End Treatment Response and Sustained Viral Response in Patients With Hepatitis C Virus Receiving Sofosbuvir and Daclatasvir.

Objective The main purpose of this study was to determine the end treatment response (ETR) and sustained viral response (SVR) in hepatitis C virus (HCV) patients receiving sofosbuvir and daclatasvir daily for 12 weeks. Methods This is a prospective open-label interventional study conducted from March 2018 to December 2020 in the outpatient departments of Abbasi Shaheed Hospital and Lyari General Hospital, Karachi. Patients with chronic infection of HCV, confirmed with ribonucleic acid (RNA) polymerase chain reaction (PCR) (qualitative analysis) were invited to participate in the study. All patients with positive HCV antibodies were evaluated clinically, with laboratory, and imaging assessment earlier to treatment. Statistical analysis was performed using SPSS version 20.0 (Armonk, NY: IBM Corp.). Results A total of 1043 patients participated in the study with a female predominance, 699 (67%) females. A majority (67.9%) of the study participants were aged between 15 and 45 years. After treatment of 12 weeks with sofosbuvir and daclatasvir 1039 (99.9%) patients achieved SVR while 1038 (99.6%) achieved an end treatment response. There was no significant association found between changes in alanine aminotransferase (ALT) levels, gender, and age among study participants. Conclusion Sofosbuvir and daclatasvir are found to be extremely effective for patients with hepatitis C in Pakistan. However, additional investigation including a larger sample size and involving a multicenter setting is recommended.

Outcome of Primary Mediastinal Large B Cell Lymphoma Treated with RCHOP.

Purpose: Primary mediastinal large B-cell Lymphoma (PMLBCL) is a rare aggressive lymphoma with unique clinical, pathological, and molecular features. The optimal frontline therapy is subject of ongoing debate. Our study aims to evaluate the outcomes of PMLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) at King Hussein Cancer Center. Patients and Methods: Adult patients >18 years of age with PMLBCL treated with RCHOP from January 2011 to July 2020 were identified. All demographics, disease and treatment related variables were retrospectively collected. Correlations of clinical and laboratory variables with progression-free survival (PFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. The PFS and OS were plotted using Kaplan‒Meier curves. Results: 49 patients were included with a median age of 29 years. 14 (28.6%) had stage III or IV, 31 (63.3%) had mediastinal bulky disease. International prognostic index (IPI) was 0-1 in 35 (71.4%). Radiotherapy was given to 32 (65.3%) patients. End of treatment (EOT) response was complete (CR) in 32 (65.3%), partial response (PR) in 8 (16.3%) and progressive disease (PD) in 9 (18.4%). Patients who achieved CR at EOT, compared favorably with those who did not in regard to 4-year OS (92.5% vs 26.9%, p=<0.001). Overall objective response to salvage chemotherapies was 26.7%. At a median follow-up of 46 months, 4-year PFS and OS were 60% and 71% respectively. In multivariate analysis, IPI > one correlated with the EOT response (p=0.009), PFS (p=0.004) and OS (p= 0.019). Conclusion: In PMLBCL, RCHOP chemotherapy backbone in the frontline therapy is suboptimal but can be used in patients with low IPI. Adapting more intensive chemoimmunotherapy regimens may be considered for patients with high IPI. Salvage chemotherapy has limited activity in patients with relapsed or refractory disease.

Predictive value on advance hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial.

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Real-world effectiveness of direct-acting antivirals in people living with human immunodeficiency virus and hepatitis C virus genotype 6 infections.

BACKGROUND: Hepatitis C virus (HCV) genotype 6 (HCV-6) infection is prevalent predominantly in Southeast Asia, and the data on the virologic response of HCV-6 to direct-acting antivirals (DAAs) are sparse in people living with human immunodeficiency virus (HIV) (PLWH). AIM: To assess the virologic response of HCV-6 to DAAs in PLWH. METHODS: From September 2016 to July 2019, PLWH coinfected with HCV-6 initiating DAAs were included. Laboratory investigations were performed at baseline, the end of treatment, and 12 wk off-therapy. RESULTS: Of the 349 PLWH included (mean age 48.9 years, 82.5% men), 80.5% comprised people who inject drugs, 18.1% men who have sex with men, and 1.4% heterosexuals. Coexistent hepatitis B virus infection was present in 12.3% of the included PLWH, liver cirrhosis 10.9%, hepatocellular carcinoma 0.9%, and previous HCV treatment experience 10.9%. The mean baseline plasma HCV RNA was 6.2 log10 IU/mL. Treatment with glecaprevir/pibrentasvir was initiated in 51.9%, sofosbuvir/ledipasvir 41.5%, sofosbuvir/velpatasvir 6.3%, and sofosbuvir/daclatasvir 0.3%. At DAA initiation, antiretroviral therapy containing tenofovir alafenamide was given in 26.4%, tenofovir disoproxil fumarate 34.4%, non-tenofovir alafenamide/tenofovir disoproxil fumarate 39.3%, non-nucleoside reverse-transcriptase inhibitors 30.4%, protease inhibitors 4.0%, and integrase strand transfer inhibitors 66.8%; 94.8% of the included patients had CD4 counts ≥ 200 cells/mm3 and 96.0% had plasma HIV RNA < 50 copies/mL. Overall, 96.8% achieved undetectable plasma HCV RNA (< 30 IU/mL) at end of treatment; and 92.3% achieved sustained virologic response 12 wk off-therapy in the intention-to-treat analysis (93.5% in patients receiving sofosbuvir-based DAAs and 91.2% in those receiving glecaprevir/pibrentasvir). CONCLUSION: Similar to the observation made in HIV-negative patients, sustained virologic response 12 wk off-therapy with DAAs is high in PLWH coinfected with HCV-6.

Real-World Experience with Coformulated Ledipasvir and Sofosbuvir for HIV-Positive Patients with HCV Genotype 2 Infection: A Multicenter, Retrospective Study.

INTRODUCTION: While coformulated ledipasvir (90 mg)/sofosbuvir (400 mg) (LDV/SOF) is approved for the treatment of hepatitis C virus (HCV) genotype 2 (GT2) infection in Taiwan, Japan, and New Zealand, data regarding its use for HIV (Human Immunodeficiency Virus)-positive patients infected with HCV GT2 are sparse. We aimed to assess the effectiveness and tolerability of LDV/SOF for HIV-positive patients with HCV GT2 coinfection. METHODS: From January 2019 to July 2020, consecutive HIV-positive Taiwanese patients infected with HCV GT2 who received LDV/SOF were retrospectively included for analysis. The effectiveness was determined by sustained virologic response 12 weeks off-therapy (SVR12). RESULTS: Of the 114 patients (mean age, 38.6 years) initiating LDV/SOF during the study period, 0.9% had liver cirrhosis and 4.4% were HCV treatment-experienced. All patients had estimated glomerular filtration rate (eGFR) > 30 ml/min/1.73 m2 and were receiving antiretroviral therapy with 98.2% having CD4 counts ≥ 200 cells/mm3 and 93.9% plasma HIV RNA load < 50 copies/ml. Antiretrovirals prescribed included tenofovir alafenamide/emtricitabine in 42.1%, tenofovir disoproxil fumarate (TDF)/emtricitabine 18.4%, other nucleoside reverse transcriptase inhibitors (NRTIs) 39.5%, non-NRTIs 12.3%, protease inhibitors 13.2%, and integrase inhibitors 74.6%. All patients had undetectable plasma HCV RNA load at the end of treatment, and 96.5% achieved SVR12 in intention-to-treat analysis. The on-treatment eGFR decline was more pronounced in those receiving TDF-containing antiretroviral therapy (mean change, - 8.33 ml/min/1.73 m2), which was reversible after discontinuation of LDV/SOF. None of the patients interrupted LDV/SOF during the 12-week treatment course. CONCLUSION: Similar to the response observed among HIV-negative patients, LDV/SOF is effective for HIV-positive patients coinfected with HCV GT2.

Outcome of hepatitis C patients in a community with predominant genotype 3 with standard-of-care treatment before and after advent of direct-acting antivirals: A retrospective-cum-prospective study.

BACKGROUND AND OBJECTIVE: Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are mainly caused by hepatitis C infection. It is a worldwide predominant pathogen and is one of the main causes of healthcare problem in Asia. In the last few decades, there has been a considerable change in the treatment regimen for hepatitis C virus. The objective of this research was to relate the treatment response with sustained viral response in various therapies which have been the standard of care from time to time. MATERIALS AND METHODS: This hospital-based, retrospective-cum-prospective research span over a period of 2 years; we enrolled hepatitis C patients who attended the Department of Gastroenterology and Hepatology, Government Medical College, Srinagar, since June 2015 till May 2017. Subsequently, the database was prepared, containing all the relevant information about these patients. CONCLUSIONS: (i) In retrospective group: The overall efficacy (sustained viral response at 24 weeks [SVR-24]) of pegylated interferon a2a and ribavirin regimen was 90.96%. (ii) In prospective group: The efficacy (SVR) of different regimens was found to be as: sofosbuvir + ribavirin + daclatasvir (SVR-24, 83.33%); sofosbuvir + ribavirin (SVR-12, 94.57%); and sofosbuvir + daclatasvir (SVR-12, 98.00%).

Results of Sofosbuvir Plus Ribavirin in Patients With Hepatitis C Related Decompensated Cirrhosis.

BACKGROUND: Sofosbuvir (SOF), a direct acting antiviral, has revolutionized the treatment of chronic Hepatitis C Virus (HCV) infection. However, data is scarce about efficacy of SOF plus Ribavarin (RBV) in Indian patients with decompensated cirrhosis. We evaluated the efficacy of SOF plus RBV in decompensated cirrhosis, and compared the outcome with compensated cirrhosis and non-cirrhotics. PATIENTS AND METHODS: Consecutive decompensated cirrhotic patients of chronic HCV with detectable HCV RNA were treated with 24-week course of SOF (400 mg) plus weight based RBV. Sustained Virological Response (SVR), Child Turcotte Pugh (CTP) and Model for Endstage Liver Disease (MELD) scores were assessed at 36 weeks (i.e. 12 weeks after completion of therapy). Non-cirrhotic chronic hepatitis C patients and patients with compensated cirrhosis treated with SOF plus RBV during the same period were used as controls. During the period of this study ledipasvir and daclatasvir were not available in India. RESULTS: A total of 47 patients [median age 50 (29-82) years, 64% males] with decompensated cirrhosis were included as 'cases' in the study; while, 27 patients with compensated cirrhosis and 29 patients with chronic hepatitis were included as 'controls'. Age, gender, HCV RNA levels, and genotype distribution were similar in cases and controls. The median CTP and MELD scores of cases were 8 (7-12) and 13 (6-25), respectively. Among cases 39 (83%) could complete the therapy, while 1 (2%) was intolerant and 7 (15%) died before completion of therapy. End of Treatment Response (ETR) was achieved in 37/39 (95%) cases. Of these, another 3 died before SVR, and 7 failed to achieve SVR, thus 27/34 (79%) could achieve SVR. Thus according to intention-to-treat analysis, only 27/47 (57%) cases could achieve SVR. In comparison, 24/28 (86%) compensated cirrhotics and 27/28 (96%) of chronic hepatitis achieved SVR. There was a significant improvement in mean CTP score in cases who achieved SVR (P < 0.01) compared to those who did not achieve SVR/ETR. On multivariate analysis the only independent factor influencing successful outcome patients was a serum albumin >3.5 g/dL. CONCLUSIONS: A 24-week course of SOF plus ribavirin in decompensated HCV cirrhosis could lead to SVR in only 57% of patients. The failure of therapy in 43% patients was either due to non-response, intolerance, or death. A serum albumin of more than 3.5 is associated with success of antiviral therapy. Thus an early initiation of antiviral therapy is recommended before decompensation sets in as it precludes successful outcome.

Efficacy And Safety of Sofosbuvir Based Regimens For Treatment of Hepatitis C Recurrence After Living Donor Liver Transplantation: An Experience From India.

INTRODUCTION: Results of Sofosbuvir based regimens for hepatitis C (HCV) recurrence after liver transplantation are available from well-designed clinical trials. Most of the data is from deceased donor liver transplant (DDLT) setting, and data on "real world" experience for HCV recurrence after living donor liver transplantation (LDLT) is limited. MATERIAL AND METHODS: Consecutive 78 patients who completed Sofosbuvir based HCV treatment after liver transplantation were included. Following Sofosbuvir based regimens were used; Sofosbuvir + Ribavirin (n = 58), Sofosbuvir + Ledipasvir ± Ribavirin (n = 5), Sofosbuvir + Daclatasvir ± Ribavirin (n = 15). Treatment was given for 12 weeks (triple therapy) or 24 weeks (dual therapy). RESULTS: A total of 74/78 (94.8%) patients achieved end of treatment response (ETR) while 4 did not achieve ETR. A total of 68/76 (89.4%) patients achieved sustained virological response at 12 weeks (SVR12). while 2 are waiting for 12 weeks follow up after ETR. Twelve patients had history of failed previous treatment with Peginterferon and Ribavirin after LDLT, all these patients achieved ETR and 11/12 had SVR12. There was no statistical difference in response rates between genotype 1 or 3. Eighteen patients (16 on Ribavirin) had hemoglobin < 8 g/dl; two patients complained fatigue in absence of anemia. CONCLUSION: Sofosbuvir based regimens are safe and highly effective in treatment of HCV recurrence after LDLT.

Impact of serum soluble programed death ligand 1 on end of treatment metabolic response of diffuse large B cell lymphoma patients.

Programmed death ligand-1 (PD-L1) plays an important role in the immune evasion of cancer cells and, in turn, can influence the outcome of many malignancies. The serum soluble PD-L1 (sPD-L1) levels were measured in diffuse large B cell lymphoma (DLBCL) patients at diagnosis and at end of treatment. Their impact on end of treatment metabolic response was analyzed. Serum sPD-L1 level was significantly elevated in DLBCL patients at diagnosis than in controls (P < 0.001). Also, serum sPD-L1 level at diagnosis was significantly higher than that at end of treatment (P < 0.001). Patients who achieved partial response (PR) had significantly higher serum sPD-L1 level at end of treatment than controls (P < 0.001). In contrast, all patients especially those who achieved complete response (CR) had insignificantly different serum sPD-L1 level at end of treatment than controls (P = 0.354 and P = 0.090, respectively). There was a significant difference between serum sPD-L1 level at diagnosis and that at end of treatment in patients who achieved PR and CR (P = 0.023 and P < 0.001, respectively). On univariate analysis, presence of comorbidities, Ann Arbor stage IV, high serum sPD-L1 level at diagnosis and high serum sPD-L1 level at end of treatment were significantly associated with achievement of PR (P = 0.018 and P = 0.043, P = 0.045 and P < 0.001, respectively). On multivariate analysis, serum sPD-L1 levels at diagnosis and at end of treatment were still influencing metabolic response significantly (P = 0.014 and P = 0.007, respectively). Serum sPD-L1 is a predictor for metabolic response to immunochemotherapy in DLBCL patients.

Safety and Efficacy of Sofosbuvir and Daclatasvir for Hepatitis C Virus Infection in Patients with ß-Thalassemia Major.

BACKGROUND AND AIMS: ß-thalassemia major patients are susceptible to Hepatitis C Virus (HCV) infection owing to life-long dependency for blood-transfusion. Moreover, this patient population is at risk of progression of liver fibrosis or development of cirrhosis as a consequence of both iron overload and HCV infection. Hence, this study was carried out to evaluate efficacy and safety of the combination regimen of sofosbuvir and daclatasvir for HCV infection in ß-thalassemia major patients. METHODS: The present study was a prospective observational study which enrolled multi-transfused ß-thalassemia major patients treated with a combination regimen of sofosbuvir (400 mg) and daclatasvir (60 mg) daily for 12 weeks for HCV infection during May 2016 and November 2016 depending upon inclusion and exclusion criteria of the study. Sustained virological response at post-treatment week-12 (SVR-12) was defined as negative HCV-RNA at week-12 after completion of antiviral treatment. RESULTS: A total of 10 multi-transfused patients with ß-thalassemia major were included in the study. Average age of the patient was 13.60 ± 4.38 years. All the included patients were treatment-naïve, non-cirrhotic and infected with HCV genotype-3. All the patients achieved SVR-12. There was significant reduction in aspartate aminotransferase (p = 0.005) and alanine aminotransferase level (p = 0.005) and serum ferritin level (p = 0.028) after completion of the antiviral treatment. The reported adverse events include nausea, vomiting and anorexia which were managed conservatively. None of the patient required dose reduction or termination of antiviral treatment. CONCLUSION: The study reports safety and efficacy of sofosbuvir-based treatment in non-cirrhotic, treatment-naive ß-thalassemia major patients infected with HCV genotype-3. However, further studies with larger patient populations are needed to build up stronger evidence of safety and efficacy of this treatment approach for HCV infection in thalassemic patients.

Impact of Direct Acting Antiviral Therapy for Treatment of Hepatitis C Genotypes 1, 3 and 4: A Real Life Experience from India.

OBJECTIVE: To assess impact of Direct Acting Antiviral (DAA) therapies for treatment of Hepatitis C Virus (HCV) genotypes 1, 3 and 4 in a real-world cohort from India. METHODS: Adults with chronic HCV infection treated with Sofosbuvir (SOF) and Ledipasvir (LDV) (genotypes 1 and 4) or SOF and Daclatasvir (DCV) (genotype 3), with or without Ribavirin (RBV) between December 2015 and December 2016 were included. The primary endpoint was Sustained Virological Response at Post-treatment Week 12 (SVR12). RESULTS: Of the 648 patients, 181 received SOF/LDV (65 with RBV) and 467 received SOF/DCV (135 with RBV). Most patients were males (65.4%), aged 41-60 years (49.4%) and treatment-naïve (92.6%). Genotype 3 (72.1%) was most common, followed by genotypes 1 (22.4%) and 4 (5.6%). Forty two percent patients (n = 271) had cirrhosis (112 patients were decompensated). SVR12 (modified intention-to-treat) was achieved by 98.1% of patients (512/522) (100% in genotypes 1 and 4, and 97.3% (362/372) in genotype 3). On intention to treat analysis, SVR12 was 88.1% (512/581) [genotype 1-96.8% (121/125), genotype 3-85.2%, genotype 4-93.5% (29/31)]. Seventy patients had treatment failure (non response in 6, virological breakthrough in 2, 10 patients relapsed, 2 died and 50 were lost to follow up). High SVR was observed regardless of HCV genotype, presence of cirrhosis or past history of treatment. No major adverse events warranting discontinuation of treatment were noted. CONCLUSIONS: DAA therapy for HCV genotypes 1, 3 and 4 achieves high SVR rates in all patients, including those with cirrhosis and previous non-responders.

Generic Direct Acting Antivirals in Treatment of Chronic Hepatitis C Infection in Patients of Thalassemia Major.

BACKGROUND: There is no published data of treating hepatitis C in thalassemia major patients with any sofosbuvir based direct acting antivirals (DAAs). This study was performed to determine the efficacy and safety of these regimes using generic drugs in the thalassemia major population. METHODS: In this observational study, 902 patients of thalassemia major from five transfusion centres in Mumbai were screened for HCV antibody. Of the 120 positive patients, HCV RNA was detected in 50%. The first 29 patients were enrolled for evaluating the efficacy and safety of generic sofosbuvir based DAAs. RESULTS: The 29 patients' had a mean age of 24 years with genotype 1 in 17, genotype 3 in 11patients, while 1 patient's genotype could not be classified. Six patients had compensated cirrhosis and 8 patients were treatment experienced. SVR 12 was achieved in 100% of patients. There was significant increase in PRC (packed red cell) requirements (P = 0.0003) during treatment. At 12 weeks post-treatment, PRC requirements returned to baseline with a significant fall in serum ferritin (P = 0.03). Headache, fatigue and diarrhoea were the most common side effects. The difference in side effects including anaemia between patients who received ribavirin (19/29) and those who did not receive ribavirin (10/29) was not significant. Presence of diabetes, splenectomy, high ferritin or liver or heart iron overload on MRI T2* did not affect the efficacy of treatment. CONCLUSION: Generic DAAs are safe in thalassemia major patients with hepatitis C with efficacy of 100%. Serum ferritin falls significantly after treatment despite an increase in transfusion requirements during treatment.

The Absence of HCV RNA and NS5A Protein in Peripheral Blood Mononuclear Cells Is a Prognostic Tool for Sustained Virological Response.

Hepatitis C Virus (HCV) infection is a major health concern worldwide. The presence of both HCV viral RNA and NS5A proteins in peripheral blood mononuclear cells (PBMCs) indicate the efficacy of the treatment during sustained virological response (SVR) and end of treatment response (ETR). The main objective of this study was to detect the absence or presence of HCV RNA and NS5A proteins in PBMCs. Blood samples were taken from selected patients (Islamabad, Pakistan) before treatment, at ETR, and during SVR. Two hundred HCV responders to pegylated IFN-α-2a plus ribavirin were selected. HCV RNA was extracted from the patients to determine the viral load by reverse transcription (RT)-polymerase chain reaction before treatment. Out of 200 patients, 152 (76%) and 48 (24%) achieved positive and negative ETR, respectively. Among ETR patients, 134 (88.2%) showed SVR, whereas 18 (11.8%) displayed relapse. The male to female ratio was 92:108 with mean age of 37.4 years. Among 152 ETR-positive patients, 29 (19%) patients' PBMCs were positive for HCV RNA and 27 (17.8%) were positive for NS55A proteins. Patients having HCV RNA in PBMCs showed higher relapse frequency compared with patients lacking it. Similarly, patients having NS5A protein showed significantly higher relapse frequency compared with patients lacking it. All PBMC-positive samples were of genotype 3a. In addition, patients with positive NS5A in their PBMCs showed greater risk of relapse compared with patients having HCV RNA. We conclude that the absence of both viral HCV and proteins can be used as an indicator for diagnosis of SVR in the future.

Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies.

BACKGROUND: Some chronic hepatitis C virus (HCV), genotype 1 infected patients treated with direct antiviral agents (DAAs) remain viremic at end of treatment (EOT+), yet go on to achieve sustained virological response 12 weeks after completion of therapy (SVR12). The incidence of EOT+/SVR in patients with genotype 1 and other genotypes, as well as whether such patients achieve SVR24 remain in question. The aims of this study were to evaluate the frequency and durability of EOT+/SVR12&24 and other response categories in HCV genotype 1, 2, or 3 infected patients treated with DAA in clinical practice. METHODS: Data from patients treated with all oral sofosbuvir-based regimens at a university hepatology practice by 1 July 2015 were reviewed retrospectively. Responses were categorized based on virus levels during and post DAA treatment. HCV RNA levels were measured by Abbott RealTime HCV (ART) or by Roche CobasTaqMan v2.0 (RCTM) assays. RESULTS: The study population included 89 patients. Participants were 62% genotype 1, 19% genotype 2 and 19% genotype 3, 54% cirrhotic and 46% treatment-experienced. A total of 45 received sofosbuvir-simeprevir, 38 sofosbuvir-ribavirin and 6 sofosbuvir-ledipasvir. The SVR12 rate was 82%. A total of 5 patients (6%), all with genotype 1, had EOT+ by ART assay and each achieved SVR12&24. CONCLUSIONS: A total of 9% of genotype 1 patients (6% overall) treated with DAAs were EOT+ by ART and all EOT+ cases achieved SVR24. EOT+/SVR was not observed with genotype 2 or 3 or by the RCTM assay. In patients treated with DAAs, EOT+ by the ART assay does not indicate treatment failure.

Noninvasive Assessment of Liver Fibrosis By Transient Elastography and FIB4/APRI for Prediction of Treatment Response in Chronic Hepatitis C-An Experience from a Tertiary Care Hospital.

BACKGROUND: Liver fibrosis and its sequel cirrhosis represent a major health care burden, and assessment of fibrosis by biopsy is gradually being replaced by noninvasive methods. In clinical practice, the determination of fibrosis stage is important, since patients with advanced fibrosis have faster progression to cirrhosis and antiviral therapy is indicated in these patients. AIMS: To assess the role of transient elastography (TE) and compare it with APRI and FIB4 for predicting liver fibrosis and assessing the effect of host and viral factors on fibrosis and treatment outcome in CHC patients. METHODS: In a retrospective analysis, 330 CHC patients underwent liver stiffness measurement (LSM) by TE and tests needed for calculating APRI and FIB4 scores at baseline. 228 patients received a combination of Pegylated IFN-based antiviral therapy and were analyzed for therapeutic response. RESULTS: The study included 330 patients (median age 39 years [range 18-67]), predominantly males (n = 227, 68.8%) with baseline LSMs. The median liver stiffness was 7.8 kPa (range 3.2-69.1 kPa). LSMs and its thresholds for severe fibrosis progression (≥9.5 kPa) and cirrhosis (≥12.5 kPa) were significantly higher in patients with age ≥40 years, diabetes mellitus, and patients with significant alcohol intake (P = 0.003 to P < 0.001). By taking TE as a reference, the diagnostic accuracy of FIB4 scores for predicting cirrhosis (AUROC 0.896) was good (+LR 13.4) compared to APRI (AUROC 0.823) with moderate likelihood ratio (+LR 6.9). Among 228 treated patients the SVR rate in genotype 3 was 70% versus 57.8% in genotype 1. Fibrosis score F4 (P = 0.023) and HCV genotype (P = 0.008) were independent predictors of SVR. CONCLUSION: The study shows that LSM by TE and fibrosis assessment by FIB4/APRI scores can be used with fair reliability to predict fibrosis and treatment response in patients with CHC infection.

Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: a multicenter experience.

BACKGROUND & AIMS: Protease inhibitors (PI) with peginterferon/ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge. METHODS: This cohort study included 37 liver transplant recipients (male, 92%, age 57 ± 11 years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage ≥F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%). RESULTS: Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen tacrolimus. After 12 weeks of PI therapy, a complete virological response was obtained in 89% of patients treated with boceprevir, and 58% with telaprevir (p=0.06). The end of treatment virological response rate was 72% (13/18) in the boceprevir group and 40% (4/10) in the telaprevir group (p=0.125). A sustained virological response 12 weeks after treatment discontinuation was observed in 20% (1/5) and 71% (5/7) of patients in the telaprevir and boceprevir groups, respectively (p=0.24). Treatment was discontinued in sixteen patients (treatment failures (n=11), adverse events (n=5)). Infections occurred in ten patients (27%), with three fatal outcomes (8%). The most common adverse effect was anemia (n=34, 92%), treated with erythropoietin and/or a ribavirin dose reduction; thirteen patients (35%) received red blood cell transfusions. The cyclosporine dose was reduced by 1.8 ± 1.1-fold and 3.4 ± 1.0-fold with boceprevir and telaprevir, respectively. The tacrolimus dose was reduced by 5.2 ± 1.5-fold with boceprevir and 23.8±18.2-fold with telaprevir. CONCLUSIONS: Our results suggest that triple therapy is effective in LT recipients, particularly those experiencing a severe recurrence. The occurrence of anemia and drug-drug interactions, and the risk of infections require close monitoring.

Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy.

BACKGROUND & AIMS: Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV. METHODS: Patients with HCV infection and thrombocytopenia (platelet count <75,000/µL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients whose platelet counts reached the predefined minimal threshold for the initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were assigned randomly (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary end point was sustained virologic response (SVR) 24 weeks after completion of antiviral therapy. RESULTS: More patients who received eltrombopag than placebo achieved SVRs (ENABLE-1: eltrombopag, 23%; placebo, 14%; P = .0064; ENABLE-2: eltrombopag, 19%; placebo, 13%; P = .0202). PEG was administered at higher doses, with fewer dose reductions, in the eltrombopag groups of each study compared with the placebo groups. More patients who received eltrombopag than placebo maintained platelet counts of 50,000/µL or higher throughout antiviral treatment (ENABLE-1, 69% vs 15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%) and thromboembolic events, which were more common in the eltrombopag group of ENABLE-2. CONCLUSIONS: Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise ineligible or marginal patients to begin and maintain antiviral therapy, leading to significantly increased rates of SVR. Clinical trial no: NCT00516321, NCT00529568.

Consensus Statement of HCV Task Force of the Indian National Association for Study of the Liver (INASL). Part II: INASL Recommendations for Management of HCV in India.

The estimated prevalence of hepatitis C virus (HCV) infection in India is between 0.5 and 1.5% with hotspots showing much higher prevalence in some areas of northeast India, in some tribal populations and in certain parts of Punjab. Genotype 3 is the most prevalent type of infection. Recent years have seen development of a large number of new molecules that are revolutionizing the treatment of hepatitis C. Some of the new directly acting agents (DAAs) like sofosbuvir have been called game-changers because they offer the prospect of interferon-free regimens for the treatment of HCV infection. These new drugs have not yet been approved in India and their cost and availability is uncertain at present. Till these drugs become available at an affordable cost, the treatment that was standard of care for the whole world before these newer drugs were approved should continue to be recommended. For India, cheaper options, which are as effective as the standard-of-care (SOC) in carefully selected patients, are also explored to bring treatment within reach of poorer patients. It may be prudent to withhold treatment at present for selected patients with genotype 1 or 4 infection and low levels of fibrosis (F1 or F2), and for patients who are non-responders to initial therapy, interferon intolerant, those with decompensated liver disease, and patients in special populations such as stable patients after liver and kidney transplantation, HIV co-infected patients and those with cirrhosis of liver.

Hepatitis C virus treatment in the 'real-world': how well do 'real' patients respond?

BACKGROUND: Published clinical trials of the treatment of HCV are largely multicentre prospective pharmaceutical trials. Patients in clinical trials tend to have more favorable outcomes than patients in the 'real-world', due to strict patient selection and differences in treatment conditions and available resources. OBJECTIVES: To assess the outcomes of Hepatitis C infected patients treated at the Barwon Health Liver Clinic with combination Pegylated interferon (PEG-IFN) and Ribavirin (RBV) therapy and to determine factors associated with a treatment response. METHODS: Retrospective review of patients who received treatment for Hepatitis C at our institution's Liver Clinic from January 2001-September 2011. Patient demographics, comorbidities, treatment-related parameters and side effects were extracted from medical records and analyzed. RESULTS: A total of 190 patients (120 male, 70 female) with a mean age of 42.8 years (range 20-68 years) commenced treatment. The most common genotype was genotype 3 (48.9%), followed by genotype 1 (42.6%). 150 of 190 patients (78.9%) completed treatment and had end of treatment data available. 107 of 182 patients, (58.8%) for whom sustained virologic response (SVR) rate data was available achieved an SVR. Overall response rates were; 46.9%, 68.8% and 62.4% in genotypes 1, 2 and 3 respectively. The response rate was significantly lower in 29 patients with documented cirrhosis (20.7%). Age, diabetes and alcohol abuse did not predict treatment response in our cohort. Side effects reported in 81.6% of patients included general malaise, hematological disturbance and psychiatric issues, and necessitated cessation of therapy in 16 patients (8.4%) and dose reduction in 26 patients (13.7%). CONCLUSIONS: Response rates to combination PEG-IFN and RBV therapy at our institution are comparable to other 'real-world' and pharmaceutical registration trials. Side effects of combination therapy were prominent but resulted in fewer discontinuations of therapy compared to pharmaceutical trials.

Sustained virological response rates to antiviral therapy in genotype 1 and 3 chronic hepatitis C patients: a study from north India.

BACKGROUND: In India, both genotype 3 and 1 are predominant genotypes in patients with chronic hepatitis C (CHC). However, there is scanty data on sustained viral response (SVR) rate with conventionally recommended dual therapy with PEG-IFN and ribavirin. METHODS: In this retrospective study, consecutive patients of CHC of genotypes 1 and 3, attending the single unit of Gastroenterology of our hospital, who received PEG-IFN and ribavirin therapy, were included. Patients who had co-infection with HIV or HBV were excluded. RESULTS: A total of 114 patients were included in the study median age 44 (15-72) years, 79% males. Most common presentation was with chronic hepatitis, while 10 (9%) patients had compensated cirrhosis. Nine (8%) patients had associated diabetes, 16 (14%) patients gave history of significant alcohol abuse. The median baseline HCV RNA level was 3.0 × 10(5) (1.7 × 10(3)-1.8 × 10(7)) IU/mL. The most common genotype was 3 (75%) followed by genotype 1 (25%). 70% patients received PegIFN-α2a (median dose 180 MIU/wk) and 30% patients received PegIFN-α2b (median dose 80 MIU/wk). The median ribavirin dose was 800 (range 800-1200) mg. SVR in genotype 1 was 64% (18/28) while SVR in genotype 3 was 73% (63/86). The factors predicting SVR on univariate analysis were a lower baseline HCV RNA level (less than 3.0 × 10(5)), higher hemoglobin level > 11.8 g/dl, and achievement of rapid virological response (RVR), early virological response (EVR) and end of treatment response (ETR). In multivariate analysis the only baseline factor found independently correlating with SVR was low HCV RNA level (<3.0 × 10(5) IU/mL) (P = 0.003). CONCLUSION: In north India, HCV genotype 3 has a SVR rate of 73%, which is comparable to genotype 1 with SVR rate of 64% when treated with PEG-IFN and ribavirin therapy. A baseline HCV RNA level lower than 3.0 × 10(5) best predicts SVR in addition to achievement of RVR, EVR or ETR.