Study Of Chronic Hepatitis Research Articles

OS091 - ALT flares were linked to HBsAg reduction, seroclearance and seroconversion: interim results from a phase IIb study in chronic hepatitis B patients with 24-week treatment of subcutaneous PD-L1 Ab ASC22 (Envafolimab) plus nucleos (t)ide analogs

OS091 - ALT flares were linked to HBsAg reduction, seroclearance and seroconversion: interim results from a phase IIb study in chronic hepatitis B patients with 24-week treatment of subcutaneous PD-L1 Ab ASC22 (Envafolimab) plus nucleos (t)ide analogs

Changes in bone mineral density during monotherapy with tenofovir disoproxil fumarate: a 6-year real life longitudinal cohort study in chronic hepatitis B caucasian patients

Introduction: In chronic hepatitis B (CHB) patients, treatment with tenofovir disoproxil fumarate (TDF) may impair bone mineral density (BMD). Aim of the study was to evaluate the BMD changes in 138 CHB NUC-naïve patients (56 yrs, 29% females, 30% compensated cirrhosis, 83% with 25(OH)-vitamin D <30 ng/mL) treated with TDF monotherapy.

Safety, efficacy and cost of two direct-acting antiviral regimens: A comparative study in chronic hepatitis C Egyptian patients.

Direct-acting antivirals (DAAs) have become the most widely used treatment of chronic hepatitis C infection. Comparative studies on DAAs regimens approved by the Egyptian Ministry of Health for easy-to-treat genotype 4 (G4) Egyptian patients are still deficient. In this prospective study, we compared the efficacy and cost of two DAA regimens that are used in the treatment of Egyptian chronic hepatitis C virus (HCV) G4. The cost-saving regimen is determined. Eligible patients were randomized into 2 groups. Group 1 (Gp 1) received sofosbuvir plus daclatasvir, and group 2 (Gp 2) received ombitasvir, paritaprevir and ritonavir plus ribavirin (RBV) for 12weeks. Data were collected and evaluated at baseline and at weeks 4, 8 and 12. Sustained virologic response 12weeks after the end of treatment (SVR12 ) was evaluated. Cost-minimization analysis (CMA) was performed. Eligibility was achieved in 107 patients, Gp1 included 57 patients, and Gp 2 included 50 patients. Two patients dropped out from Gp 2 due to non-compliance. All patients in the two groups showed negative HCV blood levels at the end of treatment. At the 24th week, 3 relapsers (5.2%) were detected in Gp1 and 2 relapsers (4.1%) were detected in Gp 2. SVR12 was 54/57 (94.7%) and 46/48 (95.8%) for Gp 1 and Gp 2, respectively. After the 12th week of treatment, a significant decrease in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and haemoglobin levels were observed in both groups. Albumin levels declined in Gp 2 only. CMA showed higher cost in Gp 2 than Gp 1, although similar efficacy and safety. The two DAA regimens showed high SVR12 and safety in Egyptian HCV G4 patients. Sofosbuvir plus daclatasvir is the cost-saving regimen.

ROLE OF CXCR3 CHEMOKINE RECEPTOR AND ITS LIGANDS IN CERTAIN DISEASES

Chemokines are a special family of cytokines whose main function is to control cell migration; they are key players in the innate and adaptive immune responses. Directed chemotaxis of specific leukocyte subpopulations is necessary not only to maintain homeostasis, but also in development of some immunopathological conditions such as cancer, inflammation, infection, allergies and autoimmune disorders. Chemokines are pleiotropic molecules that are involved in physiological and pathophysiological processes. For example, the CXCR3 chemokine receptor is expressed on various cells: activated T and B lymphocytes, natural killers, eosinophils and neutrophils, dendritic cells, fibroblasts, endothelial and epithelial cells. Hence, CXCR3 and its ligands have a wide range of functional activity. CXCR3 ligands are the IFNγ-induced chemokines: CXCL9, CXCL10, CXCL11, and platelet-derived chemokines: CXCL4, CXCL4L1. All the CXCR3 ligands share common angiostatic properties due to lack of the Glu-Leu-Arg (ELR) motif. IFNγ-induced ligands of the CXCR3 are proinflammatory chemokines, they mainly recruit activated T cells and exert an effect on T cell polarization. Due to wide spectrum of biological activity, the ligands of CXCR3 receptor are involved in pathogenesis of various disorders, such as inflammation, infection, cancer, allergies and autoimmune disorders. In this review, we discuss the role of CXCR3 ligands in immunopathogenesis of various diseases, including the results of our studies in chronic hepatitis C, rheumatoid arthritis and pulmonary tuberculosis. Moreover, we have also discussed the potential laboratory diagnostic applicability of the chemokines in various diseases. This review illustrates a universal role of IFNγ-induced chemokines as mediators of immune responses in various diseases. The studies of CXCR3 ligands, their isoforms and receptors, interactions between themselves and with their receptors can provide a significant contribution to our understanding of the chemokine network. Understanding the system of IFNγ-dependent chemokines may have clinical implications, both for diagnostic tasks, and for therapeutic purposes.

Territory-wide population-based study of chronic hepatitis C infection and implications for hepatitis elimination in Hong Kong.

To study the epidemiology of chronic hepatitis C virus infection in Hong Kong and to estimate the service gap for achieving the WHO hepatitis elimination targets of attaining a diagnosis rate of 90%, treatment rate of 80% and 65% reduction in mortality rate by 2030. From January 2005 to March 2017, patients who were tested positive for anti-HCV were retrospectively retrieved from all public hospitals in Hong Kong. The epidemiological data of 15 participating hospitals were analysed. A total of 11309 anti-HCV+ patients were identified and the estimated diagnosis rate was 50.9%. Our HCV-infected patients were ageing (median age 59). The all-cause mortality rate increased from 26.2 to 54.8 per 1000 person-years over the last decade. Our estimated treatment rate was 12.4%. Among the treated patients, 93.6% had received pegylated interferon/ribavirin (Peg-IFN/RBV) but only 10.8% had received interferon-free direct-acting antivirals (DAAs). In a cohort of 1533 patients, 39% already had advanced liver fibrosis or cirrhosis. The sustained virological response rate for Peg-IFN/RBV and DAAs were 74.8% and 97.2% respectively. However, more than 70% of patients were not subjected to interferon treatment for various reasons. Patients who achieved SVR were associated with a significantly lower risk of HCC (4.7% vs 9.6%, P=0.005) and death (1.7% vs 23.8%, P<0.001). Our diagnosis rate, treatment rate and mortality rate reduction were still low, particularly the Peg-IFN outcomes, making it difficult to meet the WHO hepatitis elimination targets. A more generalized use of DAAs is urgently needed to improve the situation.

Genetic variation in IL28B (IFNL3) and response to interferon-alpha treatment in myeloproliferative neoplasms.

In myeloproliferative neoplasms (MPN), interferon-alpha (IFN-α) is an effective treatment with disease-modifying properties but currently with no clear predictors of treatment outcome. Recent genomewide association studies in chronic hepatitis C have found a strong influence of genetic polymorphism near the IL28B (IFNL3) gene in response to IFN-α treatment. In this study, we sought to evaluate the prognostic impact of IL28B rs12979860, rs8099917, and rs12980275 on IFN-α treatment response in myeloproliferative neoplasms. We retrospectively evaluated 100 patients with MPN treated with IFN-α. The hematologic treatment response on IFN-α was compared between patients and correlated with host genetic variations in IL28B. The genotypes of IL28B were determined by allelic discrimination assays. The CC genotype of rs12979860 was found significantly associated with hematologic response in polycythemia vera (PV) with a complete response (CR) in 79% (CC) compared to 48% (non-CC), (P=.036). No association between the genotypes and treatment response on hydroxyurea was found. These results imply an effect of IL28B genotype on the outcome of IFN-α treatment in MPN.

PRM26 - Synthesis of Binary Outcome Data on the Log-Odds and Absolute Risk Scales – A Case Study in Chronic Hepatitis C

PRM26 - Synthesis of Binary Outcome Data on the Log-Odds and Absolute Risk Scales – A Case Study in Chronic Hepatitis C

Non-invasive serum fibrosis markers: A study in chronic hepatitis.

Introduction: Chronic hepatitis is specified as inflammatory disease of the liver lasting for more than six months. Role of noninvasive fibrosis markers as prognostication factors of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis is the aim of this study. Methods: Two hundred twenty-one patients with chronic hepatitis involved in the study between 2011 and 2013. Routine biochemical indices and serum fibrosis markers such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were evaluated, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Diagnostic accuracies of these markers for prediction of significant fibrosis were assessed by Receiver Operating Characteristic (ROC) curve analysis. Results: Contemporaneous laboratory indices for imputing AAR, APRI, and FIB-4 were identified with liver biopsies. From all, 135 males (61.1%) and 86 females (38.9%), with mean age of 39.6±14.4 were studied. Significant correlation between stages of fibrosis and FIB-4, APRI and AAR were detected, with a correlation coefficient higher than that of other markers in the patients with Hepatitis B (r = 0.46), C (r = 0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) were superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy. Conclusion: Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis.

Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy

This study investigated the antiviral efficacy and safety of telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients. This was a randomized, open-label, multicentre study, in treatment-naïve patients with HBeAg-positive CHB, comparing the efficacy and safety of telbivudine in combination with PegIFN alpha-2a with telbivudine monotherapy and PegIFN alpha-2a monotherapy. The study was terminated early due to increased rates of peripheral neuropathy in the combination-therapy group. Of the 159 patients randomized (from 300 planned) 50 were assigned to combination therapy, 55 to telbivudine, 54 to PegIFN, and 110 (18, 49, and 43, respectively) reached week 24. Peripheral neuropathy occurred in 7/50, 1/54, and 0/54 patients in the three groups of safety populations, respectively. No relationship between the occurrence of peripheral neuropathy and other variables (e.g., pharmacokinetic data, treatment efficacy, ALT levels, creatine kinase elevations) were observed. At week 24, undetectable HBV DNA (<300 copies/ml) was achieved by 71% (12/17), 35% (17/48), and 7% (3/42) of patients, with available data receiving combination therapy, telbivudine monotherapy and PegIFN monotherapy, respectively (p = 0.022 for combination therapy vs. telbivudine; p<0.0001 for combination therapy vs. PegIFN). Combination therapy carried an increased risk of peripheral neuropathy. Despite the rapid and profound reductions in HBV DNA levels, combination therapy with telbivudine and PegIFN should not be used.

IFNL4 polymorphism predicts response to hepatitis C treatment after liver transplantation

BackgroundRecent studies in chronic hepatitis C patients have shown that rs368234815 polymorphism nearby IL28B is a better predictor of response to antiviral treatment with pegylated interferon and ribavirin than IL28B polymorphisms (rs12979860 and rs8099917). Its effect could be related to interferon lambda 4 (IFNL4), a protein which seems to confer some paradoxical disadvantages in hepatitis C virus (HCV) immune response. ObjectivesTo assess the role of IFNL4 rs368234815 polymorphism on the response to antiviral treatment after liver transplantation (LT). Study designIFNL4 and IL28B polymorphisms were genotyped in 86 HCV-infected LT recipients and in their donors; all patients had undergone antiviral treatment with pegylated interferon and ribavirin after LT. ResultsIFNL4 polymorphism strongly correlated with IL28B ones (p<0.001). The favorable IFNL4 genotype (TT/TT) was significantly more frequent among donors than recipients (60% donors vs. 22% recipients, p<0.001). Recipient TT/TT genotype was associated with a higher sustained virological response rate after LT (p=0.024). Nevertheless, the highest sustained virological response frequency was found when both donors and recipients had favorable genotypes (73% vs. 25%, p=0.002), suggesting a role for donor genotype. ConclusionsOur study demonstrates that IFNL4 rs368234815 polymorphism is an important predictor of response to antiviral treatment in the LT setting. These findings warrant further studies on IFNL4 role in immune response against HCV.

Use of modelling and simulation techniques to support decision making on the progression of PF‐04878691, a TLR7 agonist being developed for hepatitis C

To use non-linear mixed effects modelling and simulation techniques to predict whether PF-04878691, a toll-like receptor 7 (TLR7) agonist, would produce sufficient antiviral efficacy while maintaining an acceptable side effect profile in a 'proof of concept' (POC) study in chronic hepatitis C (HCV) patients. A population pharmacokinetic-pharmacodynamic (PKPD) model was developed using available 'proof of pharmacology' (POP) clinical data to describe PF-04878691 pharmacokinetics (PK) and its relationship to 2',5'-oligoadenylate synthetase (OAS; marker of pharmacology) and lymphocyte levels (marker of safety) following multiple doses in healthy subjects. A second model was developed to describe the relationship between change from baseline OAS expressed as fold change and HCV viral RNA concentrations using clinical data available in HCV patients for a separate compound, CPG-10101 (ACTILON™), a TLR9 agonist. Using these models the antiviral efficacy and safety profiles of PF-04878691 were predicted in HCV patients. The population PKPD models described well the clinical data as assessed by visual inspection of diagnostic plots, visual predictive checks and precision of the parameter estimates. Using these relationships, PF-04878691 exposure and HCV viral RNA concentration was simulated in HCV patients receiving twice weekly administration for 4 weeks over a range of doses. The simulations indicated that significant reductions in HCV viral RNA concentrations would be expected at doses > 6 mg. However at these doses grade ≥ 3 lymphopenia was also predicted. The model simulations indicate that PF-04878691 is unlikely to achieve POC criteria and support the discontinuation of this compound for the treatment of HCV.

Predictors of Histologic Severity in Chronic Hepatitis B-infected Patients

The role of liver biopsy in chronic Hepatitis B treatment guidelines remains incompletely defined. Our aim was to correlate histologic disease severity with demographic, biochemical and virologic parameters as currently used in Hepatitis B treatment guidelines. We conducted an Institutional Review Board (IRB) approved retrospective cross-sectional study of chronic Hepatitis B patients between January 2001 and July 2009. Patients with at least two Alanine Aminotransferase (ALT) values (6 months apart), with detectable Hepatitis B DNA quantitative levels at the time of initial evaluation, unchanged HBeAg status over a minimum of 6 months but no prior history of antiviral therapy, alcohol abuse, co-infection, hepatocellular carcinoma, iron overload or liver decompensation were reviewed. Advanced histological disease was defined as a METAVIR score of greater than or equal to stage and/or grade 3 (≥S/G 3). Multivariable binary logistic regression was used to determine the independent predictors of advanced histology. One hundred and twenty-eight patients met inclusion criteria. On multivariate logistic regression analysis, viral load was not an independent predictor. However, age ≥40, abnormal ALT and HBeAg(+) were independent predictors of ≥S/G3. Controlling for ALT and HBeAg status, patients ≥40 years old had 14.5 times the adjusted odds of ≥S/G3 (95% CI, 4.24–49.54) while 31% of HBeAg(-) /Low Viral load patients had ≥S/G3. Current HBV-treatment guidelines do not fully predict advanced histological disease. In the group where all the current guidelines recommend observation without treatment, one third had advanced histology on liver biopsy.

ENCODE Tiling Array Analysis Identifies Differentially Expressed Annotated and Novel 5′ Capped RNAs in Hepatitis C Infected Liver

Microarray studies of chronic hepatitis C infection have provided valuable information regarding the host response to viral infection. However, recent studies of the human transcriptome indicate pervasive transcription in previously unannotated regions of the genome and that many RNA transcripts have short or lack 3′ poly(A) ends. We hypothesized that using ENCODE tiling arrays (1% of the genome) in combination with affinity purifying Pol II RNAs by their unique 5′ m7GpppN cap would identify previously undescribed annotated and unannotated genes that are differentially expressed in liver during hepatitis C virus (HCV) infection. Both 5′-capped and poly(A)+ populations of RNA were analyzed using ENCODE tiling arrays. Sixty-four annotated genes were significantly increased in HCV cirrhotic as compared to control liver; twenty-seven (42%) of these genes were identified only by analyzing 5′ capped RNA. Thirty-one annotated genes were significantly decreased; sixteen (50%) of these were identified only by analyzing 5′ capped RNA. Bioinformatic analysis showed that capped RNA produced more consistent results, provided a more extensive expression profile of intronic regions and identified upregulated Pol II transcriptionally active regions in unannotated areas of the genome in HCV cirrhotic liver. Two of these regions were verified by PCR and RACE analysis. qPCR analysis of liver biopsy specimens demonstrated that these unannotated transcripts, as well as IRF1, TRIM22 and MET, were also upregulated in hepatitis C with mild inflammation and no fibrosis. The analysis of 5′ capped RNA in combination with ENCODE tiling arrays provides additional gene expression information and identifies novel upregulated Pol II transcripts not previously described in HCV infected liver. This approach, particularly when combined with new RNA sequencing technologies, should also be useful in further defining Pol II transcripts differentially regulated in specific disease states and in studying RNAs regulated by changes in pre-mRNA splicing or 3′ polyadenylation status.

Thymalfasin in the treatment of hepatitis B and C

Thymalfasin exhibited an immunomodulatory and a direct antiviral mechanism of action. The low rate of sustained response of chronic hepatitis with current therapies, underscores the need for new therapeutic options. It has been suggested that thymalfasin may have efficacy in the treatment of chronic hepatitis B and C. Pilots studies in patients with chronic hepatitis B treated with thymalfasin in combination with interferon or nucleoside analogue, showed a 70% complete sustained response rate. Studies in chronic hepatitis C patients, would indicate that thymalfasin in combination with standard or pegylated interferon with ribavirin may improve response rate in hepatitis C virus (HCV) naïve and nonresponder patients. However, a large phase-III randomized study conducted in Europe in HCV patients nonresponder to Peg-interferon with ribavirin, demonstrated that thymalfasin did not improve the rate of sustained virologic responses, but, in patients who completed therapy, thymalfasin significantly diminished the relapse rate. In conclusion, thymalfasin, in combination with the standard of care, may be helpful as an adjuvant in the treatment of patients with chronic hepatitis B and C.

715 ASSESSMENT OF THE VIROLOGICAL PROFILES OF UNTREATED PATIENTS WITH CHRONIC HEPATITIS DELTA (CHD) REQUIRES LONGITUDINAL MEASUREMENTS OF HBV DNA AND HDV RNA

714 COLLABORATIVE UK STUDY OF CHRONIC HEPATITIS B VIRUS INFECTION L. Fries, A. Rodger, G. Dusheiko, S. Ijaz, R. Tedder, J. Banatvala, R. Williams, N. Naoumov, S. Puranik, S. Chokshi, T. Wong, W. Rosenberg, S. Moreea, A. Bathgate, M. Jacobs, P. Mills, D. Mutimer, M. Bassendine, S. Ryder, M. Thursz, A. Johnson. Research Department of Infection and Population Health, University College London, Royal Free Hospital, The Health Protection Agency, Guy’s and St. Thomas’ Hospital, Institute of Hepatology, UCL, University College Hospital, London, Bradford Royal Infirmary, Bradford, Royal Infirmary of Edinburgh, Edinburgh, Gartnavel General Hospital, Glasgow, Queen Elizabeth Hospital, Birmingham, Freeman Hospital, Newcastle upon Tyne, Nottingham University Hospital, Nottingham, St. Mary’s Hospital, London, UK E-mail: l.fries@ucl.ac.uk

Early HBeAg Loss During Peginterferon α-2b Therapy Predicts HBsAg Loss: Results of a Long-Term Follow-Up Study in Chronic Hepatitis B Patients

Treatment with pegylated interferon (PEG-IFN) alpha-2b results in hepatitis B e antigen (HBeAg) loss in 36% of patients at 6 months post treatment. The aim of this study was to determine whether a long-term response to PEG-IFN is dependent on the timing of HBeAg loss. A total of 91 patients treated with PEG-IFN alpha-2b alone (100 microg per week) and 81 patients treated with PEG-IFN alpha-2b and lamivudine (100 mg/day) for 52 weeks were enrolled in this study. Patients were initially followed up at 4-week intervals and had one additional long-term follow-up (LTFU) visit (mean: 3.03+/-0.77 years 26 weeks post treatment). Of the 172 patients included, 78 patients (46%) did not have loss of HBeAg, 47 (27%) lost HBeAg within 32 weeks, and 47 patients (27%) had loss of HBeAg after week 32. At LTFU, patients with HBeAg loss< or =32 weeks had hepatitis B virus DNA of <400 copies/ml significantly more often than did those who lost HBeAg after week 32 (47 vs. 21%, respectively; P=0.009). Hepatitis B surface antigen (HBsAg) negativity was also observed significantly more often in patients with early HBeAg loss (36 vs. 4%, respectively, P<0.001). Early HBeAg loss tended to occur more often in patients treated with PEG-IFN and lamivudine combination therapy than in those treated with PEG-IFN alone (35 vs. 21%; P=0.10), as did HBsAg loss (15 vs. 8%; P=0.14). Early PEG-IFN-induced HBeAg loss results in a high likelihood of HBsAg loss and may be associated with more profound viral suppression during the first 32 weeks of therapy in patients treated with lamivudine combinations.

Steatosis correlates with hepatic expression of death receptors and activation of nuclear factor‐κB in chronic hepatitis C

Steatosis is recognized as a predictor of the severity as well as the progression of fibrosis in chronic hepatitis C. The mechanisms that cause increased hepatocellular injury associated with steatosis remain largely unknown. We studied the correlation of hepatic expression of death receptors: Fas and tumour necrosis factor-alpha receptor 1 (TNF-R1), and downstream caspase (caspase-3) with hepatic steatosis by immunohistochemical study in chronic hepatitis C and determined the role of nuclear factor-kappaB (NF-kappaB). Ninety patients (49 males and 41 females, mean age of 50.5 +/- 10.4 years, genotype 1 or 2) with chronic hepatitis C virus infection were recruited. The factors associated with steatosis grade were body mass index (P=0.004) and fibrosis stage (P=0.034). Moderate/severe steatosis was an independent variable associated with advanced fibrosis stage by stepwise logistic regression analysis. The expression of immunoreactivity for Fas, TNF-R1 and active caspases-3 in liver tissues was significantly correlated with the steatosis grade (P<0.001, P<0.001 and P<0.001 respectively). The extent of active caspases-3 correlated significantly with the expression of Fas (r=0.659, P<0.001) and TNF-R1 (r=0.617, P<0.001). NF-kappaB p65 expression correlated significantly with the extent of Fas (r=0.405, P<0.001), TNF-R1 (r=0.448, P=0.002) and active caspase-3 (r=0.313, P=0.003), and correlated with steatosis grade (P<0.001) but not with inflammatory and fibrosis scores. Our observations suggest a mechanism whereby steatosis contributes to the progression of liver injury in chronic hepatitis C through upregulation of death receptors and activation of NF-kappaB.

P.289 Morphologic study of chronic hepatitis C in oriental Amazon region (Brazil) focusing on stellate hepatic cells and extracellular matrix using confocal microscopy

P.289 Morphologic study of chronic hepatitis C in oriental Amazon region (Brazil) focusing on stellate hepatic cells and extracellular matrix using confocal microscopy

Quality of life and cost-effectiveness of anti-HCV therapy in HIV-infected patients

Quality of life studies in chronic hepatitis C using specific questionnaires have been performed in mono-infected patients; however, these studies have just begun in HIV-HCV co-infected patients. The questionnaires used in mono-infected patients are not well adapted for co-infected patients and need to be redesigned. Typically, co-infected patients have multiple symptoms that may be attributable to HIV, to HCV, to a combination of both diseases or even to side effects related to drug therapy. These patients usually need substitutive therapy to manage side effects related to HCV therapy, particularly anaemia, leukopenia and depression. There are no cost-effectiveness studies published on the current HCV standard therapy with pegylated interferon and ribavirin. However, there is some research on the old standard interferon and ribavirin, which shows that HCV therapy is cost-effective. Cost-effectiveness studies in co-infected patients will have to take into account variables that do not affect mono-infected patients, such as the different levels of CD4, the increase in the fibrosis progression rate and the use of other expensive drugs for the management of side effects. Currently, the literature does not provide adequate information on the effect of HCV infection on the quality of life of HIV-HCV co-infected patients or the most cost-effective HCV therapy.

Epidemiologic study of chronic hepatitis B virus infection in male volunteer blood donors in Karachi, Pakistan

BackgroundThe magnitude of chronic infection with hepatitis B virus (HBV) varies substantially between the countries. A better understanding of incidence and/ or prevalence of HBV infection and associated risk factors provides insight into the transmission of this infection in the community. The purpose of this investigation was to estimate the prevalence of and to identify the risk factors associated with chronic infection with HBV, as assessed by HBV surface antigen (HBsAg) positivity, in asymptomatic volunteer male blood donors in Karachi, Pakistan.MethodsConsecutive blood donations made at the two large blood banks between January 1, 1998 and December 31, 2002 were assessed to estimate the prevalence of HBsAg positivity. To evaluate the potential risk factors, a case-control study design was implemented; cases (HBsAg positives) and controls (HBsAg negatives), were recruited between October 15, 2001 and March 15, 2002. A pre-tested structured questionnaire was administered through trained interviewers to collect the data on hypothesized risk factors for HBV infection. Sera were tested for HBsAg using commercially available kits for enzyme linked Immunosorbant assay-III.ResultsHBsAg prevalence in the male volunteer blood donors was 2.0 % (7048/351309). Multivariate logistic regression analysis showed that after adjusting for age and ethnicity, cases were significantly more likely than controls to have received dental treatment from un-qualified dental care provider (adjusted odds ratio (OR) = 9.8; 95% confidence interval (CI): 2.1, 46.1), have received 1–5 injections (adjusted OR = 3.3; 95% CI: 1.1, 9.6), more than 5 injections (adjusted OR = 1.4; 95% CI: 1.4, 12.7) during the last five years or have received injection through a glass syringe (adjusted OR = 9.4; 95% CI: 2.6, 34.3). Injury resulted in bleeding during shaving from barbers (adjusted OR = 2.3; 95% CI: 1.1, 4.8) was also significant predictor of HBsAg positivity.ConclusionPrevalence of HBsAg positivity in the male volunteer blood donors in Karachi was 2%. Infection control measures in health-care settings including safe injection practices and proper sterilization techniques of medical instruments and education of barbers about the significance of sterilization of their instruments may reduce the burden of HBV infection in this and similar settings. There is also an urgent need of developing locally relevant guidelines for counseling and management of HBsAg positive blood donors.