Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication:A systematic review and meta-analysis

BACKGROUND Direct-acting antiviral agents(DAAs)are highly effective treatment for chronic hepatitis C(CHC)with a significant rate of sustained virologic response(SVR).The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression.The assessment of fibrosis degree can be performed with transient elastography,magnetic resonance elastography or shear-wave elastography(SWE).Liver elastography could function as a predictor for hepato-cellular carcinoma(HCC)in CHC patients treated with DAAs.AIM To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus(HCV).METHODS A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance.In accordance with the study protocol,a qualitative and quantitative analysis of the evidence was planned.RESULTS At baseline and after 12 wk of follow-up,a trend was shown towards greater liver stiffness(LS)in those who go on to develop HCC compared to those who do not[baseline LS standardized mean difference(SMD):1.15,95%confidence interval(95%CI):020-2.50;LS SMD after 12 wk:0.83,95%CI:0.33-1.98].The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data.There was a statist-ically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not(0.64;95%CI:0.04-1.24).CONCLUSION SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs.Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Liver biopsy in the post-hepatitis C virus era in Japan

In Japan,liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus(HCV)and diagnosing HCV-related hepatocellular carcinoma(HCC).However,due to the development of effective antiviral treatments and advanced imaging,the necessity for biopsies has significantly decreased.This change has resulted in fewer chances for diagnosing liver disease,causing many general pathologists to feel less confident in making liver biopsy diagnoses.This article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in Japan.First,it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing prevalence.Second,it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions,because clinically diagnosable HCCs are not targets for biopsy.Third,the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these drugs.In conclusion,pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail.

Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population

BACKGROUND Hepatitis C virus(HCV)infection progresses through various phases,starting with inflammation and ending with hepatocellular carcinoma.There are several invasive and non-invasive methods to diagnose chronic HCV infection.The invasive methods have their benefits but are linked to morbidity and complications.Thus,it is important to analyze the potential of non-invasive methods as an alternative.Shear wave elastography(SWE)is a non-invasive imaging tool widely validated in clinical and research studies as a surrogate marker of liver fibrosis.Liver fibrosis determination by invasive liver biopsy and non-invasive SWE agree closely in clinical studies and therefore both are gold standards.AIM To analyzed the diagnostic efficacy of non-invasive indices[serum fibronectin,aspartate aminotransferase to platelet ratio index(APRI),alanine aminotransferase ratio(AAR),and fibrosis-4(FIB-4)]in relation to SWE.We have used an Artificial Intelligence method to predict the severity of liver fibrosis and uncover the complex relationship between non-invasive indices and fibrosis severity.METHODS We have conducted a hospital-based study considering 100 untreated patients detected as HCV positive using a quantitative Real-Time Polymerase Chain Reaction assay.We performed statistical and probabilistic analyses to determine the relationship between non-invasive indices and the severity of fibrosis.We also used standard diagnostic methods to measure the diagnostic accuracy for all the subjects.RESULTS The results of our study showed that fibronectin is a highly accurate diagnostic tool for predicting fibrosis stages(mild,moderate,and severe).This was based on its sensitivity(100%,92.2%,96.2%),specificity(96%,100%,98.6%),Youden’s index(0.960,0.922,0.948),area under receiver operating characteristic curve(0.999,0.993,0.922),and Likelihood test(LR+>10 and LR-<0.1).Additionally,our Bayesian Network analysis revealed that fibronectin(>200),AAR(>1),APRI(>3),and FIB-4(>4)were all strongly associated with patients who had severe fibrosis,with a 100% probability.CONCLUSION We have found a strong correlation between fibronectin and liver fibrosis progression in HCV patients.Additionally,we observed that the severity of liver fibrosis increases with an increase in the non-invasive indices that we investigated.

Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a signif icant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to antiHCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.

Relationship of hepatitis C virus infection with primary hepatic carcinoma: an investigation of serum HCV RNA in different population groups

A preliminary study on the serum hepatitis C virus(HCV)RNA in 182 pa-tients with different chronic liver diseases and 35 blood donors was carried out with“nested”polymerase chain reaction.It was found that serum HCV RNA was detected in36.6%(34/93)cases of primary hepatic carcinoma(PHC),31.7%(20/63)liver cirrhosis,15.4%(4/26)chronic hepatitis and 2.9%(1/35)blood donors;most of the HCV RNA pos-itive cases(41/58)were complicated with HBV replicating markers;the rate of single posi-tive for HCV RNA was 15.1%(14/93)in PHC,3.2%(2/63)in liver cirrhosis,and 3.8%(1/26)in chronic hepatitis.These findings imply that about 20% of PHC cases appear tobe related to the coinfection of HCV and HBV and 15% of PHC cases are related to sin-gle HCV infection.

STUDY ON THE MOTHER TO INFANT TRANSMISSIONOF HEPATITIS C VIRUS BY COMBINED ASSAYOF ANTI-HCV AND HCV-RNA

objective The mother to infant transmission of Hey was prospectively investigated.Methods Hepatitis C virus(HCV) infection was tested by the combination assay of anti-HCV andHCV- RNA. Six hundred and ten pregnant women were investigated for HCV infection, and infants from HCVinfected mothers were followed up at birth, 3, 6, 9, 12 months after birth to investigate HCV infection. HCVgenotypes were detected in all persons with HCV- RNA positive. HCV was quantified by branch DNA signalamplification assay (bDNA) in pregnant women. Results Among 610 pregnant women, 18 infected HCV, theinfection rate of HCV in pregnant women was 2.95% (18/610). Five of 18 infants from 18 HCV infected mothersinfected HCV, they had no history of operation, or blood transfusion and other risk exposure to HCV, so the HCVinfection was irc m their mothers, the rate of HCV transmission from mother to infant was 27.8%.HCVgenotype fo was found in 16 pregnant women with HCV- RNA positive, 5 infants and their mothers had the sameHCV genotype(1b) infection. All pregnant women infected HCV have low HCV titer in serum. Conclusion lnthis research, it was noted that HCV could be vertically transmitted from mother to infant even if mother had lowserum HCV titer(≤14.11 ×105/ml). The combination assay of anti - HCV and HCV- RNA was valuable ininvestigating the HCV infection in pregnant women and the transmission of HCV from mother to infant. It haspotential value in diagnosing HCV infection in other population.

Lichen planus and hepatitis c virus (HCV)-there is no association:A serological case control study

Fifty patients(28 males and 22 females)with lichen planus were tested for anti HCV antibodies.None of them gave positive result in our case control study.There were various studies conducted in different parts of the world that proved or disproved a causative role for HCV in LP.

HBV、HCV、HIV血筛多中心研究免疫学灰区的核酸检测分析与临床特征研究

目的分析化学发光灰区标本的临床特征及核酸检测对化学发光灰区标本结果判断的指导性意义。方法收集2021年7月—12月全国不同地区的5家综合医院入院患者术前/输血前血源性传播疾病样本检测结果,对化学发光灰区检测结果的标本进行核酸检测结果及临床特征分析。结果5723例样本中总计检出HBV免疫灰区样本28例(占比0.49%),HCV灰区样本20例(占比0.35%)。经核酸检测验证,28例HBV灰区样本中,15例HBV样本核酸检测为阳性(占比53.5%),其HBcAb也均为阳性;13例HBV样本核酸检测为阴性(占比46.5%),其中HBcAb阳性4例。HBV与HCV免疫检测灰区在临床各个科室均有发现,出现HBV灰区样本最多的前三科室为骨科、妇科、泌尿科,灰区样本核酸验证假阳性最多的临床科室为妇科与骨科。HCV灰区样本最多的前三科室为泌尿、肾内、外科,且均为假阳性。HBV灰区样本患者临床诊断结果有35.7%(10/28)为肿瘤类疾病,HCV灰区样本患者临床诊断结果有40%(8/20)为肿瘤类疾病。结论化学发光法容易造成假阳性结果,应注意复检验证,且设置灰区并非必要。灰区样本可见于多个临床科室,具有一定的临床分布特征。核酸检测可以提高检测灵敏度并且更大限度保证结果的准确性,能够验证免疫检测灰区。

Sequencing of hepatitis C virus cDNA with polymerase chain reaction directed sequencing *

AIM To explore a rapid and easy sequencing method for hepatitis C virus (HCV) genome, and establish a new sequencing method in China. METHODS Polymerase Chain Reaction (PCR) was combined with DNA sequencing technique. PCR products were purified by agarose gel electrophoresis, polyacrylamide gel electrophoresis (PAGE), Polyethylene glycol (PEG) respectively. Then in the presence of a 5′ labeling PCR primer, purified PCR products were directly sequenced. By this method, HCV NS5b cDNA from two HCV infected individuals (HC 42 and HC 49) were sequenced.

2018-2022年我国18家省级血液中心献血者HCV检测结果分析

目的分析我国省级血液中心服务区域献血人群丙型肝炎病毒(hepatitis C virus,HCV)检测数据。方法对我国东中西部不同地区的18家省级血液中心,2018—2022年初次献血和重复献血者抗-HCV和HCV RNA检测数据收集整理,分析献血者中抗-HCV ELISA和抗-HCV ELISA阴性中HCV RNA检测不合格率与年度、血液中心以及初次献血和重复献血者之间的关系。结果2018年—2022年HCV总不合格率从24.61/万逐年减少至15.17/万(χ^(2)=717.71,P<0.01),西部地区为25.72/万最高,东部11.96/万最低(χ^(2)=2382.54,P<0.01);初次献血者抗-HCV ELISA不合格率(30.50/万)比重复献血者(7.42/万)高(χ^(2)=9694.63,P<0.01);各血液中心抗-HCV ELISA阴性中HCV-RNA单独不合格率范围为0~7.54/万。结论我国18家血液中心服务区域献血者的HCV检测不合格率呈逐年降低趋势;HCV检测不合格率存在明显的地域分布差异;与初次献血者相比,重复献血者为HCV检测不合格低危人群;HCV-RNA检测在血液安全方面发挥重要作用。

Current perspectives of viral hepatitis

Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.

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.

基于医院感染预警系统的江西省某三甲医院就诊患者HCV微消除模式探索及评价

目的探索并评价江西省某综合医院就诊患者丙型肝炎病毒(HCV)微消除模式,为省内制定消除HCV公共健康危害策略提供参考依据。方法收集该院2021年1月—2022年12月就诊并进行HCV筛查的住院患者相关数据,其中2021年为基线数据,2022年为HCV微消除模式运行数据,分析其性别、年龄、送检科室、抗-HCV阳性率、HCV-RNA阳性率等指标,以专科就诊率、治疗率、失访率分析其运行效果,以SWOT-AHP法定量评价模式发展。结果2021—2022年共有397744例住院患者进行抗-HCV筛查,男女性别比为1.34∶1,平均年龄为54岁,送检科室主要以感染科/消化科为主。62份患者标本HCV基因亚型分型主要以1b亚型(43份)为主,其次为6亚型(9份)。模式运行后首次HCV预警率为81.20%,预警后抗-HCV送检率达93.15%,后续弹窗预警抗-HCV送检率为100%。与2021年比较,2022年HCV住院患者治疗率上升,差异有统计学意义(P<0.05);而专科就诊率、患者失访率差异均无统计学意义(均P>0.05)。模式运行重心坐标计算P(X,Y)=(0.0182,0.0069),位于第一象限。结论江西省某综合医院就诊患者HCV微消除模式可行且成效明显,下一步模式优化应重视SO策略(依靠内部优势,利用外部机会)。

丙型病毒性肝炎抗体检测与HCV高敏核酸检测对病毒性丙型肝炎的筛查价值研究

目的通过对本院2019年1月至2022年9月需进行手术、输血或其他侵入性医疗服务的住院患者的HCV血清学抗体及高敏HCV RNA筛查结果进行回顾性分析,探讨丙型病毒性肝炎抗体检测与HCV高敏核酸检测对病毒性丙型肝炎的筛查检测价值。方法对本院相关住院患者进行Elecsys Anti-HCV II或(和)高敏HCV RNA检测,统计分析其检测结果。结果HCV血清学抗体检测22443人次,阳性率为0.68%,阳性COI中位数为38.4(1.0~165)。高敏HCV RNA检测34628人次,阳性率0.30%,阳性病毒载量中位数为1.00×10^(6)IU/mL(3.50×10^(1)~4.00×10^(7)IU/mL)。两种方法学均显示45~59岁人群阳性率显著高于其他人群(P<0.001)。两种检测有重合的样本共17785人次,HCV抗体血清学阳性率为0.70%。高敏HCV RNA阳性率0.22%,如以高敏HCV RNA为丙型肝炎现症感染的标准,HCV抗体血清学检测HCV现症感染的灵敏度为100.00%(95%CI 89.09%~100.00%),特异性为99.52%(95%CI 99.41%~99.61%),现症感染阳性预测期PPV为32.00%(95%CI 23.82%~40.18%),阴性预期值为100.00%。HCV抗体血清学检测COI值与高敏HCV RNA检测的病毒载量无线性相关性,COI<10和COI>100的HCV RNA阳性率低。结论HCV抗体检测和高敏HCV RNA均为有效的丙型肝炎筛查手段,需进一步加强对重点人群的丙型肝炎感染管理。

An insight into the diagnosis and pathogenesis of hepatitis C virus infection

This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.

Significance of hepatitis virus infection in the oncogenicinitiation of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.

Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma:A meta-analysis

AIM:To investigate the impact of postoperative antiviral treatment on tumor recurrence and survival of patients with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection-related primary hepatocellular carcinoma(HCC) after curative therapy.METHODS:We performed a meta-analysis of randomized and non-randomized control trials from electronic search and manual search.The fixed effect model of Mantel-Haenszel method and the random effect model of Der Simonian and Laird method were used for homogeneous and heterogeneous studies,respectively.Seven HCV-related studies,three HBV-related studies and three studies on HBV or HCV-related HCC were identified.RESULTS:A total of 1224 patients were included in this analysis.The estimated odds ratios(OR) for the 1-,2-,3-and 5-year recurrence were 0.54 [15.4% vs 24.1%,95% confidence interval(CI):0.32-0.89,P=0.02],0.42(36.9% vs 58.0%,95% CI:0.19-0.90,P=0.03),0.37(47.9% vs 63.8%,95% CI:0.19-0.71,P=0.003),and 0.32(66.7% vs 74.3%,95% CI:0.15-0.66,P=0.002),respectively;and the OR for the 1-,2-,3-,5-and 7-year mortality were 0.23(1.2% vs 9.1%,95% CI:0.07-0.71,P=0.01),0.31(6.4% vs 22.1%,95% CI:0.12-0.79,P=0.01),0.43(12.7% vs 20.8%,95% CI:0.21-0.89,P=0.02),0.42(25.1% vs 42.0%,95% CI:0.27-0.66,P=0.0002) and 0.28(31.9% vs 52.2%,95% CI:0.13-0.59,P=0.0008).CONCLUSION:This meta-analysis indicates the postoperative antiviral therapy,interferon in particular,may serve as a favorable alternative to reduce recurrence and mortality in patients with HBV/HCV related HCCs.

Hepatitis B virus and hepatitis C virus play different prognostic roles in intrahepatic cholangiocarcinoma: A meta-analysis

AIM: To identify the prognostic value of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections in patients with intrahepatic cholangiocarcinoma.METHODS: A search was performed for relevant publications in Pub Med, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ2 and I2 tests were used to evaluate heterogeneity between studies. Pooled hazard ratios(HRs) with 95% confidence intervals(CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied.RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and diseasefree survival, and the pooled HRs were significant at 0.76(95%CI: 0.70-0.83) and 0.78(95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group(HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio(OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase(AST) and alpha-fetoprotein(AFP)(OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9(CA19-9)(OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis(OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation(OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis(OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies.CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis.

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus(HBV)and hepatitis C virus(HCV)share common mode of transmission and both are able to induce a chronic infection.Dual HBV/HCV chronic coinfection is a fairly frequent occurrence,especially in high endemic areas and among individuals at high risk of parenterally transmitted infections.The intracellular interplay between HBV and HCV has not yet been sufficiently clarified,also due to the lack of a proper in vitro cellular model.Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients.Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma.Despite the clinical importance,solid evidence and clear guidelines for treatment of this special population are still lacking.This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection,and highlights the aspects that need to be better clarified.