sc-LS by antiviral therapy (AVT) reduced the risk of developing hepatocellular carcinoma (HCC) in patients with CHB-related advanced fibrosis or cirrhosis. Methods In total, 209 patients with CHB-related advanced fibrosis or cirrhosis, who received paired transient elastography (TE) examinations during AVT between 2007 and 2012, were enrolled. The cut-off LS value for ultrasonographic cirrhosis was defined as 11.6 kPa. Results The median age of the study population was 51 years, with males predominating (n=138, 66.0%). The median LS value at enrollment was 14.1 kPa (interquartile range: 9.5–24.1 kPa). After 2 years of AVT, 140 (67.0%) patients achieved sc-LS. During the study period, 28 (13.4%) patients developed HCC after 2 years of AVT. On multivariate analysis, the achievement of sc-LS after AVT was independently associated with a decreased risk of HCC development (HR=0.485, P=0.047), whereas older age (HR=1.071) and male gender (HR=3.704) were independently associated with an increased HCC risk (both P<0.05). Patients with a cirrhotic range of LS value after 2 years of AVT were at a higher risk of HCC development than those with sc-LS (log-rank test, P=0.020). Conclusions The achievement of sc-LS after AVT can reduce the risk of HCC development in patients with CHB, even when advanced fibrosis or cirrhosis is apparent on starting AVT.

Feasibility of dynamic risk prediction for hepatocellular carcinoma development in patients with chronic hepatitis B.

Abstract: Background & Aims Several risk prediction models for hepatocellular carcinoma (HCC) development are available. We explored whether the use of risk prediction models can dynamically predict HCC development at different time points in chronic hepatitis B (CHB) patients. Methods Between 2006 and 2014, 1397 CHB patients were recruited. All patients underwent serial transient elastography at intervals of >6 months. Results The median age of this study population (931 males and 466 females) was 49.0 years. The median CU-HCC, REACH-B, LSM-HCC and mREACH-B score at enrolment were 4.0, 9.0, 10.0 and 8.0 respectively. During the follow-up period (median, 68.0 months), 87 (6.2%) patients developed HCC. All risk prediction models were successful in predicting HCC development at both the first liver stiffness (LS) measurement (hazard ratio [HR] = 1.067-1.467 in the subgroup without antiviral therapy [AVT] and 1.096-1.458 in the subgroup with AVT) and second LS measurement (HR = 1.125-1.448 in the subgroup without AVT and 1.087-1.249 in the subgroup with AVT). In contrast, neither the absolute nor percentage change in the scores from the risk prediction models predicted HCC development (all P > .05). The mREACH-B score performed similarly or significantly better than did the other scores (AUROCs at 5 years, 0.694-0.862 vs 0.537-0.875). Conclusions Dynamic prediction of HCC development at different time points was achieved using four risk prediction models, but not using the changes in the absolute and percentage values between two time points. The mREACH-B score was the most appropriate prediction model of HCC development among four prediction models.

The effect of interferon-free regimens on health-related quality of life in East Asian patients with chronic hepatitis C.

Abstract: BACKGROUND Interferon (IFN)-based regimens cause significant impairment of health-related quality of life (HRQL). Hepatitis C virus (HCV) cure with IFN-free regimens improves HRQL. The effect of these regimens on HRQL in East Asian HCV patients is unclear due to lack of published evidence. AIM To assess HRQL in East Asian HCV patients treated with an IFN-free regimen with sofosbuvir+ribavirin. METHODS Patients completed Short Form-36 (SF-36) before, during and after treatment. RESULTS 686 subjects were included (China: 56.7%; S. Korea: 18.8%; Taiwan: 12.7%; genotype 2: 40.8%; genotype 1: 29.6%; genotype 3: 18.4%; genotype 6: 11.2%; cirrhosis: 13.4%; treatment-naive: 66.5%). Patients received either pegylated-IFN, sofosbuvir, and ribavirin (IFN+SOF+RBV) for 12 weeks (n = 155, genotypes 1 and 6) or SOF+RBV for 12-24 weeks (n = 531, all genotypes). The SVR-12 rates were 95.5% and 96.0%; respectively (P = .76). Baseline HRQL scores were similar between treatment groups (all P > .05). By the end of treatment, the IFN-treated group experienced significant declines in most HRQL scores (on average, by up to -13.3 points on a 0-100 scale from the baseline level, P < .02) while subjects on SOF/RBV had milder impairments (up to -5.4 points). Achieving SVR-12 was associated with HRQL improvement regardless of regimen (up to +2.9 points, P < .05). The use of IFN-free treatment was a consistent independent predictor of higher HRQL scores during treatment (β: +2.1 to +10.7 points, P < .02). CONCLUSIONS East Asian HCV patients treated with an IFN-free regimen had better on-treatment HRQL scores. These data should inform policymakers about the comprehensive benefits of IFN-free regimens in East Asian patients with HCV.

Predictors of failure to detect early hepatocellular carcinoma in patients with chronic hepatitis B who received regular surveillance

Abstract: Background A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance. Aims To determine predictors for HCC detection failure in CHB patients who underwent regular surveillance. Methods CHB patients with well-preserved liver function, who underwent ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C. Results Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio [HR], 3.078; 95% CI, 1.389-6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307-11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341-8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066-59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613-14.297; P = 0.005) as predictors of detection failure. Conclusions In CHB patients undergoing regular surveillance with ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure.

Sofosbuvir and ledipasvir are associated with high sustained virologic response and improvement of health-related quality of life in East Asian patients with hepatitis C virus infection

Abstract: Although HCV infection is highly prevalent in East Asia, these patients have been underrepresented in HRQL studies. Here, we assess HRQL in East Asian HCV patients treated with different anti-HCV regimens. Patients completed Short Form-36 (SF-36) before, during and after treatment. A total of 989 HCV patients were enrolled in two phase 3 clinical trials [China: 60.2%, South Korea: 22.4%, Taiwan: 17.4%; genotype 1: 55.3%, treatment-naive: 57.5%; cirrhosis: 14.0%]. Patients received pegylated interferon, sofosbuvir and ribavirin (Peg-IFN + SOF + RBV; n = 130, genotypes 1, 6) or SOF + RBV (n = 475, all genotypes) or SOF and ledipasvir (LDV/SOF; n = 384, genotype 1). The SVR-12 rates were 94.6%, 96.2% and 99.2%, respectively (P = 0.005). During treatment, Peg-IFN + SOF + RBV-treated group experienced significant declines in most HRQL scores (by the end of treatment, mean decline up to -12.0 points, all P < 0.05). Patients on SOF + RBV had milder HRQL impairment (up to -5.8 points, P < 0.05 for 5 of 8 HRQL domains). In contrast, patients receiving IFN- and RBV-free regimen with LDV/SOF had their HRQL scores improve (mean up to +4.3 points, P < 0.0001 for 3 of 8 scales). In multivariate analysis, receiving Peg-IFN + SOF + RBV was consistently independently associated with HRQL impairment during treatment (β: -10.3 to -16.4) and after achieving SVR-12 (β: -4.4 to -9.1) (all P < 0.01). The results were reproduced in a subgroup of patients enrolled in China. We conclude that in East Asian patients with HCV, HRQL improved from baseline after treatment with LDV/SOF but not with Peg-IFN + RBV-containing or Peg-IFN-free RBV-containing regimens. The HRQL impairment associated with the use of Peg-IFN persists even after achieving sustained virologic clearance.

Reproducibility of European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors in patients treated with sorafenib.

Abstract: Background & aims The European Association for the Study of the Liver criteria and the modified Response Evaluation Criteria in Solid Tumors are used for assessing the treatment outcomes of hepatocellular carcinoma. We investigated the inter- and intra-observer reproducibility of the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors in patients with advanced hepatocellular carcinoma treated with sorafenib. Methods A total of 99 patients with treatment-naive advanced hepatocellular carcinoma receiving sorafenib were included. The κ-values for the inter- and intra-observer agreement of the treatment response were calculated. Results Inter-observer agreement for baseline tumour number was excellent, as reflected by the high κ-value. The κ-statistics showed "excellent" concordance between the 2 sets of measurements by observer A regarding the overall responses using the European Association for the Study of the Liver criteria (κ = .948, agreement rate = 84.8%) and modified Response Evaluation Criteria in Solid Tumors (κ = .944, agreement rate = 83.8%; all P .8) were obtained. Conclusions The reproducibility of the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors in assessing treatment outcomes was high in patients with advanced hepatocellular carcinoma treated with sorafenib.

Evolution and persistence of resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures.

Abstract: Daclatasvir plus asunaprevir (DCV+ASV) treatment is an all-oral direct-acting antiviral (DAA) therapy for the genotype 1b HCV-infected patients. In this study, we investigated how resistance-associated substitutions (RASs) evolved after treatment failures and assessed the effect of those substitutions on viral fitness. Sequencing of NS5A and NS3 revealed typical RASs after treatment failures. Interestingly, the RASs of NS3 reverted to the wild-type amino acid within 1 year after treatment failures. However, the RASs of NS5A were stable and did not change. The effect of NS5A and NS3 RASs on viral RNA replication was assessed after mutagenic substitution in the genotype 1b HCV RNA. Among single substitutions, the effect of D168V was more substantial than the others and the effect of the triple mutant combination (D168V+L31V+Y93H) was the most severe. The RAS at NS5A Y93 affected both viral RNA replication and virus production. Finally, the effect of trans-complementation of NS5A was demonstrated in our co-transfection experiments and these results suggest that such a trans-complementation effect of NS5A may help maintain the NS5A RASs for a long time even after cessation of the DAA treatment. In conclusion, the results from this investigation would help understand the emergence and persistence of RASs.

Safety and Efficacy of Transarterial Radioembolization Combined with Chemoembolization for Bilobar Hepatocellular Carcinoma: A Single-Center Retrospective Study.

Abstract: Radioembolization induced liver disease (REILD) is a possible sequela of transarterial radioembolization (TARE), particularly in cases of whole-liver treatment. To mitigate this problem, the safety and efficacy of combined transarterial chemoembolization (TACE) and TARE were evaluated for patients with bilobar hepatocellular carcinoma (HCC). Nineteen patients (mean age 60 years; range 27–82 years) treated for HCC between June 2012 and September 2014 were included in the analysis. Each patient was treated with combined TARE and TACE for bilobar HCC, with or without portal vein thrombosis. The hepatic lobe with large HCC was treated with TARE, and the other lobe with small HCC(s) was treated with TACE. Laboratory and clinical data were investigated to determine REILD occurrence. Survival data were analyzed to compare the treatment efficacy of alternative treatment modalities, including TACE and sequential TARE. All patients underwent TARE for a dominant tumor in one lobe and TACE for small nodule(s) in the other lobe of the liver. The mean yttrium-90 microspheres used in TARE were 2.8 GBq (range; 1.0-3.5 GBq), and the mean doses of doxorubicin and iodized oil were 24.5 mg and 5.2 mL, respectively, for TACE. No statistical differences were noted between laboratory data measured before and after treatment, and no procedure-related major clinical complications occurred. The median time-to-progression of patients was 10.0 months, and the median overall survival was 27.3 months. Combined radioembolization and chemoembolization appears to be a safe and effective treatment modality for bilobar HCC.

Combination of Transient Elastography and an Enhanced Liver Fibrosis Test to Assess the Degree of Liver Fibrosis in Patients with Chronic Hepatitis B.

Abstract: Background/Aims Liver stiffness (LS) was assessed using transient elastography, and the enhanced liver fibrosis (ELF) test was performed to accurately assess fibrotic burden. We validated the LS-ELF algorithm and investigated whether the sequential LS-ELF algorithm performs better than concurrent combination of these analyses in chronic hepatitis B (CHB) patients. Methods Between 2009 and 2013, 222 CHB patients who underwent liver biopsy (LB), as well as LS measurement and the ELF test, were enrolled. Results Advanced fibrosis (≥F3) and cirrhosis (F4) were identified in 141 (63.6%) and 118 (53.2%) patients, respectively. Areas under receiver operating characteristic curve for LS predictions of ≥F3 (0.887 vs 0.703) and F4 (0.853 vs 0.706) were significantly higher than the ELF test (all p＜0.001). Based on the LS-ELF algorithm, 60.4% to 71.6% and 55.7% to 66.3% of patients could have avoided LB to exclude ≥F3 and F4, respectively, whereas 68.0% to 78.7% and 63.5% to 66.1% of patients could have avoided LB to confirm ≥F3 and F4, respectively. When confirmation and exclusion strategies were applied simultaneously, 69.4% to 72.5% and 60.8% to 65.3% of patients could have avoided LB and been diagnosed as ≥F3 and F4, respectively. The proportion of patients who correctly avoided LB for the prediction of ≥F3 (69.4% to 72.5% vs 42.3% to 59.0%) and F4 (60.8% to 65.3% vs 23.9% to 49.5%) based on the sequential LS-ELF algorithm was significantly higher than the concurrent combination (all p＜0.05). Conclusions The sequential LS-ELF algorithm conferred a greater probability of avoiding LB in CHB patients to diagnose advanced fibrosis and cirrhosis, and this test performed significantly better than the concurrent combination.

Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance.

Abstract: Background/aims: It is unclear whether chronic hepatitis B (CHB) patients with antiviral resistance, who achieve a complete virologic response (CVR) with tenofovir disoproxil fumarate (TDF) and nucleoside analogue (NUC) combination therapy, maintain CVR if switched to TDF monotherapy. We investigated the persistence of CVR after cessation of NUC in virologically suppressed antiviral resistant CHB patients using TDF + NUC combination therapy. Methods: This study recruited 76 antiviral resistant CHB patients showing CVR on TDF + entecavir (ETV) (n = 52), TDF + lamivudine (LAM; n = 14) and TDF + telbivudine (LdT; n = 10) combination therapy, who were switched to TDF monotherapy as step-down therapy. Results: At baseline, 47 patients were male and the median age was 53.0 years (range: 30-78 years); 72.3% cases were hepatitis B e antigen-positive (HBeAg+) and 23.7% were of liver cirrhosis. The median duration of TDF + NUC combination therapy was 20.8 months (range: 3-46 months). At a median follow-up of 24.7 months (range: 12-48 months) after switching to TDF monotherapy, all 76 patients maintained CVR, regardless of the duration of combination therapy and the type of prior NUC and antiviral resistance. Renal dysfunction was not observed during the treatment period. Conclusions: The step-down strategy of switching from TDF + NUC combination therapy to TDF monotherapy in virologically suppressed CHB patients with antiviral resistance should be considered. This article is protected by copyright. All rights reserved

Daclatasvir Plus Asunaprevir for the Treatment of Patients with Hepatitis C Virus Genotype 1b Infection: Real-World Efficacy, Changes in Liver Stiffness and Fibrosis Markers, and Safety.

Abstract: Background/Aims The treatment with daclatasvir plus asunaprevir (DCV+ASV) is associated with potent antiviral effects in patients with genotype 1b hepatitis C virus (HCV) infection. We investigated the real-world efficacy, changes in liver stiffness and noninvasive fibrosis markers, and the safety of DCV+ASV treatment in Korean patients. Methods In total, 363 patients with chronic hepatitis C were treated with DCV+ASV between August 2015 and January 2017. Finally, we analyzed the data of 270 patients who were monitored for at least 12 weeks after the end of treatment. Results The mean age was 60.7 years, and females predominated (60.4%). Most patients (64.8%) were treatment-naive, and 56 patients (20.7%) had cirrhosis. Two hundred fifty-seven (95.2%) and 251 (93.0%) patients achieved end-of-treatment responses and sustained virological responses at 12 weeks posttreatment (SVR12), respectively. The SVR12 rates were higher in patients who were ＜65 years of age, males, without cirrhosis and had lower HCV RNA levels. All LS values and fibrosis-4 and aspartate aminotransferase-to-platelet ratio index values declined from baseline to the time of assessment of SVR12. Conclusions The DCV+ASV therapy resulted in a high SVR12 and improved liver fibrosis; the treatment was well tolerated in patients with genotype 1b HCV infections.

Responses are durable for up to 5 years after completion of peginterferon alfa‐2a treatment in hepatitis B e antigen‐positive patients

Abstract: Background In the large randomised NEPTUNE study, peginterferon alfa-2a 180 μg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 μg/wk) and/or shorter duration (24 weeks) (range 14%-26%). Aim To determine seroconversion rates 5 years after completion of treatment in NEPTUNE. Methods HBeAg-positive patients who completed 24 weeks' follow-up in NEPTUNE (with peginterferon alfa-2a 90 μg/wk × 24 weeks [group 1]; 180 μg/wk × 24 weeks [2]; 90 μg/wk × 48 weeks [3] or 180 μg/wk × 48 weeks [4]) were followed up. Results Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements. Conclusion Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 μg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration.

HBsAg-negative and anti-HBc-positive in eosinophilic granulomatosis with polyangiitis: a retrospective pilot study

Abstract: We examined whether resolved hepatitis B virus (HBV) infection was associated with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), and affected AAV activity at diagnosis and prognosis during the follow-up. We reviewed the electronic medical records of 153 AAV patients, and included 91 hepatitis B surface antigen (HBsAg)-negative patients having results of both antibody to hepatitis B core antigen (anti-HBc) and surface antigen (anti-HBs). We collected clinical and laboratory data, Birmingham vasculitis activity score (BVAS) and five factor scores (FFS) at diagnosis and relapse rates during the follow-up. We divided patients into the two groups according to the presence of anti-HBc and compared variables between them in patients with AAV or those with each variant. The mean age and follow-up duration were 59.8 ± 15.2-year-old and 48.0 ± 47.5 months. Fifty patients (54.9%) had anti-HBc, and 61 patients (67.0%) had anti-HBs. Only thirty-six (39.6%) patients had ever experienced relapse after remission. There were no remarkable differences between HBsAg-negative AAV patients with and without anti-HBc. However, in eosinophilic granulomatosis with polyangiitis (EGPA) patients, patients with HBs-negative/anti-HBc-positive (resolved HBV infection) showed the higher initial mean BVAS and FFS (2009) than those without. Patients having anti-HBc exhibited significantly increased risk of relapse of EGPA than those having not (RR 16.0). Also, EGPA patients with HBs-negative/anti-HBc-positive showed meaningfully lower cumulative relapse-free survival rates than those without during the follow-up duration (p = 0.043). In conclusion, resolved HBV infection may importantly influence vasculitis activity at diagnosis and subsequently relapse after remission in EGPA patients.

Independent imaging review (IIR) results in a phase 3 trial of lenvatinib (LEN) versus sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC).

Abstract: 345Background: LEN showed treatment effect on OS by statistical demonstration of noninferiority to SOR in a phase 3 study in pts with uHCC, with significant improvement (P < 0.00001) in median PFS ...