Weeks For Genotype Research Articles

Clinical effectiveness of pharmacist-led versus conventionally delivered antiviral treatment for hepatitis C virus in patients receiving opioid substitution therapy: a pragmatic, cluster-randomised trial

Highly effective direct-acting antiviral drugs provide the opportunity to eliminate hepatitis C virus (HCV) infection, but established pathways can be ineffective. We aimed to examine whether a community pharmacy care pathway increased treatment uptake, treatment completion, and cure rates for people receiving opioid substitution therapy, compared with conventional care. This cluster-randomised trial was done in Scottish community pharmacies. Before participants were recruited, pharmacies were randomly assigned (1:1) to refer patients with evidence of HCV antibodies to conventional care or offered them care in the pharmacy (pharmacist-led care). Pharmacies were stratified by location. All pharmacies were trained to offer dried blood spot testing. All eligible participants had received opioid substitution therapy for approximately 3 months, and those eligible to receive treatment in the pharmacist-led care pathway were HCV PCR positive, were infected with HCV genotype 1 or 3, and were willing to have a pharmacist supervise their antiviral drug administration. Neither pharmacists nor patients were masked to treatment allocation. In both groups, assessment blood samples were taken, infection with HCV was confirmed, and daily oral ledipasvir-sofosbuvir (90 mg ledipasivir plus 400 mg sofosbuvir) for 8 weeks for genotype 1 or daily oral sofosbuvir (400 mg) plus oral daclatasvir (60 mg) for 12 weeks for genotype 3 was prescribed by a nurse (conventional care group) or pharmacist (pharmacist-led care group). In the conventional care group, the patient received care at a treatment centre. Once prescribed, medication in both groups was delivered as daily modified directly observed therapy alongside opioid substitution therapy in the participants' pharmacy where treatment was observed on 6 days per week. The primary outcome was the number of patients with sustained virological response 12 weeks after completion of treatment (SVR12) as a proportion of the number of people receiving opioid substitution therapy at participating pharmacies. Participants were monitored at each visit for nausea and fatigue; other adverse events were recorded as free text. Secondary outcomes compared key points on treatment pathway between the two groups. These key points were the proportion of patients having dry blood spot testing, the proportion of patients initiating HCV treatment, the proportion of patients completing the 8 or 12 week HCV course of treatment, and the proportion of patients with sustained virological response at 12 months. This study is registered with ClinicalTrials.gov, NCT02706223. 56 pharmacies were randomly assigned (28 to each group; one pharmacy withdrew from the conventional care group). The 55 participating pharmacies included 2718 patients receiving opioid substitution therapy (1365 in the pharmacist-led care group and 1353 in the conventional care group). More patients met the primary endpoint of SVR12 in the pharmacist-led care group (98 [7%] of 1365) than in the conventional care group (43 [3%] of 1353; odds ratio 2·375, 95% CI 1·555-3·628, p<0·0001). More users of opioid substitution therapy in the pharmacist-led care group versus the conventional care group agreed to dry blood spot testing (245 [18%] of 1365 vs 145 [11%] of 1353, 2·292, 0·968-5·427, p=0·059); initiated treatment (112 [8%] of 1365 vs 61 [4%] of 1353, 1·889, 1·276-2·789, p=0·0015) and completed treatment (108 [8%] of 1365 vs 58 [4%] of 1353, 1·928, 1·321-2·813, p=0·0007). The data for sustained virological response at 12 months are not reported in this study: patients remain in follow-up for this outcome. No serious adverse events were recorded. Using pharmacists to deliver an HCV care pathway made testing and treatment more accessible for patients, improved engagement, and maintained high treatment success rates. The use of this pathway could be a key part of an integrated and effective approach to HCV elimination at a community level. Partnership between the Scottish Government, Gilead Sciences, and Bristol-Myers Squib.

State of the Art HCV Treatment in Children

Hepatitis C infection is a global issue with an estimated 5 million children with active HCV infection worldwide. The advent of oral direct-acting antiviral (DAA) regimens has revolutionized treatment in adults with excellent efficacy and tolerability. There are limited data and few approved therapies in children. The aim of this review is to discuss the currently approved regimens for children and the recently reported results of clinical trials of DAA in children. DAA regimens are currently approved only for children ≥ 12 years. For most children < 12 years, it is recommended that HCV therapy be deferred until patients are eligible for oral DAA therapies. For treatment-naive adolescents with HCV genotype 1, 4, 5, or 6, treatment with ledipasvir/sofosbuvir for 12 weeks has been reported to have sustained virologic response at 12 weeks of 98%. For treatment-naive adolescents with genotype 2 or 3 HCV, sofosbuvir- ribavirin combination therapy (12 weeks for genotype 2 and 24 weeks for genotype 3) has been reported to have SVR12 of 100% and 97%, respectively. There are promising, recently published studies showing excellent SVR12 rates for ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in adolescents with HCV genotype 1 or 4, and sofosbuvir/daclatasvir in children/adolescents with HCV genotype 4. Finally, ledipasvir/sofosbuvir ± ribavirin for children age 6–12 years with genotypes 1, 3, 4, 5, and 6 treated for either 12 or 24 weeks is reported to have an SVR12 rate of 99%. HCV treatment in children is rapidly evolving. There are now highly effective all-oral, interferon-free regimens for children ≥ 12 years. Clinical trials are on-going for adolescents and children < 12 years with a variety of pangenotypic ribavirin-free regimens, with anticipated approvals in the near future.

Ombitasvir/paritaprevir/ritonavir plus ribavirin for 24weeks in patients with HCV GT4 and compensated cirrhosis (AGATE-I Part II).

Background and AimsAGATE‐I Part I previously reported high sustained virologic response rates in hepatitis C genotype 4 patients with cirrhosis, with 12 and 16 weeks' treatment with a combination of two direct‐acting antivirals, ombitasvir and paritaprevir (codosed with ritonavir), plus ribavirin. Part II, reported here, extended the trial to include a 24‐week treatment arm to fully assess treatment duration in patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis.MethodsEnrollment took place between June and November of 2015. Treatment‐naive and interferon‐experienced patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis were enrolled into Arm C; patients previously treated with a sofosbuvir‐based regimen were enrolled into Arm D. All patients received a 24‐week treatment with ombitasvir, paritaprevir, and ritonavir plus ribavirin. The primary outcome was the proportion of patients with a sustained virologic response (hepatitis C virus RNA < 25 IU/mL) at posttreatment week 12 in the intention‐to‐treat population. The safety population included all patients who received at least one dose of study drug.ResultsIn total, 64 patients were enrolled into AGATE‐I Part II. Sustained virologic response at posttreatment week 12 was achieved in 57 of 61 patients (93.4%; 97.5% confidence interval, 92.6‐97.7) in Arm C and 3 of 3 patients (100%) in Arm D. Two patients were missing SVR12 data, and two prematurely discontinued treatment. The most common adverse events for Arm C were fatigue (16 [26%]) and asthenia (15 [25%]). Results were comparable with those reported in Part I.ConclusionsAGATE‐I Part II indicates that extending treatment beyond 12 weeks in genotype 4–infected patients with compensated cirrhosis does not offer additional benefit.

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.

Sofosbuvir/velpatasvir for 12 weeks in genotype 1–4 HCV-infected liver transplant recipients

Sofosbuvir, an NS5B inhibitor, combined with velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1-6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1-4 HCV infection after liver transplant. Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naïve with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. A total of 79 patients were enrolled and treated in this study (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naïve, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1-4 HCV-infected liver transplant recipients with and without cirrhosis. Sofosbuvir/velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus (HCV) infection. When patients with chronic HCV infection receive a liver transplant, the HCV infection usually recurs, and damages the transplanted liver. This study tested the effects of 12 weeks of sofosbuvir/velpatasvir treatment in patients who had HCV recurrence after a liver transplant. Three months following the end of treatment, 96% of patients were cured of HCV infection. Clinical trial number: NCT02781571.

Revisiting policy on chronic HCV treatment under the Thai Universal Health Coverage: An economic evaluation and budget impact analysis.

Thailand is encountering challenges to introduce the high-cost sofosbuvir for chronic hepatitis C treatment as part of the Universal Health Care’s benefit package. This study was conducted in respond to policy demand from the Thai government to assess the value for money and budget impact of introducing sofosbuvir-based regimens in the tax-based health insurance scheme. The Markov model was constructed to assess costs and benefits of the four treatment options that include: (i) current practice–peginterferon alfa (PEG) and ribavirin (RBV) for 24 weeks in genotype 3 and 48 weeks for other genotypes; (ii) Sofosbuvir plus peginterferon alfa and ribavirin (SOF+PEG-RBV) for 12 weeks; (iii) Sofosbuvir and daclatasvir (SOF+DCV) for 12 weeks; (iv) Sofosbuvir and ledipasvir (SOF+LDV) for 12 weeks for non-3 genotypes and SOF+PEG-RBV for 12 weeks for genotype 3 infection. Given that policy options (ii) and (iii) are for pan-genotypic infection, the cost of genotype testing was applied only for policy options (i) and (iv). Results reveal that all sofosbuvir-based regimens had greater quality adjusted life years (QALY) gains compared with the current treatment, therefore associated with lower lifetime costs and more favourable health outcomes. Additionally, among the three regimens of sofosbuvir, SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype are the most cost-effective treatment option with the threshold of 160,000 THB per QALY gained. The results of this study had been used in policy discussion which resulted in the recent inclusion of SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype in the Thailand’s benefit package.

Hepatitis C treatment from "response-guided" to "resource-guided" therapy in the transition era from interferon-containing to interferon-free regimens.

Peginterferon/ribavirin has been the standard-of-care for chronic hepatitis C virus (HCV) infections: 48weeks for genotype 1 or 4 (HCV-1/4) and 24weeks for HCV-2/3. Response-guided therapy recommended shorter 24- and 16-week regimens for HCV-1 with lower baseline viral loads (<400000-800000IU/mL) and rapid virological response (RVR, undetectable HCV RNA at week 4) and HCV-2/3 with RVR, respectively; and extending to 72 and 48weeks for HCV-1 slower responders and HCV-2 non-RVR patients, respectively, to improve the efficacy. The progress of directly acting antivirals (DAA), moving from interferon-containing regimens in 2011 to interferon-free regimens in 2013, has greatly improved the treatment success. Interferon-containing regimens include boceprevir or telaprevir or simeprevir or daclatasvir plus peginterferon/ribavirin, 24-48weeks, for HCV-1 or 4. However, adding these DAA has no benefit for HCV-1 with lower baseline viral loads/RVR. Instead, 12-week sofosbuvir plus peginterferon/ribavirin attained sustained virological response rates of >90% for HCV-1/3-6. Interferon-free regimens include two main categories: NS5B nucleotide inhibitor (sofosbuvir)-based regimens and NS3/4A inhibitor/NS5A inhibitor-based regimens (daclatasvir/asunaprevir, paritaprevir/r/ombitasvir/dasabuvir and grazoprevir/elbasvir). About 8-24weeks interferon-free regimens could achieve sustained virological response rates of 82-99% for corresponding HCV genotypes. Although the newly DAA interferon-free regimens have high efficacy and safety, the huge budget impact increases the treatment barriers. The current recommendation should, therefore, base on the availability, indication, and cost-effectiveness in the transition era of DAA. Based on the concept of "resource-guided therapy," peginterferon/ribavirin might be applied for easy-to-treat interferon-eligible patients in resource-constrained areas. Prioritizing patients for interferon-free regimens according to "time-degenerative factors" (age and fibrosis) is justified before the regimens becoming available and affordable.

Sofosbuvir/Velpatasvir Plus GS-9857 (100 Milligrams) for 6, 8, or 12 Weeks in Genotype 1-6 Hepatitis C Virus (HCV)-Infected Patients: An Integrated Analysis of Safety and Efficacy From Two Phase 2 Studies

Sofosbuvir/Velpatasvir Plus GS-9857 (100 Milligrams) for 6, 8, or 12 Weeks in Genotype 1-6 Hepatitis C Virus (HCV)-Infected Patients: An Integrated Analysis of Safety and Efficacy From Two Phase 2 Studies

Assessment of the Response to Treatment in Patients with the Hepatitis C Virus Infection: A Quantitative Study by Focusing on Virologic and Biochemical Responses

Objectives: The main goal of the treatment of the hepatitis C virus (HCV) infection is reduction and elimination of viruses as well as achieving high sustained viral response (SVR). The present study aimed to assess response to treatment of HCV infection by focusing on virological and biochemical aspects. Methods: This study was performed in Hamadan, Iran on HCV infected patients who were referred between 2009 and 2013. All participants were under the treatment with Pegylated Interferon (PEG-IFN) and Ribavirin (RBV). The duration of treatment varied based on the HCV genotype as 24 weeks for genotypes 2 and 3, and 48 weeks for other genotypes. Results: Of the 186 patients with HCV infection, 52.8% had a genotype of 3a and 35.6% had a genotype of 1a/b. Three months after treatment, 75 patients were willing to do quantitative PCR and early virologic response was observed in 58 cases (78.4%). Also, 112 patients were assessed after completing the treatment (75 patients in 24 weeks and 37 patients in 48 weeks treatment protocol) and the end-of-treatment response (ETR) was 94.7% and 86.5% respectively. Amongst the 103 patients with ETR, 76 were followed up six months after treatment and the PCR was negative in 71 cases (SVR = 93.4). With the progress and completion of the treatment, improvement is observed in liver function tests. Conclusions: Even with the introduction of new drugs and interferon free protocols in treatment of hepatitis C infection it seems that the IFN-based treatment is still used in low/middle income countries for treatment-naive patients with HCV genotype 3.

OC-062 Real Life Data on Sofosbuvir/Ledipasvir for 8 Weeks in Genotype 1 Treatment Naive, Non Cirrhotic Patients in the North East of Scotland: Abstract OC-062 Table 1

Introduction Studies have identified groups of patients with Genotype 1 HCV infection who may achieve greater than 90% SVR 12 with only 8 weeks of treatment with Sofosbuvir/Ledipasvir (Sof/Led) (ION3 1). Patients in clinical trials tend to be highly selected and therefore our aim was to explore if the SVRs that can be achieved by this shortened duration of treatment in a ‘real life’ setting match the experience in the trials. Methods Our local guidelines state that Genotype 1, non cirrhotic, treatment naive patients should receive 8 weeks of Sof/Led with the addition of Ribavirin if the viral load is >10 million iu/ml. Data on all patients commenced on Sof/Led between January and November 2015 was collected prospectively. Cirrhosis was defined as a fibroscan >12.5 kpa. Results In total 42 patients have received treatment with Sof/Led for 8 weeks. Of the 42 patients 26 (62%) were male. The average age was 43 years (range 18–78). Average fibroscan score was 5.6 kpa (range 2.9–10.2). There were 4 patients with a fibroscan >9 (classified as F3). All were treatment naive. Opiate substitution therapy was prescribed in 6/42 (14%). The viral load distribution was 10 M–3/42 (7%). To date all patients have completed treatment (100%). Table 1 outlines the end of treatment (EOT), Week 4 SVR (SVR 4) and Week 12 SVR (SVR 12) data. The 2 patients ‘unknown’ were lost to follow up they completed treatment but did not attend for post treatment bloods. SVR 12 data will be available for all patients at the time of presentation. Conclusion Treatment with 8 weeks of Sofosbuvir/Ledipasvir ± ribavirin is well tolerated with few side effects or premature treatment discontinuations. Our data suggest that the SVRs rates with shortened duration of therapy achieved in clinical trials are achievable in ‘real life’ settings. Reference 1 Kowdley KV, et al, Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis. N Engl J Med. 2014 May 15;370(20):1879–88. doi: 10.1056/NEJMoa1402355. Epub 2014 Apr 10. Disclosure of Interest None Declared

602 Ledipasvir/Sofosbuvir (LDV/SOF) for 8 Weeks in Genotype 1 (GT1) Treatment-Naïve (TN) Non-Cirrhotic (NC) Patients with HCV Viral load (VL)

602 Ledipasvir/Sofosbuvir (LDV/SOF) for 8 Weeks in Genotype 1 (GT1) Treatment-Naïve (TN) Non-Cirrhotic (NC) Patients with HCV Viral load (VL) <6 million IU/ml (6M); A Comparative Analysis of the Phase-3 ION-3 Data to Real World Effectiveness (RWE)

Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection.

Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic heptitis C virus (HCV) infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver.

PO-0147a Efficiency Of The Combined Antiviral Therapy Of Chronic Hepatitis C In Children

<h3>Aim</h3> The purpose of this work was to study efficiency of the combined antiviral therapy in children with chronic hepatitis C in Republic of Moldova. <h3>Methods</h3> In compliance with the National Program (2007–2016) in paediatric hepatology department 35 children, aged 4–17 years, were treated with pegylated interferon alpha 2b (60 mcg/m²/week) plus ribavirin in a dose of 15 mg/kg/day; therapy length of 24 weeks for genotype 2 and 3 or 48 weeks for genotype 1b. The diagnosis was confirmed by clinical, biochemical, immunological modification, including degree of viremia (ARN VHC PCR Real Time ROTOR Gene6000 CORBETT RESEARCH) and transient elastometry (Fibroscan) for detecting liver fibrosis. <h3>Results</h3> Chronic hepatitis C (genotype 1b – 31, genotype 2–1, genotype 3a in 3 children) was characterised by the minimal clinical signs, low biochemical activity in 60% of cases. Low virus loading ( &lt;600000 ui/ml) and a minimum degree of fibrosis of F0-F2 was identified in 29 of 35 children. 33 patients finished treatment. 2 children discontinued treatment because of the expressed headaches and in connexion with immigration. In the course of treatment by pegylated interferon and ribavirin most common of the side effects were pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema and vomiting. <h3>Conclusions</h3> Combined antiviral therapy of chronic hepatitis C in children was safe. This treatment program needs an individual approach and it was effective SRV in 73% cases, inclusive in genotype 1b – 69%, in genotypes 2 and 3a – in 100%.

High rates of early treatment discontinuation in hepatitis C-infected US veterans.

BackgroundPatients with chronic hepatitis C (HCV) frequently discontinued dual therapy with pegylated interferon alfa (Peg-IFN) plus ribavirin (RBV) before reaching the recommended duration of 48 or 24 weeks for genotypes (G) 1/4 or 2/3, respectively. We quantified rates of discontinuation despite efficacy (non-LOE) versus lack of efficacy (LOE) versus discontinuation for unknown reasons in a national database of United States veterans.MethodsWe identified a population-based cohort of U.S. veterans with encounters from 2004 through 2009 who had lab-confirmed HCV infection and initiated therapy with Peg-IFN plus RBV in Veterans Health Administration medical centers. Pharmacy data were used to determine therapy duration, defined as the sum of Peg-IFN days supplied. Patients “discontinued” if they failed to receive at least 44 (G1/4) or 20 weeks (G2/3) of therapy. We classified discontinuations as due to non-LOE, LOE, or unknown reasons using a classification rule based on treatment duration and laboratory confirmed response.ResultsOf 321,238 diagnosed HCV patients during the evaluation period, 9.7% initiated therapy and 6.4% met all other inclusion criteria. 54.9% of patients discontinued early; of these, 41.2% discontinued due to non-LOE reasons, 12.5% discontinued for LOE reasons, and 46.3% discontinued for unknown reasons. Among non-LOE discontinuers, most (60.1%) discontinued in the first 4 weeks of therapy, which constitutes 13.6% of all treated patients.ConclusionsWe observed a high proportion of early discontinuations with dual-therapy regimens in a national cohort of HCV-infected veterans. If this trend persists in the triple-therapy era, then efforts must be undertaken to improve adherence.

Recent FDA approval of sofosbuvir and simeprevir. Implications for current HCV treatment.

Recent FDA approval of sofosbuvir and simeprevir. Implications for current HCV treatment.

Diagnosis, treatment, and follow-up of hepatitis C-virus related liver disease. Hungarian national consensus guideline

Approximately 70 000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. Early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases (liver cirrhosis and liver cancer) and its complications. In addition, it may increase work productivity and life expectancy of infected individual, and can prevent further viral transmission. Early recognition can substantially reduce the long term financial burden of related morbidity from socioeconomic point of view. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can kill the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of two direct acting first generation protease inhibitor drugs (boceprevir and telaprevir) to the dual therapy increased the chance of sustained clearance of virus to 63-75% and 59-66%, respectively. These two protease inhibitor drugs are available and financed for a segment of Hungarian patients since May 2013. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. For initiation of treatment as well as for on-treatment decisions accurate and timely molecular biology tests are mandatory. Staging of liver damage (fibrosis) non-invasive methods (transient elastography and biochemical methods) are acceptable to avoid concerns of patients related to liver biopsy. Professional decision for treatment is balanced against budget limitations in Hungary, and priority is given to those with urgent need using a national Priority Index system reflecting stage of liver disease as well as additional factors (activity and progression of liver disease, predictive factors and other special circumstances). All naïve patients are given a first chance with dual therapy. Those with genotype 1 infection and with on-treatment or historic failure to dual therapy are eligible to receive protease inhibitor based triple therapy provided, they reach financial cutoff eligibility based on Priority Index. Duration of therapy is usually 48 weeks in genotype 1 with a response-guided potential to reduce duration for non-cirrhotic patients. Patients with non-1 genotypes are treated with dual therapy (without protease inhibitors) for a genotype and response driven duration of 16, 24, 48, or 72 week. Careful monitoring for early recognition and management of side-effects as well as viral response and potential breakthrough during protease-inhibitor therapy are recommended.

Hepatitis C drugs: the end of the pegylated interferon era and the emergence of all-oral interferon-free antiviral regimens: a concise review.

Between 2001 and 2011, the standard of care for chronic hepatitis C virus (HCV) infection was a combination of pegylated interferon (PEG-IFN) and ribavirin (RBV). In May 2011, boceprevir and telaprevir, two first-generation NS3/4A protease inhibitors, were approved in combination with PEG-IFN and RBV for 24 to 48 weeks in hepatitis C virus genotype 1 infections. In December 2013, simeprevir, a second-generation NS3/4A protease inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotype 1, while sofosbuvir, a NS5B nucleotide polymerase inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotypes 1 and 4, as well as with RBV alone for 12 weeks in genotype 2 and for 24 weeks in genotype 3. Sofosbuvir combined with simeprevir or an NS5A replication complex inhibitor (ledipasvir or daclatasvir) with or without RBV for 12 weeks in genotype 1 resulted in a sustained virological response >90%, irrespective of previous treatment history or presence of cirrhosis. Similarly impressive sustained virological response rates have been shown with ABT-450/r (ritonavir-boosted NS3/4A protease inhibitor)-based regimens in combination with other direct-acting antiviral agent(s) with or without RBV for 12 weeks in genotype 1. The optimal all-oral interferon-free antiviral regimen likely entails a combination of an NS5B nucleotide polymerase inhibitor with either a second-generation NS3/4A protease inhibitor or an NS5A replication complex inhibitor with or without RBV. Further research is needed to determine the role of resistance testing, clarify the optimal follow-up duration post-treatment, and evaluate the antiviral efficacy and safety in difficult-to-cure patient populations.

Hepatitis C viral infection among prisoners

Hepatitis C virus (HCV) infection is an important sociomedical problem worldwide because the chronification of the disease is frequent and the occurance of liver cirrhosis and hepatocellular carcinoma can be expected. The aim of this study was to determine the way of infection, pathohistological changes of the liver, virus genotype presence and sustained virological response after pegylated interferon and ribavirin therapy in prison inmates. The study included 52 patients with chronic HCV infection classified in two groups managed during 2008-2010. The first group consisted of prisoners (n = 22) and the second one of "non-prisoners" (n = 30). The patients from both groups underwent diagnostic preparation (biochemical analyses, liver biopsy, hepatitis virus detection and genotypisation using polymerase chain reaction issue). The treatment lasted for 24 weeks for virus genotypes 2 and 3, and 48 weeks for genotypes 1 and 4. All the patients were males, approximately the same age (35 +/- 4.1 and 31 +/- 7.6 years). Virus genotype 1 was significantly more frequent in the prisoners (p < 0.05), that demanded longer treatment (48 weeks). At the same time, statistically significant higher number of patients, "non-prisoners", achieved a sustained virological response (p < 0.01). Intravenous drug abuse and tattoos, separately or together, are the most frequent way of infection in prisoners. The dominant presence of virus genotype 1 resulted in lower number of patients with sustained virological response, probably regardless prison environment and regime.

Treatment of chronic hepatitis C among injecting drug users: A 5-year follow-up

Hepatitic C infection (HCV) is a systemic, generalised disease with the prevalence of inflammation in the liver. The aim of this study was to determine the success of treatment for chronic hepatitis C with pegilated interferon alfa 2a and ribavirin in injecting drug users. This a 5-year follow-up study included 30 patients [63.3% men and 36.7% women, average age 30.2 years (SD 7.1 years)] injecting drug users in one-year abstinence, with chronic hepatitis C, treated with the pegilated interferon alpha 2a and ribavirin. Complete history with possible route of infection, the standard biochemical tests, liver biopsy, quantification of the viral genome in sera and HCV genotyping and subtyping were done prior to the therapy initiation. Depending on the HCV genotype, the therapy was conducted over a period of 48 weeks for genotype 1 and 24 weeks for genotype non 1. Five years later all 30 patients were invited on control examination; 22 of them appeared at the check-up and quantification of the viral genome in their sera were analized. The established degree of liver fibrosis was: F0 in 40%, F1 in 23.33%, F2 in 26.67%, F3 in 3.33% and F4 in 6.67% of the patients. Genotype 3a was dominant (50.0%), 1b was registered in 40.0%, 1a in 6.66% and 2b in 3.33% of the patients. Sustained virologic response (SVR) was achieved in 86.7% of the patients, 10.0% of the patients were non-responders, while 3.33% of them revealed recurrence of HCV. Opiate abuse recurrence during antiviral therapy happened in 6.7% of the patients. Five years after the antiviral therapy 73.3% of the patients appeared at the check-up and all of them were in stable abstinence from opiate abuse. All of those, with a sustained viral response of five-year duration, had the negative PCR HCV RNA test (< 50 IU ml(-1)). In the patients showing unsatisfactory therapy response 5 years before, antiviral therapy was repeated by the same therapeutic regimen, but without adequate therapeutic response. A total of 26.7% of the patients were lost from the records. In a 5-year follow-up period 73.3% of the patients used to come regularly to check-ups and among them neither the opiate abuse recurrence nor HCV infection recurrence were registered.

The Combination Therapy with Peg-interferon Alfa and Ribavirin for Chronic Hepatitis C in Korea as an Initial Treatment

Objectives The combination therapy with peginterferon and ribavirin has been used to treat chronic hepatitis C for several years in Korea but there is a few report about the results of the treatment. We evaluated safety and efficacy of the combination therapy with Peg-interferon and ribavirin and analyzed factors that may affect treatment. Methods Total 72 untreated chronic hepatitis C patients were administered pegylated interferon alfa-2a (180µg/week) or alfa-2b (1.5µg/kg/week) and ribavirin (800 mg/day in genotype 2, 1000-1200 mg/day in genotype 1). Duration of the treatment was 24 weeks in genotype 2 and 48 weeks in genotype 1. Response of the treatment was evaluated by rapid virologic response (RVR), early virologic response (EVR), end treatment virologic response (ETR), sustained virologic response (SVR) and adverse event. Results The RVR, EVR, ETR, SVR were 61.8%, 82.5%, 88.9% and 80.5% retrospectively. The SVR of genotype 1 was 63.4% and non-genotype 1 was 96.7%. Genotype (Odds ratio: 14.92) was an independent predictor of the SVR. Leukocytopenia, flu-like symptoms, itching, rash and anemia were common adverse events of the combination therapy and if then we reduced dose and there was one case of cessation. Conclusions The combination therapy with Peg-interferon and ribavirin shows efficacy to the Korean patients with chronic hepatitis C as an initial treatment. Genotypes 2 and 3 were more likely to have a sustained virologic response.