Is HCV elimination among persons living with HIV feasible? Data from the NoCo study in the setting of the ICONA cohort

Background and Aims

Whether the HCV test-and-treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown.

Methods

Prospective study of PLWH in the ICONA network. At baseline, PLWH were tested for HCV-Ab; HCV-RNA (if HCV-Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re-infections were evaluated yearly in HCV-Ab neg and HCV-RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models.

Results

Sixteen thousand seven hundred and forty-three PLWH were included; 27.3% HCV-Ab positive; of these, 39.3% HCV-RNA positive. HCV seroconversion incidence: .48/100 PYFU (95% CI: .36–.65); re-infections incidence: 1.40/100 PYFU (95% CI: .91–2.04). The risk factor for HCV re-infection was young age: aIRR 1.85, 95% CI: 1.17–2.95) per 10 years younger. 86.4% of HCV viremic in follow-up started DAA. PWID vs. heterosexuals (aHR .75, 95% CI .62–.90), HIV-RNA >50 copies/mL (aHR .70, 95% CI .56–.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post-COVID-19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm³ (vs. CD4 ≥200/mm³ aOR .18, 95% CI: .07–.46). 95.5% of DAA-treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow-up. HCV-RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022.

Conclusions

The screening-and-treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort.     

Comparing the risk of hepatitis B virus reactivation between direct‐acting antiviral therapies and interferon‐based therapies for hepatitis C

Hepatitis B virus (HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus (HCV) and HBV co‐infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti‐HCV therapy and compared those between interferon (IFN)‐free direct‐acting antiviral (DAA) therapies and IFN‐based therapies. Three hundred and twenty‐two patients with HCV infection receiving anti‐HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV‐DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti‐HBs positivity, changes in anti‐HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN‐free DAA therapies and 72 were treated with IFN‐based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN‐free DAA therapies, while no patient developed HBV reactivation after IFN‐based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti‐HBs titre to <12 mIU mL^?1 by the end of treatment. The decline changes of anti‐HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN‐free DAA therapies. Low levels of anti‐HBs and their decrease to <12 mIU mL^?1 after treatment are significant risk factors for HBV reactivation or reappearance.     

Hepatitis C Virus Infection Outcomes Among Immigrants to Canada: A Retrospective Cohort Analysis

Introduction and aimHCV-infected immigrants contribute to the total prevalence in Canada and other developed nations. Little is known about engagement in care, access to service, and treatment outcomes in recipients of Direct Acting Antiviral (DAA) HCV therapies among immigrants living with HCV.Material and methodsHCV patients assessed at The Ottawa Hospital Viral Hepatitis Clinic between 2000-2016 were identified. Immigration history, race, socioeconomic status, HCV work-up, treatment and outcome data were evaluated. HCV fibrosis assessment, treatment and sustained virologic response (SVR) were compared using logistic regression.Results2,335 HCV-infected patients were analyzed with 91% (2114) having data on immigration (23% immigrants). A median 16 years (Quartiles: 5, 29) passed from immigration to referral. Access to diagnostic procedures (Fibroscan/liver biopsy) was greater among immigrants compared to Canadian-born (78% vs. 68%, p = 0.001) and immigrants had an odds ratio of 1.72 (95% CI: 1.18-2.51) of receiving a FibroScan compared to Canadians after adjustment for demographic characteristics, HCV risk factors, and socioeconomic status. No differences in SVR were found between immigrants for IFN recipients. Among DAA recipients, rates of SVR were > 94% among all patients, 93% in Canadian-born and 98% among immigrants (p = 0.14).ConclusionNearly 80% of immigrants in this setting had access to fibrosis assessment which was higher than Canadian-born patients. Under half of both groups had initiated HCV therapy. Delays in accessing HCV care represent a missed opportunity to engage, treat and cure HCV patients. HCV screening and health care engagement at the time of immigration would optimize HCV care and therapeutic outcomes.     

Hepatitis c virus markers in infection by hepatitis c virus: In the era of directly acting antivirals

About 130-170 million people are infected with the hepatitis C virus(HCV) worldwide and more than 350000 people die each year of HCV-related liver diseases. The combination of pegylated interferon(Peg-IFN) and ribavirin(RBV) was recommended as the treatment of choice for chronic hepatitis C for nearly a decade. In 2011 the directly acting antivirals(DAA) HCV NS3/4A protease inhibitors,telaprevir and boceprevir,were approved to treat HCV-genotype-1 infection,each in triple combination with Peg-IFN and RBV. These treatments allowed higher rates of SVR than the double Peg-IFN + RBV,but the low tolerability and high pill burden of these triple regimes were responsible for reduced adherence and early treatment discontinuation. The second and third wave DAAs introduced in 2013-2014 enhanced the efficacy and tolerability of anti-HCV treatment. Consequently,the traditional indicators for disease management and predictors of treatment response should be revised in light of these new therapeutic options. This review article will focus on the use of the markers of HCV infection and replication,of laboratory and instrumental data to define the stage of the disease and of predictors,if any,of response to therapy in the DAA era. The article is addressed particularly to physicians who have patients with hepatitis C in care in their everyday clinical practice.     

The impact of COVID-19 on the cascade of care of HCV in the US and China

Background and objectives: The COVID-19 pandemic imperiled the global health system. We aimed to determine the impact of COVID-19 on the care continuum of HCV-infected patients.Material and Methods: Two hundred and fifty-six patients who were prescribed a course of DAA therapy at three tertiary medical centers in the US and China between January 1, 2019 to June 30, 2020 were included. We assessed the proportions of patients who completed DAA therapy and had HCV RNA testing during and after the end of therapy. We also assessed the impact of utilization of telemedicine.Results: The proportion of patients undergoing HCV RNA testing during DAA treatment decreased from >81.7% before pandemic to 67.8% during the pandemic (P=0.006), with a more prominent decrease in the US. There were significant decreases in HCV RNA testing >12 (P<0.001) and >20 weeks (P<0.001) post-treatment during COVID-19 era. Compared to pre-COVID period, post-treatment clinic encounters during COVID-19 era decreased significantly in China (Xi'an: 13.6% to 7.4%; Nanjing: 16.7% to 12.5%) but increased in the US (12.5% to 16.7%), mainly due to the use of telemedicine. There was a 4-fold increase in utilization of telemedicine in the US.Conclusions: COVID-19 pandemic carried profound impact on care for HCV patients in both the US and China. HCV cure rate assessment decreased by half during COVID era but the proportion of patients finishing DAA therapy was not significantly affected. Increased utilization of telemedicine led to increased compliance with DAA therapy but did not encourage patients to have their laboratory assessment for HCV cure.     

Direct Acting Antivirals Improve HCV Treatment Initiation and Adherence Among Underserved African Americans

Introduction and aim. Adherence to hepatitis C (HCV) care was suboptimal in the interferon era among underserved African Americans (AA), but adherence data in the era of direct acting antivirals (DAA) is lacking in this population. We aimed to evaluate the impact of DAA on HCV care in underserved AA.Material and methods. Clinical records of AAs undergoing HCV evaluation attending a safety net health system liver clinic were reviewed from 2006 to 2011 (pre-DAA), and January 1, 2014 to December 31, 2016 (post-DAA).Results. 291 patients were identified (129 pre-DAA, and 162 post-DAA). Median age was 58, 66% were male, 91% had HCV genotype 1, and 70% had fibrosis ≥ stage 2. Post-DAA patients were older (60 vs. 53 years; p < 0.001), had higher rates of insurance (98% vs. 88%; p < 0.001), liver fibrosis ≥ stage 2 (77% vs. 61%; p = 0.048), ≥ 2 medical comorbidities (19 vs. 0.8%; p < 0.001), and median baseline log10 HCV RNA (6.07 vs. 5.81 IU/mL; p < 0.001), but lower median ALT (46 vs. 62 U/L; p < 0.001). Post-DAA, fewer patients were treatment ineligible (5.6% vs. 39%; p < 0.001) and more initiated therapy (71% vs. 8.5%; < 0.001), were adherent to HCV care (82% vs. 38%; p < 0.001), and achieved cure (95.7% vs. 63.6%, p < 0.001). Availability of DAA was independently associated with improved adherence to HCV care (OR 10.3, 95% CI 4.84-22.0).Conclusion. Availability of DAA is associated with increased treatment eligibility, initiation, adherence to HCV care, and cure in HCV-infected underserved AAs; highlighting the critical role of access to DAA in this population.     

Hepatitis C virus testing,liver disease assessment and treatment uptake among people who inject drugs pre‐ and post‐universal access to direct‐acting antiviral treatment in Australia: The LiveRLife study

Gaps in hepatitis C virus (HCV) testing, diagnosis, liver disease assessment and treatment uptake among people who inject drugs (PWID) persist. We aimed to describe the cascade of HCV care among PWID in Australia, prior to and following unrestricted access to direct‐acting antiviral (DAA) treatment. Participants enrolled in an observational cohort study between 2014 and 2018 provided fingerstick whole‐blood samples for dried blood spot, Xpert HCV Viral Load and venepuncture samples. Participants underwent transient elastography and clinical assessment by a nurse or general practitioner. Among 839 participants (mean age 43 years), 66% were male (n = 550), 64% (n = 537) injected drugs in the previous month, and 67% (n = 560) reported currently receiving opioid substitution therapy. Overall, 45% (n = 380) had detectable HCV RNA, of whom 23% (n = 86) received HCV treatment within 12 months of enrolment. HCV treatment uptake increased from 2% in the pre‐DAA era to 38% in the DAA era. Significant liver fibrosis (F2‐F4) was more common in participants with HCV infection (38%) than those without (19%). Age 50 years or older (aOR, 2.88; 95% CI, 1.18‐7.04) and attending a clinical follow‐up with nurse (aOR, 3.19; 95% CI, 1.61‐6.32) or physician (aOR, 11.83; 95% CI, 4.89‐28.59) were associated with HCV treatment uptake. Recent injection drug use and unstable housing were not associated with HCV treatment uptake. HCV treatment uptake among PWID has increased markedly in the DAA era. Evaluation of innovative and simplified models of care is required to further enhance treatment uptake.     

Burden of significant liver damage in people living with HIV after microelimination of the hepatitis C virus

BackgroundOnce HIV/HCV-coinfection microelimination has been virtually achieved in some countries, there is no information about the burden of liver disease among people living with HIV (PLWH). The aim of this study was to define the current prevalence and causes of significant liver damage (SLD) in PLWH.MethodsCross-sectional study including 619 PLWH. SLD was defined as liver stiffness (LS) ≥ 7.2 kPa measured by transient elastography. Nonviral liver damage (NVLD) was considered if there was no evidence injury due to chronic hepatitis C virus (HCV) infection, active hepatitis B (HBV) or E virus infections.ResultsOne hundred and twelve of 619 (18.2%) PLWH showed SLD, including 34/112 (5.5%) with LS ≥14 kPa. 72/112 (64.3%) had cured HCV infection, 4/112 (3.6%) active HBV infection, and 2/112 HBV/prior HCV coinfection. Thus, 40 (35.7%) showed NVLD. Metabolic associated steatohepatitis (MASH) was present in 29/40 (72.5%) of patients with NVLD, alcoholic liver damage in 2/40 (2.5%) and mixed steatohepatitis in 5/40 (12.5%).ConclusionsAfter HIV/HCV microelimination the burden of liver damage is high among PLWH. Persistent injury after HCV is a very frequent cause of SLD. However, NVLD, mainly due to MASH, is also a common condition in this population.     

Genotype 3-hepatitis C virus’ last line of defense

Chronic infection with hepatitis C virus (HCV) is one of the leading causes of liver disease globally, affecting approximately 71 million people. The majority of them are infected with genotype (GT) 1 but infections with GT3 are second in frequency. For many years, GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon (IFN)-based regimen. However, the growing evidence of a higher rate of steatosis, more rapid progression of liver fibrosis, and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction. This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals (DAA). The way from a standard of care therapy with pegylated IFN-alpha (pegIFNα) and ribavirin (RBV) through a triple combination of pegIFNα + RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends. Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A.     

Duration of antiretroviral therapy among people living with HIV and incidence of hypertension in Ghana

Understanding the differential rates of incident hypertension among People Living with HIV (PLWH) based of duration of exposure to combination antiretroviral therapy (cART) may provide insights into the pathogenesis of hypertension in this population. Utilizing the dataset of a prospective study conducted at a Ghanaian tertiary medical center, we evaluated factors associated with incident hypertension among PLWH previously naïve to cART before study enrollment (cART newly prescribed group, n = 221) versus PLWH established on cART for at least a year (cART established group, n = 212). New‐onset hypertension was diagnosed as clinic BP > 140/90 mmHg on two separate clinic visits over 12‐month follow‐up. Cox proportional hazards regression models were used to assess factors associated with incident hypertension. Mean age of new versus cART established was 41.1 ± 8.2 versus 45.1 ± 8.6 years (p < .001), with more women in the cART established group (68.3 vs. 82%, p = .0009). There were 105 (24.3%) episodes of incident hypertension over 328 person‐years follow‐up (PYFU), incidence rate of 320.1 (95% CI: 263.1‐385.9)/1000 PYFU, with higher rates in new versus cART established (476.6/1000 PYFU vs. 222.8/1000 PYFU, p = 0.0002). Overall, age by increasing decile (aHR 0.76; 95% CI: 0.59‐0.98), log HIV‐1 viral load (aHR 1.16; 1.04‐1.35), and use of tenofovir (aHR 1.66; 1.04‐2.64) were associated with incident hypertension. While CD4 counts, age, BMI, pre‐diabetes, and urban/peri‐urban residency were independently associated with hypertension in the cART established group; no independent predictors were identified among the cART newly prescribed group. Further studies to explore the potential mechanisms underlying incidence of hypertension in PLWH are warranted.     

Effect on the adherence to concomitant medications after initiation of treatment with direct-acting antiviral agents against hepatitis C virus

IntroductionMany patients with hepatitis C virus (HCV) have associated comorbidities that require complex treatments. We sought to determine the impact of treatment with direct-acting antiviral agents (DAAs) for HCV on adherence to prescribed concomitant medications for associated comorbidities and to identify predictors of non-adherence to comedications.Patients and methodsHCV-infected patients treated with DAAs in a Spanish hospital between January 2015 and December 2016 and followed-up by the pharmacy unit were included in the study. Adherence to concomitant comedication prescribed before and during HCV therapy with DAAs was compared to adherence during the same number of weeks before DAA initiation. Demographic, clinical and pharmacotherapy variables were analyzed to determine factors associated with non-adherence. A multivariate regression model was created for prediction of non-adherence to concomitant medication.ResultsData from 214 patients using prescribed concomitant therapies were analyzed. Significant reduction on adherence to comedications was observed after initiation of DAA treatment compared with a similar period before therapy initiation (29.9% vs. 36.9%, p = 0.032). The univariate analysis showed that polypharmacy and presence of vascular disease were associated negatively with adherence to concomitant medications (87.8%, p = 0.006 and 84.7%, p < 0.001, respectively). Multivariate analysis indicated that HIV/HBV coinfection was associated with adherence (OR 0.19; 95% CI 0.09–0.39), while polypharmacy was a predictor for non-adherence (OR 4.54; 95% CI 1.48–13.92).DiscussionAdherence to concomitant medications decreases in HCV-infected patients when DAA therapy is initiated. Polypharmacy is a predictor for non-adherence, while HIV/HBV coinfection reduce non-adherence rates. Polymedicated patients on DAAs might benefit from close follow-up and educational programmes to improve their adherence.     

Antiviral treatment of hepatitis C virus infection and factors affecting efficacy

Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular carcinoma.Currently,no effective vaccine is available for HCV infection.Polyethylene glycol interferon-α(PegIFN-α)in combination with ribavirin(RBV)is the standard of care(SOC)for chronic hepatitis C.However,the efficacy of PegIFN-αand RBV combination therapy is less than 50%for genotype 1HCV,which is the dominant virus in humans.In addition,IFN and RBV have several severe side effects.Therefore,strategies to improve sustained virological response(SVR)rates have been an important focus for clinical physicians.The serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in 2011.The addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV infection.Several direct-acting antiviral drugs currently in late-stage clinical trials,both with and without pegIFN and RBV,have several advantages over the previous SOC,including higher specificity and efficacy,fewer side effects,and the ability to be administered orally,and might be optimal regimens in the future.Factors affecting the efficacy of anti-HCV treatments based on IFN-αinclude the HCV genotype,baseline viral load,virological response during treatment,host IL28B gene polymorphisms and hepatic steatosis.However,determining the effect of the above factors on DAA therapy is necessary.In this review,we summarize the development of antiHCV agents and assess the main factors affecting the efficacy of antiviral treatments.     

Dried blood spots,valid screening for viral hepatitis and human immunodeficiency virus in real-life

AIMTo detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life.METHODSWe included prospective patients with known viral infections from drug treatment centers, a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper, and a venous blood sample was obtained. The samples were analyzed for HBsAg, anti-HBc, anti-HBs, anti-HCV, and anti-HIV levels as well as subjected to a combined nucleic acid test (NAT) for HBV DNA, HCV RNA and HIV RNA.RESULTSSamples from 404 subjects were screened (85 CHB, 116 CHC, 114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%).CONCLUSIONDBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system.     

Histopathology and the predominantly progressive,indeterminate and predominately regressive score in hepatitis C virus patients after direct-acting antivirals therapy

BACKGROUNDHistological changes after direct-acting antivirals (DAAs) therapy in hepatitis C virus (HCV) patients has not been elucidated. Whether the predominantly progressive, indeterminate and predominately regressive (P-I-R) score, evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIMTo identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODSChronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included. Sustained virologic response (SVR) was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation. The Ishak system and P-I-R score were assessed. Inflammation improvement and fibrosis regression were defined as a ≥ 2-points decrease in the histology activity index (HAI) score and a ≥ 1-point decrease in the Ishak fibrosis score, respectively. Fibrosis progression was defined as a ≥ 1-point increase in the Ishak fibrosis score. Histologic improvement was defined as a ≥ 2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy. The P-I-R score was also assessed. “absolutely reversing or advancing” was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score; and “probably reversing or advancing” was defined as only one parameter showing directionality.RESULTSThirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included. The mean age of these patients was 40.9 ± 14.6 years and there were 53% (20/38) males. Thirty-four percent (13/38) of patients were cirrhotic. Eighty-two percent (31/38) of patients achieved inflammation improvement. The median HAI score decreased significantly after SVR (pretreatment 7.0 vs posttreatment 2.0, Z = -5.146, P = 0.000). Thirty-seven percent (14/38) of patients achieved fibrosis improvement. The median Ishak score decreased significantly after SVR (pretreatment 4.0 vs posttreatment 3.0, Z = -2.354, P = 0.019). Eighty-two percent (31/38) of patients showed histological improvement. The P-I-R score was evaluated in 61% (23/38) of patients. The progressive group showed lower platelet (P = 0.024) and higher HAI scores (P = 0.070) before treatment. In patients with stable Ishak stage after treatment: Progressive injury was seen in 22% (4/18) of patients, 33% (6/18) were classified as indeterminate and regressive changes were seen in 44% (8/18) of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSIONSignificant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy. The P-I-R score has potential in predicting fibrosis in HCV patients.     

Modification of liver fibrosis,glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents

IntroductionThere is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels.Methods445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48).ResultsThe SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3–14.3) kPa at baseline to 6.4 (IQR 4.9–8.9) at SVR48 (p < 0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1–3.3) to 1.3 (IQR 0.9–2.0) (p < 0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5–1.7) to 0.3 (IQR 0.2–0.4) and from 6.2 (5.0–7.5) to 4.9 (IQR 3.8–5.9) (p < 0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172 mg/dL and 101.5 mg/dL to 191 mg/dL and 117.5 mg/dL (p < 0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7 mg/dL at baseline to 127.2 mg/dL at SVR48 (p < 0.001).DiscussionSVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48.     

Impact of all oral anti-hepatitis C virus therapy: A meta-analysis

AIM:To investigate the efficacy,safety,and cost of treatment of direct acting antivirals(DAAs) with and without peg interferon alfa2a(P),and/or ribavirin(R) in treating hepatitis C virus(HCV) genotype 1 patients.METHODS:MEDLINE was searched for randomized controlled trials(RCT) using DAAs for HCV treatment.Phase 1 trials and studies with investigational drugs on genotype 2 or 3,and on human immunodeficiency virus patients were excluded.Data were pooled for sustained virologic response(SVR),serious adverse effects,and drug discontinuation rate on various treatment arms in trials:P + R;1st generation DAA(telaprevir or boceprevir) + P + R;2nd generation DAA(sofosbuvir or simeprevir) + P + R;2nd generation DAA + R;two 2nd generation DAA + R;and two 2nd gen DAA.Data were analyzed separately for each arm for treatment naive and non-responders(NR) to previous treatment.The cost of treatment with each regimen for achieving one SVR was also compared.RESULTS:Twenty three RCTs(n = 9354,62% male,11% cirrhosis) were analyzed.All oral(P free) regimens with combination of 2 DAA achieved SVR above 95%.The cost of treatment to achieve an SVR with DAA based regimens was lower for NR compared to P+R regimen.However,the cost per SVR remained higher for treatment naive patients.CONCLUSION:Second generation and emerging DAAs are promising agents in HCV treatment,with a very high level of safety and efficacy.An important drawback is their high cost.However,the present meta-analysis shows that the cost per SVR for non responders(but not for naive patients) was lower compared to P + R.This finding together with the superior safety profile and better compliance makes these drugs highly attractive.It is possible that further reduction in treatment duration may make them even more cost effective.     

Incident hepatitis C virus infection in a community-based population in Japan

Hepatitis C virus (HCV) is an important cause of liver disease throughout the world. However, the natural history and pathogenesis of this infection is still not completely understood. The aim of this study was to characterize the evolution of incident, asymptomatic HCV infection in a community-based population in Japan. The Miyazaki Cohort Study is a prospective study of adult residents in two villages, one of which has a very high prevalence of HCV. Nine hundred and seventy-three people from this village were enrolled in the cohort between 1984 and 1995, with antibodies to HCV (anti-HCV) found in 23%. During subsequent visits to annual health screens, new HCV seroconverters were identified among susceptible individuals, and their sequential samples were tested for anti-HCV, HCV-RNA, and HCV core antigen. Fourteen participants (six males, eight females) acquired anti-HCV during the first 11 years of study follow-up, at an incidence rate of 362 per 100 000 person-years. Detectable HCV-RNA and high anti-HCV titres (> 1:2048) were observed for more than 5 years following seroconversion in 80% (8/10) of seroconverters with sufficient information, indicating the development of persistent infection in these subjects. Three (37.5%) of the eight sero converters with persistent infection had fairly consistent, albeit mild, alanine aminotransferase elevations (30–130 IU/L) during the study. Anti-HCV seroconversions occurred at a very high rate in this community-based population in Japan, in which this infection is endemic. Persistence also developed at a high frequency among the cases of newly acquired infection, although the associated liver enzyme abnormalities were mild.     

Development of a risk score to guide targeted hepatitis C testing among human immunodeficiency virus patients in Cambodia

BACKGROUNDThe World Health Organization recommends testing all human immunodeficiency virus (HIV) patients for hepatitis C virus (HCV). In resource-constrained contexts with low-to-intermediate HCV prevalence among HIV patients, as in Cambodia, targeted testing is, in the short-term, potentially more feasible and cost-effective. AIMTo develop a clinical prediction score (CPS) to risk-stratify HIV patients for HCV coinfection (HCV RNA detected), and derive a decision rule to guide prioritization of HCV testing in settings where ‘testing all’ is not feasible or unaffordable in the short term. METHODSWe used data of a cross-sectional HCV diagnostic study in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh. Key populations were very rare in this cohort. Score development relied on the Spiegelhalter and Knill-Jones method. Predictors with an adjusted likelihood ratio ≥ 1.5 or ≤ 0.67 were retained, transformed to natural logarithms, and rounded to integers as score items. CPS performance was evaluated by the area-under-the-ROC curve (AUROC) with 95% confidence intervals (CI), and diagnostic accuracy at the different cut-offs. For the decision rule, HCV coinfection probability ≥1% was agreed as test-threshold. RESULTSAmong the 3045 enrolled HIV patients, 106 had an HCV coinfection. Of the 11 candidate predictors (from history-taking, laboratory testing), seven had an adjusted likelihood ratio ≥ 1.5 or ≤ 0.67: ≥ 50 years (+1 point), diabetes mellitus (+1), partner/household member with liver disease (+1), generalized pruritus (+1), platelets < 200 × 10⁹/L (+1), aspartate transaminase (AST) < 30 IU/L (-1), AST-to-platelet ratio index (APRI) ≥ 0.45 (+1), and APRI < 0.45 (-1). The AUROC was 0.84 (95%CI: 0.80-0.89), indicating good discrimination of HCV/HIV coinfection and HIV mono-infection. The CPS result ≥0 best fits the test-threshold (negative predictive value: 99.2%, 95%CI: 98.8-99.6). Applying this threshold, 30% (n = 926) would be tested. Sixteen coinfections (15%) would have been missed, none with advanced fibrosis. CONCLUSIONThe CPS performed well in the derivation cohort, and bears potential for other contexts of low-to-intermediate prevalence and little onward risk of transmission(i.e. cohorts without major risk factors as injecting drug use, men having sex with men), and where available resources do not allow to test all HIV patients as recommended by WHO. However, the score requires external validation in other patient cohorts before any wider use can be considered.