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.     

特殊人群丙型肝炎病毒感染特征分析

目的 了解近年来就诊我院各科患者丙型肝炎病毒（HCV）的感染情况,以及抗-HCV阳性者一般临床特征。方法对2007年1月至12月我院门诊、急诊、病房等就诊患者抗-HCV检测的结果和阳性分布状况进行分析。同时,对2006年1月至2007年12月的全部抗-HCV阳性者分析其临床及病毒学特征。结果在2007年22146例无重复检测人群中,498人（2．25％）抗-HCV阳性。其中,手术前筛查人群的阳性率为0．72％,感染科和肾脏疾病相关科室阳性率分别为8．80％和7．43％。0～20岁组及21～40岁组中男性的阳性率显著高于女性。此外,抗-HCV阳性人群中近30％伴抗-HBc阳性,14％伴HBsAg阳性。HCV1b型是最主要的基因型（60．98％）,其次是2a（19．51％）和3a型（9．76％）。结论近年来因非肝功能异常而就诊我院的患者HCV感染率处于较低水平,现阶段通过输血传播HCV的概率已较低,可能存在其他感染途径。     

Epidemiology of hepatitis C in Greece

Hepatitis C is a global health issue and constitutes a major cause of chronic liver disease worldwide. In this article, a comprehensive literature search was conducted for the prevalence of hepatitis C virus (HCV) infection in Greece, since data on the HCV prevalence, viremia and genotypes are important for developing strategies to manage or eliminate HCV infection. In addition, the pattern of HCV infection was analyzed according to the geographic region and the risk factors. These differences reflect not only distinct epidemiological characteristics among populations, but also differences on the strategy of data acquisition and quantification. Although there are not enough data, the estimation of the current prevalence of Hepatitis C in Greece ranges from 0.5% to 2%. The most important risk factors for HCV infection include blood product transfusion, intravenous drug use, chronic hemodialysis, organ transplantation, occupational exposure, sexual transmission, and vertical transmission. Because of lack of vaccine or effective post-exposure prophylaxis for HCV, the main focus of prevention is to recognize and control these risk factors. HCV infection in Greece is closely associated with the development of chronic liver disease, cirrhosis, and primary hepatocellular carcinoma. As far as the genotype distribution is concerned genotype 1 estimated to be 45%-47% and it constitutes the prevalent genotype in Greece, followed by genotype 3.     

广东地区丙型肝炎病毒的感染途径及其变化

HCV感染是慢性肝炎的主要病因之一,是肝硬化和原发性肝细胞癌的重要危险因素.既往调查结果显示HCV的主要感染途径是输血和血制品以及静脉吸毒.我国从1992年起,采取多种措施加强对献血员的管理和对供血的检测,输血的安全性得到显著提高[1].     

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.     

Prevalence of type 2 diabetes in Algerian patients with hepatitis C virus infection

AIM:To investigate the prevalence of,and risk factors for,diabetes mellitus(DM) in Algerian patients with chronic hepatitis C virus(HCV) infection and in a control group.METHODS:A cross-sectional study was undertaken.A total of 416 consecutive patients with viral chronic hepatitis attending the Internal Medicine Department of the University Hospital Center Touhami Benflis in Batna [290 HCV-infected and 126 hepatitis B virus(HBV)-infected patients] were prospectively recruited.RESULTS:The prevalence of DM wa...     

Hepatitis C virus infection in the human immunodeficiency virus infected patient

Human immunodeficiency virus(HIV)and hepatitis C virus(HCV)share the same transmission routes;therefore,coinfection is frequent.An estimated 5-10 million individuals alone in the western world are infected with both viruses.The majority of people acquire HCV by injection drug use and,to a lesser extent,through blood transfusion and blood products.Recently,there has been an increase in HCV infections among men who have sex with men.In the context of effective antiretroviral treatment,liver-related deaths are now more common than Acquired Immune Deficiency Syndromerelated deaths among HIV-HCV coinfected individuals.Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20%of chronically infected individuals.HCV treatment has rapidly changed with the development of new direct-acting antiviral agents;therefore,cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle.In this review,we focus on the epidemiology,diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.     

MiR-122 in hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched microRNA-122 (miR-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that the level of miR-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the well-documented phenomenon that miR-122 promotes HCV accumulation, inhibition of miR-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, miR-122 is also known to block HBV replication, and HBV has recently been shown to inhibit miR-122 expression; such a reciprocal inhibition between miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of miR-122.     

Association of hepatitis C virus infection and diabetes

Epidemiologic studies have suggested a relation between hepatitis C virus (HCV) infection and diabetes mellitus. HCV infection is emerging as a metabolic disease, and diabetes mellitus as a risk factor for HCV infection. However, some data on the prevalence of antibodies to HCV in patients with diabetes are conflicting. These seroprevalence data should be interpreted with caution. Some potential bias may occur in those clinic-based studies that target a specific disease group. In this letter we explain some reasons for these conflicting studies.     

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.     

Prevalence of occult hepatitis B virus infection in hemodialysis patients from egypt with or without hepatitis C virus infection

Background

While prevalence of Hepatitis B virus (HBV) in patients with end-stage renal failure (ESRF) who are undergoing dialysis has decreased significantly during the past few decades, it still remains a distinct clinical problem. The immunosuppressive nature of renal disease often leads to chronicity of the HBV infection and an opportunity for nosocomial spread of the infection among dialysis patients. Egypt is among the countries with intermediate endemicity of HBsAg (range, 2%–7%). Large-scale geographic heterogeneity in HBV prevalence has been reported worldwide and HBV prevalence is especially heterogeneous in Egypt.

Objectives

To assess the prevalence of occult HBV infection (OBI) in hemodialysis patients with or without chronic hepatitis C (HCV) from Minia and Assuit, Upper Egypt, using HBV DNA assays.

Patient and Methods

Sera from 145 hemodialysis patients with negative HbsAg were investigated for HBV DNA using real-time polymerase chain reaction (RT-PCR). Only serum samples with repeatedly detectable HBV DNA were considered positive. Patients were divided into 2 groups: HCV RNA positive and HCV RNA negative, based on the results of a third generation enzyme linked immunosorbent assay (ELISA) anti-HCV test and HCV RNA PCR.

Results

HBV DNA was detected in 6 of the 145 patients (4.1%) and HBcAb was detected in 29/145 patients (20%). There were no statistically significant differences in the age, duration of hemodialysis, biochemical parameters, serological markers of HBV, or HBV DNA between patients with and without HCV infection.

Conclusions

Four percent of the hemodialysis patients had OBI. There was no significant difference in the prevalence of OBI between hemodialysis patients with or without HCV co-infection.     

Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.     

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.     

Epidemiology and natural history of hepatitis C virus infection

Hepatitis C virus (HCV) affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma. Globally, at least one third of hepatocellular carcinoma cases are attributed to HCV infection, and 350000 people died from HCV related diseases per year. There is a great geographical variation of HCV infection globally, with risk factors for the HCV infection differing in various countries. The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations. A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma, and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma. However, prospective cohorts comprising individuals with HCV infection are still uncommon. The risk evaluation of viral load elevation and associated liver disease/cancer in HCV (REVEAL-HCV) study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years. Most of them have acquired HCV infection through iatrogenic transmission routes. As the participants in the REVEAL-HCV study rarely receive antiviral therapies, it provides a unique opportunity to study the natural history of chronic HCV infection. In this review, the prevalence, risk factors and natural history of HCV infection are comprehensively reviewed. The study cohort, data collection, and findings on liver disease progression of the REVEAL-HCV study are described.     

乙型与丙型肝炎病毒感染对小肝癌患者预后的影响

目的 探讨HBV、HCV感染对小肝癌的外科治疗策略及其预后的影响.方法 回顾性分析1997年1月-2003年12月天津医科大学附属肿瘤医院413例手术根治切除治疗的小肝痛(≤3 cm)患者的临床资料,将其分为4组:HCV感染组75例、HBV感染组251例、HCV、HBV混合感染组33例和尢HCV、HBV感染组54例,对可能影响预后的因素采用Kaplan-Meier生存分析、log-rank时序检验.结果 413例患者术后1、3、5年尢瘤生存率分别为83%、66%和58%,术后共有168(40.8%)例患者出现肝内复发,5年复发率HCV感染组最高(64.2%),其次为HBV/HCV感染组(48.4%),HBV感染组(37.8%)及无感染组(32.3%).肝内复发肿瘤为多发者在HCV感染组发生率最高(占肝内复发肿瘤的66.0%),其次为HBV/HCV感染组(28.6%),HBV感染组(23.3%)及无感染组(17.6%).413例小肝癌患者术后1、3、5年总生存率分别为89%、70%和61%,HCV感染组预后最差.和其他组相比,HCV感染组肝硬化程度严重,肿瘤细胞分化低,更易发生血管侵犯.在随访过程中,HCV感染组肝内复发率高,且复发类型常为多结节型.结论 HCV感染相关肝癌的临床肝硬化症状更重,而且术后复发率较高,预后更差.     

Reduction of virus burden-induced splenectomy in patients with liver cirrhosis related to hepatitis C virus infection

AIM: To examine the hepatitis C virus (HCV) levels and immunological markers in cirrhotic patients after splenectomy. METHODS: HCV RNA titers as well as cellular and humoral immune markers were determined in 20 cirrhotic patients after splenectomy and in 32 cirrhotic controls with an intact spleen. RESULTS: Serum HCV RNA titers were lower in the splenectomized patients than in the controls (186±225×103 copies/ml vs 541±417×103 copies/mL, P<0.01). HCV RNA was judged to have been spontaneously eradicated in 4 splenectomized patients, but in none of the controls. Natural killer cell activity was higher in the splenectomized patients than in the controls (41.2±19.3% vs 24.7±15.3%, P<0.01), and natural killer cell activity was negatively correlated to HCV RNA titers in the splenectomized patients except in those with serotype 2-related infection. The CD4/CD8 ratio was significantly lower in the splenectomized patients than in the controls. CONCLUSION: The findings suggest that splenectomy may diminish virus burden in cirrhotic patients with HCV infection at least in part, through augmentation of natural killer cell activity.     

重型丙型肝炎肝外组织丙型肝炎病毒感染状态免疫组化研究

目的　探讨丙型肝炎患者肝外组织丙型肝炎病毒（ＨＣＶ） 感染状态、致病性及其意义。方法　采用免疫组化法检测９ 例重型丙型肝炎患者肾、心、胰腺和肠等肝外组织内ＨＣＶ 多种抗原表达,并观察各组织病理改变。结果　９ 例中６ 例（６６ ．７ ％ ） 在肝外组织检出ＨＣＶ 抗原。抗原定位于细胞浆内,呈均质型、包涵体型和膜下型。组织内抗原表达阳性细胞数量较少,不同组织间阳性细胞种类、数量和分布略有差异。病理学观察未发现细胞内ＨＣＶ 抗原阳性表达与组织病变有明确相关性。结论　ＨＣＶ 可以感染肝外组织,但未显示显著致病性。作为致病因子的ＨＣＶ 持续存在肝外多种脏器细胞内,在丙型肝炎慢性化和干扰素治疗后病情复发中可能起重要作用     

Progress in the development of vaccines for hepatitis C virus infection

The hepatitis C virus(HCV), first described in 1989, is now a leading cause of liver cirrhosis and hepatocellular carcinoma. With more than 170 million people infected globally, this virus is a major public health issue. The current standard therapy is based on interferon in combination with ribavirin. This costly therapy often fails to completely clear the infection and is associated with adverse side effects. Recent anti-HCV therapies are interferon-free direct-acting antiviral(DAA) regimens for HCV, including simeprevir, sofosbuvir, and ledipasvir, which have effects on non-structural proteins. DAA regimens have several advantages, such as specifically targeting HCV viral replication, accompanied by very high sustained virological response rates and lower side effects like flu-like syndrome. These facts plus the fact that most HCV cases progress to chronic infection suggest the potential need for an efficient HCV vaccine. Different innovative methods, including methods based on peptide, recombinant protein, DNA, vector-based, and virus-like particles, have been introduced for the development of HCV vaccines. An extensive number of studies have been published on these vaccines, and some vaccines were even tested in clinical trials. In the current review, progress in the development of preventive and therapeutic vaccines against the HCV is reviewed in the context of peptide vaccines, recombinant protein vaccines, HCV-like particle, DNA vaccines and viral vectors expressing HCV genes.     

Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children

AIM: To identify the prevalence, risk factors and manifestations of asymptomatic hepatitis C virus (HCV) infection in Egyptian children. METHODS: Children at the age of 1-9 years were screened for HCV antibodies and alanine aminotransferase (ALT) levels. Every child with elevated ALT and/or detectable HCV antibodies was tested for HCV RNA by RT-PCR and compared with two negative controls for risk factors and signs and symptoms of liver disease.RESULTS: We screened 1042 children, six of them had elevated ALT, negative HCV antibody and positive RNA, likely representing acute hepatitis C cases. Fifteen children were HCV seropositive, 5 of them were HCV RNA positive. Asymptomatic HCV infection was present in 2.02% (positive results for either HCV antibodies or HCV-RNA or both). Symptoms such as diarrhea, abdominal pain, history of fatigue and school absence because of illness and risk factors such as dental care were significantly more common among HCV positive cases than among controls. None of the HCV positive children was diagnosed as having signs of advanced liver disease upon clinical or ultrasonographic examination. CONCLUSION: Asymptomatic HCV infection is detectable in 2.02% Egyptian children.     

合并乙型肝炎病毒感染对丙型肝炎病毒核心抗原检测的影响

目的 探讨合并HBV感染对慢性HCV感染者血清丙型肝炎病毒核心抗原(HCVcAg)检出情况的影响. 方法 收集2005年12月-2009年10月慢性丙型肝炎患者和HBV/HCV合并感染者资料,检测血清HCVcAg和HCV RNA,对后者血清进行HBV DNA、HBeAg检测,分析HCVcAg检出率与HBeAg、HBV DNA定量检测的关系.用独立两组多分类的X2检验方法进行统计学分析. 结果 共收集88例慢性丙型肝炎患者和62例HBV/HCV合并感染者资料,血清HCVcAg的检出率分别为72.7％(64/88)和38.7％ (24/62),两者比较,x2= 17.358,P＜0.01,差异有统计学意义.HCV RNA检出率分别为81.8％ (72/88)和53.2％ (33/62),两者比较,x2=20.110,P＜0.01,差异有统计学意义.62例HBV/HCV合并感染者血清中,HBeAg阳性和HBeAg阴性感染者HCVcAg检出率分别为28.6％ (12/42)和60.0％ (12/20),两者比较,x2=5.641,P=0.011,差异有统计学意义.HCV RNA阳性率分别为42.9％ (18/42)和80.0％ (16/20),两者比较,X2=7.547,P＜ 0.01,差异有统计学意义.HBV DNA阳性和阴性时HCVcAg检出率分别为39.1％ (18/46)和37.5％ (6/16),两者比较,P＞0.05,差异无统计学意义.与单纯HCV感染者血清HCVcAg检出率72.7％ (64/88)比较,HBeAg阴性合并感染者为60.0％ (12/20),x2=1.266,P=0.261,差异无统计学意义;HBV DNA阴性合并感染者为37.5％ (6/16),x2=7.635,P＜0.01,差异有统计学意义.结论 HBV/HCV合并感染时HCVcAg检出率较低,可能是由于HBeAg抑制HCV的复制,从而减少HCVcAg的表达所致.