Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes

AIM To review Hepatitis C virus(HCV) prevalence and genotypes distribution worldwide.METHODS We conducted a systematic study which represents one of the most comprehensive effort to quantify global HCV epidemiology,using the best available published data between 2000 and 2015 from 138 countries(about 90% of the global population),grouped in 20 geographical areas(with the exclusion of Oceania),as defined by the Global Burden of Diseases project(GBD). Countries for which we were unable to obtain HCV genotype prevalence data were excluded from calculations of regional proportions,although their populations were included in the total population size of each region when generating regional genotype prevalence estimates.RESULTS Total global HCV prevalence is estimated at 2.5%(177.5 million of HCV infected adults),ranging from 2.9% in Africa and 1.3% in Americas,with a global viraemic rate of 67%(118.9 million of HCV RNA positive cases),varying from 64.4% in Asia to 74.8% in Australasia. HCV genotype 1 is the most prevalent worldwide(49.1%),followed by genotype 3(17.9%),4(16.8%) and 2(11.0%). Genotypes 5 and 6 are responsible for the remaining 5%. While genotypes 1 and 3 are common worldwide,the largest proportion of genotypes 4 and 5 is in lower-income countries. Although HCV genotypes 1 and 3 infections are the most prevalent globally(67.0% if considered together),other genotypes are found more commonly in lowerincome countries where still account for a significant proportion of HCV cases.CONCLUSION A more precise knowledge of HCV genotype distribution will be helpful to best inform national healthcare models to improve access to new treatments.     

Molecular epidemiology of hepatitis C virus infection among intravenous drug users

Background/Aims: The clinico-pathologic features of hepatitis C virus infection intravenous drug users are different from those found in other hepatitis C virus-infected patients. Our airm was to test whether specific viral variants circulate within this particular patient population.Methods: We studied the distribution of hepatitis C virus genotypes in 90 drug addicts and 484 controls, according to the method described by Okamoto.Results: Hepatitis C virus type 1a and 3a infections were more frequent among intravenous drug users than in 125 age-matched controls (48.8% and 21.1% vs 17.6% and 11.2%), accounting for the majority of infections in intravenous drug users. Analysis of hepatitis C virus genotypes according to age showed that, in the general population, hepatitis C virus types 1a and 3a were more prevalent among patients younger than 40 years of age than in older individual (17.6% and 11.2% vs. 1.4% and 0.6%).Conclusions: These findings suggest that hepatitis C virus types 1a and 3a were recently introduced in Italy, presumably via needle-sharing among intravenous drug users, and from this reservoir they are extending to the general population, particularly among younger subjects.     

Scotomas in molecular virology and epidemiology of hepatitis C virus

In the 1970s,scientists learned of a new pathogen causing non-A,non-B hepatitis.Classical approaches were used to isolate and characterize this new pathogen,but it could be transmitted experimentally only to chimpanzees and progress was slow until the pathogen was identified as hepatitis C virus(HCV)in 1989.Since then,research and treatment of HCV have expanded with the development of modern biological medicine:HCV genome organization and polyprotein processing were delineated in 1993;the first three-dimensional structure of HCV nonstructural protein(NS3 serine protease)was revealed in 1996;an infectious clone of HCV complementary DNA was first constructed in 1997;interferon and ribavirin combination therapy was established in 1998 and the therapeutic strategy gradually optimized;the HCV replicon system was produced in1999;functional HCV pseudotyped viral particles were described in 2003;and recombinant infectious HCV in tissue culture was produced successfully in 2005.Recently,tremendous advances in HCV receptor discovery,understanding the HCV lifecycle,decryption of the HCV genome and proteins,as well as new anti-HCV compounds have been reported.Because HCV is difficult to isolate and culture,researchers have had to avail themselves to the best of modern biomedical technology;some of the major achievements in HCV research have not only advanced the understanding of HCV but also promoted knowledge of virology and cellular physiology.In this review,we summarize the advancements and remaining scotomas in the molecular virology and epidemiology of HCV.     

Hepatitis C virus genotype 6:Virology,epidemiology,genetic variation and clinical implication

Hepatitis C virus(HCV)is a serious public health problem affecting 170 million carriers worldwide.It is a leading cause of chronic hepatitis,cirrhosis,and liver cancer and is the primary cause for liver transplantation worldwide.HCV genotype 6(HCV-6)is restricted to South China,South-East Asia,and it is also occasionally found in migrant patients from endemic countries.HCV-6 has considerable genetic diversity with23 subtypes(a to w).Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping,there are also now rapid genotyping tests available such as the reverse hybridization line probe assay(INNO-LiPAⅡ;Innogenetics,Zwijnaarde,Belgium).HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes.Based on current evidence,the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk,although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response.In addition,the development of direct-acting antiviral agents is ongoing,and they give high response rate when combined with standard therapy.Herein,we review the epidemiology,classification,diagnosis and treatment as it pertain to HCV-6.     

Changing pattern of hepatitis a virus epidemiology in an area of high endemicity

Background

Continuous assessment of hepatitis A virus (HAV) seroepidemiology is a useful tool to control the risk of infection.

Objectives

This study aimed to evaluate the changing patterns of anti-HAV seroprevalence in a population,which isgenerally considered to be anarea ofhigh endemicity.

Patients and Methods

Overall, the results of 3349 sera collected during the period 2005-2008 from patients attending the University Hospital of Cagliari, Italy were studied; their mean age was 52.7 years, (s + 16.22). Patients with liver disease were excluded from the study. Age specific seroprevalence results were compared with those observed in similar previous studies carried out in the same area.

Results

The overall prevalence of anti-HAV was 74.6% with consistently lower values in subjects younger than 40 years (17.5%; P < 0.0001) particularly in those under 30 years of age (8.9%, CI 5.8-11.9). A significant declining trend in age specific seroprevalence has been foundin people under 30 years;61% in 1988, 33% in 1995 and 8.9% in 2005-2008.

Conclusions

Our findings show that a significant decline inherd immunity has occurred in the last 20 years as a consequence of lower HAV circulation due to improvementsin socio-economical and hygienic conditions. Adolescents and young adults are becoming increasingly susceptible to HAV infections, as recent outbreaks of acute HAV hepatitis have occurred. Persistent environmental monitoring and the implementation of prevention measures must be considered in order to contain the risk related to this epidemiological shift.     

淋巴细胞恶性增殖病患者丙型肝炎病毒感染的研究

目的：研究淋巴细胞恶性增殖性疾病（ＭＰＬＤ）患者丙型肝炎病毒感染情况及病毒基因分布。方法：用逆转录ＰＣＲ（ＲＴ－ＰＣＲ）法对７６例ＭＰＬＤ和１１８例体检人群血清进行ＨＣＶ－ＲＮＡ检测,同时用Ｏｋａｍｏｔｏ ＨＣＶ基因分型法进行ＨＣＶ基因分型。结果：７６例ＭＰＬＤ中ＨＣＶ－ＲＮＡ阳性１０例（１３．１６％）,其中２１例非霍奇金淋巴瘤（ＮＨＬ）中２例阳性（９．５２％）,３９例多发性骨髓瘤（ＭＭ）中７例阳     

Epidemiology of hepatitis C virus infection

Hepatitis C is a global health problem, with an estimated 71·1 million individuals chronically infected worldwide, accounting for 1% (95% uncertainty interval: 0.8–1.1) of the population. HCV transmission is most commonly associated with direct exposure to blood, via blood transfusions, unsafe health-care-related injections and intravenous drug use. The global incidence of HCV was 23·7 cases per 100 000 population (95% uncertainty interval 21·3–28·7) in 2015, with an estimated 1·75 million new HCV infections diagnosed in 2015. An estimated 2.3 millions of people living with HIV have serological markers of past or current HCV infection. Globally, the most common infections are with HCV genotypes 1 (44% of cases), 3 (25% of cases), and 4 (15% of cases). Approximately 10–20% of individuals who are chronically infected with HCV develop complications, such as cirrhosis, end stage liver disease, and hepatocellular carcinoma over a period of 20–30 years. Direct-acting antiviral therapy is curative, dramatically reducing the mortality related to HCV and the need for liver transplantation, but it is estimated that only 20% of individuals with hepatitis C know their diagnosis, and only 15% of those with known hepatitis C have been treated. Increased diagnosis and linkage to care through universal access to affordable point-of-care diagnostics and pangenotypic direct-acting antiviral therapy is essential to achieve the WHO 2030 elimination targets.     

Sofosbuvir treatment and hepatitis C virus infection

Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a “chain terminator”. Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy.     

丙型肝炎病毒血清抗体分型研究

为探讨丙型肝炎病毒（ＨＣＶ）血清抗体分型的可能性及其意义，采用酶联免疫技术（ＥＩＡ）对１４０例丙型肝炎患者血清抗－ＨＣＶ型特异性抗体进行检测，并比较其与基因分型的检测结果。结果显示６３．６％（８９）的患者检测出ＨＣＶ血清型特异性抗体，其中血清１型占８７．６％（７８／８９），血清型占６．７％（６／８９），血清１＋２型占５．６％（５／８９）。对其中７１例血清ＨＣＶ ＲＮＡ阳性者的血清型结果与基因型结果     

肝特异性自身抗体与丙型肝炎病毒感染的关系

本研究探讨了HCV感染时体内产生免疫应答并出现多种自身抗体的特点,试图通过检测分析HCV感染与自身抗体的相关性,对丙型肝炎的诊断及治疗提供一些实验数据.     

北京市吸毒人群丙型肝炎病毒感染的流行病学监测

目的探讨吸毒人群丙型肝炎病毒(HCV)感染的流行率,并分析HCV感染的可能危险因素。方法 2006-2009年于在押吸毒人群中,采用标准化问卷收集人口学、危险行为等信息,采用酶联免疫吸附试验(ELISA)检测HCV抗体。结果 1 253名吸毒者中,总的HCV抗体阳性率为25.3%,注射吸毒者HCV抗体阳性率为66.6%。多因素Logistic回归分析提示,注射吸毒(调整OR=18.988,95%CI:13.860～26.013)为吸毒人群感染HCV的最主要危险因素;其次是共用注射器(调整OR=1.025,95%CI:0.604～1.739)。注射吸毒时间≥5年者感染HCV的危险性较<5年者高(调整OR=0.669,95%CI:0.084～1.089);没有职业的吸毒者感染HCV的危险性较有职业者高(调整OR=1.280,95%CI:0.866～1.893)。结论吸毒人群HCV流行水平较高,注射吸毒是流行的最主要原因。应采取有效措施预防该人群HCV的二代传播,为阳性患者提供治疗刻不容缓。     

丙型肝炎基因型定量检测及分型检测方法的研究进展

丙型肝炎病毒(hepatitis C virus,HCV)是一种RNA病毒,可以引发各种慢性肝病,其中包括肝硬化和肝细胞癌.全球每年HCV感染的患者数呈上升趋势,他已成为人类亟待解决的公共卫生难题.HCV可以分为6种主要的基因型以及70多种亚型,不同的基因型对抗病毒治疗的效果不同.如果在治疗前能通过准确灵敏的检测手段确定HCV的基因型,将会对临床治疗有重要的意义.本文对HCV基因型全球分布、临床表症与治疗、分型依据以及基因型与定量关系进行了概述,并重点阐述HCV基因分型的检测技术.     

Association of hepatitis C virus infection and diabetes in central Tunisia

AIM：To investigate hepatitis C virus （HCV） seroprevalence in Tunisian patients with diabetes mellitus and in a control group. METHODS： A cross-sectional study was conducted to determine the HCV seroprevalence in 1269 patients with diabetes （452 male, 817 female） and 1315 nondiabetic patients, attending health centers in Sousse, Tunisia. HCV screening was performed in both groups using a fourth-generation enzyme immunoassay. RESULTS： In the diabetic group, 17 （1.3%） were found to be HCV-infected compared with eight （0.6%） in the control group, although the difference was not significant （P = 0.057）. Quantitative PCR was performed in 20 patients. Eleven patients were positive and showed HCV genotype lb in all cases. CONCLUSION： Frequency of HCV antibodies was low in patients with diabetes and in the control group in central Tunisia, with no significant difference between the groups.     

Management of hepatitis C virus infection in hemodialysis patients

The prevalence of hepatitis C virus(HCV) infection in patients on maintenance hemodialysis(MHD) is relatively higher than those without MHD. Chronic HCV infection detrimentally affects the life quality and expectancy, leads to renal transplant rejection, and increases the mortality of MHD patients. With the application of erythropoietin to improve uremic anemia and avoid blood transfusion, the new HCV infections during MHD in recent years are mainly caused by the lack of stringent universal precautions. Strict implementation of universal precautions for HCV transmission has led to markedly decreased HCV infections in many hemodialysis units, but physicians still should be alert for the antiHCV negative HCV infection and occult HCV infection in MHD patients. Standard interferon alpha and pegylated interferon alpha monotherapies at a reduced dose arecurrently the main treatment strategies for MHD patients with active HCV replication, but how to increase the sustained virological response and decrease the side effects is the key problem. IFNα-free treatments with two or three direct-acting antivirals without ribavirin in MHD patients are waiting for future investigations.     

新疆地区118例丙型肝炎患者的病毒基因型分析

对新疆地区118例HCV感染患者的血清基因型进行了分析,旨在了解近年来新疆地区HCV流行株的基因型,并探讨基因型与临床意义的相关性,现报道如下.     

中国HCV基因型分布的Meta分析

目的 分析中国不同地区、民族和感染途径人群丙型肝炎病毒(HCV)基因型的分布特点.方法 通过检索万方数据库和NCBI数据库中有关中国HCV基因型分布的文献,按照地区、民族和感染途径进行数据分类,应用Meta分析研究HCV基因型的分布特点.结果 在我国,HCV1型流行最广泛,北部地区主要为1型(52.7％ ～79.7％)...     

Chaperones in hepatitis C virus infection

The hepatitis C virus(HCV) infects approximately 3% of the world population or more than 185 million people worldwide. Each year, an estimated 350000-500000 deaths occur worldwide due to HCV-associated diseases including cirrhosis and hepatocellular carcinoma. HCV is the most common indication for liver transplantation in patients with cirrhosis worldwide. HCV is an enveloped RNA virus classified in the genus Hepacivirus in the Flaviviridae family. The HCV viral life cycle in a cell can be divided into six phases:(1) binding and internalization;(2) cytoplasmic release and uncoating;(3) viral polyprotein translation and processing;(4) RNA genome replication;(5) encapsidation(packaging) and assembly; and(6) virus morphogenesis(maturation) and secretion. Many host factors are involved in the HCV life cycle. Chaperones are an important group of host cytoprotective molecules that coordinate numerous cellular processes including protein folding, multimeric protein assembly, protein trafficking, and protein degradation. All phases of the viral life cycle require chaperone activity and the interaction of viral proteins with chaperones. This review will present our current knowledge and understanding of the role of chaperones in the HCV life cycle. Analysis of chaperones in HCV infection will provide further insights into viral/host interactions and potential therapeutic targets for both HCV and other viruses.     

丙型肝炎病毒负荷和基因型与干扰素治疗应答关系的研究

目的　研究丙型肝炎 (简称丙肝 )病毒基因分型和病毒负荷与干扰素抗病毒治疗的应答关系。方法　用特异性引物PCR的改良法检测基因型 ,用荧光PCR方法检测病毒负荷 ,接受干扰素治疗的慢性丙肝患者根据不同的基因型及病毒负荷进行应答分组比较。结果　治疗前HCV -RNA负荷小于 10 9eq·L-1患者经干扰素治疗后表现为持续应答状态占总人数的 4 2 9% ,HCV -RNA负荷大于 10 9eq·L-1患者经干扰素治疗后呈部分应答(2 8 6 % )或无应答状态 (2 8 6 % )。统计学上差异非常显著 (P <0 0 0 1)。 2a型和 1b +2a型 (共 11例 )疗效明显优于 1b型 (2 2例 ) ,差异非常显著 (P <0 0 0 1)。结论　对HCV -RNA负荷小于 10 9eq·L-1及 2a +1b、2a型患者干扰素治疗效果较好。HCV病毒负荷及基因分型可能影响对干扰素治疗的应答。     

Prevalence of hepatitis C virus infection among patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is defined as inappropriate ventricular hypertrophy without a cardiac or systemic cause. On the other hand, hepatitis C virus (HCV) causes extrahepatic manifestations as well as chronic persistent infection in hepatocytes. We studied the association of HCV infection with HCM, comparing the prevalence of HCV antibodies between HCM patients and age- and gender-matched controls with other cardiovascular diseases at a single institution, for reasons of exclusion of bias. We then described the clinical features and genotype analysis of HCV RNA in HCM. The diagnosis of HCM was established by echocardiographic demonstration of a hypertrophied (15mm), nondilated left ventricle in the absence of another systemic or cardiovascular disease capable of producing the magnitude of hypertrophy observed. The study population consisted of 80 patients with HCM, in whom HCV antibody was examined (55 men and 25 women; mean age 56.6 ± 12.4 years; ranging from 19 to 80 years), compared with a total of 80 age- and gender-matched controls without HCM. The prevalence of HCV infection in patients with HCM (18/80) was significantly higher than in control subjects (5/80) (² = 7.312, P = 0.007). Of the 12 patients in whom the genotype of HCV was analyzed, 7 had type 1b and 5 had type 2a. The prevalence of HCV infection was higher in patients with HCM than in age- and gender-matched control subjects with other cardiovascular diseases. The result suggests that HCV may play an important role in these HCV-positive HCM patients.