Hepatitis C virus antigen detection is an appropriate test for screening and early diagnosis of hepatitis C virus infection in at-risk populations and immunocompromised hosts.

Early diagnosis remains key for effective prevention and treatment. Unfortunately, current screening with anti-hepatitis C virus antibody (anti-HCV Ab) test may have limited utility in the diagnosis of HCV infection and reinfection. This is of special concern to at-risk population, such as immunocompromised hosts and end-stage renal failure patients on hemodialysis. HCV antigen (Ag) could be useful in identifying the ongoing infection in such clinical scenarios. Hence, we aimed to study the utility of HCV Ag testing for the diagnosis of acute and chronic hepatitis C. Of 89 samples studied, 19 were from acute hepatitis C patients who were immunocompromised or were on hemodialysis, 43 were from active chronic hepatitis C patients and 27 were from patients treated for chronic hepatitis C. All samples were tested for HCV Ag using the Abbott ARCHITECT HCV Ag assay. HCV Ag was reactive in 19/19 samples from acute hepatitis C patients and 42/43 samples from active chronic hepatitis C patients. It was nonreactive in all samples from treated patients. The test showed a sensitivity and specificity of 98.4% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 96.4%, respectively. The HCV antigen test has high clinical sensitivity and specificity and is useful for the diagnosis of acute and chronic hepatitis C infection in at-risk and immunocompromised patients. Its short turnaround time and relatively low cost are advantageous for use in patients on hemodialysis and other at-risk patients who require monitoring of HCV infection and reinfection.

HCV treatment initiation in persons with chronic kidney disease in the directly acting antiviral agents era: Results from ERCHIVES.

BACKGROUND: Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. METHODS: We identified HCV+ persons in ERCHIVES between October 1999 and July 2016. We excluded HIV+ and HBsAg+ and those with missing baseline HCV RNA and baseline eGFR data. We identified persons initiated on any approved DAA-regimen through July 2016, by CKD stage. Logistic regression analyses were used to determine factors associated with treatment initiation. RESULTS: Among 83 706 evaluable persons, 21.1% initiated treatment. Rates differed significantly by CKD stage: 22.1% for eGFR>90 mL/min/1.73 m2 and CKD stage-2; 14.9% for CKD stage 3; and 8.0% for CKD stage-4/5. Those with CKD stage-3 were 33% less likely and those with CKD stage-4/5 were 60% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90 mL/min/1.73 m2 . Treatment initiation was less likely in HCV genotype 2 (OR 0.59; 95%CI 0.53,0.66) or 3 (OR 0.53; 95%CI 0.47,0.61) and those with diabetes (OR 0.87, 95% CI 0.81,0.94), cardiovascular disease (OR 0.77, 95% CI 0.70,0.84), alcohol abuse or dependence (OR 0.74, 95% CI 0.70,0.79) or cirrhosis (OR 0.86, 95% CI 0.80,0.92) at baseline. CONCLUSIONS: Persons with more advanced CKD are less likely to receive treatment for HCV despite recent data on safety and efficacy. Strategies are needed to improve treatment rates in the HCV/CKD population.

Treatment adherence and virological response rates in hepatitis C virus infected persons treated with sofosbuvir-based regimens: results from ERCHIVES.

BACKGROUND & AIMS: Role of non-adherence upon virological success with newer oral regimens is unknown. We sought to determine the impact of treatment adherence upon virological outcomes in hepatitis C virus (HCV) infected persons on sofosbuvir (SOF)-based regimens, using pharmacy prescription data as a measure of adherence. METHODS: We analysed HCV infected persons in Electronically Retrieved Cohort of HCV Infected Veterans, who were initiated on SOF-based regimens, excluding those with human immunodeficiency virus, positive hepatitis-B surface antigen, hepatocellular carcinoma and missing HCV RNA. RESULTS: The final dataset included following regimens: SOF+simeprevir (SIM) (n = 1050), SOF+ledipasvir (LDV) (n = 974), SOF+ribavirin (RBV) (n = 663, genotype 2 or 3), and SOF+pegylated interferon (PEG)+RBV (n = 519, genotype 1 or 4). Those treated with a SOF-based regimen were older and more likely to have cirrhosis, diabetes, chronic kidney disease, higher HCV RNA levels, higher body mass index, compared with 1652 controls receiving a boceprevir-based (BOC) regimen. Sustained virological response (SVR12) rates for the SOF+SIM and SOF+LDV groups did not decline significantly even when as low as 50% of the full course was prescribed (except SOF+LDV, 90-99% prescriptions had SVR12 of 84.6%; n = 13). SOF+RBV for genotype 2/3 who received 50-80% of the prescriptions, 23/34 (67.6%) achieved SVR12. For persons with genotype 1/4 infection treated with SOF+PEG+RBV, no declines in SVR12 were seen with lower rates of prescriptions (40/43, or 93% SVR12 rate). CONCLUSIONS: Sofosbuvir-based treatment regimens are highly effective in achieving SVR12. This efficacy is not significantly affected when treated persons receive less than a full prescribed course of treatment.

Virologic response and haematologic toxicity of boceprevir- and telaprevir-containing regimens in actual clinical settings.

Effectiveness, safety and tolerability of boceprevir (BOC) and telaprevir (TPV) in actual clinical settings remain unknown. We determined rates of sustained virologic response (SVR) and haematologic adverse effects among persons treated with BOC- or TPV-containing regimens, compared with pegylated interferon/ribavirin (PEG/RBV). Using an established cohort of hepatitis C virus (HCV)-infected persons, Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), we identified those treated with a BOC- or TPV-containing regimen and HCV genotype 1-infected controls treated with PEG/RBV. We excluded those with HIV coinfection and missing HCV RNA values to determine SVR. Primary endpoints were SVR (undetectable HCV RNA ≥12 weeks after treatment completion) and haematologic toxicity (grade 3/4 anaemia, neutropenia and thrombocytopenia). We evaluated 2288 persons on BOC-, 409 on TPV-containing regimen and 6308 on PEG/RBV. Among these groups, respectively, 31%, 43% and 9% were treatment-experienced; 17%, 37% and 14% had baseline cirrhosis; 63%, 54% and 48% were genotype 1a. SVR rates among noncirrhotics were as follows: treatment naïve: 65% (BOC), 67% (TPV) and 31% (PEG/RBV); treatment experienced: 57% (BOC), 54% (TPV) and 13% (PEG/RBV); (P-value not significant for BOC vs TPV; P < 0.0001 for BOC or TPV vs PEG/RBV). Haematologic toxicities among BOC-, TPV- and PEG/RBV-treated groups were as follows: grade 3/4 anaemia 7%, 11% and 3%; grade 4 thrombocytopenia 2.2%, 5.4% and 1.7%; grade 4 neutropenia 8.2%, 5.6% and 3.4%. SVR rates are higher and closer to those reported in pivotal clinical trials among BOC- and TPV-treated persons compared with PEG/RBV-treated persons. Haematologic adverse events are frequent, but severe toxicity is uncommon.

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

The Safety of The Directly Acting Antiviral Treatment For Hepatitis C Virus According To The Egyptian National Program Protocol In Patients With Midrange Ejection Fraction.

Background: The Egyptian National Committee of Viral Hepatitis program is the leading national hepatitis C virus (HCV) management program globally. However, limited data is available about the effect of the new directly acting antiviral agents on the cardiovascular system. Objectives: Our study aimed to assess the safety of the relatively new directly acting antiviral agents approved by the National Health Committee in Egypt to treat patients infected with hepatitis C virus who have midrange left ventricular ejection fraction. Methods: This multicenter study included 400 successive patients with an ejection fraction (40-49%) from May 2017 to December 2019. We classified them into two groups: Group I (Child A), who received Sofosbuvir and Daclatasvir for twelve weeks, and Group II (Child B), who received Sofosbuvir, Daclatasvir, and Ribavirin for twelve weeks. Patients were evaluated for their symptoms, ejection fraction, brain natriuretic peptide, lipid profile, fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance levels, and Holter monitoring (just before the start of treatment and within three days after completing therapy). Results: We found New York Heart Association Class, ejection fraction, brain natriuretic peptide, premature ventricular contractions burden, as well as highest and lowest heart rate did not show a statistically significant difference in both groups after treatment. The treatment did not cause bradycardia or non-sustained ventricular tachycardia. Fasting blood glucose and fasting insulin levels declined, with improved insulin resistance after treatment in both groups. Both low and high-density lipoprotein cholesterol increased after treatment in Group II. Conclusions: Both regimens of directly acting antiviral agents used in Egypt to treat chronic hepatitis C virus infection are safe in patients with New York Heart Association Class I and II with midrange left ventricular ejection fraction (40-49%). There are beneficial metabolic changes following HCV clearance as an improvement of insulin resistance.

Hepatitis C and kidney transplant: The eradication time of the virus has arrived. / Hepatitis C y trasplante renal: el tiempo de la erradicación del virus ha llegado.

Hepatitis C virus (HCV) infection is a factor that reduces the survival of the patient and the graft in renal transplant (RT). The availability of directly acting antivirals agents (DAAs), very effective and with an excellent safety profile, it allows eradicate HCV from patients with kidney disease, and this is a revolutionary radical change in the natural evolution of this infection, until now without effective and safe treatment for the contraindication use of interferon in kidney transplant patients. The efficiency of some DAAs for all genotypes, even in patients with renal insufficiency constitutes a huge contribution to eradicate HCV in the RT population independently the genotype, severity of kidney failure, progression of liver disease and previous anti HCV therapy. All this is raising, although with controversies, the possibility of use kidneys from infected HCV+ donors for transplant in uninfected receptors and can be treated successfully in the early post-TR, thus increasing the total "pool" of kidneys for RT.

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016.

India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects.

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection in 2015.

Overall prevalence of HCV infection in India has been estimated to be approximately 1.3% in the general population. Recent introduction of sofosbuvir in India at a relatively affordable price has led to great optimism about prospects of cure for these patients. This drug is likely to form the backbone of current and future treatment regimes for HCV infection, displacing pegylated interferon. Availability of directly acting antiviral drugs (DAAs) has necessitated revision of INASL guidelines for the treatment of HCV published in 2014, as has happened across the world. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. Since only one DAA, sofosbuvir, is available in India, only two sofosbuvir-based regimes are possible: either dual drug therapy in combination with ribavirin alone for 6 months or triple drug therapy in combination with ribavirin and pegylated interferon for 3 months. The utility of these regimes in various situations has been discussed. Availability of a few other newer DAAs, expected in 2016, is expected to lead to more widespread use of these agents. Current guidance will be updated once newer DAAs, newer evidence with DAAs and 'real-life experience' with use of DAAs accumulate in India.

Metabolic syndrome in chronic hepatitis C infection: does it still matter in the era of directly acting antiviral therapy?

Metabolic syndrome is prevalent in patients with hepatitis C virus (HCV) infection. Given the pandemic spread of HCV infection and metabolic syndrome, the burden of their interaction is a major public health issue. The presence of metabolic syndrome accelerates the progression of liver disease in patients with HCV infection. New drug development in HCV has seen an unprecedented rise in the last year, which resulted in better efficacy, better tolerance, and a shorter treatment duration. This review describes the underlying mechanisms and clinical effects of metabolic syndrome in HCV infection, as well as their importance in the era of new directly acting antiviral therapy.

A pharmacological profile of ribavirin and monitoring of its plasma concentration in chronic hepatitis C infection.

Chronic hepatitis C (CHC) infection, usually an asymptomatic infection, has long-term serious complications such as cirrhosis, hepatocellular carcinoma, and end-stage liver disease requiring liver transplantation (LT). Several novel drugs against hepatitis C which form part of 'specifically targeted antiviral therapy for hepatitis C' (STAT-C) have been developed. These include NS3/4A protease inhibitors telaprevir, boceprevir, and nucleoside/non-nucleoside polymerase inhibitors (NS5A) which hold promise for future therapy. Despite the development of new anti-hepatitis C virus (HCV) drugs, ribavirin (RBV) remains the single most important drug to prevent relapse and is frequently included among newer regimens being developed with novel small molecule anti-HCV drugs. The current approved treatment is a combination therapy of once weekly subcutaneous pegylated-interferon (PEG-IFN)-α plus body-weight-based oral RBV regimen. The most significant dose-dependent side effect of RBV is hemolytic anemia warranting dose reduction or discontinuation in severe cases compromising sustained virological response (SVR). Monitoring RBV plasma concentration has been challenging due to its peculiar pharmacokinetics and has been done to predict both efficacy and toxicity. Herein, we review the pharmacological profile of RBV and the monitoring of its plasma concentration, monitoring in renal impairment, post-LT, and human immunodeficiency virus (HIV)-HCV co-infection in patients being treated with combination therapy of PEG-IFN-α and RBV.