Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection:A systematic review

BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma(HCC)in people with cirrhosis.Of the 6 HCV genotypes(G1-G6),genotype-3 accounts for 17.9%of infections.HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings.Consequently,we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations.We searched Web of Science,Medline,EMBASE,and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings,1946-2023.RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates.Three thousand eight hundred and eighty-four records were screened with 3514 excluded.Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis.Of the seven studies,three studies were retrospective case-control trials,two retrospective cohort studies,one a prospective cohort study and one a cross-sectional study design.All were based in hospital settings with four in Pakistan,two in South Korea and one in the United States.The total number of participants were 9621 of which 167 developed HCC(1.7%).All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age(five-studies),with two studies each showing male sex,high alpha feto-protein,directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC.CONCLUSION Although,studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease,HCC,and liver-related death,there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3.Only cirrhosis and age have demonstrated an association;however,the number of studies is very small,and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.

Hepatitis C virus infection in the human immunodeficiency virus infected patient

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

Pulmonary hypertension,nephrotic syndrome,and polymyositis due to hepatitis C virus infection:A case report

BACKGROUND Hepatitis C infection not only damages the liver but also often accompanies many extrahepatic manifestations.Incidences of pulmonary hypertension(PH)caused by hepatitis C are rare,and incidences of concurrent nephrotic syndrome and polymyositis are even rarer.CASE SUMMARY Herein we describe the case of a 57-year-old woman who was admitted to our department for intermittent chest tightness upon exertion for 5 years,aggravated with dyspnea for 10 d.After relevant examinations she was diagnosed with PH,nephrotic syndrome,and polymyositis due to chronic hepatitis C infection.A multi-disciplinary recommendation was that the patient should be treated with sildenafil and macitentan in combination and methylprednisolone.During treatment autoimmune symptoms,liver function,hepatitis C RNA levels,and cardiac parameters of right heart catheterization were monitored closely.The patient showed significant improvement in 6-min walking distance from 100 to 300 m at 3-mo follow-up and pulmonary artery pressure drops to 50 mmHg.Long-term follow-up is needed to confirm further efficacy and safety.CONCLUSION Increasing evidence supports a relationship between hepatitis C infection and diverse extrahepatic manifestations,but it is very rare to have PH,nephrotic syndrome,and polymyositis in a single patient.We conducted a literature review on the management of several specific extrahepatic manifestations of hepatitis C.

Analysis of the effects of donor and recipient hepatitis C infection on kidney transplant outcomes in the United States

BACKGROUND As Hepatitis C virus infection(HCV+)rates in kidney donors and transplant recipients rise,direct-acting antivirals(DAA)may affect outcomes.AIM To analyze the effects of HCV+in donors,recipients,or both,on deceased-donor(DD)kidney transplantation(KT)outcomes,and the impact of DAAs on those effects.METHODS The Organ Procurement and Transplantation Network data of adult first solitary DD-KT recipients 1994-2019 were allocated into four groups by donor and recipient HCV+status.We performed patient survival(PS)and death-censored graft survival(DCGS)pairwise comparisons after propensity score matching to assess the effects of HCV+in donors and/or recipients,stratifying our study by DAA era to evaluate potential effect modification.RESULTS Pre-DAA,for HCV+recipients,receiving an HCV+kidney was associated with 1.28-fold higher mortality(HR 1.151.281.42)and 1.22-fold higher death-censored graft failure(HR 1.081.221.39)compared to receiving an HCV-kidney and the absolute risk difference was 3.3%(95%CI:1.8%-4.7%)for PS and 3.1%(95%CI:1.2%-5%)for DCGS at 3 years.The HCV dual-infection(donor plus recipient)group had worse PS(0.56-fold)and DCGS(0.71-fold)than the dual-uninfected.Donor HCV+derived worse post-transplant outcomes than recipient HCV+(PS 0.36-fold,DCGS 0.34-fold).In the DAA era,the risk associated with HCV+in donors and/or recipients was no longer statistically significant,except for impaired PS in the dual-infected vs dual-uninfected(0.43-fold).CONCLUSION Prior to DAA introduction,donor HCV+negatively influenced kidney transplant outcomes in all recipients,while recipient infection only relatively impaired outcomes for uninfected donors.These adverse effects disappeared with the introduction of DAA.

Peginterferon and ribavirin treatment for hepatitis C virus infection

Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, novel modified IFNα and ribavirin or combinations with specifically targeted antiviral therapy for HCV agents, are currently being investigated. The purpose of this review is to address some issues and epoch-making topics in the treatment of chronic HCV infection, and to discuss more optimal and highly individualized therapeutic strategies for HCV-infected patients.

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.

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.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV. In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging

Hepatitis C virus(HCV)infection represents a major public health issue.Hepatitis C can be cured bytherapy,but many infected individuals are unaware of their status.Effective HCV screening,fast diagnosis and characterization,and hepatic fibrosis staging are highly relevant for controlling transmission,treating infected patients and,consequently,avoiding end-stage liver disease.Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays.Additionally,the use of point-of-care tests can increase HCV screening opportunities.However,active HCV infection must be confirmed by direct diagnosis methods.Additionally,HCV genotyping is required prior to starting any treatment.Increasingly,high-volume clinical laboratories use different types of automated platforms,which have simplified sample processing,reduced hands-on-time,minimized contamination risks and human error and ensured full traceability of results.Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods,such as imaging techniques and serum-based tests.However,no single test is currently available that is able to completely replace liver biopsy.This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests.

Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

Treatment of patients with chronic kidney disease(CKD) and chronic hepatitis C(CHC) differs from that used in the general CHC population mostly when glomerular filtration rate(GFR) is below 30 m L/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvirbased regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response(SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current managementof CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.

Alcohol use disorder and its impact on chronic hepatitis C virus and human immunodeficiency virus infections

Alcohol use disorder(AUD) and hepatitis C virus(HCV) infection frequently co-occur. AUD is associated with greater exposure to HCV infection, increased HCV infection persistence, and more extensive liver damage due to interactions between AUD and HCV on immune responses, cytotoxicity, and oxidative stress. Although AUD and HCV infection are associated with increased morbidity and mortality, HCV antiviral therapy is less commonly prescribed in individuals with both conditions. AUD is also common in human immunodeficiency virus(HIV) infection, which negatively impacts proper HIV care and adherence to antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are also frequent within a proportion of patients with HIV infection, which negatively impacts liver disease. This review summarizes the current knowledge regarding pathological interactions of AUD with hepatitis C infection, HIV infection, and HCV/HIV co-infection, as well as relating to AUD treatment interventions in these individuals.

Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection

AIM： To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus （HCV） infection, and its relation to disease severity. METHODS： We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen （HBsAg）, antibody to hepatitis B surface antigen （anti- HBs）, and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study. RESULTS： Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis （CAH）. Of these 169 patients, 85 （50.3%） tested positive for anti-HBc. Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 （6d.5%） and 14 （23.7%） respectively （P 〈 0.001）. Twenty-five patients were tested for HBV DNA by qualitative PCR. The test was positive in 3 of them （12%; occult HBV infection）. CONCLUSION： Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.

Spontaneous elimination of hepatitis C virus infection: A retrospective study on demographic, clinical, and serological correlates

To find correlates to spontaneous clearance of hepatitis C virus （HCV） infection, this study compared individuals with self-limited and chronic infection with regard to clinical, demographic, and serological pa- rameters. METHODS： Sixty-seven anti-HCV positive and repeatedly HCV RNA negative individuals were considered to have resolved HCV infection spontaneously. To determine the viral genotype these patients had been infected with HCV serotyping was performed. For comparison reasons, 62 consecutive patients with chronic hepatitis C were enrolled. Cases and controls were compared stratified for age and sex. RESULTS： Retrospective analysis showed （1） a lower humoral reactivity to HCV in patients with self-limited compared to chronic HCV-infection and （2） that younger age, history of iv drug use, and acute/post-acute hepatitis A or B co-infections, but not viral genotypes, are independent correlates for spontaneous HCV clearance. CONCLUSION： The stronger humoral reactivity to HCV in patients with persistent infections and in those with a history of iv drug use is supposed to be due to continuous or repeated contact（s） to the antigen. Metachronous hepatitis A or hepatitis B infections might favor HCV clearance.

Recently acquired hepatitis C virus infection among people living with human immunodeficiency virus at a university hospital in Taiwan

BACKGROUND Little is known about the engagement in hepatitis C virus(HCV)care and completion of HCV treatment in people living with human immunodeficiency virus(HIV)(PLWH)who have HCV coinfection in the Asia-Pacific region.Examining the HCV care cascade can identify barriers to the completion of HCV treatment and facilitate achievement of HCV micro-elimination in PLWH.AIM To investigate the care cascade of incident HCV infections among PLWH in Taiwan.METHODS PLWH with incident HCV infections,defined as HCV seroconversion,were retrospectively identified by sequential anti-HCV testing of all archived blood samples at National Taiwan University Hospital between 2011 and 2018.All PLWH with incident HCV infections were followed until December 31,2019.The care cascade of HCV examined included all incident HCV-infected patients,the percentages of anti-HCV antibodies detected by HIV-treating physicians in clinical care,plasma HCV RNA load tested,HCV RNA positivity diagnosed,referral to treatment assessment made,anti-HCV treatment initiated,and sustained virologic response achieved.Those who had HCV seroconversion during the interferon(IFN)era(2011–2016)and the direct-acting antiviral(DAA)era(2017–2018)were analyzed separately.The duration of HCV viremia—from the date of seroconversion to viral clearance by treatments or until the end of observation—and the incidence of sexually transmitted infections(STIs)during the HCV viremic period were estimated.RESULTS During the study period,287 of 3495(8.2%)PLWH(92.3%being men who have sex with men)who were HCV-seronegative at baseline developed HCV seroconversion by retrospective testing of all archived blood samples.Of the 287 incident HCV infections,277(96.5%)had anti-HCV antibodies detected by HIV-treating physicians,270(94.1%)had plasma HCV RNA determined and 251(87.5%)tested positive for HCV RNA.Of those with HCV viremia,226(78.7%)were referred to treatment assessment,215(74.9%)initiated anti-HCV treatment,and 202(70.4%)achieved viral clearance.Compared with that in the IFN era,the median interval from HCV seroconversion by retrospective testing to detection of HCV seropositivity by HIV-treating physicians was significantly shorter in the DAA era{179 d[interquartile range(IQR)87-434]vs 92 d(IQR 57-173);P<0.001}.The incidence rate of STIs in the DAA vs the IFN era was 50.5 per 100 person-years of follow-up(PYFU)and 38.5 per 100 PYFU,respectively,with an incidence rate ratio of 1.31(95%confidence interval 0.96-1.77),while the duration of HCV viremia was 380 d(IQR 274-554)and 735 d(IQR 391-1447)(P<0.001),respectively.CONCLUSION While anti-HCV therapies are effective in achieving viral clearance,our study suggests more efforts are needed to expedite the linkage of PLWH diagnosed with incident HCV infections to HCV treatment.

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.

Hepatitis B virus and hepatitis C virus infection inhealthcare workers

Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus(HBV) and 1000000 to hepatitis C virus(HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.

Alcoholic liver disease and hepatitis C virus infection

Alcohol consumption and hepatitis C virus(HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher(up to 50%) in alcoholic patients than in the general po pulation. However, the presence of advanc e d alcoholic liver disease(ALD) or intravenous drug use(IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefi t from addi tionalsupport during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection.

Hepatitis C and HIV co-infection:a review

Co-infection with hepatitis C virus and humanimmunodeficiency virus is common in certainpopulations. Among HCV(+) persons, 10 % are alsoHIV (+), and among HIV (+) persons, 25 % are alsoHCV(+). Many studies have shown that in intravenousdrug users, co-infection prevalence can be as high as90-95 %. There is increasing evidence supporting theconcept that people infected with HIV have a muchmore rapid course of their hepatitis C infection.Treatment of co-infection is often challenging becausehighly active anti-retroviral therapy (HAART) therapyis frequently hepatotoxic, especially in the presence ofHCV. The purpose of this review is to describe theeffects that HIV has on hepatitis C, the effects thathepatitis C has on HIV, and the treatment options inthis challenging population.

Health care-associated hepatitis C virus infection

Hepatitis C virus(HCV)is a blood-borne pathogen that has a worldwide distribution and infects millions of people.Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminated blood and unsafe injections and continue to be a serious problem of public health.The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified:(1)infected patient to non-infected patient;(2)infected patient to non-infected health careworker(HCW);and(3)infected HCW to non infected patient.For each condition,the circumstances of contamination are described together with the means to prevent them.As a whole,the more important risk is represented by unsafe practices regarding injections,notably with the improper use of multidose vials used for multiple patients.The questions of occupational exposures and infected HCWs are also discussed.In terms of prevention and surveillance,the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares,with training programs and audits to verify their good application.HCWs must be sensitized to the risk of blood-borne pathogens,notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures.The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay.With the need to stay vigilant because HCV infection is often a hidden risk,it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years.

Hepatitis C virus infection down-regulates the expression of peroxisome proliferator-activated receptor a and carnitine palmitoyl acyl-CoA transferase 1A

AIM： To elucidate the role of the peroxisome proliferator-activated receptor α （PPARα） and its target gene camitine palmitoyl acyl-CoA transferase 2A （CPT1A） in the pathogenesis of hepatitis C virus （HCV） infection.METHODS： Liver samples were collected from the patients with chronic HCV infection and controls. HepG2 cells were transfected with vector pEF352neo carrying. Two independent clones （clone N3 and N4） stably expressing HCV core protein were analyzed. Total RNA was extracted from cells and liver tissues. PPARα and CPT1A mRNAs were quantified by real-time polymerase chain reaction （PCR） using SYBR Green Master. Total extracted proteins were separated by polyacrylamide gel electrophoresis, and electroblotted. Membranes were incubated with the anti-PPARα antibody, then with a swine anti-rabbit IgG conjugated to horseradish peroxidase for PPARα. Protein bands were revealed by an enhanced chemiluminescence reaction for PPARα. For immunohistochemical staining of PPARα, sections were incubated with the primary goat polyclonal antibody directed against PPARα at room temperature.RESULTS： Real-time PCR indicated that the PPARα level and expression level of CPT1A gene in hepatitis C patients lowered significantly as compared with the controls （1.8±2.8 vs 13±3.4, P = 0.0002; 1.1±1.5 vs 7.4±1, P = 0.004）. Western blot results showed that the level of PPARα protein in the livers of hepatitis C patients was lower than that in controls （2.3±0.3 vs 3.6±0.2, P = 0.009）. The immunohistochemical staining results in chronic hepatitis C patients indicated a decrease in PPARα staining in hepatocytes compared with those in the control livers. The in vitro studies found that in the N3 and N4 colon stably expressing HCV core protein, the PPARα mRNA levels were significantly lower than that in the controls.CONCLUSION： The impaired intrahepatic PPARα expression is associated with the pathogenic mechanism in hepatic injury during chronic HCV infection. HCV infection reduced the expression of PPARα and CPT1A at the level of not only mRNAs but also proteins. PPARα plays an important role in the pathogenesis of chronic HCV infection, but the impaired function of this nuclear receptor in HCV infection needs further studies.