Ki Tae Yoon

Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: A randomised, non-inferiority, open trial

BACKGROUND & AIMS Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition. METHODS In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddreys discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone. RESULTS The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, -4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 5 9): 0.35 vs. 0.50 (p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups. CONCLUSIONS The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.

Endoscopic papillary large balloon dilation in Billroth II gastrectomy patients with bile duct stones

Background and Aims:  Patients with Billroth II (B‐II) gastrectomy present technical difficulties during endoscopic stone removal due to altered anatomy. Although endoscopic sphincterotomy alone or endoscopic balloon dilation alone has been used for removal of bile duct stones in patients with B‐II gastrectomy, the results are not satisfactory. The aim of this study was to evaluate the efficacy and safety of endoscopic papillary large balloon dilation (EPLBD) for removal of bile duct stones in patients with B‐II gastrectomy.

Is high-dose nafamostat mesilate effective for the prevention of post-ERCP pancreatitis, especially in high-risk patients?

Objective: Infusion of the protease inhibitor nafamostat mesilate (20 mg) effectively prevents post-ERCP pancreatitis, but only in low-risk groups. This study was performed to evaluate the use of high-dose nafamostat mesilate (50 mg) for prevention of post-ERCP pancreatitis (PEP), especially in high-risk groups. Methods: A total of 608 patients who underwent ERCP were included; 13 patients were excluded. Patients were divided into 3 groups: controls (group A), infusion with 20 mg of nafamostat mesilate (group B), or infusion with 50 mg of nafamostat mesilate (group C). The incidence of PEP was analyzed. Results: The overall incidence of acute pancreatitis was 7.4% (44/595). There was a significant difference in the incidence of PEP with or without nafamostat mesilate (13.0% vs 4.0% and 5.1%, respectively; P < 0.0001). Subgroup analysis showed that in low-risk patients, the rate of PEP was significantly different with nafamostat (11.9% vs 2.7% and 4.0%, respectively; P = 0.007). In high-risk patients, the rate of PEP was not significantly different among treatment groups (14.6% vs 5.9% vs 6.9%, respectively; P = 0.108). Conclusions: Nafamostat mesilate prophylaxis (20 or 50 mg) is effective in preventing post-ERCP pancreatitis. However, the preventive effect of high-dose nafamostat mesilate (50 mg) is not significant in high-risk patients.

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

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

Factors influencing the diagnostic accuracy of acoustic radiation force impulse elastography in patients with chronic hepatitis B

Background/Aims To determine factors predictive of discordance in staging liver fibrosis using liver biopsy (LB) and acoustic radiation force impulse (ARFI) elastography in patients with chronic hepatitis B (CHB). Methods Consecutive patients with CHB who underwent LB and ARFI elastography on the same day from November 2010 to March 2013 were prospectively recruited from three tertiary hospitals. Results We analyzed 105 patients (median age of 47 years). The F0–1, F2, F3, and F4 fibrosis stages were identified in 27 (25.7%), 27 (25.7%), 21 (20.0%), and 30 (28.6%) patients, respectively. The areas under the receiver operating characteristics curves for ARFI elastography in assessing ≥F2, ≥F3, and F4 was 0.814, 0.848, and 0.752, respectively. The discordance of at least one stage between LB and ARFI was observed in 68 patients (64.8%) and of at least two stages in 16 patients (15.2%). In a multivariate analysis, advanced fibrosis stage (F3–4) was the only factor that was negatively correlated with one-stage discordance (p=0.042). Moreover, advanced fibrosis stage was negatively (p=0.016) correlated and body mass index (BMI) was positively (p=0.006) correlated with two-stage discordance. Conclusions Advanced fibrosis stage (F3–4) was a predictor of nondiscordance between LB and ARFI elastography; BMI also influenced the accuracy of ARFI elastography.

Clinical efficacy and safety of the combination therapy of peginterferon alpha and ribavirin in cirrhotic patients with HCV infection

BACKGROUND/AIMS The combination therapy of peginterferon (PEG-IFN) and ribavirin is the standard treatment for hepatitis C virus (HCV) infection. However, few trials have involved patients with cirrhosis. The purpose of this study was to elucidate the efficacy and safety of treatment with PEG-IFN and ribavirin in patients with cirrhosis associated with HCV infection. METHOD A total of 65 patients were treated with PEG-IFN alpha-2a/ribavirin (n=32) or PEG-IFN alpha-2b/ribavirin (n=33). PEG-IFN alpha-2a and PEG-IFN alpha-2b were administered at doses of 180 microg/week and 1.5 microg/kg/week, respectively, and ribavirin was administered orally at doses of 800-200 mg. Patients with HCV genotype 1 and genotype non-1 were treated for 48 and 24 weeks, respectively. The treatment response was assessed based on the sustained virologic response (SVR). RESULTS The early virologic response (EVR), end-of-treatment response (ETR), and SVR were 70.0%, 52.0%, and 24.0%, respectively, in genotype 1 (n=50). In genotype non-1 (n=15), the ETR was 53.3% and the SVR was 33.3%. The overall SVR did not differ with genotype (1 vs non-1, 24.0% vs. 33.3%; P=0.471) or between decompensated cirrhosis and compensated cirrhosis (20.0% vs. 27.3%, P=0.630). Ten patients developed cirrhotic complications during the treatment, and 11 stopped treatment due to treatment-related adverse events. CONCLUSION The combination therapy of PEG-IFN and ribavirin exhibited a low efficacy in cirrhotic patients with HCV infection and was associated with frequent serious complications. However, with careful management of complications, the therapy may have a considerable efficacy in some patients with cirrhosis and HCV infection.

Clinical course of sorafenib treatment in patients with hepatocellular carcinoma

Abstract Objective. Sorafenib has been shown to improve survival of patients with advanced hepatocellular carcinoma (HCC). However, its tolerance in clinical practice has not been well evaluated, and whether sorafenib should be continued in cases of tumor progression or intolerance has not been established. The authors retrospectively assessed sorafenib tolerability, and evaluated the clinical course in patients who showed progression during sorafenib treatment. Material and methods. Between March 2008 and July 2010, 80 patients with advanced HCC were treated with sorafenib. Results. With a median of 78.5 days of treatment, 15% discontinued sorafenib due to adverse events. The duration was significantly longer in patients with Child–Pugh class A liver function (233 ± 240 days) than in those with Child–Pugh class B (100 ± 136 days; p = 0.006). The overall progression rate was 53% (43/80), with a median time to progression of 105 days (95% confidence interval, 59–150 days). After progression, 14 patients received conservative care only (group 1), 14 continued sorafenib monotherapy (group 2), 6 changed to treatment without sorafenib (group 3) and 9 underwent additional treatment with concomitant sorafenib (group 4). Survival after progression was significantly better in groups 2, 3 and 4 than in group 1 (p = 0.001). Conclusions. Sorafenib was tolerable for most patients in clinical practice and may be continued in patients who show progression during sorafenib therapy. However, it was less well tolerated in patients with Child–Pugh class B liver function and should be used with caution in these patients.

A 96-week randomized trial of switching to entecavir in chronic hepatitis B patients with a partial virological response to lamivudine

BACKGROUND Growing numbers of chronic hepatitis B (CHB) patients in the Asia-Pacific region have failed first-line therapy with low genetic barrier drugs. This prospective, 96-week study investigated the antiviral efficacy, safety and tolerability of switching to entecavir versus maintaining lamivudine in CHB patients with a partial virological response to lamivudine. METHODS A total of 72 hepatitis B e antigen (HBeAg)-positive patients, with serum HBV DNA≥60 IU/ml after ≥6 months lamivudine monotherapy were randomized 1:1 to receive either entecavir 1.0 mg/day, or continued lamivudine 100 mg/day. RESULTS Mean duration of prior lamivudine treatment was 15.1 months in the lamivudine-maintained patients and 16.1 months in the entecavir-switch patients, with mean baseline HBV DNA levels of 4.66 and 4.55 log(10) IU/ml, respectively. A greater proportion of entecavir-switch than lamivudine-maintained patients achieved undetectable HBV DNA at all time points (67.6% versus 11.4% at week 96; P<0.001). Entecavir-switch patients achieved a greater mean decrease in HBV DNA level by week 4, maintained through week 96. Entecavir-switch patients with baseline HBV DNA<5 log(10) IU/ml were more likely to achieve a virological response at week 96. A total of 6 (17.6%) entecavir-switch and 2 (5.7%) lamivudine-maintained patients achieved HBeAg loss, and 3 (8.8%) entecavir and 1 (2.9%) lamivudine patients achieved HBeAg seroconversion. Genotypic resistance to the assigned intervention emerged in 82.9% (29/35) of lamivudine-maintained patients, and in 3% (1/34) of entecavir-switch patients after 96 weeks. CONCLUSIONS Switching to entecavir in patients with a partial virological response to lamivudine resulted in increased virological efficacy and lower rates of antiviral resistance than maintaining lamivudine.

Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1

This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all‐oral, ribavirin‐free, fixed‐dose combination (DCV‐TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype‐1 infection, with or without compensated cirrhosis.

Thromboelastographic Evaluation of Coagulation in Patients With Liver Disease

Background The aims of this study were to investigate the parameters of thromboelastography (TEG) for evaluating coagulopathy and to reveal an association with disease severity and/or transfusion requirement in patients with chronic liver disease (CLD) in a clinical laboratory setting. Methods We enrolled two groups of adult patients with cirrhotic (N=123) and non-cirrhotic liver disease (N=52), as well as 84 healthy controls. Reaction time (R), kinetic time (K), α-angle (α), maximal amplitude (MA), and coagulation index (CI) were measured with kaolin-activated citrated blood with the TEG 5000 system (Haemonetics Corporation, USA). Platelet count, prothrombin time international normalized ratio (PT INR), albumin, bilirubin, and creatinine were simultaneously measured. The CLD severity was calculated by using the Child-Pugh (C-P) and Model for End-stage Liver Disease (MELD) scores. Transfusion history was also reviewed. Results All TEG parameters, PT INR, and platelet count in the cirrhotic group showed significant differences from those in other groups. At least one or more abnormal TEG parameters were identified in 17.3% and 44.7% of patients in the non-cirrhotic and cirrhotic group, respectively. Patients with cirrhotic disease had hypocoagulability. A weak correlation between R and PT INR (r=0.173) was noted. The TEG parameters could not predict CLD severity using the C-P and MELD scores. Patients with normal TEG parameters did not receive transfusion. Conclusions Clinical application of TEG measurements in CLD can be informative for investigating coagulopathy or predicting the risk of bleeding. Further studies are warranted.