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.

Hepatic steatosis as a possible risk factor for the development of hepatocellular carcinoma after eradication of hepatitis C virus with antiviral therapy in patients with chronic hepatitis C

AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.

Extrahepatic immune related manifestations in chronic hepatitis C virus infection

The association of chronic hepatitis C with immune related syndromes has been frequently reported.There is a great range of clinical manifestations affecting various systems and organs such as the skin,the kidneys,the central and peripheral nervous system,the musculoskeletal system and the endocrine glands.Despite the high prevalence of immune related syndromes in patients with chronic hepatitis C,the exact pathogenesis is not always clear.They have been often associated with mixed cryoglobulinemia,a common finding in chronic hepatitis C,cross reaction with viral antigens,or the direct effect of virus on the affected tissues.The aim of this review is to analyze the reported hepatitis C virus immune mediated syndromes,their prevalence and clinical manifestations and to discuss the most supported theories regarding their pathogenesis.

Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.

Circulating autoantibodies to endogenous erythropoietin are associated with chronic hepatitis C virus infection-related anemia

BACKGROUND： Chronic hepatitis C virus （HCV） infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin （anti-EPO） have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in pa- tients with chronic HCV infection and investigate its possible association with anemia. METHODS： Ninety-three consecutive patients （62 males and 31 females） with chronic HCV infection, who had never re- ceived antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load t and genotype sequencing were also performed. RESULTS： Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia （19.4% vs 5.3%, P=0.040） compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia （70.0% vs 34.9%, P=0.030）, lower EPO concentrations （median 16.35 vs 30.65 mU/mL, P=0.005）, and higher HCV RNA viral load （median 891.5x103 vs 367.5x 103 IU/mL, P=0.016）. In multivariate regression anal- ysis the presence of anti-EPO remained an independent predictor of anemia （adjusted OR： 14.303, 95% CI： 1.417-36.580, P=0.024）. EPO response to anemia was less prominent among anti-EPO positive patients （P=0.001）. CONCLUSIONS： Circulating anti-EPO are detected in a significant proportion of treatment-naive HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.

Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis

AIM:To investigate and characterise patients with chronic hepatitis C virus(HCV) infection presenting with hepatocellular carcinoma(HCC) in the absence of cirrhosis.METHODS:Patients with chronic hepatitis C infection without cirrhosis presenting with HCC over a 2-year period were identified.The clinical case notes,blood test results and histological specimens were reviewed to identify whether additional risk factors for the development of HCC were present.RESULTS:Six patients(five male,one female) with chronic hepatitis C infection without cirrhosis presented to a single centre with HCC over a 2-year period.Five patients were treated by surgical resection and one patient underwent liver transplantation.Evaluation of generous histological specimens confirmed the presence of HCC and the absence of cirrhosis in all cases.The degree of fibrosis of the background liver was staged as mild(n = 1),moderate(n = 4) or bridging fibrosis(n = 1).Review of the clinical case notes revealed that all cases had an additional risk factor for the development of HCC(four had evidence of past hepatitis B virus infection;two had a history of excessive alcohol consumption;a further patient had prolonged exposure to immune suppression).CONCLUSION:HCC does occur in patients with non-cirrhotic HCV infection who have other risk factors for hepatocarcinogenesis.

Opportunities for treatment of the hepatitis C virus-infected patient with chronic kidney disease

The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 m L/min per 1.73 m^2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.

Effect of in vitro interferon-beta administration on hepatitis C virus in peripheral blood mononuclear cells as a predictive marker of clinical response to interferon treatment for chronic hepatitis C

AIM:To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was associated with clinical response to IFN.METHODS:Twenty-seven patients with histologically proven chronic hepatitis C were given intravenous administration of 6 million units (MU) IFN-β daily for 6 weeks followed by three times weekly for 20 weeks. PBMC collected before IFN therapy were incubated with IFN-β and HCV-RNA in PMBC was semi-quantitatively determined.RESULTS: Twenty-five patients completed IFN therapy.Eight patients (32%) had sustained loss of serum HCV-RNA with normal serum ALT levels after IFN therapy (complete responders).HCV-RNA in PBMC was detected in all patients,whereas it was not detected in PBMC from healthy subjects.In vitro administration of IFN-β decreased the amount of HCV-RNA in PMBC in 18 patients (72%). Eight of these patients obtained complete response. On the other hand,none of the patients whose HCV-RNA in PBMC did not decrease by IFN-β was complete responders. Multiple logistic regression analysis revealed that the decrease of HCV-RNA amount in PBMC by IFN-β was the only independent predictor for complete response (P<0.05).CONCLUSION:The effect of in vitro IFN-β on HCV in PBMC reflects clinical response and would be taken into account as a predictive marker of IFN therapy for chronic hepatitis C.

FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE～TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan～ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV.

Associations of content and gene polymorphism of macrophage inhibitory factor-1 and chronic hepatitis C virus infection

BACKGROUND The expression of macrophage inhibitory factor-1(MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether MIC-1 gene polymorphism is correlated with relevant diseases is not yet reported.AIM To explore the correlation between gene polymorphism in MIC-1 exon region and chronic hepatitis C virus(HCV) infection.METHODS This case-control study enrolled 178 patients with chronic hepatitis C(CHC) in the case group, and 82 healthy subjects from the same region who had passed the screening examination comprised the control group. The genotypes of rs1059369 and rs1059519 loci in the MIC-1 gene exon were detected by DNA sequencing. Also, the MIC-1 level, liver function metrics, liver fibrosis metrics, and HCV RNA load were determined. Univariate analysis was used to compare the differences and correlations between the two groups with respect to these parameters. Multivariate logistic regression was used to analyze the independent relevant factors of CHC.RESULTS The plasma MIC-1 level in the CHC group was higher than that in the control group(P < 0.05), and it was significantly positively correlated with alanine aminotransferase, aspartate aminotransferase(AST), type III procollagen N-terminal peptide(known as PIIINP), type IV collagen, and HCV RNA(P < 0.05), whereas negatively correlated with total protein and albumin(P < 0.05). The genotype and allele frequency distribution at the rs1059519 locus differed between the two groups(P < 0.05). The allele frequency maintained significant difference after Bonferroni correction(Pc < 0.05). Logistic multiple regression showed that AST, PIIINP, MIC-1, and genotype GG at the rs1059519 locus were independent relevant factors of CHC(P < 0.05). Linkage disequilibrium(LD) was found between rs1059369 and rs1059519 loci, and significant difference was detected in the distribution of haplotype A-C between the CHC and control groups(P < 0.05). Meanwhile, we found the MIC-1 level trend to increase among rs1059519 genotypes(P = 0.006) and the level of MIC-1 in GG genotype to be significantly higher than CC genotype(P = 0.009, after Bonferroni correction).CONCLUSION Plasma MIC-1 level was increased in CHC patients and correlated with liver cell damage, liver fibrosis metrics, and viral load. The polymorphism at the MIC-1 gene rs1059519 locus was correlated with HCV infection, and associated with the plasma MIC-1 level. G allele and GG genotype may be an important susceptible factor for CHC.

Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) worldwide due to the high prevalence of HCV infection and the high rate of HCC occurrence in patients with HCV cirrhosis. A striking increase in HCC incidence has been observed during the past decades in most industrialized countries, partly related to the growing number of patients infected by HCV. HCC is currently the main cause of death in patients with HCV-related cirrhosis, a fact that justifies screening as far as curative treatments apply only in patients with small tumors. As a whole, treatment options are similar in patients with cirrhosis whatever the cause. Chemoprevention could be also helpful in the near future. It is strongly suggested that antiviral treatment of HCV infection could prevent HCC occurrence, even in cirrhotic patients, mainly when a sustained virological response is obtained.

Noninvasive assessment of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection

AIM: To evaluate the accuracy of specific biochemical markers for the assessment of hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. METHODS: One hundred and fifty-four patients with chronic HCV infection were included in this study; 124 patients were non-cirrhotic, and 30 were cirrhotic. The following measurements were obtained in all patients: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total bilirubin, prothrombin time and concentration, complete blood count, hepatitis B surface antigen (HBsAg), HCVAb, HCV-RNA by quantitative polymerase chain reaction, abdominal ultrasound and ultrasonic-guided liver biopsy. The following ratios, scores and indices were calculated and compared with the results of the histopathological examination: AST/ALT ratio (AAR), age platelet index (API), AST to platelet ratio index (APRI), cirrhosis discriminating score (CDS), Pohl score, G teborg University Cirrhosis Index (GUCI). RESULTS: AAR, APRI, API and GUCI demonstrated good diagnostic accuracy of liver cirrhosis (80.5%, 79.2%, 76.6% and 80.5%, respectively); P values were: < 0.01, < 0.05, < 0.001 and < 0.001, respectively. Among the studied parameters, AAR and GUCI gave the highest diagnostic accuracy (80.5%) with cutoff values of 1.2 and 1.5, respectively. APRI, API and GUCI were significantly correlated with the stage of fibrosis (P < 0.001) and the grade of activity (P < 0.001, < 0.001 and < 0.005, respectively), while CDS only correlated significantly with the stage of fibrosis (P < 0.001) and not with the degree of activity (P > 0.05). In addition, we found significant correlations for the AAR, APRI, API, GUCI and Pohl score between the non-cirrhotic (F0, F1, F2, F3) and cirrhotic (F4) groups (P values: < 0.001, < 0.05, < 0.001, < 0.001 and < 0.005, respectively; CDS did not demonstrate significant correlation (P > 0.05). CONCLUSION: The use of AAR, APRI, API, GUCI and Pohl score measurements may decrease the need for liver biopsies in diagnosing cirrhosis, especially in Egypt, where resources are limited.

Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.

Smad3 phospho-isoform signaling in hepatitis C virus-related chronic liver diseases

The risk of hepatocellular carcinoma (HCC) development increases as hepatitis virus C (HCV)-related liver diseases progress, especially in patients with active inflammation. Insight into hepatic carcinogenesis have emerged from recent detailed analyses of transforming growth factor-&#x003b2; and c-Jun-N-terminal kinase signaling processes directed by multiple phosphorylated (phospho)-isoforms of a Smad3 mediator. In the course of HCV-related chronic liver diseases, chronic inflammation and host genetic/epigenetic alterations additively shift the hepatocytic Smad3 phospho-isoform signaling from tumor suppression to carcinogenesis, increasing the risk of HCC. Chronic inflammation represents an early carcinogenic step that provides a nonmutagenic tumor-promoting stimulus. After undergoing successful antiviral therapy, patients with chronic hepatitis C could experience a lower risk of HCC as Smad3 phospho-isoform signaling reverses from potential carcinogenesis to tumor suppression. Even after HCV clearance, however, patients with cirrhosis could still develop HCC because of sustained, intense carcinogenic Smad3 phospho-isoform signaling that is possibly caused by genetic or epigenetic alterations. Smad3 phospho-isoforms should assist with evaluating the effectiveness of interventions aimed at reducing human HCC.

Construction of a chimeric hepatitis C virus replicon based on a strain isolated from a chronic hepatitis C patient

Subgenomic replicons of hepatitis C virus （HCV） have been widely used for studying HCV replication.Here,we report a new subgenomic replicon based on a strain isolated from a chronically infected patient.The coding sequence of HCV was recovered from a Chinese chronic hepatitis C patient displaying high serum HCV copy numbers.A consensus sequence designated as CCH strain was constructed based on the sequences of five clones and this was classified by sequence alignment as belonging to genotype 2a.The subgenomic replicon of CCH was replication-deficient in cell culture,due to dysfunctions in NS3 and NS5B.Various JFH1/CCH chimeric replicons were constructed,and specific mutations were introduced.The introduction of mutations could partially restore the replication of chimeric replicons.A replication-competent chimeric construct was finally obtained by the introduction of NS3 from JFH1 into the backbone of the CCH strain.

Beneficial effects of fucoidan in patients with chronic hepatitis C virus infection

AIM:To evaluate the effects of fucoidan,a complex sulfated polysaccharide extract from marine seaweed,on hepatitis C virus(HCV) RNA load both in vitro and in vivo.METHODS:HCV-1b replicon-expressing cells were cultured in the presence of fucoidan obtained from Cladosiphon okamuranus Tokida cultivated in Okinawa,Japan,and quantified the level of HCV replication.In an open-label uncontrolled study,15 patients with chronic hepatitis C,and HCV-related cirrhosis and hepatocellular carcinoma were treated with fucoidan(0.83 g/d) for 12 mo.The clinical symptoms,biochemical tests,and HCV RNA levels were assessed before,during,and after treatment.RESULTS:Fucoidan dose-dependently inhibited the expression of HCV replicon.At 8-10 mo of treatment with fucoidan,HCV RNA levels were significantly lower relative to the baseline.The same treatment also tended to lower serum alanine aminotransferase levels,and the latter correlated with HCV RNA levels.However,the improved laboratory tests did not translate into significant clinical improvement.Fucoidan had no serious adverse effects.CONCLUSION:Our findings suggest that fucoidan is safe and useful in the treatment of patients with HCVrelated chronic liver diseases.Further controlled clinical trials are needed to confirm the present findings.

Values of high-resolution computed tomography and pulmonary function tests in managements of patients with chronic hepatitis C virus infection

AIM:To investigate pulmonary involvement via pulmonary function tests (PFT) and high-resolution computed tomocjraphy (HRCT) in patients with chronic hepatitis C virus (HCV) infection. METHODS:Thirty-four patients with chronic HCV infection without diagnosis of any pulmonary diseases and 10 healthy cases were enrolled in the study,PFT and HRCT were performed in all cases. RESULTS:A decrease lower than 80% of the predicted value was detected in vital capacity in 9/34 patients,in forced expiratory volume in one second in 8/34 patients,and in forced expiratory flow 25-75 in 15/34 patients,respectively.Carbon monoxide diffusing capacity (DLCO) was decreased in 26/34 patients.Findings of interstitial pulmonary involvement were detected in the HRCT of 16/34 patients.Significant difference was found between controls and patients with HCV infection in findings of HRCT (X^2=4.7,P=0.003).Knodell histological activity index (KHAI) of 28/34 patients in whom liver biopsy was applied was 9.0±4.7.HRCT findings,PFT values and DLCO were not affected by KHAI in patients with HCV infection.In these patients,all the parameters were related with age. CONCLUSION:We suggest that chronic hepatitis C virus infection may cause pulmonary interstitial involvement without evident respiratory symptoms.

Establishment of chronic hepatitis C virus infection:Translational evasion of oxidative defence

Hepatitis C virus(HCV)causes a clinically important disease affecting 3%of the world population.HCV is a single-stranded,positive-sense RNA virus belonging to the genus Hepacivirus within the Flaviviridae family.The virus establishes a chronic infection in the face of an active host oxidative defence,thus adaptation to oxidative stress is key to virus survival.Being a small RNA virus with a limited genomic capacity,we speculate that HCV deploys a different strategy to evade host oxidative defence.Instead of counteracting oxidative stress,it utilizes oxidative stress to facilitate its own survival.Translation is the first step in the replication of a plus strand RNA virus so it would make sense if the virus can exploit the host oxidative defence in facilitating this very first step.This is particularly true when HCV utilizes an internal ribosome entry site element in translation,which is distinctive from that of cap-dependent translation of the vast majority of cellular genes,thus allowing selective translation of genes under conditions when global protein synthesis is compromised.Indeed,we were the first to show that HCV translation was stimulated by an important prooxidant-hydrogen peroxide in hepatocytes,suggesting that HCV is able to adapt to and utilize the host antiviral response to facilitate its own translation thus allowing the virus to thrive under oxidative stress condition to establish chronicity.Understanding how HCV translation is regulated under oxidative stress condition will advance our knowledge on how HCV establishes chronicity.As chronicity is the initiator step in disease progression this will eventually lead to a better understanding of pathogenicity,which is particularly relevant to the development of anti-virals and improved treatments of HCV patients using anti-oxidants.

Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection

AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients.

Is chronic hepatitis C virus infection a risk factor for breast cancer?

AIM:To evaluate the prevalence of breast tumors in adult females with chronic hepatitis C virus(HCV) infection.METHODS:Prospective,single-center study,based on female outpatients consulting in a liver unit,for 1 year.The study group included females with present and/or past history of chronic infection by HCV.Patients with spontaneous recovery were excluded.Chronic hepatitis had been proved by liver biopsy in the majority of cases and/or biological markers of inflammation and fibrosis.The control group included female patients with other well documented chronic liver diseases:chronic hepatitis B,alcoholic liver disease,autoimmune hepatitis,hemochromatosis,non alcoholic liver disease,chronic cholangitis.Participating patients were prospectively questioned during consultation about past breast history and follow-up by mammography.RESULTS:Breast carcinoma was recorded in 17/294 patients with HCV infection(5.8%,95% CI:3.1-8.4) vs 5/107 control patients(4.7%,95% CI:0.67-8.67).Benign tumors of the breast(mastosis,nodules,cysts) were recorded in 75/294 patients with HCV infection(25.5%,95% CI:20.5-30.5) vs 21/107(19.6%,95% CI:12.1-27.1) in the control group.No lesion was noted in 202 patients with HCV(68.7%,95% CI:63.4-74) vs 81 control patients(75.7%,95% CI:67.6-83.8).Despite a trend to an increased prevalence in the group with HCV infection,the difference was not significant compared to the control group(P=NS).In patients over 40 years,the results were,respectively,as follows:breast cancer associated with HCV:17/266 patients(6.3%,95% CI:3.4-9.3) vs 5/95 patients(5.2%,95% CI:0.7-9.7) in the control group;benign breast tumors:72/266 patients with HCV infection(27%,95% CI:21.7-32.4) vs 18/95 patients(18.9%,95% CI:11-26.8) in the control group;no breast lesion 177/266(66.5%,95% CI:60.9-72.2) in patients with HCV infection vs 72/95(75.7%,95% CI:67.1-84.4) in the control group.The differences were not significant(P=NS).CONCLUSION:These results suggest that chronic HCV infection is not a strong promoter of breast carcinoma in adult females of any age.