Search

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero‐surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)‐positive) prevalence and HCV exposure (HCV antibody (HCV‐Ab)‐positive) prevalence between two sero‐surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population‐attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2–2.9) in 2007 to 1.1% (95% CI: 0.8–1.3) in 2019, while HCV‐Ab prevalence increased from 5.1% (95% CI: 4.6%–5.5%) to 6.2% (95% CI: 5.6%–6.8%). The age and gender‐adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1–0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3–0.6) among adults over 2007–2019, while HCV‐Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2–0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2–1.7) in adults. HCV‐Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5–0.8) and higher (aOR = 0.5, 95%CI:0.3–0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2–2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9–3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6–2.7), being tattooed (aOR = 1.4, 95% CI: 1.0–1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0–1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7–48.4%). Overall HCV has increased over 2007–2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities. [ABSTRACT FROM AUTHOR]

UnlabelledSubstantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon-free direct-acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three-quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (

Background: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. Methods: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. Conclusion: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. Study registration: This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021. [ABSTRACT FROM AUTHOR]

To evaluate the safety and tolerability of the fixed‐dose, single‐tablet regimen sofosbuvir/velpatasvir (SOF/VEL) for the treatment of hepatitis C virus (HCV) infection in three Phase 3 studies in patients with and without compensated cirrhosis. Data from three registrational trials (ASTRAL‐1, NCT02201940; ASTRAL‐2, NCT02220998; ASTRAL‐3, NCT02201953) were pooled by treatment regimen. Researchers assessed treatment‐emergent adverse events (TEAEs) and laboratory abnormalities in patients randomized to SOF/VEL or placebo for 12 weeks in ASTRAL‐1 and SOF/VEL for 12 weeks in ASTRAL‐2 and ASTRAL‐3. Overall, 1035 patients were treated with SOF/VEL, and 116 patients received placebo. Rates of any TEAE were generally similar between patients receiving SOF/VEL (79.4%) and those receiving placebo (76.7%). The majority of TEAEs were mild to moderate, with 23 (2.2%) treatment‐emergent serious AEs in patients treated with SOF/VEL. Of these treatment‐emergent serious AEs, none led to premature study discontinuation, nor were they considered related to treatment. Presence of compensated cirrhosis, greater age and mild renal impairment did not impact incidence or severity of TEAEs with SOF/VEL treatment. The most common TEAEs (incidence ≥10%) were headache, fatigue, nausea and nasopharyngitis in patients receiving SOF/VEL; similar rates were observed in placebo‐treated patients. Three deaths (<1%) were reported in patients treated with SOF/VEL, all posttreatment and none assessed as related to study treatment. Similar to that of placebo, SOF/VEL treatment of HCV infection had a safety/tolerability profile that was not affected by baseline factors, such as the presence of compensated cirrhosis, mild renal impairment or advanced age. [ABSTRACT FROM AUTHOR]

Background: People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes.Methods: We employed population-wide electronic health records (EHRs; from 1998 to 2020) consisting of almost 4 million adults to assess regional variations in disease burden of five liver conditions, alcoholic liver disease (ALD), autoimmune liver disease, chronic hepatitis B infection (HBV), chronic hepatitis C infection (HCV) and NAFLD, in England. We analysed regional differences in incidence rates for 17 manifestations of CVD in people with or without liver disease. The associations between biomarkers and comorbidities and risk of CVD in patients with liver disease were estimated using Cox models. For each liver condition, we estimated excess years of life lost (YLL) attributable to CVD (i.e., difference in YLL between people with or without CVD).Results: The age-standardised incidence rate for any liver disease was 114.5 per 100,000 person years. The highest incidence was observed in NAFLD (85.5), followed by ALD (24.7), HCV (6.0), HBV (4.1) and autoimmune liver disease (3.7). Regionally, the North West and North East regions consistently exhibited high incidence burden. Age-specific incidence rate analyses revealed that the peak incidence for liver disease of non-viral aetiology is reached in individuals aged 50-59 years. Patients with liver disease had a two-fold higher incidence burden of CVD (2634.6 per 100,000 persons) compared to individuals without liver disease (1339.7 per 100,000 persons). When comparing across liver diseases, atrial fibrillation was the most common initial CVD presentation while hypertrophic cardiomyopathy was the least common. We noted strong positive associations between body mass index and current smoking and risk of CVD. Patients who also had diabetes, hypertension, proteinuric kidney disease, chronic kidney disease, diverticular disease and gastro-oesophageal reflex disorders had a higher risk of CVD, as do patients with low albumin, raised C-reactive protein and raised International Normalized Ratio levels. All types of CVD were associated with shorter life expectancies. When evaluating excess YLLs by age of CVD onset and by liver disease type, differences in YLLs, when comparing across CVD types, were more pronounced at younger ages.Conclusions: We developed a public online app ( https://lailab.shinyapps.io/cvd_in_liver_disease/ ) to showcase results interactively. We provide a blueprint that revealed previously underappreciated clinical factors related to the risk of CVD, which differed in the magnitude of effects across liver diseases. We found significant geographical variations in the burden of liver disease and CVD, highlighting the need to devise local solutions. Targeted policies and regional initiatives addressing underserved communities might help improve equity of access to CVD screening and treatment. [ABSTRACT FROM AUTHOR]

Many people with chronic hepatitis C infection don't engage in treatment. To eliminate hepatitis C and avoid health inequalities therapy must be provided to everyone. In other diseases peers with lived experience of the condition have improved care but, for hepatitis C, studies have not shown unequivocal benefit. We completed a retrospective analysis of the English National Health Service treatment registry comparing treatment networks with and without peers using Bayesian Poisson (for count outcomes) or Bayesian Binomial (for proportion outcomes) mixed effects models with time fixed effects. For each outcome, we estimated relative ratio (RR‐Poisson model) or odds ratio (Odds Ratio (OR)‐Binomial model) between peer and non‐peer networks. We analysed 30,729 patients within 20 operational delivery networks. In networks with peers there was an increase in the number of people initiating therapy (RR 1.12 95%, credible interval 1.02–1.21) and an increase in the proportion completing therapy (OR 2.45 95%, credible interval 1.49–3.84). However, we saw no change in proportions of people using drugs who initiated therapy nor any significant change in virological response (OR 1.14 95% credible interval 0.979–1.36). We repeated the analysis looking at the impact of peers two months after they had been introduced, when they had established networks of contacts, and saw an increase in the proportion of people treated in addiction services. In treating patients with chronic hepatitis C infection the inclusion of peer supporters may increase the number of people who initiate and complete antiviral therapy. [ABSTRACT FROM AUTHOR]

Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease, worldwide. With the development of direct-acting antivirals, treatment of chronically infected patients has become highly effective, although a subset of patients responds less well to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies, that targets the HCV NS5B polymerase. We use pre-treatment whole-genome sequences of HCV from 507 patients infected with HCV subtype 3a and treated with sofosbuvir containing regimens to detect viral polymorphisms associated with response to treatment. We find three common polymorphisms in non-targeted HCV NS2 and NS3 proteins are associated with reduced treatment response. These polymorphisms are enriched in post-treatment HCV sequences of patients unresponsive to treatment. They are also associated with lower reductions in viral load in the first week of therapy. Using in vitro short-term dose-response assays, these polymorphisms do not cause any reduction in sofosbuvir potency, suggesting an indirect mechanism of action in decreasing sofosbuvir efficacy. The identification of polymorphisms in NS2 and NS3 proteins associated with poor treatment outcomes emphasises the value of systematic genome-wide analyses of viruses in uncovering clinically relevant polymorphisms that impact treatment. Sofosbuvir is a common therapy in hepatitis C virus infection, which targets the NS5B polymerase. Here, Smith et al. analyze the association between whole genome HCV polymorphisms and sofosbuvir treatment failure and identify three common polymorphisms present in non-targeted NS2 and NS3 proteins associated with reduced treatment response. [ABSTRACT FROM AUTHOR]

Summary: Background: In England, choice of hepatitis C therapy is determined by national contracts that change with time, facilitating comparisons between different regimens. England has a diverse population with hepatitis C including large proportions of uncommon viral genotypes. Aim: To evaluate efficacy of directly acting anti‐viral treatments for hepatitis C in England using real‐world data from the national treatment registry. Methods: Sustained virological response (SVR) rates 12 weeks after treatment completion for patients treated between 2014 and August 2018 who attended for SVR tests were analysed in univariate subgroups using Chi‐squared tests. Multivariate models were constructed with clinically relevant variables to determine predictors of SVR and evaluate the impact of treatment regimens. Results: SVR data were available on 14,603 treated patients. The overall SVR rate was 95.59% [95% CI 95.25%‐95.91%]. Multivariable regression modelling in patients with genotype 1 infection showed that the odds of SVR with elbasvir/grazoprevir were higher than for those treated with sofosbuvir/ledipasvir (OR 1.891, 95% CI 1.072‐3.336, P = 0.028). For genotype 3, we found no significant difference between any of the treatment regimens. Patients who completed at least one third of the planned treatment duration achieved SVR rates in excess of 80%. Conclusions: All of the currently licensed hepatitis C direct‐acting anti‐viral regimens had similar efficacy (>95%) in an unselected population. Noncompletion of planned treatment duration still resulted in over 80% SVR rates provided that more than one third of treatment was completed. [ABSTRACT FROM AUTHOR]

Ruzasvir (MK‐8408, an NS5A inhibitor) and uprifosbuvir (MK‐3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct‐acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two‐drug combination of ruzasvir 60 mg plus  uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C‐BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C‐BREEZE 2: NCT02956629/Merck protocol PN041). Treatment‐naïve or interferon (with or without ribavirin)‐experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12), and safety and tolerability of the study drug. Overall, 282 participants were enrolled. SVR12 (n/N) was 91.3% (42/46) in participants infected with HCV genotype (GT) 1a; GT1b, 96.7% (29/30); GT2, 91.5% (43/47); GT3, 73.8% (45/61); GT4, 98.2% (55/56); GT5, 100.0% (18/18); and GT6, 90.9% (20/22). Adverse events (AEs) were reported by 61.3% of participants; drug‐related AEs were reported by 33.3%. The most frequent (≥5% of participants) drug‐related AEs in all participants were fatigue (7.8%) and headache (7.4%). In conclusion, the two‐drug combination of ruzasvir 180 mg plus uprifosbuvir 450 mg for 12 weeks was highly effective and well tolerated in participants infected with HCV GT1, GT2, GT4, GT5 and GT6, with a lower efficacy in GT3‐infected persons. [ABSTRACT FROM AUTHOR]

Summary: Background: Direct‐acting anti‐viral therapy (DAA) has transformed hepatitis C virus (HCV) care, particularly in patients with decompensated cirrhosis. However, their impact on hepatocellular carcinoma (HCC) remains unclear. Aim: To use a national registry of patients with advanced liver disease to explore the relationship between DAA therapy and HCC. Methods: All patients with de novo HCC post DAA therapy were frequency matched with patients who did not develop HCC. Demographic, clinical and laboratory data were obtained. Cross‐sectional imaging and multidisciplinary team reports were reviewed for dates of HCC diagnosis and HCC progression. Patients were categorised by treatment outcome and time of HCC development. Data were examined by multivariable analysis and Kaplan‐Meier estimation. Results: Eighty patients with HCC were compared with 165 patients without HCC, treated between June 2014 and September 2015. Mean follow‐up from start of DAA therapy was 32.4 months. Twenty‐eight patients were diagnosed with early HCC (within 6 months of therapy) and 52 presented late. Baseline nonmalignant lesions (HR: 1.99), thrombocytopaenia (HR: 1.59) and diabetes (HR: 1.68) increased likelihood of HCC. Response to therapy was reduced in patients who developed liver cancer (SVR in patients with HCC = 54/80 (68%), SVR in patients without HCC = 143/165 (87%), P < 0.001, OR: 3.13, 95% CI: 1.64‐5.99). We found no difference between tumour size, progression or survival between viraemic and nonviraemic patients. Conclusion: There is no alteration in prognosis or cancer progression following HCC development after HCV treatment. However, baseline nonmalignant liver lesions, diabetes and thrombocytopaenia increase the risk of HCC, and HCC is associated with a decreased SVR rate. Linked Content This article is linked to Hollande and Pol paper. To view this article, visit https://doi.org/10.1111/apt.15328. [ABSTRACT FROM AUTHOR]

Background and Aims: Previous studies have shown low rates of diagnosis and treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID). Our aims were to test the effect of a complex intervention [Hepatitis C Awareness Through to Treatment (HepCATT)] in drug and alcohol clinics—primarily, on engagement of HCV‐positive PWID with therapy and, secondarily, on testing for HCV, referral to hepatology services and start of HCV treatment. Design and setting: A non‐randomized pilot study in three specialist addiction clinics in England comparing an intervention year (starting between September 2015 and February 2016) with a baseline year (2014), together with three control clinics. Participants: Analysis included all attendees at the intervention and control specialist addiction clinics identified as PWID. Intervention: The intervention comprised the placement of a half‐time facilitator in each clinic for 12 months with the brief to increase diagnosis of HCV infection within clients at those services and the engagement of diagnosed individuals with an appropriate care pathway. The facilitator undertook various activities, which could include training of key workers, direct interaction with clients, streamlining and support for hepatology appointments and introduction of dried blood‐spot testing. Measurements For each clinic and period, we obtained the total number of clients and, as relevant, their status as PWID, tested for HCV, known HCV‐positive, engaged with HCV therapy or treated. Findings Compared with baseline, there was strong evidence that engagement with HCV therapy in the intervention year increased (P < 0.001) more in the HepCATT centres than controls, up +31 percentage points [95% confidence interval (CI) = 19–43] versus −12 (CI = –31 to +6) and odds ratio (OR) = 9.99 (CI = 4.42–22.6) versus 0.35 (CI = 0.08–1.56). HepCATT centres also had greater increases in HCV testing (OR = 3.06 versus 0.78, P < 0.001), referral to hepatology (OR = 9.60 versus 0.56, P < 0.001) and treatment initiation (OR = 9.5 versus 0.74, P < 0.001). Conclusions: Introducing a half‐time facilitator into drug and alcohol clinics in England increased engagement of HCV‐positive people who inject drugs with hepatitis C virus care pathways, with increased uptake also of testing, referral to hepatology and initiation of treatment. [ABSTRACT FROM AUTHOR]

Background: Injection drug use is the primary mode of transmission for hepatitis C virus (HCV), and treatment guidelines recommend treating HCV-infected people who use drugs; however, concerns about adherence, effectiveness, and reinfection have impeded treatment uptake.Methods: Data were pooled from seven phase III trials that evaluated the efficacy and safety of 8 or 12 weeks of glecaprevir/pibrentasvir (G/P) in patients chronically infected with HCV genotypes 1-6. Patients had compensated liver disease, with or without cirrhosis, and were HCV treatment-naïve or -experienced with interferon or pegylated interferon ± ribavirin, or sofosbuvir plus ribavirin ± pegylated interferon. Patients were grouped into recent drug users (injection drug use ≤12 months before screening, positive urine drug screen [UDS], and/or drug-related adverse event), former drug users (>12 months before screening and negative UDS), or non-drug users. Assessments included sustained virologic response at 12 weeks posttreatment (SVR12), treatment adherence, and safety.Results: Among 1819 patients, 5%, 34%, and 61% were recent, former, and non-drug users, respectively. Treatment adherence and completion were high (≥96%) regardless of drug use status. SVR12 was achieved by 93% (n/N = 91/98), 97% (n/N = 591/610), and >99% (n/N = 1106/1111) of recent, former, and non-drug users, respectively (intention-to-treat analysis). The overall rates of virologic failure were ≤1.5% across all three subpopulations, with no HCV reinfections among recent drug users. Drug-related serious adverse events and adverse events leading to treatment discontinuation were experienced by ≤1% of patients.Conclusions: G/P is a well-tolerated and efficacious pangenotypic regimen for chronic HCV-infected people with recent or active drug use. [ABSTRACT FROM AUTHOR]

Background & Aims Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93–100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1–6 infection was performed. Methods Data were pooled from nine phase II and III trials including patients with chronic HCV GT 1–6 infection without cirrhosis who received G/P (300 mg/120 mg) for either 8 or 12 weeks. Patients were treatment naïve or treatment experienced with peginterferon, ribavirin, and/or sofosbuvir; all patients infected with HCV GT 3 were treatment naïve. Efficacy was evaluated as the SVR12 rate. Results The analysis included 2,041 patients without cirrhosis. In the intent-to-treat population, 943/965 patients (98%) achieved SVR12 when treated for eight weeks, and 1,060/1,076 patients (99%) achieved SVR12 when treated for 12 weeks; the difference in rates was not significant ( p  = 0.2). A subgroup analysis demonstrated SVR12 rates > 95% across baseline factors traditionally associated with lower efficacy. G/P was well tolerated, with one DAA-related serious adverse event (<0.1%); grade 3 laboratory abnormalities were rare. Conclusions G/P therapy for eight weeks in patients with chronic HCV GT 1–6 infection without cirrhosis achieved an overall SVR12 rate of 98% irrespective of baseline patient or viral characteristics; four additional weeks of treatment did not significantly increase the SVR12 rate, demonstrating that the optimal treatment duration in this population is eight weeks. Lay summary In this integrated analysis of nine clinical trials, patients with chronic HCV genotype 1–6 infection without cirrhosis were treated for either 8 or 12 weeks with the direct-acting antiviral regimen glecaprevir/pibrentasvir (G/P). The cure rate was 98% and 99% following 8 and 12 weeks of treatment, respectively; the difference in rates was not significant ( p  = 0.2), nor was there a significant difference in the cure rates across the two treatment durations on the basis of baseline patient or viral characteristics. These results, along with a favourable safety profile, indicate that G/P is a highly efficacious and well-tolerated pangenotypic eight-week therapy for most patients with chronic HCV infection. [ABSTRACT FROM AUTHOR]

Background: The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection.Methods: ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment).Results: Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed >1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9-193.8).Conclusions: This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy. ACTIVATE trial registration number: NCT01364090 - May 31, 2011. [ABSTRACT FROM AUTHOR]

Background. Until recently, the approved treatment regimens for patients with hepatitis C virus (HCV) genotypes (GTs) 2 and 3 contain sofosbuvir (SOF) and ribavirin (RBV) for 12 or 24 weeks. The impact of RBV-free pan-genotypic regimen with SOF and velpatasvir (SOF/VEL) on patient-reported outcomes (PROs) of patients with genotype 2 and 3 has not been described. Methods. PROs data were collected from participants of ASTRAL-2 and ASTRAL-3 studies before, during, and after treatment using 4 PRO instruments (Short Form-36, Chronic Liver Disease Questionnaire-HCV, Functional Assessment of Chronic Illness Therapy-Fatigue, and Work Productivity and Activity Index: Specific Health Problem), and compared between the SOF/VEL and SOF + RBV groups. Results. A total of 818 HCV patients were included: 78% treatment naive, 25% cirrhosis. The rates of nearly all adverse events were lower in the RBV-free SOF/VEL group (all P < .03). The SOF/VEL group also experienced improvement of their PROs by treatment week 4 (+1.8% on average across all PROs), which continued throughout treatment (+4.1%) and post-treatment (+5.5%). In contrast, those in the SOF + RBV group had a modest decline in their PROs starting at treatment week 4 (up to -3.7%), which lasted until the end of treatment (up to -6.4%). In multiple regression analysis, the association of a treatment regimen with end-of-treatment PROs was significant for nearly all PROs; the average beta was +5.0% for the use of SOF/VEL (reference: SOF + RBV). Conclusions. Patients receiving ribavirin-free SOF/VEL reported significantly better PRO scores during treatment compared with those receiving the RBV-containing regimen. Furthermore, the interferon- and ribavirin-free SOF/VEL regimen resulted in a rapid improvement of PROs in HCV GTs 2 and 3 patients during treatment and after achieving sustained virologic response. [ABSTRACT FROM AUTHOR]

Introduction & aim. Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-naïve patients with chronic HCV genotype-1 infection. Material and methods. Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24-48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12). Results. SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17-31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16-30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious AEs were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively. Conclusion. Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270. [ABSTRACT FROM AUTHOR]

Background: Effective strategies are needed to provide screening and treatment for hepatitis B and C to immigrant groups in the UK at high risk of chronic infection. This study aimed to build an understanding of the knowledge, beliefs and attitudes towards these conditions and their management in a range of high-risk minority ethnic communities and health professionals, in order to inform the design of a screening and treatment programme in primary care. Methods: Qualitative data collection consisted of three sequential phases- (i) semi-structured interviews with key informants (n = 17), (ii) focus groups with people from Chinese, Pakistani, Roma, Somali, and French- and Englishspeaking African communities (n = 95), and (iii) semi-structured interviews with general practitioners (n = 6). Datasets from each phase were analysed using the Framework method. Results: Key informants and general practitioners perceived that there was limited knowledge and understanding about hepatitis B and C within high-risk immigrant communities, and that chronic viral hepatitis did not typically feature in community discourses about serious illness. Many focus group participants were confused about the differences between types of viral hepatitis, held misconceptions regarding transmission, and were unaware of the asymptomatic nature of chronic infection. Most welcomed the idea of a screening programme, but key informants and focus group participants also identified numerous practical barriers to engagement with primary care-based screening and treatment; including language and communication difficulties, limited time (due to long working hours), and (for some) low levels of trust and confidence in general practice-based care. General practitioners expressed concerns about the workload implications and sustainability of screening and treating immigrant patients for chronic viral hepatitis in primary care. Conclusions: Strategies to reduce the burden of chronic viral hepatitis in immigrant communities will need to consider how levels of understanding about hepatitis B and C within these communities, and barriers to accessing healthcare, may affect capacity to engage with screening and treatment. Services may need to work with community groups and language support services to provide information and wider encouragement for screening. Primary care services will need ongoing consultation regarding their support needs to deliver hepatitis screening and treatment programmes. [ABSTRACT FROM AUTHOR]

Viral hepatitis is responsible for great health, social and economic burden both globally and in the UK. This study aimed to assess the research funding awarded to UK institutions for viral hepatitis research and the relationship of funded research to clinical and public health burden of viral hepatitis. Databases and websites were systematically searched for information on infectious disease research studies funded for the period 1997-2010. Studies specifically related to viral hepatitis research were identified and categorized in terms of funding by pathogen, disease and by a research and development value chain describing the type of science. The overall data set included 6165 studies (total investment £2.6 billion) of which £76.9 million (3.0%) was directed towards viral hepatitis across 323 studies (5.2%). By pathogen, there were four studies specifically investigating hepatitis A (£3.8 million), 69 studies for hepatitis B (21.4%) with total investment of £14.7 million (19.1%) and 236 (73.1%) hepatitis C studies (£62.7 million, 81.5%). There were 4 studies investigating hepatitis G, and none specifying hepatitis D or E. By associated area, viral hepatitis and therapeutics research received £17.0 million, vaccinology £3.1 million and diagnostics £2.9 million. Preclinical research received £50.3 million (65.4%) across 173 studies, whilst implementation and operational research received £19.4 million (25.3%) across 128 studies. The UK is engaged in much hepatology research, but there are areas where the burden is great and may require greater focus, such as hepatitis E, development of a vaccine for hepatitis C, and further research into hepatitis-associated cancers. Private sector data, and funding information from other countries, would also be useful in priority setting. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B and C (HBV, HCV) infections are associated with high morbidity and mortality. Many countries with traditionally low prevalence (such as UK) are now planning interventions (screening, vaccination, and treatment) of high-risk immigrants from countries with high prevalence. This review aimed to synthesise the evidence on immigrants’ knowledge of HBV and HCV that might influence the uptake of clinical interventions. The review was also used to inform the design and successful delivery of a randomised controlled trial of targeted screening and treatment. Methods: Five databases (PubMed, CINHAL, SOCIOFILE, PsycINFO & Web of Science) were systematically searched, supplemented by reference tracking, searches of selected journals, and of relevant websites. We aimed to identify qualitative and quantitative studies that investigated knowledge of HBV and HCV among immigrants from high endemic areas to low endemic areas. Evidence, extracted according to a conceptual framework of Kleinman’s explanatory model, was subjected to narrative synthesis. We adapted the PEN-3 model to categorise and analyse themes, and recommend strategies for interventions to influence help-seeking behaviour. Results: We identified 51 publications including quantitative (n = 39), qualitative (n = 11), and mixed methods (n = 1) designs. Most of the quantitative studies included small samples and had heterogeneous methods and outcomes. The studies mainly concentrated on hepatitis B and ethnic groups of South East Asian immigrants residing in USA, Canada, and Australia. Many immigrants lacked adequate knowledge of aetiology, symptoms, transmission risk factors, prevention strategies, and treatment, of hepatitis HBV and HCV. Ethnicity, gender, better education, higher income, and English proficiency influenced variations in levels and forms of knowledge. Conclusion: Immigrants are vulnerable to HBV and HCV, and risk life-threatening complications from these infections because of poor knowledge and help-seeking behaviour. Primary studies in this area are extremely diverse and of variable quality precluding meta-analysis. Further research is needed outside North America and Australia. [ABSTRACT FROM AUTHOR]

Background: South Asians often present late with HCV or HBV related liver disease which could have been avoided with early diagnosis and subsequent treatment; however the prevalence of HCV/HBV among South Asians in Glasgow is not known. Accordingly, to inform the need for case finding among this group we aimed to examine the prevalence of Hepatitis C virus (HCV) among South Asians living in Glasgow. Methods: A community-based survey recruited individuals at six mosques and four community centres serving the South Asian community during 2009-2010; participants had predominantly never been HCV tested. Laboratory surveillance data involving all individuals tested for HCV during 1993-2009 were examined and South Asians were identified using Nam Pehchan software. Results: In the community-based survey, 2.6% of 1288 participants tested HCV-antibody positive; the prevalence ranged from 0.6% among those born in the UK to 3.1% among those born in Pakistan. The odds of testing HCV-antibody positive were significantly raised among those who had surgery in South Asia (aOR: 5.0, 95% CI: 2.0-12.3) and had either medical/dental treatment or an injection in South Asia (aOR: 2.2, 95% CI: 1.0-5.0). Of 6404 South Asians identified from laboratory surveillance data, 9.3% tested HCV positive. An estimated 38% (330/870) of HCV-infected South Asians living in Glasgow remain undiagnosed. Conclusions: South Asians living in Glasgow, particularly those born outside the UK are at greater risk of HCV infection than the general population. Efforts to increase awareness and testing in this population are warranted. [ABSTRACT FROM AUTHOR]

Study C209 evaluated the activity of telaprevir in treatment-naïve patients with genotypes 2 or 3 (G2, G3) hepatitis C virus (HCV) infection. Telaprevir monotherapy showed potent activity against HCV G2, but limited activity against G3. This analysis was performed to characterize HCV viral variants emerging during telaprevir-based treatment of G2/G3 HCV-infected patients. Patients were randomized to receive 2 weeks of treatment with telaprevir (telaprevir monotherapy), telaprevir plus peginterferon alfa-2a and ribavirin (triple therapy), or placebo plus peginterferon alfa-2a and ribavirin (control), followed by 22-24 weeks of peginterferon/ribavirin alone. Viral breakthrough was defined as an increase >1 log10 in HCV RNA from nadir, or HCV RNA >100 IU/mL in patients previously reaching <25 IU/mL. Twenty-three patients (47%) had G2 and 26 (53%) had G3 HCV. Viral breakthrough occurred during the initial 2-week treatment phase in six G2 patients (66.7%; subtypes 2, 2a and 2b) and three G3 patients (37.5%; all subtype 3a), all in the telaprevir monotherapy arm. Four breakthrough patients (three G2, one G3) subsequently achieved sustained virologic response (SVR). In all patients with breakthrough and available sequence data, mutations associated with reduced susceptibility to telaprevir in genotype 1 (G1) HCV were observed. No novel G2/G3-specific mutations were associated with telaprevir resistance. The telaprevir resistance profile appeared consistent across HCV genotypes 1, 2 and 3. Although viral breakthrough with resistance occurred in patients receiving telaprevir monotherapy, half of these patients achieved an SVR upon addition of peginterferon/ribavirin highlighting the importance of combination therapy. [ABSTRACT FROM AUTHOR]

Background: Previous evidence synthesis estimates of Hepatitis C Virus (HCV) in England did not consider excess HCV risk in ethnic minority populations. We incorporate new information on HCV risk among non-injectors by ethnic group, and additional information on injecting prevalence in order to generate new and updated estimates of HCV prevalence risk in England for 2005. Methods: Bayesian evidence synthesis was used to combine multiple sources of data that directly or indirectly provide information on the populations at risk, or prevalence of HCV infection. HCV data were modelled by region, age group and sex as well as ethnicity for never-injectors and by injecting status (ex and current). Results: Overall HCV antibody prevalence in England was estimated at 0.67% [95% credible interval (95% CrI): 0.50–0.94] of those aged 15–59 years, or 203 000 (153 000, 286 000) individuals. HCV prevalence in never-injectors remains low, even after accounting for ethnicity, with a prevalence of 0.05% (95% CrI 0.03–0.10) in those of white/other ethnicity and 0.76% (0.48–1.23) in South Asians. Estimates are similar to 2003, although patterns of injecting drug use are different, with an older population of current injecting drug users and lower estimated numbers of ex-injectors, but higher HCV prevalence. Conclusions: Incorporating updated information, including data on ethnicity and improved data on injectors, gave similar overall estimates of HCV prevalence in England. Further information on HCV in South Asians and natural history of injecting are required to reduce uncertainty of estimates. This method may be applied to other countries and settings. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C infection represents a significant and growing health problem worldwide. Patients with genotype 1 hepatitis C respond poorly to the current standard of care, pegylated interferon and ribavirin, which is frequently associated with unpleasant side effects. Consequently new agents with improved efficacy and tolerability are needed. The efficacy and safety of the direct-acting antiviral agent telaprevir in the treatment of genotype 1 hepatitis C infection have been demonstrated in a number of clinical trials. The addition of telaprevir to standard therapy considerably improves response rates and allows response-guided shortening of treatment duration in a substantial number of treatment-naïve patients. Side effects associated with telaprevir therapy include rash, anaemia, gastrointestinal disturbance and anorectal discomfort. Telaprevir-resistant variants have been identified in patients who have failed telaprevir-containing therapy, and whether selection of these variants will compromise future therapeutic options is currently unknown. The efficacy and safety of telaprevir in the treatment of the most challenging patients, including those with recurrent hepatitis C following liver transplantation and those co-infected with HIV, remains to be established. [ABSTRACT FROM PUBLISHER]

Background & Aims: It is recommended that patients with chronic hepatitis C virus (HCV) genotype 3 infections receive 24 weeks of treatment. A rapid virologic response (RVR; at week 4) predicts a sustained virologic response (SVR), although not all patients with an RVR achieve an SVR. We explored the relationships among hepatic steatosis, level of HCV RNA, relapse, and RVR in a phase 3 randomized controlled trial of 932 patients infected with HCV genotype 2 (n = 427) or 3 (n = 505) who received 24 weeks of therapy with interferon-α. Methods: In patients with an RVR (HCV RNA <43 IU/mL), the presence of an SVR was modeled using multivariate logistic regression as a function of age, sex, weight, body mass index, insulin resistance, steatosis, and levels of γ-glutamyl transpeptidase, alanine aminotransferase, liver fibrosis, and baseline HCV RNA. Results: RVR, SVR, and relapse rates among patients with HCV genotype 3 were 79.6%, 79.2%, and 15.6%, respectively; corresponding rates among patients with HCV genotype 2 were 86.7%, 84.3%, and 10.1%. An RVR had high predictive value for an SVR in patients with HCV genotypes 2 (88.9%) and 3 (88.1%). The strongest independent predictors of relapse in patients with genotype 3 and an RVR were steatosis (odds ratio 3.0; P = .003) and HCV RNA ≥400,000 IU/mL (odds ratio 2.5; P = .04). Relapse rates in patients with steatosis were 17.4% and 20.9% for low and high baseline levels of HCV RNA, respectively; corresponding rates in those without steatosis were 2.5% and 8.8%. Conclusions: Steatosis was associated with significantly higher rates of relapse, irrespective of viral load, in patients infected with HCV genotype 3 who had an RVR. Further studies are needed to determine if longer treatment durations are effective in patients with an RVR and these risk factors. [Copyright &y& Elsevier]

The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients. A total of 303 treatment-naïve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24 weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR) > 2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4). Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2] = 171, HCV-3 = 92), and 433 non-Asian region patients (407 'Caucasian'); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis) = 201 (77%) and F2-F4 (significant fibrosis) = 59 (23%), and steatosis prevalence of grade 0 = 169 (65%), grade 1 = 64 (25%), grade 2/3 = 27 (10%). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7); 100 (38%) patients had HOMA-IR > 2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR] = 8.42), necro-inflammatory grade (OR = 3.17), age (OR = 1.07) and serum total cholesterol levels (OR = 0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Chronic infection with the hepatitis C virus (HCV) has a profound effect on health-related quality of life (HRQoL) – with fatigue, depression and neurocognitive deficits among the most common complaints. Neuropsychiatric symptoms have prompted research to determine whether the HCV acts within the central nervous system. Replicating virus has been found in central nervous tissues, and changes in neurotransmitter levels in the frontal white matter of patients with chronic hepatitis C are correlated with impaired attention and concentration. Other symptoms of chronic hepatitis C that decrease HRQoL include associated sexual dysfunction and depression. Treatment of chronic HCV infection may temporarily worsen HRQoL, and common adverse effects of currently available agents include fatigue, muscle aches, depression and cognitive deficits. The relationship between sustained viral response and improvement in HRQoL is nonetheless well accepted. Although treatment-related adverse effects may dissuade people from starting therapy and reduce compliance with associated reductions in sustained viral response, for the majority of patients viral clearance produces improvements in both HRQoL and long-term prognosis. Novel agents, with improved adverse effect profiles, may afford more patients the opportunity to achieve a sustained viral response. [ABSTRACT FROM AUTHOR]

Background Chronic hepatitis C infection is common in drug users. Treatment of injectors is possible under controlled conditions, but many have not yet been included in treatment programmes as there are concerns about their ability to comply with therapy. It is not known which factors influence compliance. Aim To examine the hypothesis that active drug users would comply with anti-viral therapy if treatment was delivered in a convenient manner. Methods We established a community-based treatment programme and offered anti-viral therapy to all drug users who wanted it. Few pre-treatment requirements were imposed and, by design, compliance with therapy was reviewed after 50 patients had completed treatment. Results Of the 441 patients who were known to be HCV RNA positive and attended the specialist addiction services during the period of this study, eighty three patients considered therapy. Twenty patients did not undergo treatment: 14 declined and 6 had medical conditions that precluded it. In 60 episodes (58 patients) where treatment had been completed, compliance was greater than 80% and homelessness, active illicit drug use and pre-treatment antidepressant therapy were not associated with noncompliance. In 25 of 49 treatment episodes that were assessed 6 months after treatment cessation, a sustained virological response (51%) was seen. Conclusion Active drug users using illicit drugs can be successfully treated in community-based clinics. [ABSTRACT FROM AUTHOR]

Objective. Patient- and virus-related factors influence the response of patients with chronic hepatitis C to interferon-based therapy. The purpose of this study was to model the probability of achieving a sustained virological response in individual patients, taking into consideration various predictive factors. Material and methods. We combined data from two randomized, multinational trials in which patients received peginterferon alfa-2a (40KD) plus ribavirin. The logistic regression model for patients infected with hepatitis C virus genotype 1 included age, viral load, histology, alanine aminotransferase quotient, body mass index, treatment duration, ribavirin dose and adherence. Results. In the genotype 1 model, varying baseline factors had a striking effect on the probability of sustained virological response. A dramatic difference in the probability of sustained virological response was seen in a series of hypothetical patients in whom five factors were varied to represent best and worst case scenarios. The best case scenario (age 20 years; no cirrhosis/bridging fibrosis; alanine aminotransferase quotient =7; body mass index 20 kg/m2; viral load 40,000 IU/mL) was associated with a 97% probability of sustained virological response, compared with 7% in the worst case scenario (age 60 years; cirrhosis/bridging fibrosis; alanine aminotransferase quotient =1; body mass index 30 kg/m2; viral load 9,000,000 IU/mL). Both adherence to treatment and achieving an early virological response increased the probability of sustained virological response. Conclusions. In treatment-naïve patients with chronic hepatitis C, host factors play a major role in determining treatment outcome and the logistic regression model is useful for predicting the probability of sustained virological response in individual patients. [ABSTRACT FROM AUTHOR]

Objective. To study the relationship between health-related quality of life (HRQOL) and mode of acquisition, treatment discontinuations, drop in haemoglobin levels and treatment outcome in patients with chronic hepatitis C (CHC). Material and methods. Consecutive unselected Swedish patients with CHC completed the SF-36 questionnaire before, during and after treatment with interferon and ribavirin. Results. At baseline, HRQOL was reduced in all SF-36 subscales in our patients ( n =147) as compared with the general Swedish population. Former intravenous drug users (IVDUs) scored significantly lower in social function ( p =0.03) and mental health ( p =0.03) than patients who had acquired their infection from blood transfusions (PTH). A decline of >40 points in HRQOL from baseline to week 12 was noticed in the role limitations-physical (RP) score for the IVDU and PTH groups ( p [ABSTRACT FROM AUTHOR]

OBJECTIVES : To assess whether insulin resistance is associated with liver fibrosis in a group of patients with chronic hepatitis C virus (HCV) infection and whether there were any differences in insulin resistance between Asians and the indigenous Caucasian population. Secondly, to assess whether insulin resistance is associated with sustained virological response to antiviral therapy. METHODS : We determined insulin resistance in 59 (30 Caucasians; 29 Asians) consecutive patients with HCV prior to starting antiviral therapy. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship between insulin resistance and biochemical, virological, and histological data together with response to antiviral therapy was assessed. RESULTS : In multivariable analyses, insulin resistance as measured using the HOMA-IR model correlated positively with the stage of fibrosis, with higher degrees of insulin resistance in those with greater degrees of fibrosis ( p < 0.001). This significant relationship remained even after excluding cirrhotic patients, or after adjusting for other factors associated with fibrosis in univariable analyses. Insulin resistance was significantly higher in Asians than Caucasians ( p= 0.004). Around half (55.6%) of patients completing a course of antiviral treatment had a sustained virological response. Multivariable logistic regression identified HCV genotype 3, lower fasting glucose levels, and lower aspartate transaminase (AST) levels as being associated with a higher odds of a sustained virological response. After adjusting for these variables, Asian ethnicity, higher fasting insulin levels, and higher HOMA-IR levels were all associated with a poorer virological response to therapy. CONCLUSIONS : Insulin resistance contributes to liver fibrosis in chronic HCV infection; this relationship is not genotypic specific. Asian patients had higher insulin resistance than Caucasians. Insulin resistance is also an important predictor of sustained response to antiviral therapy. (Am J Gastroenterol 2005;100:1–7) [ABSTRACT FROM AUTHOR]

: Chronic infection with the hepatitis C virus affects over 170 million individuals worldwide and 20% of patients develop cirrhosis after 20 years. Increased iron stores and hepatic iron content have been suggested to be important in fibrosis progression. The increased prevalence of diabetes mellitus has been associated with increased iron deposits in patients with chronic hepatitis C.: To assess the potential relationship between serum ferritin and hepatic iron staining and liver fibrosis in patients with chronic hepatitis C virus infection and whether these factors are increased in diabetic patients with hepatitis C virus.: This was a cross-sectional, multi-centre study involving hospitals in the north-east of London between 1992 and 2003. Chronic hepatitis C patients with a liver biopsy and data concerning age, sex, basal metabolic index, diabetes mellitus or impaired glucose tolerance, alcohol intake, serum ferritin level and ethnicity were enrolled. Each biopsy was scored for fibrosis and stained for hepatic iron.: Three hundred and thirty nine patients (200 Caucasian; 139 Asian) were enrolled. Fifty three patients had no fibrosis, 131 had mild fibrosis (stage one to two Modified Ishak), 68 moderate fibrosis (stage three to four) and 87 cirrhosis (stage five to six). 4.4% of patients had elevations in serum ferritin, whilst 11% had increased hepatic iron staining. The serum ferritin and hepatic iron staining were unrelated to the degree of fibrosis. Serum ferritin was significantly higher in patients with diabetes or impaired glucose tolerance compared to non-diabetics. No association was seen between diabetes and hepatic iron staining.: Many patients with chronic hepatitis C virus infection may have elevated serum ferritin and/or iron deposition within the liver. However, both played no significant role in the progression of hepatitis C virus related liver injury. The association between chronic hepatitis C virus infection and type II diabetes mellitus exists, however the biological mechanism of this association still remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background and aims: A reliable non-invasive assessment of the severity of diffuse liver disease is much needed. We investigated the utility of hepatic vein transit times (HVTT) for grading and staging diffuse liver disease in a cohort of patients with hepatitis C virus (HCV) infection using an ultrasound microbubble contrast agent as a tracer. Materials and methods: Eighty five untreated patients with biopsy proven HCV induced liver disease were studied prospectively. All were HCV RNA positive on polymerase chain reaction testing. Based on their histological fibrosis (F) and necroinflammatory (NI) scores, untreated patients were divided into mild hepatitis (F &les; 2/6, NI &les; 3/18), moderate/severe hepatitis (3 &les; F <6 or NI &ges; 4), and cirrhosis (F = 6/6) groups. In addition, 20 age matched healthy volunteers were studied. After an overnight fast, a bolus of contrast agent (Levovist) was injected into an antecubital vein and spectral Doppler signals were recorded from both the right and middle hepatic veins for analysis. HYTTs were calculated as the time from injection to a sustained rise in Doppler signal >10% above baseline. The Doppler signals from the carotid artery were also measured in 60 patients and carotid delay times (CDT) calculated as the difference between carotid and hepatic vein arrival times. The earliest HVTT in each patient was used for analysis. Results: Mean (SEM) HVTT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis groups showed a monotonic decrease of 38.1 (2.8), 38.8 (2.4), 26.0(2.4), and 15.8 (0.8) seconds, respectively. Mean (SEM) CDT for the control, mild hepatitis, moderate/severe hepatitis, and cirrhosis patients again showed progressive shortening of 30.3 (2.6), 25.9 (2.6), 14.8 (2.1), and 5.6 (1.2) seconds, respectively. There were significant differences between the groups for HVTT (ANOVA, p<0.001) and CDT (ANOVA, p<0.001). There was 100% sensitivity and 80% specificity for diagnosing cirrhosis and 95% sensitivity and 86% specificity for differentiating mild hepatitis from more severe liver disease. Conclusion: We have shown, for the first time, that HVTT using an ultrasound microbubble contrast agent can assess HCV related liver disease with clear differentiation between mild hepatitis and cirrhosis. There were significant differences between these two groups and the moderate/severe hepatitis group. CDT offers no additional benefit or greater differentiation than NYU and can be omitted, thus simplifying this technique. HVTT may complement liver biopsy and may also be a useful alternative for assessment of liver disease in patients who have contraindications to biopsy. [ABSTRACT FROM AUTHOR]

: Current therapy for chronic hepatitis C infection involves a course of pegylated interferon and ribavirin. Patients who do not show a virological response after 12 weeks of therapy have a low probability of sustained virological response and it is therefore recommended that such patients stop treatment.: To assess patients’ views of early treatment cessation.: We conducted a open-labelled study in three UK centres, in which patients with biopsy-proven chronic hepatitis C requiring therapy were offered the choice of a full course of therapy with 40 kDa pegylated interferon-α 2a plus ribavirin (24 or 48 weeks depending on viral genotype) or early cessation if therapy had failed after 12 weeks.: Ninety-five participants were enrolled and the majority (69%) did not wish to discontinue therapy even if it had low probability of success. In this unselected UK population, very few patients (4%) did not achieve an early virological response with the 40-kDa pegylated interferon-α 2a plus ribavirin and two of the four early virological non-responders decided to continue therapy.: Early discontinuation of‘ineffective’ anti-viral therapy may prove less popular with patients than with health care providers, and further patient-directed education regarding the cost-effectiveness of therapy will be needed if early discontinuation of unsuccessful therapy is to be accepted by patients. [ABSTRACT FROM AUTHOR]

The role of virus-related apoptosis in hepatic injury in chronic HCV is unclear. It is unknown whether HCV induces apoptosis directly or whether cellular injury is immunologically mediated. We studied the relationship between infected hepatocytes, apoptosis and necroinflammation. We established a Fluorescence Activated Cell Sorter (FACS) basedintracellular staining technique for the HCV NS3 protein and examined intrahepatic viraemia, disease activity and apoptosis. We also stained infected cells for expression of human leucocyte antigen (HLA) class I and Fas antigens. We examined 34 liver biopsies (24 from patients with HCV) and found marked variation in the proportion of infected cells (2.5–42%). The number of infected cells correlated with serum viraemia but not histology. The number of infected cells was inversely related to the number of apoptotic cells (P < 0.001); infected cells expressed both HLA class I (14 cases) and Fas antigens (12 cases). The number of hepatocytes infected with hepatitis C is variable and does not influence histological activity. In infected patients, the majority of HCV-positive hepatocytes express target molecules for activated lymphocytes (Fas and HLA class I antigens) but they do not undergo apoptosis, suggesting that hepatitis C may inhibit apoptosis by modulating intracellular pro-apoptotic signals. [ABSTRACT FROM AUTHOR]

The article elaborates the effect of the increasing rates of global hepatitis and migration on medical care in Western countries as of August 2010. According to data from the World Health Organization (WHO), about 350 million individuals are infected with hepatitis B virus and more than 170 million people are chronically infected with the hepatitis C virus (HCV). The epidemic of chronic hepatitis C4 in Egypt between 1961 and 1986 was reportedly caused by the administration of parenteral therapy for schistosomiasis. Data on immigrants in Canada is given.