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.

Locked nucleic acid real-time polymerase chain reaction method identifying two polymorphisms of hepatitis B virus genotype C2 infections,rt269L and rt269I

BACKGROUND The presence of two distinct hepatitis B virus(HBV)Pol RT polymorphisms,rt269L and rt269I,could contribute to the unique clinical or virological phenotype of HBV genotype C2.Therefore,a simple and sensitive method capable of identifying both types in chronic hepatitis B(CHB)patients infected with genotype C2 should be developed.AIM To develop a novel simple and sensitive locked nucleic acid(LNA)-real timepolymerase chain reaction(RT-PCR)method capable of identifying two rt269 types in CHB genotype C2 patients.METHODS We designed proper primer and probe sets for LNA-RT-PCR for the separation of rt269 types.Using synthesized DNAs of the wild type and variant forms,melting temperature analysis,detection sensitivity,and endpoint genotyping for LNA-RT-PCR were performed.The developed LNA-RT-PCR method was applied to a total of 94 CHB patients of genotype C2 for the identification of two rt269 polymorphisms,and these results were compared with those obtained by a direct sequencing protocol.RESULTS The LNA-RT-PCR method could identify two rt269L and rt269I polymorphisms of three genotypes,two rt269L types[‘L1’(WT)and‘L2’]and one rt269I type(‘I’)in single(63 samples,72.4%)or mixed forms(24 samples,27.6%)in 87(92.6%sensitivity)of 94 samples from Korean CHB patients.When the results were compared with those obtained by the direct sequencing protocol,the LNA-RT-PCR method showed the same results in all but one of 87 positive detected samples(98.9%specificity).CONCLUSION The newly developed LNA-RT-PCR method could identify two rt269 polymorphisms,rt269L and rt269I,in CHB patients with genotype C2 infections.This method could be effectively used for the understanding of disease progression in genotype C2 endemic areas.

Glecaprevir/pibrentasvir+sofosbuvir for post-liver transplant recurrent hepatitis C virus treatment

Glecaprevir/pibrentasvir in combination with sofosbuvir may serve as a safe and effective option for treatment of recurrent hepatitis C virus post-liver transplant in patients who previously failed direct-acting antivirals.

Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine:Three case reports

BACKGROUND Highly effective and well-tolerated direct-acting antiviral(DAA)therapies have revolutionised the management of hepatitis C virus(HCV);however,niche populations face treatment barriers.DAAs co-prescribed with several firstgeneration anti-epileptic drugs(AEDs)are contraindicated due to drug-drug interactions.A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir,glecaprevir and pibrentasvir due to potent cytochrome P450(CYP)3A4 induction.Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir’s area under curve to infinite time.Sofosbuvirvelpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently,virological treatment failure.This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible,impractical or unacceptable.However,the properties of current generation DAA therapies,including high-potency non-structural protein 5A inhibitory effect,may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction.CASE SUMMARY We present a case series of three patients with non-cirrhotic,treatment-naïve,genotype 1a,1b,and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir,while co-prescribed carbamazepine for seizure disorders.Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants.DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration,and taken with meals to improve absorption.Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes.CONCLUSION DAA therapies,including glecaprevir-pibrentasvir,warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine,particularly if AED substitution is not feasible.

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.

Immunological crossroads:The intriguing dance between hepatitis C and autoimmune hepatitis

Delving into the immunological crossroads of liver diseases,this editorial explores the dynamic interplay between hepatitis C virus(HCV)and autoimmune hepatitis(AIH).While HCV primarily manifests as a viral infection impacting the liver,previous studies unveil a captivating connection between HCV and the emergence of AIH.The dance of the immune system in response to HCV appears to set the stage for an intriguing phenomenon-an aberrant autoimmune response leading to the onset of AIH.Evidence suggests a heightened presence of autoimmune markers in individuals with chronic HCV infection,hinting at a potential overlap between viral and autoimmune liver diseases.Navigating the intricate terrain of viral replication,immune response dynamics,and genetic predisposition,this editorial adds a layer of complexity to our understanding of the relationship between HCV and AIH.In this immunological crossroads,we aim to unearth insights into the complex interplay,using a compelling case where AIH and primary sclerosing cholangitis overlapped following HCV treatment with direct-acting antivirals as background.

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.

Bridging the gap: Addressing disparities in hepatitis C screening, access to care, and treatment outcomes

Hepatitis C virus(HCV)is a significant public health challenge globally,with substantial morbidity and mortality due to chronic liver disease.Despite the availability of highly effective and well-tolerated direct-acting antiviral therapies,widespread disparities remain in hepatitis C screening,access to treatment,linkage to care,and therapeutic outcomes.This review article synthesizes evi-dence from various studies to highlight the multifactorial nature of these dispari-ties,which affects ethnic minorities,people with lower socioeconomic status,in-dividuals with substance use disorders,and those within correctional facilities.The review also discusses policy implications and targeted strategies needed to overcome barriers and ensure equitable care for all individuals with HCV.Recom-mendations for future research to address gaps in knowledge and evaluation of the effectiveness of interventions designed to reduce disparities are provided.

Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation(LT)provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma.Despite the increasing number of liver transplants performed each year,the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality.Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates.Nevertheless,further strategies can be implemented to increase the pool of potential donors in deceased donor LT,such as reducing the rate of organ discards.Utilizing hepatitis C virus(HCV)seropositive liver grafts is one of the expanded donor organ criteria.A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients.Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation.The American Society of Transplantation advises against performing transplants from HCV-infected liver donors(D+)into HCV-negative recipient(R-)unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants.Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is im-portant.National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

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.

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.

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。

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.

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.