Similarities,differences,and possible interactions between hepatitis E and hepatitis C viruses:Relevance for research and clinical practice

Hepatitis E virus(HEV)and hepatitis C virus(HCV)are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations.Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise,jaundice,nausea and vomiting.Rarely,HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women.Parenteral HCV infection is typically asymptomatic for decades until chronic complications,such as cirrhosis and cancer,occur.Despite being two very different viruses in terms of phylogenetic and clinical presentations,HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion,pathogenesis(production of antinuclear antibodies and cryoglobulins)and response to treatment with some direct-acting antiviral drugs.Although both HEV and HCV are well studied individually,there is a lack of knowledge about coinfection and its consequences.The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.

Incidence and prevalence of hepatitis B and hepatitis C viruses in hemodialysis patients in Lebanon

AIM： To determine the incidence and the prevalence of hepatitis B and C viral infections in patients on hemodialysis （HD） across Lebanon.METHODS： We reviewed the data registry at the Lebanese Ministry of Public Health where records of monthly hepatitis B surface antigen （HBsAg） and hepatitis C virus （HCV） serology are reported from 60 affiliated HD centers across Lebanon. All patients who were on HD or who started HD between October 2010 and July 2012 were included in the study. Patients from seven HD centers were excluded due to inadequate and incomplete results reporting. During the selected period, HBsAg and HCV serology were available for 3769 patients from 53 HD centers distributed at all Lebanese governorates. The prevalence was calculated by dividing the number of patients with positive HBsAg or HCV serology to the total number of patients. The Incidence was calculated by dividing the number of newly acquired infection to number of patients-years （p-y）. Incidence rates at different governorates were compared to each other using two tailed Z test and a P value of 〈 0.05 was considered signifcant.RESULTS： Sixty out of 3769 HD patients were found to have positive HBS Ag and 177 out of 3769 were positive for HCV Antibodies. The prevalence of hepatitis B virus （HBV） and HCV in HD patients across Lebanon was 1.6%, and 4.7%, respectively. The comparison of prevalence according to geographic distribution could not be done accurately due to the frequent shift of patients between dialysis centers at different governorates. The incidence rate was 0.27 per 100 p-y for HBV and 0.37 per 100 p-y for HCV. There was no signifcant difference concerning the incidence of HBV between HD centers at different governorates （all P values 〉 0.1）, but this difference was highly significant concerning the incidence rates of HCV which occurred predominantly in the southern centers （1.47 per 100 p-y） with a P value of 0.00068 and 0.00374 when compared to Mount Lebanon （0.21 per 100 p-y） and the Northern centers （0.19 per 100 p-y）, respectively.CONCLUSION： The incidence rate of HBV and HCV is very low in the Lebanese HD centers and their prevalence is decreasing over the last two decades.

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.

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.

Complex interactions between microRNAs and hepatitis B/C viruses

MicroRNAs(miRNAs) are a class of small noncoding RNAs that post-transcriptionally regulate the expression of many target genes via mRNA degradation or translation inhibition. Many studies have shown that miRNAs are involved in the modulation of gene expression and replication of hepatitis B virus(HBV) and hepatitis C virus(HCV) and play a pivotal role in host-virus interactions. Increasing evidence also demonstrates that viral infection leads to alteration of the miRNA expression profile in hepatic tissues or circulation. The deregulated miRNAs participate in hepatocellular carcinoma(HCC)initiation and progression by functioning as oncogenes or tumor suppressor genes by targeting various genes involved in cancer-related signaling pathways. The distinct expression pattern of miRNAs may be a useful marker for the diagnosis and prognosis of virus-related diseases considering the limitation of currently used biomarkers. Moreover, the role of deregulated miRNA in host-virus interactions and HCC development suggested that miRNAs may serve as therapeutic targets or astools. In this review, we summarize the recent findings about the deregulation and the role of miRNAs during HBV/HCV infection and HCC development, and we discuss the possible mechanism of action of miRNAs in the pathogenesis of virus-related diseases. Furthermore, we discuss the potential of using miRNAs as markers for diagnosis and prognosis as well as therapeutic targets and drugs.

Human hepatitis viruses-associated cutaneous and systemic vasculitis

Human hepatitis viruses(HHVs)include hepatitis A virus,hepatitis B virus(HBV),hepatitis C virus(HCV),hepatitis delta virus,and hepatitis E virus and can cause liver inflammation in their common human host.Usually,HHV is rapidly cleared by the immune system,following acute HHV invasion.The morbidities associated with hepatitis A virus and hepatitis E virus infection occur shortly after their intrusion,in the acute stage.Nevertheless,the viral infectious process can persist for a long period of time,especially in HBV and HCV infection,leading to chronic hepatitis and further progressing to hepatic cirrhosis and liver cancer.HHV infection brings about complications in other organs,and both acute and chronic hepatitis have been associated with clinical presentations outside the liver.Vascular involvement with cutaneous and systemic vasculitis is a well-known extrahepatic presentation;moreover,there is growing evidence for a possible causal relationship between viral pathogens and vasculitis.Except for hepatitis delta virus,other HHVs have participated in the etiopathogenesis of cutaneous and systemic vasculitis via different mechanisms,including direct viral invasion of vascular endothelial cells,immune complex-mediated vessel wall damage,and autoimmune responses with stimulation of autoreactive B-cells and impaired regulatory T-cells.Cryoglobulinemic vasculitis and polyarteritis nodosa are recognized for their association with chronic HHV infection.Although therapeutic guidelines for HHV-associated vasculitis have not yet been established,antiviral therapy should be initiated in HBV and HCV-related systemic vasculitis in addition to the use of corticosteroids.Plasma exchange and/or combined cyclophosphamide and corticosteroid therapy can be considered in patients with severe life-threatening vasculitis manifestations.

Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of patients.The remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the illness.Nearly a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular carcinoma.The indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity levels.The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

Hepatitis B and C viruses are not risks for pancreatic adenocarcinoma

AIM: To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) increase risk of pancreatic ductal adenocarcinoma (PDAC).

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.

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.

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.

Subversion of cellular autophagy during virus infection:Insights from hepatitis B and hepatitis C viruses

Autophagy is a self-eating process,in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular microenvironment.Autophagy is generally thought of as a pro-survival mechanism which is not only important for balancing energy supply at times of nutrient deprivation but also in the removal of various stress stimuli to ensure homeostasis.In addition to the target materials of“self”origin,autophagy can also eliminate intracellular pathogens and acts as a defense mechanism to curb infections.In addition,autophagy is linked to the host cell's innate immune response.However,viruses have evolved various strategies to manipulate and overtake host cell machinery to establish productive replication and maintain infectious process.In fact,replication of many viruses has been found to be autophagy-dependent and suppression of autophagy can potentially affect the viral replication.Thus,autophagy can either serve as an anti-viral defense mechanism or a pro-viral process that supports viral replication.Hepatitis B virus(HBV)and hepatitis C virus(HCV)are known to co-opt cellular autophagy process as a pro-viral tool.Both viruses also induce mitophagy,which contributes to the establishment of chronic hepatitis.This review focuses on the roles of autophagy and mitophagy in the chronic liver disease pathogenesis associated with HBV and HCV infections.

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.

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.

Prevalence of transfusion transmissible infections among various donor groups:A comparative analysis

BACKGROUND Transfusion transmissible infections(TTIs)are illnesses spread through contaminated blood or blood products.In India,screening for TTIs such as hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency virus(HIV)-I/II,malaria,and syphilis is mandatory before blood transfusions.Worldwide,HCV,HBV,and HIV are the leading viruses causing mortality,affecting millions of people globally,including those with co-infections of HIV/HCV and HIV/HBV.Studies highlight the impact of TTIs on life expectancy and health risks,such as liver cirrhosis,cancer,and other diseases in individuals with chronic HBV.Globally,millions of blood donations take place annually,emphasizing the importance of maintaining blood safety.AIM To study the prevalence of TTIs,viz.,HBV,HCV,HIV I/II,syphilis,and malaria parasite(MP),among different blood donor groups.METHODS The study assessed the prevalence of TTIs among different blood donor groups in Delhi,India.Groups included total donors,in-house donors,total camp donors,institutional camp donors,and community camp donors.Tests for HIV,HBV,and HCV were done using enzyme-linked immunosorbent assay,while syphilis was tested with rapid plasma reagins and MP rapid card methods.The prevalence of HBV,HCV,HIV,and syphilis,expressed as percentages.Differences in infection rates between the groups were analyzed usingχ²tests and P-values(less than 0.05).RESULTS The study evaluated TTIs among 42158 blood donors in Delhi.The overall cumulative frequency of TTIs in total blood donors was 2.071%,and the frequencies of HBV,HCV,HIV-I/II,venereal disease research laboratory,and MP were 1.048%,0.425%,0.221%,0.377%,and 0.0024%,respectively.In-house donors,representing 37656 donors,had the highest transfusion transmissible infection(TTI)prevalence at 2.167%.Among total camp donors(4502 donors),TTIs were identified in 1.266%of donors,while community camp donors(2439 donors)exhibited a prevalence of 1.558%.Institutional camp donors(2063 donors)had the lowest TTI prevalence at 0.921%.Statistical analysis revealed significant differences in overall TTI prevalence,with total and in-house donors exhibiting higher rates compared to camp donors.CONCLUSION Ongoing monitoring and effective screening programs are essential for minimizing TTIs.Customizing blood safety measures for different donor groups and studying socio-economic-health factors is essential to improving blood safety.

Aptamers Against Viral Hepatitis:from Rational Design to Practical Application

Aptamers are short nucleic acids or peptides that strongly bind to a protein of interest and functionally inhibit a given target protein at the intracellular level. Besides high affinity and specificity, aptamers have several advantages over traditional antibodies. Hence, they have been broadly selected to develop antiviral agents for therapeutic applications against hepatitis B and C viruses (HBV, HCV). This review provides a summary of in vitro selection and characterization of aptamers against viral hepatitis, which is of practical significance in drug discovery.

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.

Epidemiology of hepatitis C virus infection

Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.

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.

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis,cancer,and liver failure.Liver cancer is the third leading cause of cancer-associated mortality,of which hepatocellular carcinoma(HCC)represents 90%of all primary liver cancers.Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management.Chronic infection with hepatitis B virus(HBV),hepatitis delta virus(HDV),and hepatitis C virus(HCV)are the greatest etiological risk factors for HCC.Due to the significant role of chronic viral infection in HCC development,it is important to investigate direct(viral associated)and indirect(immune-associated)mechanisms involved in the pathogenesis of HCC.Common mechanisms used by HBV,HCV,and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response,immune and viral protein-mediated oxidative stress,and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection,and metabolic reprogramming leading to steatosis is driven by HCV infection.The current review aims to provide a brief overview of HBV,HCV and HDV molecular biology,and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC,and current as well as emerging treatments for HCC.