Hepatitis C Virus Antiviral Treatment Research Articles

HCV Antiviral Drugs Have the Potential to Adversely Perturb the Fetal-Maternal Communication Axis through Inhibition of CYP3A7 DHEA-S Oxidation.

The hepatitis C virus (HCV) poses a great risk to pregnant people and their developing fetus, yet no HCV antiviral treatment guidelines have been established. While there has been a substantial increase in the development of HCV antivirals, the effect they have on the developing fetus remains poorly defined. Many of these drugs are metabolized through the cytochrome P450 CYP3A pathway, which is mediated by cytochrome P450 3A7 (CYP3A7) in the fetus and developing infant. In this study, we sought to investigate the effect HCV antivirals have on CYP3A7 metabolism, as this CYP enzyme plays a vital role in proper fetal and neonatal development. Of the 13 HCV antivirals we investigated, 8 (∼62%) inhibited CYP3A7 metabolic activity by 50% or more at a concentration of 20 µM. Furthermore, paritaprevir, asunaprevir, simeprevir, danoprevir, and glecaprevir all had observed half-maximal inhibitory concentrations between the range of 10 and 20 µM, which is physiologically relevant in comparison with the Km of dehydroepiandrosterone-sulfate (DHEA-S) oxidation (reported to be between 5 and 20 µM). We also discovered that paritaprevir is a time-dependent inhibitor of CYP3A7, which shifts the IC50 ∼twofold from 11 µM to 5 µM. Upon further characterization, paritaprevir inactivates DHEA-S metabolism by CYP3A7, with KI and Kinact values of 4.66 µM and 0.00954 minute-1, respectively. Depending on treatment plan and off-label drug use, HCV treatment could adversely affect the fetal-maternal communication axis by blocking fetal CYP3A7 metabolism of important endogenous hormones. SIGNIFICANCE STATEMENT: The prevalence of HCV in pregnant people is estimated at between 1% and 8% of the global population, yet little to no information exists about the risk antiviral treatment poses to the developing fetus. There is a potential risk of drugs adversely affecting mother-fetal communication by inhibiting fetal hepatic CYP3A7, an integral enzyme for estriol production. We discovered that five HCV antivirals inhibited DHEA-S metabolism by CYP3A7, and paritaprevir inactivated the enzyme. Our studies demonstrate the potential threat these drugs pose to proper fetal development.

Global, regional, and country-level coverage of testing and treatment for HIV and hepatitis C infection among people who inject drugs: a systematic review

People who inject drugs are disproportionately affected by HIV and hepatitis C virus (HCV) infections, while there is little global data on HIV and HCV testing and treatment coverage of this population. We conducted a systematic review to evaluate country-level, regional, and global coverage of HIV and HCV testing and treatment among people who inject drugs. We did a systematic review, and searched bibliographic databases (MEDLINE, Embase, and PsycINFO) and grey literature for studies published between Jan 1, 2017, and April 30, 2022, that evaluated the proportion of people who inject drugs who received testing or treatment for HIV or HCV. For each country, we estimated the proportion of people who inject drugs tested for HIV antibodies in the past 12 months (recent), people who inject drugs ever tested for HCV antibodies and HCV RNA, people who inject drugs with HIV currently receiving antiretroviral therapy, and people who inject drugs with HCV ever receiving HCV antiviral treatment. Regional and global estimates, weighted by the population size of people who inject drugs, were generated where sufficient data were available. This study is registered with PROSPERO (CRD42020173974). 512 documents reported data eligible for analyses, including 337 peer-reviewed articles, 27 conference abstracts or presentations, and 148 documents from grey literature or supplementary searches. Data of recent HIV antibody testing were available for 67 countries and ever having had HCV antibody testing were available for 49 countries. Globally, an estimated 48·8% of people who inject drugs were recently tested for HIV antibodies (95% uncertainty interval [UI] 43·3-54·2%; range 0·9-86·0%), and 47·1% had ever been tested for HCV antibodies (95% UI 43·4-51·0%; range 0·0-93·3%). HCV RNA testing data were available from three countries. Coverage of HIV antibody testing was high (>75%) in four countries and for HCV antibody testing in 15 countries. The estimated uptake of current HIV treatment (18 countries) ranged from 2·6% to 81·9%, and the estimated uptake of ever having HCV treatment (23 countries) ranged from 1·8% to 88·6% across countries. Uptake of HIV treatment was high in two countries, and of HCV treatment in one country. HIV and HCV testing and treatment uptake among people who inject drugs was highly variable, and suboptimal in most countries. Strategies to improve access to HIV and HCV care among people who inject drugs and the availability of public health surveillance are urgently required. Australian National Health and Medical Research Council and UK National Institute for Health and Care Research Health Protection Research Unit in Behavioural Science and Evaluation.

Association between treatment of hepatitis C virus and risk of cardiovascular disease among insured patients with the virus in the United States.

Hepatitis C virus (HCV) infection has been associated with increased risk of cardiovascular disease (CVD). It is unclear whether HCV treatment affects risk of CVD among patients infected with HCV. We assessed the incidence and risk of CVD among insured patients with HCV infection and evaluated if HCV treatment was associated with reduced CVD risk. This retrospective cohort study used MarketScan Commercial and Medicare Supplement databases. Patients newly diagnosed with HCV (vs. patients without HCV) between January 2008 and August 2015 were categorized by treatment (none, insufficient, or minimum effective) based on receipt and duration of anti-HCV treatments. After propensity score matching, time-dependent Cox proportional hazards models were used to compare CVD risk between patients with HCV versus without and between patients with HCV by treatment type and duration. HCV was associated with 13% increased risk of developing CVD overall (adjusted hazard ratio [aHR] 95% CI 1.26-1.35) and with 13% (aHR 1.07-1,18), 9% (aHR 1.03-1.15), and 32% (aHR 1.24-1.40) significantly increased risks of developing coronary artery disease, cerebrovascular disease, and peripheral vascular disease, respectively. Among patients with HCV, compared with no treatment, receipt of minimum effective treatment was associated with 24% decreased risk of CVD, and receipt of insufficient treatment was associated with 14% decreased risk of CVD. Individuals chronically infected with HCV had a higher incidence of CVD. Among patients with HCV, receipt of antiviral treatment for HCV was associated with decreased risk of CVD.

Rescue Therapy after Failure of HCV Antiviral Treatment with Interferon-Free Regimens.

Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness.

Usefulness of dried blood spot samples for monitoring hepatitis C treatment outcome and reinfection among people who inject drugs in a test-and-treat program.

Dried blood spots (DBS) are a reliable tool to diagnose viremic hepatitis C virus (HCV) infection. We evaluated the clinical performance of a DBS-based molecular assay for the assessment of cure and reinfection after on-site treatment at a harm reduction center (HRC). Genotyping from DBS samples was also assessed to discriminate reinfection from treatment failure. People who inject drugs (PWID) from an ongoing test-and-treat pilot at the largest HRC in Barcelona were included in the study. HCV-RNA detection from DBS collected after treatment (with follow-up at 12, 36, and 60 weeks) was compared with a molecular point-of-care test using finger-stick blood (GeneXpert). Baseline and follow-up DBS samples were genotyped by NS5B sequencing or commercial real-time PCR. Among treated patients, 193 follow-up DBS samples were tested. The DBS-based assay showed 100% specificity (129/129), and sensitivity ranged from 84.4% to 96.1% according to different viral load cut-offs (from detectable to 3000 IU/mL). Sensitivity as test of cure (follow-up 12) ranged from 85.1% to 97.4%. Among the 64 patients with recurrent viremia, 10.9% had low viral loads (≤1000 IU/mL); HCV genotyping allowed us to classify 73.5% of viremic cases either as reinfection or as treatment failure. DBS samples are useful to assess cure and differentiate reinfection from relapse after HCV antiviral treatment in the real world, facilitating decentralization of treatment and posttreatment follow-up in PWID. However, a fraction of patients presented with low viral loads, limiting viremia detection and genotyping in DBS and, therefore, repeat testing is recommended.

Management of HCV Positive Patients on Maintenance Dialysis

The prevalence of hepatitis C virus (HCV) is quite high in Pakistan, especially among patients on maintenance hemodialysis (MHD). HCV infection is associated with increased morbidity and mortality among patients on maintenance hemodialysis. The current availability of direct-acting antiviral therapy has changed the picture of HCV prevalence in many countries. Objective: The aim of our study is to assess the prevalence and treatment of HCV infection among patients on maintenance hemodialysis in our setting. Methods: This descriptive cross-sectional study was held in the Medicine department of Mayo Hospital, Lahore for six-months duration from 13th January 2022 to 12th July 2022. The study was conducted on 130 patients to assess HCV seroprevalence among patients on MHD. Data on HCV status, PCR positivity and number of patients receiving active treatment were evaluated. Results: A total of 130 patients on maintenance hemodialysis were included in this study. The incidence of HCV infection was 49 (37.7%). All patients underwent PCR and 32 patients were PCR positive. All except 5 of the 32 PCR positive patients started HCV antiviral treatment. Conclusions: In conclusion, our study helps highlight the high prevalence of HCV among maintenance hemodialysis patients and the need to maintain adequate infection control measures. However, it is encouraging to know that most patients have been treated, and future research will highlight the importance of prompt treatment for MHD patients. It is recommended that all of HCV PCR positive patients were being treated with DAA. Keywords: HCV, Hemodialysis, Antivirals, Seroconversion, Health insurance, Infection.

Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.

The standard algorithm for diagnosing hepatitis C virus (HCV) infection has two steps, an HCV antibody test for screening and a nucleic acid amplification test (NAAT) for confirmation. However, the HCV core antigen (HCVcAg) detection assay is an alternative for one-step diagnosis. We aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay to detect active hepatitis C in serum/plasma in people living with HIV/AIDS (PLWHA), through a systematic review and meta-analysis. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched until 20 September 2022 (PROSPERO, CRD42022348351). We included studies evaluating Abbott ARCHITECT HCV Ag assay (index assay) versus NAATs (reference test) in PLWHA coinfected with HCV who did not receive antiviral treatment for HCV. Meta-analysis was performed with the MIDAS module using Stata and random-effects models. The QUADAS-2 tool evaluated the risk of bias. The bivariate analysis was conducted on 11 studies with 2,407 samples. Pooled sensitivity was 0.95 (95% CI = 0.92 to 0.97), specificity 0.97 (95% CI = 0.93 to 0.99), positive likelihood ratio 37.76 (95% CI = 12.84 to 111.02), and negative likelihood ratio 0.06 (95% CI = 0.04 to 0.09). The area under the curve was 0.97 (95% CI = 0.20 to 1.00). For low prevalence (≤5%), the posttest probability that an individual with a positive test was a true positive ranged from 4% to 67%, whereas, at high prevalence (≥10%), the posttest probability was between 81% and 87%, indicating that a confirmatory test should be necessary, particularly with prevalence values of ≤1%. Regardless of prevalence, the probability that an individual with a negative test was a false negative was close to zero, indicating that the individual was not infected with HCV. In conclusion, the accuracy of the Abbott ARCHITECT HCV Ag assay was very good for HCV screening in serum/plasma samples from PLWHA. The clinical utility to confirm HCV infection was acceptable in high-prevalence settings (≥10%) but poor in low-prevalence settings (≤1%). Furthermore, it was excellent in excluding active HCV infection.

Dialysis and advanced chronic kidney disease population Free from Hepatitis C virus infection: A safe nephrology approach

Background: One of the most prevalent viruses among dialysis patients is Hepatitis C as it affects 8.4% of the dialysis patients in Qatar1. It causes serious complications including end-stage liver disease. There is no available vaccine to protect against the transmission of the Hepatitis C virus (HCV). However, antiviral drugs lead to precious benefits including reducing the risk of morbidity/mortality, increasing life expectancy, and eventually nominating them for kidney transplant2. The Qatar National Plan for HCV control by 2020 was launched in December 2014. In 2017, the World Health Organization accepted to support the development and implementation of national multispectral policies and strategies for its prevention and control in Qatar3. The treatment of HCV in dialysis patients has been a challenge since its launch in 2020. Methods: This is a single-center cohort study, including a retrospective collection of data from 70 dialysis patients infected with Hepatitis C virus. 44 of them were treated with Ombitasvir 12.5 mg, Paritaprevir 75 mg, and Ritonavir 50 mg over 12 weeks and 12-week follow up period. As per all guidelines of the American Association for the Study of Liver Disease (AASLD), the European Association for the Study of the Liver (EASL), and the Asian Pacific Association for the Study of the Liver (APASL), sustained virological response indicates a patient has cured. Results: From the 70 HCV-positive patients, the 44 patients who received the 12-week treatments were cured (Figure 1). During the treatment phase, their biochemical values were normal (Figure 2). Conclusion: The outcome of the first phase treatment of Hepatitis C in dialysis patients is highly effective. Moreover, the successful HCV antiviral treatment will decrease the risk of infection transmission within dialysis patients and reduce the occurrence of complications occurring after kidney transplantation.

Prior antiviral treatment and mortality among patients with hepatitis C virus-related hepatocellular carcinoma: A national cohort study.

BackgroundThe current antiviral treatments available for hepatitis C virus (HCV) infection decrease the risk of hepatocellular carcinoma (HCC). Hence, patients with HCV infection who have not received antiviral treatment and have developed HCC may be those who missed timely antiviral treatment for HCV. However, the proportion of patients who missed timely antiviral treatment and its implications are largely unexplored.MethodsA nationwide retrospective cohort of 4,592 newly diagnosed HCV-related HCC patients (2013–2017) was identified from the Korean National Health Insurance Service database. Prior antiviral treatment for HCV was defined as a history of at least one HCV-specific antiviral treatment before HCC diagnosis. The outcome was all-cause mortality.ResultsPrior antiviral treatment for HCV was identified in 802 (17.4%) patients, and 16%, 16%, 17%, 19%, and 19% of patients received antiviral treatment in the years 2013, 2014, 2015, 2016, and 2017, respectively (P = 0.21). During 8,085 person-years of follow-up (median, 1.4; maximum, 5.3 years of follow-up), 1,970 patients died. Mortality rates were lower in patients with prior antiviral treatment (15 deaths/100 person-years) than in those without prior antiviral treatment (27 deaths/100 person-years). The adjusted hazard ratio (95% confidence interval) for all-cause mortality on comparing patients who did and did not receive prior antiviral treatment was 0.68 (0.59, 0.79).ConclusionTimely antiviral treatment for HCV was suboptimal at the population level. Prior antiviral treatment for HCV reduced mortality rate in HCV-related HCC patients. Intensive HCV control strategies are needed to reduce the number of patients with HCV infection who miss timely HCV treatment.

Direct-acting antiviral treatment for Hepatitis C Virus in geriatric patients: a real-world retrospective comparison between early and late elderly patients.

IntroductionChronic hepatitis C virus (HCV) infection rates are high in the geriatric population considering that interferon-based therapy is usually intolerable. With the introduction of oral antiviral therapy for HCV, increased treatment tolerability and good treatment responses have been observed. However, treatment data regarding the geriatric population have been limited. Therefore, this retrospective study aimed to evaluate the efficacy and safety of direct-acting antiviral therapy for HCV in the geriatric population.Materials and MethodsThe primary end point was sustained virologic response (SVR) 12 weeks after treatment completion, whereas the secondary end points were treatment-related side effects and short-term survival rate following treatment.ResultsIn total, 492 patients (median age, 73 years; 43.9% males), including 278 early elderly patients, were enrolled. Among the included patients, 45% had cirrhosis. HCV genotypes 1 (72.4%) and 2 (25.4%) were the most common. The overall SVR rate was 96.7%, with no difference in SVR rates observed between early and late elderly groups (96.8% vs. 96.7%; p = 0.983). Both groups showed similar side effects, including dizziness (11.4%), and fatigue (8.7%), with three patients discontinuing therapy owing to side effects. Both groups had a similar 3-year survival rate. Significant factors associated with post-treatment survival included cirrhosis, albumin, and creatinine level.ConclusionsOur real-world data showed that both early and late elderly patients could undergo direct-acting antiviral treatment for HCV with excellent treatment outcomes.

Hepatocellular carcinoma in transfusion dependent thalassemia patients: a review from a clinical perspective

Survival in patients with transfusion-dependent thalassemias (TDT) has increased, and complications such as hepatocellular carcinoma (HCC) are emerging. Risk factors include viral infection, mainly hepatitis C virus (HCV), iron overload, the presence of cirrhosis, and immune dysregulation. Median survival after HCC occurrence has been estimated at 12 months, while data regarding the incidence of HCC in this population are minimal. Implementing effective hepatitis B virus (HBV)/HCV antiviral treatment and universal HBV vaccination programs is expected to decrease the risk for hepatocarcinogenesis substantially. Significant hemosiderosis and hepatic fibrosis are common in patients with TDT despite chelation therapy and have been correlated with HCC development. Thus, iron overload should be monitored with liver iron concentration and ferritin levels, and effective chelation therapy should be applied. In addition, all TDT patients, particularly those with cirrhosis, should be under surveillance every six months with abdominal ultrasound ± alpha-fetoprotein levels, as this combination seems to provide better sensitivity for early HCC detection.

Metabolic Impact of Diabetes Mellitus Type 2 in Hepatitis C Virus Infected Patients.

Objective: Patients with chronic hepatitis C are subjected to a greater risk of cardiovascular disease and difficult to control diabetes mellitus type 2 (T2DM) comparatively to people that have never contracted Hepatitis C Virus (HCV). We aimed to investigate the impact of T2DM on HCV patients with the help of Fibromax test results compared to nonT2DM patients, and the metabolic differences between the 2 study groups. Our long term goals are to observe the long term impact of achieving systemic virusologic response (SVR) by means of Direct-Acting antivirals (DAA) between the 2 cohorts. Research Design and Methods: We selected a lot of 200 patients with HCV that will undergo interferon-free DAA-based antiviral treatment for HCV and we used the results of the Fibromax Test to compare the biological parameters of T2DM and nonT2DM patients. RESULTS Among patients with T2DM compared to NonT2DM there is a significant correlation on Steatotest, NashTest, GGT, Glycemia, body weight, height and BMI. Test also showed that 15,5% of the test group had elevated glycemia, indicating the probability of developing diabetes in the future. Conclusions: Our results suggest that HCV patients that also have T2DM are subjected to a combined higher risk of accelerated steatosis development, steatohepatitis, added difficulty in controlling glycemic levels. All these previous elements combined with a prevalence for patients to be overweight have a negative metabolic impact. Eradication of HCV with the help of DAA is important in order to help improving the metabolic impact of diabetes on steatosis, steatohepatitis. An added benefit is better management of glycemic control by decreasing insulin use and eliminating one risk factor of T2DM.

Assessment of Incidence of and Surveillance Burden for Hepatocellular Carcinoma Among Patients With Hepatitis C in the Era of Direct-Acting Antiviral Agents

In the US, hepatocellular carcinoma (HCC), primarily associated with hepatitis C virus (HCV) infection, is the fastest rising cause of cancer-related death. Wider use of highly effective direct-acting antiviral agents (DAAs) substantially reduces the burden of chronic HCV infection, but the subsequent impacts with HCV-associated HCC remain unknown. To assess projected changes in the incidence rate of and surveillance burden for HCC in the era of DAA treatment for HCV. This decision analytical model study was performed from January 2019 to February 2020, using an individual-level state-transition simulation model to simulate disease progression, screening, and different waves of antiviral treatments for HCV in the US from 2012 to 2040. Current clinical management for chronic HCV infection. Model outcomes were projected temporal trends and age distribution of incident HCC cases and candidates for HCC surveillance among patients with viremia and patients with virologically cured HCV. The simulation model projected that the annual incidence of HCC among patients with viremia and patients with virologically cured HCV will continue increasing to 24 000 (95% uncertainty interval [UI], 18 000-31 000) cases until 2021. In patients with virologically cured HCV, incident HCC cases are projected to increase from 1000 (95% UI, 500-2100) in 2012 to the peak of 7000 (95% UI, 5000-9600) in 2031 with a subsequent decrease to 6000 (95% UI, 4300-8300) by 2040. The proportion of incident HCC cases that occur in individuals with virologically cured HCV is estimated to increase from 5.3% in 2012 to 45.8% in 2040. The number of candidates for HCC surveillance in the population with virologically cured HCV is projected to increase from 106 000 (95% UI, 70 000-178 000) in 2012 to the peak of 649 000 (95% UI, 512 000-824 000) in 2030 and decrease to 539 000 (95% UI, 421 000-687 000) by 2040, while the proportion of all candidates for surveillance who are virologically cured is estimated to increase from 8.5% to 64.6% during the same period. The average age of HCC incidence and surveillance candidates is estimated to increase from 55 in 2012 to 72 and 71, respectively, by 2040. The results of this study suggest that the burden of HCC will shift from patients with viremia to patients with virologically cured HCV, and to older populations. Appropriate management may be warranted for early detection of HCC in patients who may no longer be receiving specialty care for liver conditions.

Telemedicine successfully engages marginalized rural hepatitis C patients in curative care.

Rurally located individuals living with hepatitis C virus (HCV) face barriers to engagement and retention in care. Telemedicine technologies coupled with highly curative direct acting antiviral (DAA) treatments may increase accessibility to HCV care while achieving high sustained virologic response (SVR) rates. We compared clinical and socio-economic characteristics, SVR, and loss to follow-up among telemedicine (TM), mixed delivery (MD), and outpatient clinic (OPC) patients receiving care through The Ottawa Hospital Viral Hepatitis Program (TOHVHP). TOHVHP clinical database was used to evaluate patients engaging HCV care between January 1, 2012, and December 31, 2016. SVR rates by HCV care delivery method (TM versus OPC versus MD) were calculated. Analysis included 1,454 patients who engaged with TOHVHP at least once. Patients were aged almost 50 years on average and were predominately male and Caucasian. A greater proportion of TM patients were rurally based, were Indigenous, had a history of substance use, and had previously been incarcerated. Per-protocol DAA SVR rates for TM, OPC, and MD patients were 100% (26/26), 93% (440/472), and 94% (44/47), respectively. Loss-to-follow-up rates for HCV-treated TM and MD patients were higher (27% [10/37], 95% CI 0.58 to 0.88, and 11% [7/62], 95% CI 0.81 to 0.97, respectively) than for those followed exclusively in the OPC (5% [39/800], 95% CI 0.94 to 0.97). TM can successfully engage, retain, and cure rurally based HCV patients facing barriers to care. Strategies to improve TM retention of patients initiating HCV antiviral treatment are key to optimizing the impact of this model of care.

Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: A systematic literature review and meta-analysis

BackgroundRecent approval and adoption of pangenotypic direct acting antivirals (DAAs) necessitated a revision of the 2015 World Health Organization guidelines for the management of persons with hepatitis C virus (HCV) infection. MethodsWe searched MEDLINE, EMBASE, CENTRAL, and relevant conference proceedings to identify randomized and non-randomized trials, as well as prospective observational studies of DAAs. The proportions of persons with events were pooled for sustained virological response at 12 weeks post-treatment (SVR12), discontinuations due to adverse events (DAEs), serious adverse events (SAEs), and all-cause mortality. Analyses were stratified by HCV genotype and antiviral treatment experience, with subgroup analyses based on presence of cirrhosis and HIV-HCV coinfection. FindingsThe evidence base consisted of 238 publications describing 142 studies. In the overall analysis, which included all persons irrespective of treatment experience or comorbidities, the pooled proportion achieving SVR12 exceeded 0.94 for all pangenotypic regimens across genotypes 1, 2, and 4. Some heterogeneity may have led to lower SVR rates in persons with genotype 3 infection. High SVR12 (>0.90) was observed in persons with genotype 1 infection with cirrhosis, though evidence varied and was limited for genotypes 2–4. Evidence was sparse for persons with HIV–HCV coinfection. All regimens were associated with small proportions of persons with DAEs, SAEs, or all-cause mortality. InterpretationBased on this and other supporting evidence, the WHO issued updated guidelines with a conditional recommendation, based on moderate quality evidence, for the use of pangenotypic DAA regimens for persons with chronic HCV infection aged 18 years and older (July 2018). FundingThis study was funded by the World Health Organization.

The change in the nationwide seroprevalence of hepatitis C virus and the status of linkage to care in South Korea from 2009 to 2015

Hepatitis C virus (HCV) requires epidemiological monitoring to estimate its disease burden and to develop countermeasures. This study aimed to investigate the difference between the 2015 and 2009 nationwide anti-HCV seroprevalence and to determine linkage to care estimates in South Korea. A total 268,422 examinees ≥ 20years old were included in 2015 from 33 medical institutions nationwide. Electronically extracted data were retrospectively analyzed to calculate the age-, sex-, and area-adjusted anti-HCV prevalence. Seroprevalence in 2015 was measured using the same method as that in 2009. For anti-HCV-positive subjects, medical records were reviewed to see whether HCV RNA testing or antiviral treatment was performed. Adjusted anti-HCV prevalence was 0.60% (95% confidence interval, 0.57-0.63) based on general Korean population in 2015. It showed an increasing trend according to age; 0.23% in thirties, 0.38% in forties, 0.63% in fifties, 1.08% in sixties, and 1.65% in those aged ≥ 70years. From 2009 to 2015, the adjusted anti-HCV prevalence decreased by 30%, with odds ratio of 0.70 (95% CI 0.70-0.71). There was significant intranational regional variation and changing pattern of seroprevalence. Among 1359 anti-HCV-positive subjects, HCV RNA test was performed in 60% and 25.4% had positivity. Treatment-initiated and cured rates in 2015 were 18.5% and 10.9%, respectively. Anti-HCV prevalence in South Korea was 0.6% in 2015, showing a 30% decrease from that in 2009. Although the HCV RNA testing rate was increased since 2009, this remains suboptimal. Moreover, the treatment uptake rate should be improved in South Korea.

Increased Risk for Hepatocellular Carcinoma Persists Up to 10 Years After HCV Eradication in Patients With Baseline Cirrhosis or High FIB-4 Scores

It is unclear if hepatocellular carcinoma (HCC) risk declines over time after hepatitis C virus (HCV) eradication. We analyzed changes in HCC annual incidence over time following HCV eradication and identified dynamic markers of HCC risk. We identified 48,135 patients who initiated HCV antiviral treatment from 2000 through 2015 and achieved a sustained virologic response (SVR) in the Veterans Health Administration (29,033 treated with direct-acting antiviral [DAA] agents and 19,102 treated with interferon-based regimens). Patients were followed after treatment until February 14, 2019 (average 5.4 years), during which 1509 incident HCCs were identified. Among patients with cirrhosis before treatment with DAAs (n= 9784), those with pre-SVR fibrosis-4 (FIB-4) scores ≥3.25 had a higher annual incidence of HCC (3.66%/year) than those with FIB-4 scores <3.25 (1.16%/year) (adjusted hazard ratio 2.14; 95% confidence interval 1.66-2.75). In DAA-treated patients with cirrhosis and FIB-4 scores ≥3.25, annual HCC risk decreased from 3.8%/year in the first year after SVR to 2.4%/year by the fourth year (P=.01). In interferon-treated patients with FIB-4 scores ≥3.25, annual HCC risk remained above 2%/year, even 10 years after SVR. A decrease in FIB-4 scores from ≥3.25 pre-SVR to <3.25 post-SVR was associated with an approximately 50% lower risk of HCC, but the absolute annual risk remained above 2%/year. Patients without cirrhosis before treatment (n= 38,351) had a low risk of HCC, except for those with pre-SVR FIB-4 scores ≥3.25 (HCC risk 1.22%/year) and post-SVR FIB-4 scores ≥3.25 (HCC risk 2.39%/year); risk remained high for many years after SVR. Patients with cirrhosis before an SVR to treatment for HCV infection continue to have a high risk for HCC (>2%/year) for many years, even if their FIB-4 score decreases, and should continue surveillance. Patients without cirrhosis but with FIB-4 scores ≥3.25 have a high enough risk to merit HCC surveillance, especially if FIB-4 remains ≥3.25 post-SVR.

Effect of Treatment of Hepatitis C by Directly Acting Antivirals (DAA) on Chronic Hepatitis C, B Coinfected Patients

Background: Persons with hepatitis C virus (HCV) who are co-infected with hepatitis B virus (HBV) may be at risk for reactivation of HBV infection during or following HCV treatment. HBV and HCV share similar modes of transmission, and co-infection with the two viruses does occur. Objectives: This study aimed to evaluate the effect of HCV anti-viral treatment (DAAS) on HBV in HCV and HBV Coinfected patients. Patients and methods: The study was performed in Internal Medicine Department (Outpatient Clinic and the Inpatient Ward), Mahalla Hepatology Teaching Hospital, Gharbia, Egypt during the period from August 2016 to November 2017 on 20 HCV and HBV co-infected patients ranged from 18-70 years old. Results: The age of patients ranging from 26 to 65 years old (median 44). Male represent 55% and female represent 45% which showed male predominance. Patients were treated by different types by Hcv antiviral treatment (DAAS) like (SOF+DAC), (SOF+SIM), (SOF+DAC+RBV). At baseline, 12 patients had detectable HBV viral load, 5 Patients had positive (HBsAg) and undetectable HBV viral load and 3 patients had negative (HBsAg) and undetectable HBV viral load. Total number of HBV reactivated cases were 12 patients, 3 of them reactivated by increasing HBV DNA, and 5 of them reactivated by both increasing HBVDNA and ALT flare. Conclusion: HBV reactivation is a severe, life-threatening consequence of chemotherapy and immunotherapy in patients with chronic hepatitis B infection. Reactivation may be associated with DAA therapy in patients with HCV/HBV co-infection. HBV reactivation can be prevented through the use of pretreatment screening and anti-HBV prophylactic treatment.

Effect of Treatment of Hepatitis C by Directly Acting Antivirals (DAA) on Chronic Hepatitis C, B Coinfected Patients

Background: Persons with hepatitis C virus (HCV) who are co-infected with hepatitis B virus (HBV) may be at risk for reactivation of HBV infection during or following HCV treatment. HBV and HCV share similar modes of transmission, and co-infection with the two viruses does occur. Objectives: This study aimed to evaluate the effect of HCV anti-viral treatment (DAAS) on HBV in HCV and HBV Coinfected patients. Patients and methods: The study was performed in Internal Medicine Department (Outpatient Clinic and the Inpatient Ward), Mahalla Hepatology Teaching Hospital, Gharbia, Egypt during the period from August 2016 to November 2017 on 20 HCV and HBV co-infected patients ranged from 18-70 years old. Results: The age of patients ranging from 26 to 65 years old (median 44). Male represent 55% and female represent 45% which showed male predominance. Patients were treated by different types by Hcv antiviral treatment (DAAS) like (SOF+DAC), (SOF+SIM), (SOF+DAC+RBV). At baseline, 12 patients had detectable HBV viral load, 5 Patients had positive (HBsAg) and undetectable HBV viral load and 3 patients had negative (HBsAg) and undetectable HBV viral load. Total number of HBV reactivated cases were 12 patients, 3 of them reactivated by increasing HBV DNA, and 5 of them reactivated by both increasing HBVDNA and ALT flare. Conclusion: HBV reactivation is a severe, life-threatening consequence of chemotherapy and immunotherapy in patients with chronic hepatitis B infection. Reactivation may be associated with DAA therapy in patients with HCV/HBV co-infection. HBV reactivation can be prevented through the use of pretreatment screening and anti-HBV prophylactic treatment.

Opportunistic assessment and treatment of people with hepatitis C virus infection admitted to hospital for other reasons: A prospective cohort study

BackgroundIt will be essential to find novel ways to access, diagnose and treat people with Hepatitis C Virus (HCV) infection in Australia to achieve HCV elimination. AimWe assessed the effectiveness of opportunistic HCV assessment and antiviral treatment in patients admitted to hospital for other reasons. MethodsPatients with HCV infection were referred from inpatient services at a tertiary referral centre in Sydney. Patients were assessed for HCV treatment with transient elastography (TE), HCV genotype and a clinical assessment and a summary letter was generated for all patients with a general practitioner (GP). Patients were offered treatment commencement at hospital discharge or after discharge with their GP, the infectious diseases clinic or with a gastroenterologist if they had cirrhosis. The primary outcome was the proportion of eligible patients who commenced treatment. We also undertook an intention to treat (ITT), modified intent to treat (mITT) analysis for virologic outcome (SVR12) and per protocol cure rates. An assessment of potential efficiency gains was undertaken. ResultsA total of 100 patients with a positive HCV antibody test were enrolled, of whom 70 were viraemic. The cohort included a high proportion of people who currently or previously injected drugs, indigenous patients and people previously lost to follow-up from other services. Treatment was initiated in 46 (66%) patients. The ITT was 80.4% (37/46) and mITT rate was 84.1% (37/44).The per-protocol SVR12 rate was 94.9%. Two subjects with genotype 3 and cirrhosis failed treatment, two subjects died and five were lost to follow up. The key barrier to uptake of DAA was incomplete assessment. Key inefficiencies of this model of care included referral of non-viraemic subjects, limited TE access and virologic test turnaround times. ConclusionThis model of care can complement the current efforts to increase HCV treatment in the community for those who do not access care elsewhere or are lost to follow-up.