如何提高代偿期丙型肝炎肝硬化患者抗病毒治疗的疗效

丙型肝炎病毒感染是肝硬化和肝细胞癌(HCC)的重要病因.HCV感染后20年肝硬化的发生率约为12.5％.2005年,美国丙型肝炎肝硬化患者为21.25万例,估计到2015年这一数字会增加到37.5万例,按美国的计算标准,2005年世界范围内丙型肝炎肝硬化患者约为780万例,2015年约为1380万例[1].目前慢性丙型肝炎(chronic hepatitis C,CHC)的持续病毒应答(sustained virologic response,SVR)率在1型HCV感染患者已经超过66％[2];2、3型HCV感染患者在80％以上;但丙型肝炎肝硬化患者抗病毒治疗后的SVR率仅为30％左右[3].     

输血后丙型肝炎患者的临床特点及自然病程

目的了解输血后慢性丙型肝炎病毒(HCV)感染者的临床特点及自然病程。方法采用回顾性调查与前瞻性研究相结合的方法,进行定群随访观察。结果(1)在99例HCV感染病例中,输血时间主要集中于1989—1994年,其中1990—1992年最为多见。(2)99例随访患者中,90例临床诊断为慢性丙型肝炎,9例诊断为丙型肝炎肝硬化(代偿期)。(3)99例患者自输血距首次诊断丙型肝炎的时间为(7．4± 6．6)年,其中9例患者首次诊断丙型肝炎肝硬化距输血时间为(12．7±5．8)年。(4)在63例男性患者中, 慢性丙型肝炎59例,丙型肝炎肝硬化4例；36例女性患者中,慢性丙型肝炎31例,丙型肝炎肝硬化5例；按男女分组比较丙型肝炎与肝硬化的构成比,差异无统计学意义(P＞0．05)。(5)丙型肝炎肝硬化组患者病程中均有反复肝功能异常,并且两氨酸氨基转移酶异常时波动的幅度较大。(6)本组病例在观察期间未发现肝癌的发生。结论(1)在广州地区,目前经输血感染HCV的可能性较1995年前大幅度降低。(2)9．1％ (9／99)的慢性丙型肝炎感染者在HCV感染13(12．7±5．8)年左右已进展为肝硬化(代偿期)。(3)对于反复出现肝功能异常的慢性丙型肝炎患者,应尽可能采用干扰素联合利巴韦林进行抗病毒治疗。     

慢性丙型肝炎抗病毒治疗研究的进展

丙型肝炎是由HCV引起的一种主要经血液传播的慢性进展性肝脏疾病.据世界卫生组织统计,全球HCV感染率约为3％,估计约1.7 ～2.0亿人感染了HCV,每年新发丙型肝炎病例约为3.5万例[1,3].HCV感染后约50％～85％转化为慢性感染[4-5].HCV慢性感染可导致肝脏慢性炎症坏死及纤维化,部分患者可发展为肝硬化甚至肝细胞癌,对患者的健康及生命危害极大,已成为严重的社会和公共卫生问题[5-7].HCV感染后的疾病进展与HCV的病毒复制活跃有密切关系,经有效的抗病毒治疗后能控制病毒的复制和肝脏的炎症活动,并阻断疾病的进展,可减少急性丙型肝炎向慢性丙型肝炎发展的概率,也可减少慢性丙型肝炎转为肝硬化和肝癌的可能性[8-10].慢性丙型肝炎抗病毒的治疗目标是清除体内HCV.治疗后能获得持续病毒学应答(sustained virological response,SVR)者,99％可达到临床治愈的目标[11,12].因此,抗病毒治疗是治疗丙型肝炎的关键措施.只要没有干扰素使用的禁忌证,所有的丙型肝炎患者均应进行抗病毒治疗.近来年,慢性丙型肝炎抗病毒治疗有较大的进展,现从三个方面介绍如下:     

慢性丙型肝炎肝硬化患者脾切除术后抗病毒治疗的疗效与安全性

干扰素联合利巴韦林治疗HCV感染是最有效的治疗手段,并可以延缓肝纤维化及肝硬化的发展[1].但临床上部分慢性丙型肝炎肝硬化患者,即使肝功能比较理想,但因脾功能亢进导致白细胞和血小板明显下降而不能进行抗病毒治疗,而且,终未期肝病模型(MELD)评分低,也不适合肝移植.本研究的目的在于探讨因脾功能亢进导致血小板减少的慢性丙型肝炎肝硬化患者行脾切除术后,用十扰素和利巴韦林抗病毒治疗的疗效与安全性.     

丙型肝炎肝硬化相关肝细胞癌患者的临床特征及其危险因素

目的 分析丙型肝炎肝硬化相关肝细胞癌(HCC)患者的流行病学特征、临床特点和相关危险因素.方法 对89例丙型肝炎肝硬化患者进行长期随访观察,并对HCC发生的危险因素进行单因素和多因素分析.结果 在86.5(60～120)个月随访过程中,89例患者中35例发生HCC,第5、第10年HCC累计发生率分别为16.9%、40.4%.4例有丙型肝炎家族史、12例有HCC家族史和7例有饮酒史的患者均在随访中发生HCC.89例中50例存在肝脂肪变患者第5、第10年HCC累计发生率分别为24.6%、51.0%;39例无肝脂肪变的患者第5、第10年HCC累计发生率分别为8.7%、26.2%,两组间差异有统计学意义(P＜0.05),慢性丙型肝炎肝硬化患者肝脂肪变与肝硬化的严重程度相关,肝脂肪变患者抗病毒治疗持续应答率低于无脂肪变患者,两组间差异有统计学意义(P＜0.05).HCC患者的ALT和总胆红素水平高于非HCC患者,白蛋白水平低于非HCC患者,两组间差异有统计学意义(P＜0.05).多因素回归分析结果显示肝功能分级和肝脂肪变与HCC独立相关.结论 慢性丙型肝炎肝硬化是一个缓慢进行性疾病,HCC是其重要并发症,肝功能分级和肝脂肪变是HCC发生的高危因素,饮酒和HCC家族史对HCC的发生有一定影响.丙型肝炎肝硬化伴肝脂肪变的患者病情进展速度明显加快,应定期筛查以降低HCC发病的危险.     

慢性丙型肝炎病毒感染者2型糖尿病流行病学调查

目的研究慢性丙型肝炎病毒感染者2型糖尿病的发病情况。方法对221例慢性丙型肝炎感染者(其中肝硬化72例)2型糖尿病发病情况进行调查,并与慢性乙型肝炎病毒感染者660例(其中肝硬化220例)2型糖尿病发病情况进行对照。结果慢性丙型肝炎感染者2型糖尿病的发病率为21.2%(47/221),高于慢性乙型肝炎感染者的10.9%(72/660)(P<0.02);丙型肝炎病毒致肝硬化2型糖尿病的发病率为30.6%(22/72),明显高于慢性丙型肝炎患者2型糖尿病发病率23.4%(35/149),(P<0.05),并明显高于对照组乙型肝炎病毒致肝硬化2型糖尿病的发病率11.3%(25/220),(P<0.05)。结论肝硬化是慢性丙型肝炎感染者发生2型糖尿病的危险因素;肝硬化和丙型肝炎病毒共同作用导致了2型糖尿病危险性的增加。丙型肝炎病毒致肝硬化2型糖尿病的发病率明显高于乙型肝炎病毒致肝硬化。     

难治性丙型肝炎治疗方案的优化

丙型肝炎慢性化几率为50%-80%[1].感染HCV后10～20年,至少20%患者发展为肝硬化,其中约15%肝硬化患者可发展为失代偿期肝硬化,失代偿期肝硬化10年的生存率仅为25%.     

慢性丙型肝炎的抗病毒治疗及早期疗效预测

目前,在全世界范围内丙型肝炎病毒(HCV)感染者已达1.7亿,其中约70%～80%的受感染者可发展成为慢性丙型肝炎(chronic hepatitis C).慢性丙型肝炎患者经过10～30年,其中20%可发展为肝硬化及出现相关并发症,这其中又有约1%～4%发展为肝细胞癌.自1989年Houghton等发现HCV以来,对HCV的认识及慢性丙型肝炎的诊断与治疗研究都有了很大的进展. 慢性丙型肝炎的抗病毒治疗经历了由单一干扰素治疗到干扰素联合利巴韦林再到目前长效干扰素以及长效干扰素联合利巴韦林治疗的发展过程.抗病毒治疗的疗效也不断提高,仅仅在10年前抗病毒治疗的持久病毒应答率仅达5%～10%.随着治疗的不断改进,目前抗病毒治疗的疗效几乎提高了近10倍.抗病毒治疗不仅可抑制HCV病毒复制,改善肝脏炎症活动,防止肝纤维化及肝硬化的进展,也可防止和减少肝细胞癌的发生.本文对慢性丙型肝炎的抗病毒治疗、HCV对治疗应答的病毒动力学以及早期疗效预测等3个方面作一综述.     

丙型肝炎肝硬化抗病毒治疗现状

目前干扰素联合利巴韦林是慢性HCV感染的主要抗病毒治疗方案,但丙型肝炎肝硬化患者对于抗病毒治疗耐受性差.目前研究报道对于丙型肝炎肝硬化患者进行抗病毒治疗,如能获得持续病毒学应答(SVR),有利于缓解肝纤维化进展,并减少肝移植术后HCV再感染的发生.因此,应对丙型肝炎肝硬化患者进行仔细评估,对于进行抗病毒治疗的患者可给予适当干预以维持抗病毒治疗的进行,并在治疗过程中密切监测不良反应的发生.     

广州市2005-2008年丙型肝炎疫情分析

丙型肝炎病毒(HCV)感染是一个易被忽视的社会公众问题.HCV感染慢性化程度高,可发展为肝硬化及肝癌~([1]).目前丙型肝炎已有特效的药物治疗,如能及早治疗,可防止其发展为肝硬化和肝癌~([2-3]).     

Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%‐8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long‐term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis‐related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow‐up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow‐up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow‐up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942‐2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407‐3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333‐1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.     

艾尔巴韦/格拉瑞韦治疗慢性丙型肝炎患者疗效初步观察

目的 初步探讨应用艾尔巴韦/格拉瑞韦治疗慢性丙型肝炎(CHC)患者的疗效。方法 2017年3月~2018年3月仙桃市第一人民医院感染病科收治的CHC患者82例,被随机分为对照组41例和观察组41例,分别给予聚乙二醇干扰素-α联合利巴韦林治疗和艾尔巴韦/格拉瑞韦治疗,两组均连续治疗24周。采用RT- PCR法检测血清 HCV RNA,采用全基因序列测定法行病毒基因分型。比较两组早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)和持续病毒学应答(SVR)。结果 在治疗结束时,观察组血清丙氨酸氨基转移酶(ALT)水平为(47.9±19.7)U/L,显著低于对照组【(63.5±21.2)U/L,P<0.05】,天冬氨酸氨基转移酶(AST)水平为(55.5±22.3)U/L,显著低于对照组【(81.3±25.8)U/L,P<0.05】;观察组EVR、ETVR和SVR分别为48.8%、63.4%和70.7%,与对照组的41.5%、53.7%和65.8%比,无统计学差异(P>0.05);18例观察组非HCV Ⅰ型感染者EVR、ETVR和SVR分别为88.9%、94.4%和88.9%,显著高于同组23例HCV Ⅰ型感染者(分别为52.2%、60.9%和52.2%, P<0.05),而与对照组15例非HCV Ⅰ型感染者比,无统计学差异(分别为86.7%、93.3%和73.3%, P>0.05);观察组SVR₁₂为87.8%(36/41),显著高于对照组的73.2%(30/41,P<0.05)。结论 应用直接抗病毒(DAA)药物艾尔巴韦/格拉瑞韦治疗CHC患者近期疗效达到,但远期疗效似优于标准治疗方案, 值得临床进一步验证。     

直接抗病毒药物治疗慢性丙型肝炎48周临床观察

背景慢性丙型肝炎(chronic hepatitis C,CHC)是全球公共卫生问题,随着直接抗病毒药(direct antiviral therapy,DAA)在中国的应用,DAA药物成为目前国内慢性丙型肝炎抗病毒一线方案,但目前真实世界DAA治疗后长期疗效数据尚少.目的观察慢性丙型肝炎患者接受直接抗病毒药物抗病毒治疗后48 wk病毒学应答及临床疗效.方法连续收集2018-04-01/2020-04-30在天津市第三中心医院接受DAA治疗的初治CHC患者,评估治疗基线、治疗结束、治疗后12 wk及48 wk的病毒学应答及肝肾功能、肝硬度、APRI及临床结局.结果共收集291例应用DAA治疗的CHC患者,纳入145例完成抗病毒治疗及随访的CHC患者进入本研究.其中肝硬化患者占28.3%,基因型1b、2a、3a、6a分别占78.0%、17.2%、2.8%、2.0%.DAA治疗结束、治疗后12 wk及48 wk获得持续病毒学应答(sustained virological response,SVR)比例分别为100%、97.9%和97.2%,其中基因型1b、2a、3a、6a的SVR48分别为97.3%、96%、100%、100%.治疗结束后48 wk与基线相比较,丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素及白蛋白的复常率分别为93.2%、91.7%、73.3%及97.7%.治疗结束后48 wk肝硬度(liver stiffness measurement,LSM)及APRI与基线水平相比均明显下降(LSM 12.5 vs 10.2kpa P<0.01;APRI 0.34 vs 0.13 P<0.01),肝硬化组及非肝硬化组患者均有明显下降(P<0.05).48 wk随访期间,其中4例(2.8%)CHC患者进展为肝硬化,8例(5.6%)肝硬化患者进展为肝硬化失代偿,3例(2.1%)肝硬化患者发生新发肝细胞癌(hepatocellular carcinoma,HCC).结论本研究真实世界中慢性丙型肝炎患者应用DAA治疗后48 wk,总体病毒持续应答率较高,肝功能、肝硬度及APRI值均明显改善.2.1%患者出现新发HCC.     

Liver steatosis is a major predictor of poor outcomes in chronic hepatitis C patients with sustained virological response

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all‐cause mortality and HCC in CHC patients with SVR following direct‐acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow‐up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all‐cause mortality and HCC at 2 years of follow‐up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5‐fold increased risk of all‐cause mortality and HCC (HR 7.51, 95% C.I 3.61‐13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97‐6.59, P = 0.06). In conclusion, LS is a major predictor of all‐cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.     

泛基因型与特异基因型DAAs方案精准治疗基因1b型慢性丙型肝炎患者疗效对比分析*

目的 比较采用泛基因型与特异基因型直接抗病毒药物(DAAs)方案精准治疗基因1b型慢性丙型肝炎(CHC)患者的疗效。方法 2018年1月～2020年6月我院诊治的基因1b型CHC患者75例,其中34例对照组患者接受泛基因型DAAs治疗,即19例接受索非布韦/维帕他韦口袋,15例口服索磷布韦/达拉他韦;41例研究组接受特异基因型DAAs治疗,即23例口服艾尔巴韦/格拉瑞韦,18例口服奥比帕利/达塞布韦。两组均持续治疗12周。采用实时荧光定量PCR法检测血清HCV RNA。比较两组超快速病毒学应答(SRVR)、快速病毒学应答(RVR)、早期病毒学应答(EVR)和持续病毒学应答(SVR)。结果 在治疗12周末,研究组血清ALT和AST水平分别为(31.9±4.1)U/L和(32.5±4.1)U/L,与对照组[分别为(32.7±4.2)U/L和(31.9±3.7)U/L,P＞0.05]比,无显著性差异;研究组SRVR、RVR、EVR和SVR分别为87.8%、97.6%、100.0%和100.0%,与对照组(分别为88.2%、94.1%、100.0%和100.0%)比,差异均无统计学意义(P＞0.05);索非布韦/维帕他韦治疗患者SRVR、RVR、EVR和SVR分别为84.2%、100.0%、100.0%和100.0%,索磷布韦/达拉他韦治疗患者分别为86.7%、93.3%、100.0%和100.0%,艾尔巴韦/格拉瑞韦治疗患者分别为91.3%、100.0%、100.0%和100.0%,奥比帕利/达塞布韦治疗患者分别为88.9%、94.4%、100.0%和100.0%,四组所有病毒学应答率均无显著性差异(P＞0.05);治疗期间两组不良反应发生率为11.8%对12.2%,差异无统计学意义(P＞0.05)。结论 当前应用的无论是泛基因型还是特异基因型DAAs方案治疗基因1b型CHC患者均具有良好的疗效,且安全性良好。是否可以不区分感染病毒基因型选择药物治疗,值得进一步研究。     

Epidemiology and outcomes of hepatitis C infection in elderly US Veterans

The chronic hepatitis C (CHC) cohort in the United States is getting older. Elderly patients with CHC may be at a high risk of cirrhosis and hepatocellular carcinoma (HCC), but also other nonhepatic comorbidities that negatively impact their likelihood of receiving or responding to antiviral treatment. There is little information on the clinical epidemiology or outcomes of CHC and its treatment in the elderly. We conducted a retrospective cohort study of 1 61 744 patients with a positive Hepatitis C virus RNA in the Veterans Health Administration Hepatitis C Clinical Case Registry to examine the association between age subgroups (20–49, 50–64, 65–85 years) and risk of cirrhosis, HCC or death using Cox proportional hazards models. We also examined the effect of treatment with a sustained viral response (SVR) on these outcomes in each age subgroup. The age distribution was 36.8% 20‐ to 49‐year‐olds, 57.6% 50‐ to 64‐year‐olds and 5.6% 65‐ to 85‐year‐olds (i.e. elderly). Risk of cirrhosis, HCC and death was significantly elevated in elderly patients [HR cirrhosis = 1.14 (1.00–1.29), HR HCC = 2.44 (1.99–2.99); HR death 2.09 (1.98–2.22)] compared with younger patients. The incidence of HCC was than 8.4 per 1000 PY in the elderly compared with 2.6 per 1000 PY and 5.7 per 1000 PY, among the 20–49 and 50–64 age groups, respectively. Elderly patients were significantly less likely to receive antiviral treatment (3.8% vs 14.8% and 19.1%, P < 0.0001), but among those who received treatment SVR was not different among the age groups (33.5% vs 33.2% and 32.1%). In an analysis limited to those who received treatment, SVR compared to treatment receipt with no SVR was associated with a reduction in risk of developing cirrhosis (HR = 0.34; 0.18–0.66) and HCC (HR = 0.60; 0.22–1.61) and all‐cause mortality risk (HR = 0.52, 0.33–0.82). Elderly patients with CHC are more likely to develop HCC than younger patients but have traditionally received less antiviral treatment than younger patients. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC and overall mortality, irrespective of age.     

Hepatitis B Co-Infection Has Limited Impact on Liver Stiffness Regression in Chronic Hepatitis C Patients Treated with Direct-Acting Antivirals

Introduction: High sustained virological response (SVR) rate (>95%) and liver stiffness regression can be achieved with direct acting antivirals treatment (DAA) in patients with chronic hepatitis C virus (CHC) infection. Reactivation of hepatitis B virus (HBV) was reported during DAA treatment in patients co-infected with HBV, although its impact on liver stiffness remains unknown. This study aims to investigate whether the liver stiffness (LSM) regression is different between HBV/HCV co-infected and mono-HCV-infected patients. Materials and Methods: CHC patients with/without HBV co-infection who received DAA treatment and achieved SVR12 between March 2015 and December 2019 in Chang Gung Memorial Hospital, Linkou branch were prospectively enrolled. LSM was assessed by transient elastography (TE, Fibroscan) at baseline and after SVR. Propensity score matching (PSM) at 3:1 ratio, adjusted for age, gender, pre-DAA alanine aminotransferase (ALT), platelet count, and LSM, between CHC with and without HBV co-infection, was performed before further analysis. Results: Among 906 CHC patients enrolled, 52 (5.7%) patients had HBV/HCV co-infection. Patients with HBV/HCV co-infection were of younger age (61.8 vs. 63.2, p = 0.31), with a higher proportion of males (53.8% vs. 38.9%, p = 0.03), and lower pretreatment LSM level (8.15 vs. 10.2 kPa, p = 0.09), while other features were comparable. After PSM, patients with HBV/HCV co-infection had insignificantly lower LSM regression compared to mono-HCV-infected patients (−0.85 kPa vs. −1.65 kPa, p = 0.250). Conclusions: The co-infection of HBV among CHC patients has limited impact on liver stiffness regression after successful DAA treatment.     

Eradication of hepatitis C virus profoundly prolongs survival in hepatocellular carcinoma patients receiving transarterial chemoembolization

Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C (CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC‐HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence‐free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient‐based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child‐Turcotte‐Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2‐year cumulative overall survival rate and recurrence‐free survival rate among patients with SVR, non‐SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non‐SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC‐HCC patients receiving TACE treatment after complete response.     

索非布韦联合达卡他韦治疗慢性丙型肝炎:真实世界临床研究

目的 评价直接抗病毒药物(DAAs)索非布韦(SOF)联用达卡他韦(DCV)治疗慢性丙型肝炎(CHC)患者真实世界研究(RWS)的疗效和安全性。方法 2015年9月～2017年9月广州市第八人民医院肝病门诊诊治的CHC患者43例,接受SOF联用DCV治疗12 w,随访12～48 w。结果 43例均完成12 w疗程及停药12 w观察,23例完成停药24 w观察、18例完成停药48 w观察;在治疗2 w、4周 w和12 w时,血清HCV RNA转阴率分别77.0％(33/43)、93.0％(40/43)和100.0％(43/43);在停药12 w时,持续病毒学应答率(SVR12)为100.0%,23例停药24周HCV RNA仍阴性,18例停药48周HCV RNA仍阴性;在治疗2 w、4 w和12 w及停药12 w时,血清ALT水平分别为(28.3±14.4)U /L、(25.4±12.9)U /L、(22.5±9.4)U /L和(21.8±8.6) U /L,显著低于治疗前水平,血清AST水平分别为(25.4±10.4)U /L、(24.7±9.6)U /L、(22.8±7.7)U /L和(22.3±6.5)U /L,也显著低于治疗前水平; 在停药12 w时,血生化学应答率为100.0%,23例停药24 w、18例停药48 w时,肝功能仍持续正常,8例基线估算的肾小球滤过率(eGFR)小于90 ml·min^-1·1.73 m²,治疗期间部分有不同程度的下降(eGFR最低降至60.76 ml·min^-1·1.73 m²),停药后恢复至治疗前水平,未因eGFR下降而需调整用药或停药情况;用药期间发生失眠3例、恶心2例、乏力1例、头痛1例、脱发1例,均发生于治疗的早期,未特殊处理,均自行缓解,无严重不良事件发生。结论 采用SOF联合DCV治疗CHC患者可获得极高的SVR12和生化学应答率,且安全性良好。长期疗效仍需观察。     

Long-term follow-up of cumulative incidence of hepatocellular carcinoma in hepatitis B virus patients without antiviral therapy

BACKGROUNDChina has a high prevalence of hepatitis B virus (HBV), but most chronic hepatitis B (CHB) patients do not receive standardized antiviral therapy. There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy.AIMTo observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment.METHODSThis study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998. The median follow-up times were 10 and 7 years, respectively. A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups. The median follow-up times were 8 and 7 years, respectively. Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma (HCC), and the Cox regression model was used to analyze the risk factors for HCC.RESULTSAmong the patients in the non-antiviral group, 16.9% had spontaneous decreases in HBV DNA to undetectable levels, and 32.8% showed hepatitis B e antigen (HBeAg) seroconversion. In the antiviral group, 87.2% of patients had undetectable HBV DNA, and 52% showed HBeAg seroconversion. Among CHB and hepatitis B cirrhosis patients, the cumulative incidence rates of HCC were 14.9% and 53.1%, respectively, in the non-antiviral group and were 10.7% and 31.9%, respectively, in the antiviral group. There was no difference between the two groups regarding the CHB patients (P = 0.842), but there was a difference between the groups regarding the hepatitis B cirrhosis patients (P = 0.026). The cumulative incidence rates of HCC were 1.6% and 22.3% (P = 0.022) in the groups with and without spontaneous HBeAg seroconversion, respectively. The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6% and 19.1%, respectively (P = 0.051). There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB (P = 0.119), but there was a significant difference between the two groups regarding the patients with cirrhosis (P = 0.004). The Cox regression model was used for regression of the corrected REACH-B score, which showed that alanine aminotransferase > 400 U/L, history of diabetes, and family history of liver cancer were risk factors for HCC among men aged > 40 years (P < 0.05). Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC.CONCLUSIONAntiviral therapy and non-antiviral therapy with liver protection and anti-inflammatory therapy can reduce the risk of HCC. Antiviral therapy may mask the spontaneous serological response of some patients during CHB. Therefore, the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.