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.

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.

Hepatitis C virus micro-elimination:Where do we stand?

Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviraltreatments, has been promoted by the World Health Organization. Thisachievement is not attainable, however, particularly after the 2020 pandemic ofthe coronavirus disease 2019. Consequently, the more realistic objective ofeliminating HCV from population segments for which targeted strategies ofprevention and treatment are easily attained has been promoted in Europe, as avalid alternative. The underlying idea is that micro-elimination will ultimatelylead to macro-elimination. The micro-elimination strategy may target differentspecific populations and at-risk groups. Different settings, including prisons andhospitals, have also been identified as micro-elimination scenarios. In addition,dedicated micro-elimination strategies have been designed that are tailored at thegeographical level according to HCV epidemiology and individual country’sincome. The main elements of a valid and successful micro-elimination project arereliable epidemiological data and active involvement of all the stakeholders.Community involvement represents another essential component for a successfulprogram.

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.

Innovations in education:A prospective study of storytelling narratives to enhance hepatitis C virus knowledge among substance users

BACKGROUND Even though substance users have the highest hepatitis C virus(HCV)burden,many lack knowledge about the infection.Lack of knowledge is an important obstacle to pursuing HCV care.Although printed materials are conventionally utilized to disseminate HCV-related knowledge,narrative story-telling videos may be an alternative.Data are extremely limited,however,in the ability of storytelling videos to increase HCV knowledge among substance users.In this study,we hypothesized that a story-telling narrative video would increase substance user’s immediate and 1-month HCV-related knowledge compared to a printed format.AIM To assess immediate and 1-month HCV-related knowledge retention among substance users comparing education delivered via a storytelling narrative video compared to a printed format.METHODS We conducted a prospective matched,case-control study among substance users actively prescribed buprenorphine enrolled from two sites.The intervention site received the video and the control site,the brochure.Participants(n=176)were matched on age,gender,and race.We obtained extensive patient and stakeholder input on the video’s design,validated the video’s content,and developed a recruitment plan to guide participant enrollment.Knowledge was assessed by administration of a 25-item instrument immediately before,immediately after,or one month after the intervention.Data were analyzed using nonparametric and generalized linear mixed-effects models.RESULTS We recruited a total of 176 substance users,90 and 86 individuals,from each site,respectively.One-month follow up occurred in 92%and 94%of enrollees in the control and intervention groups,respectively.In comparison with the pre-intervention scores,immediate knowledge recall increased significantly for both the intervention(P<0.0001)and control(P<0.0001)groups.Multivariate modeling revealed a significant improvement in HCV-related knowledge and retention(P=0.033)among participants who viewed the storytelling video.CONCLUSION Storytelling narratives emphasizing HCV education appear to be an effective method to increase HCV-related knowledge among substance users.They should become an educational cornerstone to promote HCV management among this population.

S-adenosyl-L-methionine modifies antioxidant-enzymes,glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells

AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine(SAM) decreases hepatitis C virus(HCV) expression.METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell culture system. Huh7 HCV-replicon cells were treated with 1 mmol/L SAM for different times(24-72 h), then total RNA and proteins were isolated. c DNA was synthesized and real time-PCR was achieved to quantify HCV-RNA, superoxide dismutase 1 and 2(SOD-1, SOD-2) catalase, thioredoxin 1, methionine adenosyltransferase 1A and 2A(MAT1A, MAT2A) expression, and GAPDH and RPS18 as endogenous genes. Expression of cellular and viral protein was evaluated by western-blot analysis using antibodies vs HCV-NS5 A, SOD-1, SOD-2, catalase, thioredoxin-1, MAT1 A, MAT2 A, GAPDH and actin. Total glutathione levels were measured at different times by Ellman's recycling method(0-24 h). Reactive oxidative species(ROS) levels were quantified by the dichlorofluorescein assay(0-48 h); Pyrrolidin dithiocarbamate(PDTC) was tested as an antioxidant control and H2O2 as a positive oxidant agent.RESULTS: SAM exposition decreased HCV-RNA levels 50%-70% compared to non-treated controls(24-72 h). SAM induced a synergic antiviral effect with standard IFN treatment but it was independent of IFN signaling. In addition, 1 mmol/L SAM exposition did not modify viral RNA stability, but it needs cellular translation machinery in order to decrease HCV expression. Total glutathione levels increased upon SAM treatment in HCV-replicon cells. Transcriptional antioxidant enzyme expression(SOD-1, SOD-2 and thioredoxin-1) was increased at different times but interestingly, there was no significant change in ROS levels upon SAM treatment, contrary to what was detected with PDTC treatment, where an average 40% reduction was observed in exposed cells. There was a turnover from MAT1A/MAT2 A, since MAT1 A expression was increased(2.5 fold-times at 48 h) and MAT2 A was diminished(from 24 h) upon SAM treatment at both the transcriptional and translational level. CONCLUSION: A likely mechanism(s) by which SAM diminish HCV expression could involve modulating antioxidant enzymes, restoring biosynthesis of glutathione and switching MAT1/MAT2 turnover in HCV expressing cells.

Direct antiviral agents in hepatitis C virus related liver disease:Don’t count the chickens before they’re hatched

Since molecules with direct-acting antiviral(DAA)became available,the landscape of the treatment of hepatitis C virus(HCV)infection has completely changed.The new drugs are extremely effective in eradicating infection,and treatment is very well tolerated with a duration of 8-12 wk.This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages,identifying some clinically relevant hot topics.First,do the rates of virological response remain as high when patients with more advanced cirrhosis are considered?Large studies have shown slightly lower but still satisfactory rates of response in these patients.Nevertheless,modified schedules with an extended treatment duration and use of ribavirin may be necessary.Second,does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer?Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis.In contrast,the risk of recurrence seems to be unaffected by viral clearance;however,DAA treatment improves survival because of the reduced risk of progression of liver disease.Third,can HCV treatment also have favorable effects on major comorbidities?HCV eradication is associated with a reduced incidence of diabetes,an improvement in glycemic control and a decreased risk of cardiovascular events;nevertheless,a risk of hypoglycemia during DAA treatment has been reported.Finally,is it safe to treat patients with HCV/hepatitis B virus(HBV)coinfection?In this setting,HCV is usually the main driver of viral activity,while HBV replication is suppressed.Because various studies have described HBV reactivation after HCV clearance,a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.

Pathogenesis and treatment of hepatitis C virus-related liver diseases

BACKGROUND: Few comprehensive reviews on the pa- thogenesis of hepatitis C virus (HCV)-related liver diseases have been presented to the present. This article was to re- view the pathogenesis and treatment of HCV-related liver diseases. DATA SOURCES: Data presented here are mostly taken from Japanese studies. RESULTS: HCV infection is characterized by persistent in- flammation of the liver and frequent development of hepa- tocellular carcinoma (HCC) in most cases. These charac- teristic evidences could be explained by immunological al- terations and oxidative stress in the hepatocyte caused by HCV infection. Interferon (IFN) treatment is carried out, at present, not only for the elimination of infected HCV for the treatment of chronic liver diseases, but also for both the prevention of HCC and the treatment of advanced HCC with chemotherapy. The treatment for oxidative stress is al- so important for non-responders to IFN. CONCLUSION: It is important to understand the pathoge- nesis of HCV-related liver diseases for a successful treat- ment.

Global prevalence of occult hepatitis C virus: A systematic review and meta-analysis

BACKGROUND Occult hepatitis C infection(OCI)is characterized by the presence of hepatitis C virus(HCV)RNA in the liver,peripheral blood mononuclear cells(PBMC)and/or ultracentrifuged serum in the absence of detectable HCV-RNA in serum.OCI has been described in several categories of populations including hemodialysis patients,patients with a sustained virological response,immunocompromised individuals,patients with abnormal hepatic function,and apparently healthy subjects.AIM To highlight the global prevalence of OCI.METHODS We performed a systematic and comprehensive literature search in the following 4 electronic databases PubMed,EMBASE,Global Index Medicus,and Web of Science up to 6th May 2021 to retrieve relevant studies published in the field.Included studies were unrestricted population categories with known RNA status in serum,PBMC,liver tissue and/or ultracentrifuged serum.Data were extracted independently by each author and the Hoy et al tool was used to assess the quality of the included studies.We used the random-effect meta-analysis model to estimate the proportions of OCI and their 95%confidence intervals(95%CI).The Cochran's Q-test and the I2 test statistics were used to assess heterogeneity between studies.Funnel plot and Egger test were used to examine publication bias.R software version 4.1.0 was used for all analyses.RESULTS The electronic search resulted in 3950 articles.We obtained 102 prevalence data from 85 included studies.The pooled prevalence of seronegative OCI was estimated to be 9.61%(95%CI:6.84-12.73)with substantial heterogeneity[I^(2)=94.7%(95%CI:93.8%-95.4%),P<0.0001].Seropositive OCI prevalence was estimated to be 13.39%(95%CI:7.85-19.99)with substantial heterogeneity[I^(2)=93.0%(90.8%-94.7%)].Higher seronegative OCI prevalence was found in Southern Europe and Northern Africa,and in patients with abnormal liver function,hematological disorders,and kidney diseases.Higher seropositive OCI prevalence was found in Southern Europe,Northern America,and Northern Africa.CONCLUSION In conclusion,in the present study,it appears that the burden of OCI is high and variable across the different regions and population categories.Further studies on OCI are needed to assess the transmissibility,clinical significance,long-term outcome,and need for treatment.

Global elimination of hepatitis C virus infection:Progresses and the remaining challenges

Today, with the introduction of interferon-free direct-acting antivirals and outstanding progresses in the prevention, diagnosis and treatment of hepatitis C virus(HCV) infection, the elimination of HCV infection seems more achievable. A further challenge is continued transmission of HCV infection in high-risk population specially injecting drug users(IDUs) as the major reservoir of HCV infection. Considering the fact that most of these infections remain undiagnosed, unidentified HCVinfected IDUs are potential sources for the rapid spread of HCV in the community. The continuous increase in the number of IDUs along with the rising prevalence of HCV infection among young IDUs is harbinger of a forthcoming public health dilemma, presenting a serious challenge to control transmission of HCV infection. Even the changes in HCV genotype distribution attributed to injecting drug use confirm this issue. These circumstances create a strong demand for timely diagnosis and proper treatment of HCV-infected patients through risk-based screening to mitigate the risk of HCV transmission in the IDUs community and, consequently, in the society. Meanwhile, raising general awareness of HCV infection, diagnosis and treatment through public education should be the core activity of any harm reduction intervention, as the root cause of failure in control of HCV infection has been lack of awareness among young drug takers. In addition, effective prevention, comprehensive screening programs with a specific focus on high-risk population, accessibility to the new anti-HCV treatment regimens and public education should be considered as the top priorities of any health policy decision to eliminate HCV infection.

Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indicates that HCV-associated insulin resistance may cause(1) hepatic steatosis;(2) resistance to anti-viral treatment;(3) hepatic f ibrosis and esophageal varices;(4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma;and(5) extrahepatic manifestations.Thus,HCV-associated insulin resistance is a therapeutic target at any stage of HCV infection.Although the risk of insulin resistance in HCV-infected patients has been documented,therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been established.In addition,mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin resistance.In order to ameliorate HCV-associated insulin resistance and its complications,the eff icacy of the following interventions is discussed:a late evening snack,coffee consumption,dietary iron restriction,phlebotomy,and zinc supplements.Little is known regarding the effect of anti-diabetic agents on HCV infection,however,a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been reported.On the other hand,insulin-sensitizing agents are reported to improve sustained virologic response rates.In this review,we summarize distinctive complications of,and therapeutic strategies for,HCVassociated insulin resistance.Furthermore,we discuss supplementation with branched-chain amino acids as a unique insulin-sensitizing strategy for patients with HCVassociated insulin resistance.

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 was higher in HCV-infected patients in comparison with HBV-infected patients(39.1% vs 5%,P < 0.0001).Among patients without cirrhosis,diabetes was more prevalent in HCV-infected patients than in HBV-infected patients(33.5% vs 4.3%,P < 0.0001).Among patients with cirrhosis,diabetes was more prevalent in HCV-infected patients,but the difference was not significant(67.4% vs 20%,P = 0.058).The logistic regression analysis showed that HCV infection [odds ratio(OR) 4.73,95% CI:1.7-13.2],metabolic syndrome(OR 12.35,95% CI:6.18-24.67),family history of diabetes(OR 3.2,95% CI:1.67-6.13) and increased hepatic enzymes(OR 2.22,95% CI:1.1-4.5) were independently related to DM in these patients.CONCLUSION:The high prevalence of diabetes in HCV-infected patients,and its occurrence at early stages of hepatic disease,suggest that screening for glucose abnormalities should be indicated in these patients.

Effect of hepatitis C virus core protein on modulation of cellular proliferation and apoptosis in hilar cholangiocarcinoma

BACKGROUND: Hepatitis C virus (HCV) is believed to be an important human pathogen causing carcinoma. But the effect of HCV infection on the alteration of cellular pro- liferation and apoptosis and the relationship between the effect and the development of hilar cholangiocarcinoma are largely unknown. The aim of this study was to assess the effect of HCV core protein on proliferation and apoptosis of hilar cholangiocarcinoma. METHODS: HCV core protein (HCV C protein) was de- tected by peroxidase-antiperoxidase assay in surgical speci- mens from 48 patients with hilar cholangiocarcinoma. The apoptosis index ( AI) and PCNA index ( PI) in hilar cholangiocarcinoma were detected by in situ end labeling assay and streptavidin-biotin assay respectively. RESULTS: The expression of HCV C protein was observed in 32 (67.7%) of the 48 specimens of hilar cholangiocarci- noma. The mean ± standard deviation for AI and PI was 3.52%±0.64% and 46.24%±11.46% respectively. The AI of hilar cholangiocarcinoma specimens with HCV C protein expression was significantly lower than that of HCV C pro- tein negative specimens (P<0.01), whereas the PI of HCV C protein positive specimens was significantly higher than that of HCV C protein negative specimens (P<0.01). CONCLUSION: HCV C protein may promote the cellular proliferation of hilar cholangiocarcinoma and inhibit its cel- lular apoptosis.

Distribution and changes in hepatitis C virus genotype in China from 2010 to 2020

BACKGROUND Hepatitis C virus(HCV)causes a large number of infections worldwide.New infections seem to be increasing according to a report of the World Health Organization in 2015.Although direct-acting antivirals are quite effective for most genotypes of the HCV,some genotypes fail to respond.Therefore,the trend of genotype distribution is vital to better control the development of this infection.AIM To analyze the distribution and trends of the HCV genotype before and after the emergence of direct-acting antivirals in China.METHODS We searched all literature published in five electronic databases-China National Knowledge Infrastructure,Wan Fang Data,VIP Chinese Journal Database,Chinese Biomedical Literature Service System,and PubMed-from January 1,2010 to December 31,2020.The search strategy combined medical subject headings and free-text terms,including“hepatitis C virus”or“HCV”and“genotype”or“subtype”and“China”or“Chinese”.Additional relevant articles were searched by manual selection.Data were extracted to build a database.All of the data were totaled according to regions,periods,routes of transmission,and sexes.The percentages in various stratifications were calculated.RESULTS There were 76110 samples from 30 provinces included in the study.Genotype 1(G1)accounted for 58.2%of cases nationwide,followed by G2,G6,G3b,G3a,unclassified and mixed infections(17.5%,7.8%,6.4%,4.9%,1.8%,and 1.2%,respectively).The constitution of genotype varied among different regions,with G6 and G3b being more common in the south and southwest,respectively(28.1%,15.4%).The past ten years have witnessed a decrease in G1 and G2 and an increase in G3 and G6 in almost all regions.The drug-use population had the most abundant genotypes,with G6 ranking first(33.3%),followed by G1 and G3b(23.4%,18.5%).CONCLUSION G3 and G6 pose a new challenge for HCV infection.This study revealed the distribution of HCV genotypes in China over the past 10 years,providing information for HCV management strategies.

Hepatitis C virus infection and biological falsepositive syphilis test:a single-center experience

BACKGROUND:Rapid plasma regain positive and/or treponema pallidum hemagglutination negative [RPR(+)/TPHA(-)] results were designated as biologic false-positive (BFP).There are limited data about BFP reactions against syphilis in patients with hepatitis C virus (HCV) infection.This study aimed to determine the prevalence of BFP reactions for syphilis in patients with HCV infection in a large sample and assess the relationship between BFP reactions and HCV infection.METHODS:A total of 2656 patients with positive anti-HCV and 5600 healthy control subjects were enrolled in this study.Hepatitis C serology was determined by a second generation ELISA test for HCV antibody.Syphilis serology was determined by the RPR test.Those subjects with reactive RPR positive underwent the TPHA test.Demographics and laboratory data were collected by trained clinicians.RESULTS:Among 2656 patients,111 (4.2%) had a reactive RPR test.Of the 111 patients who were subjected to reactive RPR test,30 (27.0%) showed HCV(+)/RPR(+).Of 5600 healthy controls,80 (1.4%) had a reactive RPR test.Fourteen (17.5%) controls with HCV(-)/RPR(+) had a non-reactive TPHA test.These represented 1.1% of all HCV-positive and 0.3% of all HCV-negative subjects (P<0.001).A significantly increased prevalence shown by false-positive tests for syphilis was observed in elderly HCV-seropositive patients.BFP-HCV positive group had a higher prevalence of eosinophilia.The eosinophil abnormality was compared between the patients and controls (66.7% vs 21.4%,P=0.0043).No significant results were observed in antinuclear antibodies,antiphospholipid and complement (C3,C4) (P>0.05).CONCLUSIONS:The data of this study demonstrate that HCV infection is associated with a false-positive RPR test.In this study BFPs were significantly more common in HCV positive patients compared to HCV-negative ones.Eosinophil abnormality can be considered as a predictor for BFP.Excessive BFPs must be considered in assessing the frequency of syphilis in a HCV-positive population and the importance of the treponemal specific serologic test should be emphasized for a diagnosis of syphilis in such population.

Molecular basis of hepatocellular carcinoma induced by hepatitis C virus infection

Present study outlines a comprehensive view of published information about the underlying mechanisms operational for progression of chronic hepatitis C virus(HCV) infection to development of hepatocellular carcinoma(HCC). These reports are based on the results of animal experiments and human based studies. Although, the exact delineated mechanism is not yet established, there are evidences available to emphasize the involvement of HCV induced chronic inflammation, oxidative stress, insulin resistance, endoplasmic reticulum stress, hepato steatosis and liver fibrosis in the progression of HCV chronic disease to HCC. Persistent infection with replicating HCV not only initiates several liver alterations but also creates an environment for development of liver cancer. Various studies have reported that HCV acts both directly as well as indirectly in promoting this process. Whereas HCV related proteins, like HCV core, E1, E2, NS3 and NS5A, modulate signal pathways dysregulating cell cycle and cell metabolism, the chronic infection produces similar changes in an indirect way. HCV is an RNA virus and does not integrate with host genome and therefore, HCV induced hepatocarcinogenesis pursues a totally different mechanism causing imbalance between suppressors and proto-oncogenes and genomic integrity. However, the exact mechanism of HCC inducement still needs a full understanding of various steps involved in this process.

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications.HCV genotyping was done using INNO-LiPATM HCV in serum,PBMCs,and liver biopsy specimens and then conf irmed by sequencing of 5'-UTR fragments.RESULTS:The mean age of patients was 30.3 ± 17.1 years.Multiple transfusion was seen in 124(93.2%) of patients.Multiple HCV genotypes were found in 3(2.3%) of 133 plasma samples,9(6.8%) of 133 PBMC samples,and 8(18.2%) of 44 liver biopsy specimens.It is notable that the different genotypes found in PBMCs were not the same as those found in plasma and liver biopsy specimens.CONCLUSION:Our study shows that a signif icant proportion of patients with chronic hepatitis C are affected by multiple HCV genotypes which may not be detectable only in serum of patients.

Impact of alcohol on hepatitis C virus replication and interferon signaling

Hepatitis C virus (HCV) is one of the main etiological factors responsible for liver disease worldwide. It has been estimated that there are over 170 million people infected with HCV worldwide. Of these infected individuals, approximately 75% will go on to develop a life long necroinflammatory liver disease, which over decades, can result in serious complications, such as cirrhosis and hepatocellular carcinoma. Currently there is no effective vaccine and whilst antiviral therapies have been improved, they are still only effective in approximately 50% of individuals. HCV infection stands as a major cause of global morbidity and suffering, and places a signifi cant burden on health systems. The second highest cause of liver disease in the western world is alcoholic liver disease. Frequently, HCV infected individuals consume alcohol, and the combined effect of HCV and alcohol consumption is deleterious for both liver disease and response to treatment. This review discusses the impact of alcohol metabolism on HCV replication and the negative impact on interferon (IFN)-α treatment, with a particular focus on how alcohol and HCV act synergistically to increase oxidative stress, ultimately leading to exacerbated liver disease and a reduction in the effi cacy of IFN-α treatment. A better understanding of the complicated mechanisms at play in hepatocytes infected with HCV and metabo- lizing alcohol will hopefully provide better treatment options for chronic hepatitis C individuals that consume alcohol.

New hope for hepatitis C virus:Summary of global epidemiologic changes and novel innovations over 20 years

Hepatitis C virus(HCV)is a global health concern associated with significant morbidity and mortality.Before the approval of second-generation direct-acting antiviral agents(DAAs),interferon therapy and liver transplantation constituted the mainstay of treatment.The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95%cure rates.The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs.Despite the unparallel efficacy observed among these novel therapies,pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally.To reduce the burden of disease worldwide,essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies.Through transparent negotiations with the pharmaceutical industry,the consideration for compassionate release of medications to promote equitable division of care is paramount.Here we provide a literature review of HCV,changes in epidemiologic trends,access issues for current therapies,and global inequities in disease burden.