Hepatitis B Surface Antigen and Hepatitis C Virus Antibodies among Drug Users in Burkina Faso

Introduction: The epidemiology of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among drug users (DUs) is little known in West Africa. The study aimed to assess the prevalence of hepatitis B and C viruses among drug users in Burkina Faso. Methodology: This was a cross-sectional biological and behavioral survey conducted between June and August 2022, among drug users in Ouagadougou and Bobo Dioulasso, the two main cities of Burkina Faso. A respondent-driven sampling (RDS) was used to recruit drug users. Hepatitis B surface antigen was determined using lateral flow rapid test kits and antibodies to hepatitis C virus in serum determined using an Enzyme-Linked Immunosorbent Assay. Data were entered and analyzed using Stata 17 software. Weighted binary logistic regression was used to identify the associated factors of hepatitis B and C infections and a p-value Results: A total of 323 drug users were recruited with 97.5% males. The mean age was 32.7 years old. The inhaled or smoked mode was the most used by drug users. The adjusted hepatitis B and hepatitis C prevalence among study participants were 11.1% and 2.3% respectively. The marital status (p = 0.001), and the nationality (p = 0.011) were significantly associated with hepatitis B infection. The type of drug used was not significantly associated with hepatitis B infection or hepatitis C infection. Conclusion: The prevalence of HBsAg and anti-HCV antibodies among DUs are comparable to those reported in the general population in Burkina Faso. This result suggests that the main routes of contamination by HBV and HCV among DUs are similar to those in the population, and could be explained by the low use of the injectable route by DUs in Burkina Faso.

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.

Hepatitis C virus molecular evolution:Transmission,disease progression and antiviral therapy

Hepatitis C virus(HCV)infection represents an important public health problem worldwide.Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors.Virus molecular evolution plays an important role in HCV transmission,disease progression and therapy outcome.The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures(e.g.,host immune responses and antiviral therapy).HCV molecular evolution is shaped by different mechanisms including a high mutation rate,genetic bottlenecks,genetic drift,recombination,temporal variations and compartmentalization.These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner.Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV.As a result,superior sustained viral responses have been attained.The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer,more potent antivirals,bringing us one step closer to the interferon-free era.

Prevalence of hepatitis C infection among intravenous drug users in Shanghai

AIM:To characterize the prevalence of hepatitis C virus(HCV)infection among Chinese intravenous drug users(IDUs).METHODS:A total of 432 adult IDUs(95 women and337 men)in Shanghai were included in the study.The third-generation Elecsys Anti-HCV assay(Roche Diagnostics GmbH,Sandhofer Strasse 116,D-68305,Mannheim,Germany)was used to screen for antibodies against HCV.The RIBA strip,a supplemental antiHCV test with high specificity,was performed on all of the samples that tested positive during the initial screening.All of the anti-HCV positive samples were analyzed with a Cobas TaqMan 48 Analyzer(Roche Diagnostics)for direct detection of HCV RNA.All of the HCV RNA-positive samples were sequenced for genotype determination.RESULTS:The preliminary screening identified 262(60.6%)subjects who were seropositive for HCV.Of the 62 females and 200 males seropositive subjects,16(16.7%)and 65(19.3%),respectively,were confirmed by RIBA,yielding an overall HCV seropositive rate of18.8%.Four female(6.5%)and 14 male(7.0%)subjects tested positive for HCV RNA,indicating an active infection rate of 4.2%for the entire study population.The 18 HCV RNA-positive serum samples were genotyped.Seven individuals were genotype 1b,and four were genotype 1a.One individual each was infected with genotypes 2a,2b and 3a.Four subjects were coinfected with multiple strains:two with genotypes 1a and 2a,and two with genotypes 1b and 2a.The active infection rate among HCV-seropositive individuals was22.2%,which was significantly lower than most estimates.CONCLUSION:The prevalence of HCV is relatively low among IDUs in Shanghai,with a spontaneous recovery rate much higher than previous estimates.

Combination therapy with daclatasvir and asunaprevir for dialysis patients infected with hepatitis C virus

The standard antiviral therapy for dialysis patients infected with hepatitis C virus(HCV) is(pegylated) interferon monotherapy, but its efficacy is insufficient. Oral direct-acting antiviral agents(DAAs) have recently been developed for chronic hepatitis C patients. However, some DAAs have contraindications for chronic renal failure(CRF). Daclatasvir and asunaprevir are metabolized largely in the liver and are not contraindicated in CRF. Combination therapy with daclatasvir and asunaprevir was used for 4 dialysis patients infected with genotype 1b HCV. One patient had viral breakthrough, and the 3 others had sustained virological response 12. One patient was admitted for heart failure and percutaneous coronary intervention due to concomitant ischemic disease. Heart failure was unlikely to be caused by the combination therapy, as it was probably due to water overload. The patient continued to receive the combination therapy after the remission of the heart failure. The combination therapy was well tolerated in the other patients.

Hepatitis C virus control among persons who inject drugs requires overcoming barriers to care

Despite a high prevalence of hepatitis C virus(HCV)infection,the vast majority of persons who inject drugs(PWID)have not engaged in HCV care due to a large number of obstacles.Education about the infection among both PWID and providers remains an important challenge as does discrimination faced by PWID in conventional health care settings.Many providers also remain hesitant to prescribe antiviral therapy due to concerns about adherence and relapse to drug use resulting in reinfection.Presently,however,as a result of improvements in treatment efficacy combined with professional society and government endorsement of HCV treatment for PWID,a pressing need exists to develop strategies to engage these individuals into HCV care.In this article,we propose several strategies that can be pursued in an attempt to engage PWID into HCV management.We advocate that multidisciplinary approaches that utilize health care practitioners from a wide range of specialties,as well as co-localization of medical services,are strategies likely to result in increased numbers of PWID entering into HCV management.Pursuit of HCV therapy after stabilization through drug treatment is an additional strategy likely to increase PWID engagement into HCV care.The full impact of direct acting antivirals for HCV will only be realized if innovative approaches are pursued to engage all HCV infected individuals into treatment.

Prevalence of hepatitis C virus infection and its related risk factors in drug abuser prisoners in Hamedan-Iran

AIM: Recent studies in Iran has shown that prevalence of hepatitis C virus (HCV) infection among Iranian prisoners is high, in spite of low HCV seroprevalence in general population.METHODS: This study was carried out in the central prison of Hamedan - Iran, in year 2002. Inmates were interviewed using a standard questionnaire including demographic,imprisonment history and HCV-related risk behaviors items. Thereafter, the sera drawn from the participants were tested for anti-HIV and anti-HCV antibodies.RESULTS: A total number of 427 drug abuser inmates participated in our study. Three hundred and ninety-seven (93%) were men and 30 (7%) were women. Total number of Ⅳ drug abusers (IDA) and non-Ⅳ drug abusers (NIDA)was 149 (34.9%) and 278 (65.1%), respectively. The overall rate of antibody positivity among inmates was 0.9% for HIV and 30% for HCV. Of all IDAs, 31.5% and of NIDAs, 29.1% had serological evidence of HCV infection.CONCLUSION: The seroprevalence of HCV infection among drug abuser prisoners in comparison with the general population in Iran, is very high (30% vs in italics 0.2%).Our results indicate the importance of policies to prevent transmission of HCV infection during and following incarceration.

Sequence diversity of hepatitis C virus: Implications for immune control and therapy

With approximately 3% of the world’s population (170 million people) infected with the hepatitis C virus (HCV), the WHO has declared HCV a global health problem. Upon acute infection about 50%-80% of subjects develop chronic hepatitis with viral persistence being at risk to develop liver cirrhosis and hepatocellular carcinoma. One characteristic of HCV is its enormous sequence diversity, which represents a significant hurdle to the development of both effective vaccines as well as to novel therapeutic interventions. Due to a polymerase that lacks a proofreading function HCV presents with a high rate of evolution, which enables rapid adaptation to a new environment including an activated immune system upon acute infection. Similarly, novel drugs designed to specifically inhibit viral proteins will face the potential problem of rapid selection of drug resistance mutations. This review focuses on the sequence diversity of HCV, the driving forces of evolution and the impact on immune control and treatment response. An important feature of any therapeutic or prophylactic intervention will be an efficient attack of a structurally or functionally important region in the viral protein. The understanding of the driving forces, but also the limits of viral evolution, will be fundamental for the design of novel therapies.

Optimizing hepatitis C virus treatment through pharmacist interventions: Identification and management of drug-drug interactions

AIM To quantify drug-drug-interactions(DDIs) encountered in patients prescribed hepatitis C virus(HCV) treatment, the interventions made, and the time spent in this process.METHODS As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral(DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir(LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir(OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV). This retrospective analysis reviewed the work completed by the clinical pharmacist in order to measure the aims identified for the study. The number and type of DDIs identified were summarized with descriptive statistics.RESULTS Six hundred and sixty four patients(83.4% Caucasian, 57% male, average 56.7 years old) were identified; 369 for LDV/SOF, 48 for OBV/PTV/r + DSV, 114 for SIM/SOF, and 133 for SOF/RBV. Fifty-one point five per cent of patients were cirrhotic. Overall, 5217 medications were reviewed (7.86 medications per patient) and 781 interactions identified (1.18 interactions per patient). The number of interactions were fewest for SOF/RBV (0.17 interactions per patient) and highest for OBV/PTV/r + DSV (2.48 interactions per patient). LDV/SOF and SIM/SOF had similar number of interactions (1.28 and 1.48 interactions per patient, respectively). Gastric acid modifiers and vitamin/herbal supplements commonly caused interactions with LDV/SOF. Hypertensive agents, analgesics, and psychiatric medications frequently caused interactions with OBV/PTV/r + DSV and SIM/SOF. To manage these interactions, the pharmacists most often recommended discontinuing the medication (28.9%), increasing monitoring for toxicities (24.1%), or separating administration times (18.2%). The pharmacist chart review for each patient usually took approximately 30 min, with additional time for more complex patients. CONCLUSION DDIs are common with HCV medications and management can require medication adjustments and increased monitoring. An interdisciplinary team including a clinical pharmacist can optimize patient care.

Real life efficacy and safety of direct-acting antiviral therapy for treatment of patients infected with hepatitis C virus genotypes 1, 2and 3 in northwest China

BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asia.AIM To investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODS This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December 2018.They were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more wk.The participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary endpoint.The occurrence of adverse events and drug-drug interactions were recorded.RESULTS In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)patients.Fifty(13.7%)patients were treatment-experienced.Intention-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype 3.Most of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HCV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the adverse events were mild.We found two cases of special adverse events.One case involved facial and bilateral lower extremity edema,and the other case showed an interesting change in lipid levels while on medication.No severe adverse events were noted.CONCLUSION The DAA-based regimens tested in this study have excellent effectiveness and safety in all patients infected with HCV genotypes 1,2 and 3,including those with cirrhosis.

Hepatitis C virus/human T lymphotropic virus 1/2 coinfection:Regional burden and virological outcomes in people who inject drugs

This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the on-going and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the Pub Med literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes.

Hepatitis C in injection drug users: It is time to treat

Injection drug users(IDUs)are at risk of hepatitis C virus(HCV)infection,due to needle and syringe sharing.Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cured with antiviral treatment leading to sustained viral response(SVR).It is well demonstrated that,when close cooperation between specialists in drug addiction and psychiatrists is assured,patients on maintenance treatment with methadone/buprenorphine can be treated for HCV with response rate,tolerability and side effects similar to those reported in non-IDUs.Current guidelines recommend that active injection drug use should not exclude patients from HCV treatment,but many services remain reluctant to treat IDUs.No significant pharmacodynamic interactions were reported between approved direct anti-viral agents(DAAs)and buprenorphine or methadone.Dose adjustments are not recommended;therefore DAAs appear to be the"perfect"therapy for patients taking opiate substitutive therapy.These suggestions have been recently recognized by the European Association for the Study of the Liver(EASL)and included in EASL Recommendations on Treatment of Hepatitis C 2016.Guidelines confirm that HCV treatment for IDUs should be considered on an individualized basis and delivered within a multidisciplinary team setting;a history of intravenous drug use and recent drug use at treatment initiation are not associated with reduced SVR and decisions to treat must be made on a case-by-case basis.

Hepatitis C Virus Experimental Model Systems and Antiviral drug Research

An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.

Impact of cigarette smoking on response to interferon therapy in chronic hepatitis C Egyptian patients

AIM: Smoking may affect adversely the response rate to interferon-α. Our objective was to verify this issue among chronic hepatitis C patients. METHODS: Over the year 1998, 138 chronic hepatitis C male Egyptian patients presenting to Cairo Liver Center, were divided on the basis of smoking habit into: group I which comprised 38 smoker patients (>30 cigarettes/d) and group II which included 84 non-smoker patients. Irregular and mild smokers (16 patients) were excluded. Non eligible patients for interferon-~ therapy were excluded from the study and comprised 3/38 (normal ALT) in group I and 22/84 in group II (normal ALT, advanced cirrhosis and thrombocytopenia). Group I was randomly allocated into 2 sub-groups: group Ia comprised 18 patients who were subjected to therapeutic phlebotomy while sub-group Ib consisted of 17 patients who had no phlebotomy. In sub-group Ia, 3 patients with normal ALT after repeated phlebotomies were excluded from the study. Interferon-α2b 3 MU/TIW was given for 6 mo to 15 patients in group Ia, 17 patients in group Ib and 62 patients in group II. Biochemical, virological end-of- treatment and sustained responses were evaluated.RESULTS: At the end of interferon-α treatment, ALT was normalized in 3/15 patients (20%) in group Ia and 2/17 patients (11.8%) in group Ib compared to17/62 patients (27.4%) in group II (P=0.1). Whereas 2/15 patients (13.3%) in group Ia. and 2/17 patients (11.8%) in group Ib lost viraemia compared to 13/62 patients (26%) in group II(P=0.3). Six months later, ALT was persistently normal in 2/15 patients (13.3%) in group la and 1/17 patients (5.9%) in group Ib compared to 9/62 patients (14.5%) in group Ⅱ (P= 0.47). Viraemia was eliminated in 1/15 patients (6.7%) in group Ia and 1/17 patients (5.9%) in group Ib compared to 7/62 patients (11.3%) in group Ⅱ, but the results did not mount to statistical significance (P = 0.4). CONCLUSION: Smokers suffering from chronic hepatitis C tend to have a lower response rate to interferon-α compared to non-smokers. Therapeutic phlebotomy improves the response rate to interferon-α therapy among this group.

Eligibility of persons who inject drugs for treatment of hepatitis C virus infection

In this decade, an increase is expected in end-stageliver disease and hepatocellular carcinoma, most commonly caused by hepatitis C virus(HCV) infection.Although people who inject drugs(PWID) are the ma-jor source for HCV infection, they were excluded fromantiviral treatments until recently. Nowadays there isincontrovertible evidence in favor of treating these patients, and substitution therapy and active substanceuse are no longer contraindications for antiviral treatment. The viral clearance in PWID after HCV antiviraltreatment with interferon or pegylated interferon combined with ribavirin is comparable to the viral clearancein non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are advised, and their treatment should be considered on anindividualized basis. To prevent the spread of HCV inthe PWID community, recent active PWID are eligiblefor treatment in combination with needle exchange programs and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treatment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID assessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strategies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detecting HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evidence concerning HCV infection and treatment strategies in PWID.

Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report

The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA) combination hepatitis C virus(HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin(PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment withPODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C:Data from the Polish EpiTer-2 cohort study

BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.

Viral hepatitis prevalence in patients with active and latent tuberculosis

AIM: To assess the prevalence of hepatitis B virus(HBV) and hepatitis C virus(HCV) infection and association with drug induced liver injury(DILI) in patients undergoing anti-tuberculosis(TB) therapy.METHODS: Four hundred and twenty nine patients with newly diagnosed TB- either active disease or latent infection- who were due to commence antiTB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus(HIV) infections- hepatitis B core antigen(HBc Ag), hepatitis B surface antigen(HBs Ag), hepatitis B e antigen, Ig G and Ig M antibody to HBc Ag(anti-HBc), HCV Ig G antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of antiTB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher's exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant.RESULTS: Of the 429 patients, 270(62.9%) had active TB disease and 159(37.1%) had latent TB infection. 61(14.2%) patients had isolated anti-HBc positivity, 11(2.6%) were also HBs Ag positive and 7(1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis(HBs Ag or HCV antibody positive; P = 0.023). Similarly the proportion of HBs Ag positive patients were significantly greater in the active vs latent TB infection group(10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three(5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25(9.5%) patients without; P = 0.04.CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV.

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.

Hepatitis C virus-associated B cell non-Hodgkin's lymphoma

The hepatitis C virus(HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin's lymphoma(BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin's lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Posttransplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they seem to be safe and highly effective. The use of chemotherapy in combination with rituximab for the treatment of BCNHL in patients infected with HCV can produce liver dysfunction. The addition of immunotherapy with rituximab can increase the viral replication, and severe complications can occure especially in patients co-infected with hepatitis B virus or immune immunodeficiency virus, in those with hepatocarcinoma,cirrhosis, or liver cytolysis. But the final result of standard immunochemotherapy applied to diffuse large BCNHL patients with HCV infection is not notably worse than in those without this viral infection. The treatment of patients chronically infected with HCV and having BCNHL is complex and requires a multidisciplinary approach and the risk / benefit ratio of rituximab treatment must be evaluated especially in those with liver cytolysis.