Comparison between clevudine and entecavir treatment for antiviral‐naïve patients with chronic hepatitis B

Background and Aims: There has been no study comparing the clinical efficacy of clevudine and entecavir in antiviral‐naïve patients with chronic hepatitis B (CHB). Methods: A total of 128 antiviral‐naïve CHB patients were included to receive clevudine 30 mg (n=55) or entecavir 0.5 mg (n=73) once daily for a mean follow‐up period of 18.4 months. Results: Thirty‐three (60.0%) in the clevudine group and 40 (54.8%) in the entecavir group were HBeAg positive (P>0.05). At 6 months from the baseline, the mean decreases in HBV‐DNA were 4.86 and 4.72 log₁₀ copies/ml in the clevudine and entecavir groups respectively (P>0.05). The proportion of patients with undetectable serum HBV‐DNA (<300 copies/ml) at 6 months was 65.5 and 74.0% in the clevudine and entecavir groups respectively (P>0.05). The proportion of patients with normal alanine aminotransferase levels at 6 months was 74.5 and 84.9% in the clevudine and entecavir groups respectively. During the mean follow‐up of 18.4 months, genotypic resistance was noted in three patients (5.5%) in the clevudine group and no cases in the entecavir group. Eight patients (14.6%) in the clevudine group experienced symptoms, signs and laboratory abnormalities relevant to clevudine‐induced myopathy. Conclusions: Clevudine and entecavir treatment effectively suppresses HBV replication in most antiviral‐naïve patients with CHB. During a mean follow‐up of 18.9 months, a small proportion (5.5%) of patients in the clevudine group developed genotypic resistance. However, a substantial proportion (14.6%) of patients in the clevudine group had an adverse effect of clevudine‐induced myopathy.     

Biochemical response to ursodeoxycholic acid predicts long‐term outcome in Japanese patients with primary biliary cirrhosis

Aim: There is an ongoing need for predictors of long‐term outcomes for patients with primary biliary cirrhosis (PBC). Biochemical response to ursodeoxycholic acid (UDCA) has been introduced to predict development of symptoms by our group (Ehime criteria) and to predict long‐term outcomes in Western countries (Paris, Barcelona and Rotterdam criteria). The aim of this study was to evaluate whether these criteria are also useful to predict long‐term outcomes in Japanese patients with PBC. Methods: A retrospective chart review was conducted for 227 Japanese patients with PBC. Patients taking UDCA with an observation period of more than 6 months were included in the study. Data collection included demographics, biochemical and serological markers, and histological stage. Four different criteria regarding biochemical response to UDCA were compared and evaluated. Results: In total, 138 patients met the inclusion criteria and underwent analysis. Using the Ehime criteria, the transplant‐free survival rate was significantly higher in responders than in non‐responders (P = 0.010). The Paris criteria also predicted long‐term outcomes in our population (P = 0.003), whereas the Barcelona and Rotterdam criteria showed no such association (P = 0.282 and P = 0.553, respectively). Conclusion: Good biochemical response to UDCA according to the Ehime and Paris criteria is associated with long‐term outcome in Japanese patients with PBC and allows identification of non‐responders who may benefit from further trials. Finally, Ehime criteria should be validated in a different patient cohort.     

Treatment of HCV infection in Poland at the beginning of the interferon‐free era—the EpiTer‐2 study

The aim of the EpiTer‐2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon‐free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon‐free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two‐third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir‐based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3‐infected patients. Efficacy of treatment in the whole study population measured as intent‐to‐treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer‐2 study confirmed the excellent efficacy and safety profile of the real‐world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.     

替比夫定治疗乙型肝炎肝硬化患者48周临床观察

目的观察替比夫定治疗乙型肝炎肝硬化患者48周疗效。方法采用随机、对照队列研究方法,将93例乙型肝炎肝硬化患者分成三组,替比夫定（LDT）组32例,拉米夫定（LAM）组31例,对照组30例,采用常规保肝对症治疗,疗程均为48周。观察治疗不同时间点患者的病毒学、生化学、凝血酶原时间（PT）、肝纤维化指标及Child—Pugh计分等变化情况。结果LDT组患者HBVDNA水平显著下降,HBVDNA转阴率优于LAM组和对照组,差异均有统计学意义（P〈0．05）。在24和48周LDT组患者血清HBeAg阴转率及HBeAg／抗-HBe血清学转换率与对照组比较,差异有统计学意义（P〈0．05）。AⅡ、AST、TBil明显下降,肝纤维化指标改善,Child—Pugh计分下降,在24和48周,LDT组和LAM组较治疗前比较差异有统计学意义（P〈0．05）。结论LDT治疗乙型肝炎肝硬化患者能有效、快速抑制病毒复制,改善肝功能、肝纤维化指标及Child—Pugh计分等。     

Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment

BACKGROUND & AIMS: Patients with chronic hepatitis C who do not respond rapidly to therapy have a low chance of developing a sustained virologic response (SVR) when treated for 48 weeks. This study investigated whether treatment for 72 weeks increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA levels at week 4 of treatment. METHODS: A total of 510 treatment-naive patients were treated with peginterferon-alfa2a (180 microg/wk) plus ribavirin (800 mg/day). Patients with detectable HCV-RNA levels at week 4 (n = 326) were randomized to complete 48 (group A, n = 165) or 72 weeks (group B, n = 161) of treatment. Patients with undetectable HCV-RNA levels at week 4 (n = 184) were allocated into group C (n = 148) or group D (n = 36), according to HCV genotype and baseline viremia, and treated for 24 or 48 weeks, respectively. All patients were followed-up for 24 weeks after the end of treatment. RESULTS: The end-of-treatment response rate (61%) was similar in groups A and B, but the SVR rate was higher in group B (45% vs 32% in A; P = .01). In genotype 1-infected patients randomized to group A (n = 149) or B (n = 142), SVR rates were 28% and 44%, respectively (P = .003). The incidence of adverse events was similar in all groups. Treatment discontinuation was more frequent in group B (36%) than in group A (18%) (P = .0004). SVR rates in groups C and D were 79% and 64%, respectively. CONCLUSIONS: Extension of treatment with peginterferon-alfa2a plus ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients with detectable viremia at week 4 of treatment.     

Comparison of liver biochemical abnormality between COVID-19 patients with liver cirrhosis versus COVID-19 alone and liver cirrhosis alone: A STROBE observational study

Coronavirus disease (COVID-19) patients frequently develop liver biochemical abnormality. However, liver biochemical abnormality in COVID-19 patients with liver cirrhosis is under-recognized.Patients hospitalized during COVID-19 pandemic in China (ie, from February to April 2020) were screened. All of 17 COVID-19 patients with liver cirrhosis consecutively admitted to the Wuhan Huoshenshan Hospital were identified. Meanwhile, 17 age-, sex-, and severity-matched COVID-19 patients without liver cirrhosis admitted to this hospital were selected as a control group; all of 14 cirrhotic patients without COVID-19 consecutively admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command were selected as another control group. Incidence of liver biochemical abnormality and decompensated events were primarily compared.Among the COVID-19 patients with liver cirrhosis, the incidence of liver biochemical abnormality at admission and during hospitalization were 76.50% and 84.60%, respectively; 7 (41.20%) had decompensated events at admission; 1 was transferred to intensive care unit due to gastrointestinal bleeding. Among the COVID-19 patients without liver cirrhosis, the incidence of liver biochemical abnormality at admission and during hospitalization were 58.80% (P = .271) and 60.00% (P = .150), respectively. Among the cirrhotic patients without COVID-19, the incidence of liver biochemical abnormality at admission and during hospitalization were 69.20% (P = .657) and 81.80% (P = .855), respectively; 11 (78.60%) had decompensated events at admission (P = .036). None died during hospitalization among the three groups.Liver biochemical abnormality is common in COVID-19 patients with liver cirrhosis. Management of decompensated events in cirrhotic patients without COVID-19 should not be neglected during COVID-19 pandemic.     

恩替卡韦治疗中重度肝纤维化慢性乙型肝炎患者48周的疗效分析

目的III期临床研究结果显示恩替卡韦(ETV)治疗48周,在组织学改善、ALT复常和HBVDNA抑制方面均优于拉米夫定(LMV);肝纤维化的改善在核苷类似物初治患者中2个治疗组相似,在拉米夫定失效患者中,ETV明显优于LMV。对基线时表现为中重度肝纤维化/硬化患者(Ishak评分:4-6)进行亚组分析,评估ETV或LMV治疗48周的疗效。方法纤维化评分是由1位病理学家对基线和48周时标本进行评估,治疗组及标本先后顺序均对他设盲。结果对HBeAg( )核苷类似物初治的患者,48周时肝纤维化发生改善的患者比例ETV组为57%,LMV组为49%;肝纤维化没变化的患者比例ETV组35%,LMV组为28%;肝纤维化恶化的患者比例ETV组为0,LMV组为6%;对HBeAg(-)核苷类似物初治的患者,48周时肝纤维化发生改善的患者比例ETV组为59%,LMV组为53%;肝纤维化没变化的患者比例ETV组为31%,LMV组为18%;肝纤维化恶化的患者比例ETV组为2%,LMV组为5%;对HBeAg( )LMV失效的患者,48周时肝纤维化发生改善的患者比例ETV组为43%,LMV组为33%;肝纤维化没变化的患者比例ETV组为35%,LMV组为29%;肝纤维化恶化的患者比例ETV组为0,LMV组为19%。结论接受ETV治疗的中重度肝纤维化/硬化患者比接受LMV治疗更可能获得纤维化改善或不变,这些数据与其他治疗终点(全组人群的病毒学、生化学和Knodell评价的组织学改善情况)结果一致,均为ETV优于LMV。     

Predicting the response to 48‐week combination therapy with peginterferon α‐2b plus ribavirin from the estimated HCV RNA load index after negative serum change in genotype 1b hepatitis C patients

Aim: We estimated viral dynamics after serum hepatitis C virus (HCV) RNA became negative and assessed the relation between the estimated viral load at the end of treatment (EVE) index and the response to the combination therapy with peginterferon α‐2b plus ribavirin. Methods: Patients with chronic HCV, genotype 1b, and a high viral load were treated with this combination therapy for 48 weeks, and serum HCV RNA was measured frequently during the treatment period. In the patients showing an end‐of‐treatment response (ETR), the viral load profile from the start of treatment until serum HCV RNA became negative was expressed by an approximate curve. Then the EVE index was calculated by using the expression obtained from the curve, and differences between the sustained virologic response (SVR) and relapse groups were investigated. Results: The SVR rate increased as the EVE index became lower, and the EVE index was significantly lower in the SVR group than in the relapse group. The SVR rate was higher for those in whom the EVE index was below the cut‐off point. Conclusion: Prediction of SVR and relapse from the EVE index is more useful than prediction from viral dynamics at the time when HCV RNA becomes negative or when HCV RNA shows a decrease of 2‐log or more.     

慢性HCV感染DAA应答特点和长期预后观察研究

目的 本研究旨在观察不同疾病进展阶段的HCV感染者直接抗病毒药物(direct-acting antiviral agents,DAA)治疗的应答特点和长期预后.方法 纳入2016年7月—2017年3月就诊于我中心的慢性HCV感染者127例,其中慢性丙型肝炎(chronic hepatitis C,CHC)患者85例,代偿期肝硬化(compensated-liver cirrhosis,CLC)患者32例,失代偿期肝硬化(decompensated-liver cirrhosis,DLC)患者10例.DAA治疗12或24周.比较3组患者HCV RNA转阴时间、停药后12周持续病毒学应答(sustained virologic response 12,SVR12)率以及停药后2年的转归情况.结果 所有CHC、CLC、DLC患者均完成DAA治疗.CHC、CLC和DLC患者的SVR12率分别为98.82％(84/85)、96.88％(31/32)和100％(10/10);CHC患者HCV RNA转阴时间明显早于CLC和DLC患者(P均<0.05).在2年随访期间,1例CLC患者发生病毒学复发,2例DLC患者分别出现肝功能恶化和肝细胞癌.结论 目前常用的DAA治疗方案对CHC、CLC和DLC的患者均有高效的抑制病毒复制的作用,并且SVR12率在96％～100％之间,有很高治愈率.对于肝硬化患者停药后仍须监测肝癌的发生或个别病例HCV复发等情况.     

Role of IL‐28B and inosine triphosphatase polymorphisms in efficacy and safety of Peg‐Interferon and ribavirin in chronic hepatitis C compensated cirrhosis with and without oesophageal varices

Summary. Genetic factors can influence the outcome of antiviral therapy in chronic hepatitis C (HCV). We evaluated the role of interleukin‐28B single nucleotide polymorphisms (SNPs) and inosine triphosphatase (ITPA) gene variants in HCV cirrhosis treated with Peg‐Interferon and ribavirin. A prospective cohort of 233 patients with compensated cirrhosis received 1–1.5 μg/kg/week of Peg‐Interferon alpha‐2b plus 1000–1200 mg/day of RBV for 48 weeks. A sustained virologic response (SVR) was achieved in 27% of patients. On multivariate logistic analysis, the absence of oesophageal varices (OR 3.64 CI 95% 1.27–10.44 P = 0.016), infection with genotype 2 or 3 (OR 4.06, CI 95% 1.08–15.26, P = 0.038), C/C alleles of rs12979860 SNP (OR 7.04, CI 95% 2.40–20.72, P < 0.001) and rapid virologic response (RVR) (OR 78.29, CI 95% 16.07–381.29, P < 0.001) were independently associated with SVR. Patients who experienced post‐treatment relapse received lower total doses of Peg‐Interferon (52.0 ± 15.8 μg/kg vs 65.7 ± 13.3 μg/kg, P < 0.001) and lower total dose of RBV (3829 ± 1210 mg vs 4709 ± 954 mg, P < 0.001) than patients who achieved an SVR. ITPA variants predictive of high ITPase activity were associated with reduction of haemoglobin ≥3 g/dL in the first 4 weeks (P < 0.001), and with reduction of haemoglobin <10 g/dL (P = 0.03) on treatment. In conclusion, combination therapy with Peg‐Interferon and RBV in patients with HCV cirrhosis must be guided by virus genotype, severity of portal hypertension, favourable IL‐28B polymorphisms and ITPA variants, and RVR on treatment.