End Of Treatment Response Research Articles

Dual treatment with sofosbuvir plus ribavirin is as effective as triple therapy with pegylated interferon plus sofosbuvir plus ribavirin in predominant genotype 3 patients with chronic hepatitis C

Sofosbuvir (SOF) was the first directly acting antiviral made available for chronic hepatitis C (CHC) in India. We describe our "real life" experience of using SOF with ribavirin (RBV) with or without pegylated interferon (Peg-IFN) in predominant genotype 3 patients with CHC. A total of 158 patients (men 99 [62.6%], mean age 40.3 ± 12.8 years) with CHC treated with dual therapy (SOF + RBV) for 24 weeks or triple therapy (Peg-IFN + SOF + RBV) for 12 weeks were included prospectively. Patients with co-infection, decompensated liver disease, and post-organ transplantation were excluded. Data were analysed for the preference of treatment regimen, end of treatment response (ETR), sustained virological response at 12 weeks, and side effects. Genotype 3 was the predominant genotype (105 [66.4%]) followed by genotype 1 (40 [25.3%]) and genotype 4 (13[8.2%]). Forty-eight (30.37%) patients had cirrhosis (LSM ≥ 13 kPa), and 30 (19%) were treatment experienced with Peg-IFN + RBV. A total of 103 (65.18%) patients received dual therapy, and 55 (34.81%) received triple therapy. Resentment to receive injections, inaccessibility to a facility, fear of injection or its side effects, and financial constraints were the reasons to refuse triple therapy. All patients in triple therapy group and all but two patients (98%) in the dual therapy group attained ETR. All those who achieved ETR achieved sustained virological response at 12 weeks in both groups. But for anemia in three patients (two in triple, one in dual therapy), there were no major side effects. Most patients with CHC prefer an oral treatment with directly acting antivirals. Both oral and interferon-based regimens achieve high response rate.

Efficacy and safety of sofosbuvir-based regimens in chronic hepatitis C patients on dialysis.

Patients with end-stage renal disease (ESRD) have poor treatment tolerance and outcome to interferon-based regimens. Sofosbuvir-based regimens have improved treatment success in chronic hepatitis C. There is limited data in ESRD patients as sofosbuvir is excreted by the kidney. Several small studies have shown good results. Sixteen consecutive patients of ESRD (on dialysis) and chronic hepatitis C were treated with sofosbuvir-based regimens as they were prospective kidney transplantation recipients, at a tertiary care center in north India. Sofosbuvir was given 400mg on alternate days. Data is shown as number, mean (SD), and median (range). Sixteen patients (12 males) aged 45±12 years received sofosbuvir-based treatment. These patients were on hemodialysis from 10 (2-48) months. Eleven of these patients had genotype 1, four had genotype 3, and one had genotype 4 infection; baseline RNA was 7 (5-8) log. The following treatment regimens were used: sofosbuvir, ribavirin, and low dose peginterferon (n=8; 6 genotype 1 and one each had genotype 3 and 4); sofosbuvir and daclatasvir (n=7); sofosbuvir, ribavirin, and daclatasvir (n=1). Ten patients achieved end of treatment response and 8 (80%) of these achieved sustained virological response at 12weeks (SVR12); six are on treatment. Two patients with genotype one (including one with cirrhosis) had relapse. Seven patients needed blood transfusion; interferon was stopped in one due to thrombocytopenia. Fatigue was present in 4 patients. Sofosbuvir-based regimens can be used in ESRD patients on dialysis with good efficacy.

Job performance in chronic hepatitis C virus patients treated with pegylated interferon-\u03b12b plus ribavirin: an observational study

BackgroundThe employment status of workers with chronic hepatitis C has important implications for society and labor market, for organizations and for the individuals and their economic, social and psychological status. To evaluate the effects to Peg-IFN-α and RBV treatment on work ability (WAI) and perceived on work stress (PWS). One hundred forty-four patients consecutive with chronic hepatitis C had been enrolled and treated with Pegylated-Interferon-α 2b at dose 1.5 mg/kg per week plus daily oral Ribavirin for 12 months. The work ability (WA) and perceived work stress (PWS) were evaluated. The baseline value of PWS and WAI were compared to the values obtained at end of months 1, 3, 6, 12 and at follow up. At the end of the study we have also compared the following groups: pretreatment, end treatment response (ETR), sustained response, no response, and relapse.ResultsThe comparison between end treatment response (ETR) and sustained viral response (SVR) showed a significant difference in PWS. Comparison between ETR and both non responders (NR) and relapser showed significant differences in perceived work stress p < 0.01 and work ability index p < 0.05.ConclusionsHCV workers, treated with Peg-IFNα 2b plus Ribavirin, shows work performance loss, a decrease of work ability at 1 month and increase in work ability in patients with end on treatment response and in sustained responders decrease in perceived work stress.Trial registrationThis is not a registered study as an observational study. We measured the job performance in subjects who was undergoing to the gold standard therapy for Hepatitis C at the moment of our evaluation.

INF-free sofosbuvir-based treatment of post-transplant hepatitis C relapse – a Swedish real life experience

Background: Relapse of hepatitis C virus (HCV) infection after liver transplantation has been universal, and the fibrosis progression faster than in non-transplanted patients. Interferon (IFN)-free treatment with direct antiviral agents (DAA) has improved the treatment outcome dramatically. We here report on the outcome of IFN-free treatment for HCV relapse after liver transplantation in a real life setting in Sweden.Material: In total, 93 patients with a mean age of 60 years (range 32–80) with HCV relapse after liver transplantation were given sofosbuvir-based treatment in combination with a protease inhibitor (simeprevir) or a NS5A inhibitor (daclatasvir or ledipasvir) with or without addition of ribavirin (RBV), or sofosbuvir and RBV only. Treatment was generally given during 24 weeks for advanced fibrosis or cirrhosis cases and 12 weeks for mild fibrosis with fibrosis stage 2 or less. The distribution of genotype 1, 2, 3, 4 in our patients was 58, 7.5, 26.5 and 7.5%, respectively.Results: All recipients reached end-of-treatment response (ETR) with HCV RNA <15 IU/mL. Sustained viral response 12 weeks after treatment cessation (SVR12) was achieved in 91/93 (97.8%) recipients. The SVR12 rates for genotype 1, 2, 3 and 4 were the SVR12 rate were 96, 100, 100 and 100%, respectively (p = .04).Conclusion: It is concluded that IFN-free treatment with DAAs for HCV relapse after liver transplantation is highly effective also in a real life setting and offers cure for most recipients.

Effectiveness of Sofosbuvir and Ribavirin for Eradicating Hepatitis C Virus in Renal Transplant Recipients in Pakistan: Where Resources Are Scarce.

Although direct-acting antiviral agents have revolutionized hepatitis C virus treatment, these novel agents are not widely available in the developing world. Further, no treatment recommendation for renal transplant recipients includes these agents. We aimed to evaluate the effectiveness of sofosbuvir and ribavirin, the only direct-acting antiviral agents available in Pakistan, in renal transplant recipients. All renal transplant recipients receiving sofosbuvir and ribavirin from August 2015 to March 2016 were enrolled in the study. Patients' demographics and baseline laboratory parameters were collected. Rapid virologic response, early virologic response, end-of-treatment response, and sustained virologic response at 12 and 24 weeks were analyzed. Statistical analyses were performed using IBM SPSS Statistics software, version 20.0. Of the 37 renal transplant recipients, the mean age was 37.2 ± 10.7 years and the majority (33 [89.2% ]) were men. Twenty-five patients were treatment naive; of the remaining 12 patients, 10 were responders, 2 were nonresponders, and 5 were relapsers to pretransplant hepatitis C treatment. The genotype most commonly seen posttransplant was genotype 1 (56.8%). Rapid virologic response was achieved in 33 patients (89.2%). Early virologic response, end-oftreatment response, and sustained virologic response at 12 weeks were achieved in all 37 patients (100%). Until the time of data collection, 14 patients had achieved a sustained virologic response at 24 weeks. No complications were noted during therapy. In 2 of 4 patients who developed decompensated cirrhosis, treatment led to the resolution of ascites. Sofosbuvir and ribavirin are well tolerated and effective in renal transplant recipients for eradicating hepatitis C virus. Their effectiveness is not limited to renal transplant recipients with genotypes 1, 2, 3, and 4 but also extends to those with mixed genotype (in this study, genotypes 1 and 3).

Pegylated Interferon, Ribavirin, and Sofosbuvir Combination versus Pegylated Interferon, Ribavirin in the Management of Chronic Hepatitis C Egyptian Patients

Objective: The aim of this study is to comprehensively evaluate the safety and efficacy of the 20-kDa linear (Pegylated Interferon) PEGIFN alpha-2a and Ribavirin combination versus Sofosbuvir, 20-kDa linear PEGIFN alpha-2a and Ribavirin combination in treatment of chronic hepatitis C (CHC) Egyptian patients as well as studying variables that affect the response to this treatment. Methods: A total of 202 adult Egyptian patients divided into 2 groups; IR group composed of 97 patients enrolled to receive PEG-IFN and RBV combination treatment, and IRS group composed of 105 patients enrolled to receive PEG-IFN, RBV, and sofosbuvir combination. Results: In IR group 62 (63.92%) had end of treatment response (ETR), of the 62 patients with ETR, 11(11.34%) had a relapse while 51 (52.58%) patients achieved sustained virological response (SVR). In IRS group six (5.72%) patients were non-responders, where as 99 (94.28%) patients attained ETR of whom 29 (27.62%) had a relapse while 70 (66.67%) patients achieved SVR. Conclusion: This new combination containing sofosbuvir is still ineffective enough so that more researches and treatment combination needed to combat hepatitis C epidemic in Egypt at reasonable cost.

Interleukin-28B Polymorphism is a Pharmacogenetic Predictor during Sofosbuvir Plus Pegylated Interferon and Ribavirin Therapy for Chronic Hepatitis C Egyptian Patients

Background and Aim: Interleukin-28B (IL-28B) polymorphism is a predictor of sustained virologic response (SVR), spontaneous clearance and personalizing therapy of hepatitis C virus (HCV). This study aimed to determine IL28B rs12979860 polymorphism among chronic hepatitis C (CHC) Egyptian patients as a step in personalized HCV therapy and pharmacogenomics. Methods: CHC Egyptian patients were received sofosbuvir (SOF) plus pegylated interferon (PEG-IFN) and ribavirin (RBV) for 12 weeks. A total of 82 HCV infected Egyptian patients and 27 healthy individuals were included in the present study. CHC Patients were classified as achieving SVR if plasma HCV-RNA was undetectable (group A) and non-responders if plasma HCV-RNA was detectable (group B). IL28B genotypes were analyzed and their associations with SVR were selected. Results: The end of treatment response (ETR) rate was 100%. However, SVR12 was 76.8% (group A) and 23.2% relapsed (group B). Among studied CHC patients, 50% were IL-28B TT, 40.2% CT, and 9.8% CC. while the percentage of their frequencies in the healthy persons were 18.5%, 51.8%, and 29.6%, respectively. These results showed that the frequencies of TT genotypes were more prevalent in HCV patients. The genotype CC (n=8) achieved higher rates of SVR in group A (87.5%) than relapsed patients in group B (12.5%) and it had the least prevalence in group B compared with the frequencies of CT (21.2%) and TT (26.9%) genotypes. These results showed that CC genotype was associated with SVR. Conclusions: It can be concluded that the individuals with IL28B TT genotype are more susceptible to HCV infection in Egyptian patients and relapse. Moreover, IL-28B CC is useful for pretreatment prediction of the outcome of HCV treatment. Hence, IL28B polymorphism could be considered as a pharmacogenetic predictor in personalized HCV therapy and pharmacogenomics during SOF plus PEG-IFN and RBV therapy for chronic hepatitis C Egyptian patients.

Association of TNF-α and CCL5 with response to interferon-based therapy in patients with HCV 1 genotype.

Aim of the studyTo evaluate the role of potential genetic predictors –308G/A TNF-α and –403G/A CCL5 in treatment for HCV 1 genotype.Material and methodsTreatment results of 130 patients with chronic hepatitis C 1 genotype according to different genotypes of IL28B, CCL5, and TNF-α were analysed using multiple logistic regression.ResultsIL28B genotypes CC/CT/TT were found in 27 (20.8%), 74 (56.9%), and 29 (22.3%) patients. Genotypes GG/GA/AA of –308G/A TNF-α were revealed in 98 (75.4%), 30 (23.1%), and 2 (1.5%) patients. Genotypes GG/GA/AA of –403G/A CCL5 were revealed in 86 (66.2%), 39 (30%), and 5 (3.8%) patients, respectively. The previously known effect of IL28B was observed. IL28B TT genotype decreased end of treatment response (EOTR) rates by a factor of 29.0 (95% CI: 6.4-183). The combination of CCL5 GG and IL28B CT genotypes increased the risk of failure to achieve EOTR by a factor of 28.5 (95% CI: 7.2-160). Genotypes GA and AA of TNF-α (–308) G/A SNP increased the risk of relapse in patients who achieved EOTR (OR = 9.4; 95% CI: 2.4-48).ConclusionsPractitioners may benefit from using these predictors when considering indications for the antiviral therapy and deciding on the treatment regimen.

Sub-Clinical Thyroid Disorders in Patients With Hepatitis C Before and After Conventional Treatment

Objective: Thyroid dysfunction represents one of the commonest endocrine manifestations of chronic hepatitis C infection, exaggerated by interferon based treatment. The purpose of this study was to assess the frequency of hepatitis C virus and sub-clinical thyroid disorder in patients with hepatitis C before and after treatment. Methods: This is an observational, cross sectional analysis conducted in Lyari general hospital and Abbasi Shaheed hospital from January 2009 to December 2015. Patients with a positive rt-PCR and genotype 3 were included in the study. After a positive rt-PCR, patients were screened by thyroid stimulating hormone before starting the treatment. All patients were given therapy of conventional interferons (3 million units thrice weekly) and ribavirin (800 mg per day in two divided doses) for a period of 6 months. Patient with normal TSH level was included and patients with a co-existing hepatitis B or D were excluded from the study. After 6 months of therapy all patients had a repeat rt-PCR to see the end treatment response to therapy and a thyroid stimulating hormone to screen for thyroid disorders. Results: A total of 129,430 patients have visited the medical outpatient department of which, 4069 were HCV RNA PCR positive. The prevalence of unrecognized hepatitis C Virus was 13.4% in the study population. The prevalence of sub-clinical thyroid disorders was 9%. Of which 6.5% had sub-clinical hypothyroidism and 2.5% had overt or subclinical hyperthyroidism. A total of 2196 patients were included in the analysis. Mean age was 36.22 ±10.01 years range from 16 to 63 years. Among all 36.9% were male and 5.1% were known diabetics. On the whole 14.8% were non-responders, 80.9% achieved an end treatment response and 4.3% lost to follow up. We observed an association between the post treatment TSH level and the ETR of HCV (p=0.015). A statistically significant difference (p<0.001; 95% CI -3.008-1.577) was observed in the thyroid stimulating hormone at the baseline and following the conventional interferon and ribavirin therapy for a period of 6 months. 388 (17.6%) patients had abnormal thyroid function tests after conventional interferon treatment. These 388 patients were further followed up for 6 months. Conclusion: In conclusion, this study results shows 13.4% prevalence of HCV in Karachi and the prevalence of sub-clinical thyroid disorders was 9%, of which 6.5% and 2.5% had overt hypothyroidism and hyperthyroidism respectively.

Rapid virological&End treatment response of patients treated with Sofosbuvir in Chronic Hepatitis C.

Objective:To determineRapid & End treatment response of patients treated with Sofosbuvir in Chronic Hepatitis C at tertiary care hospital.Methods:It was an observational study conducted at Memon Medical Institute from January 2016 to July 2017. The inclusion criteria for patients was 18 years of age or older, having chronic infection with HCV. Total=201 received sofosbuvir with or without interferon in our OPDs. Patients were categorized into Treatment naïve, treatment experienced and decompensated chronic liver disease. Pregnant patients and those not willing to participate were excluded. Initially genotyping and Quantitative HCV RNA test was done.Results:A total of 201 subjects were included in the study with mean age of the patients was 46.22± 14.41 years. Of 201 patients, n= 131 (65.2%) chronic hepatitis C, compensated cirrhosis n= 47(23.4%), and with decompensated cirrhosis n=23(11.4%). Most commonly genotype 3 n= 180 (89.6%) was present followed by genotype 1 n=9(4.5%), genotype 2 n=1(0.5%), genotype 4 n=1(0.5%). Of patients with genotype 3, 123 received dual therapy and 57 were given triple therapy. After one month of therapy HCV RNA by PCR, 200(99.5%) achieved RVR, 199(99%) achieved ETR and SVR achieved in 178(88.5%) while remaining 1 patient did not achieved RVR, 2 ETR and 12 patients did not achieved SVR and remaining 11 SVR lost follow up.Conclusion:Sofosbuvir has shown to be very effective andsuccessfulwith achievement of virological response with little or no resistance in all genotypes mainly genotype 3 treated in our study population. The promising results of our study will aid in better outcomes and therefore help in eradication of the virus.

Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients.

The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group (p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group (p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344-13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse.

Outcome of Combination Therapy with Sofosbuvir and Ledipasvir for Chronic Type C Liver Disease

Introduction: Recently, the treatment of chronic hepatitis C has markedly advanced. A phase III clinical study of combination therapy with sofosbuvir (SOF) and ledipasvir (LDV) was conducted in Japan, and the additive therapeutic effects were reported. In this study, we report the results of treatment in our hospital. Methods: Of 147 patients with chronic type C liver disease who had consulted our hospital since September 2015 and received SOF/LDV therapy, in 91 subjects a sustained virological response of 12 weeks (SVR12) could be evaluated. Results: In all 91 patients, end treatment response was achieved. Subsequently, recrudescence was noted in 1 before the completion of treatment (week 12); an SVR12 was achieved in 90 patients (99%). The following adverse reactions were observed in 3 patients (3.3%): bradycardia, paroxysmal atrial fibrillation, and heart failure with QT prolongation, which were associated with heart disease. Conclusion: A favorable SVR was achieved by SOF/LDV therapy even in elderly patients, those with liver cirrhosis, or those having undergone radical treatment of liver cancer. Furthermore, a high tolerance was demonstrated, but adverse reactions associated with the heart may appear in patients with heart disease as an underlying disease; strict management during treatment is necessary.

Results of a Phase Ib Study of Venetoclax Plus R- or G-CHOP in Patients with B-Cell Non-Hodgkin Lymphoma

Results of a Phase Ib Study of Venetoclax Plus R- or G-CHOP in Patients with B-Cell Non-Hodgkin Lymphoma

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.

Prognostic Value of Transient Elastography in Human Immunodeficiency Virus-Infected Patients With Chronic Hepatitis C.

Background.Our objective was to study the prognostic value of liver stiffness (LS) in HIV-infected patients with chronic hepatitis C (CHC).Methods.We analyzed HIV-infected patients with compensated CHC and at least 1 determination of LS. The primary outcome was the occurrence of liver-related events (LRE), namely, decompensation or hepatocellular carcinoma, whichever occurred first. We selected patients without sustained viral response (SVR) or end-of-treatment response (ETR) during follow-up and allocated them to an estimation cohort (EC) and a validation cohort (VC).Results.The study population comprised 1292 patients. After a median follow-up of 5.8 years, 90 patients experienced LRE and 73 died. In the subgroup of 957 patients without SVR or ETR, the area under the receiver operating characteristic curves (AUROCs) (95% confidence interval [CI]) of LS for prediction of LRE in the EC (n = 634) and the VC (n = 323) were 0.87 and 0.88, respectively. The best cutoff value of LS to rule out LRE in the EC was 12 kPa, with a negative predictive value of 98.3% in the EC and 98.2% in the VC. Per each 1 kPa and 5 kPa increase above 12 kPa, the hazard ratio of LRE (taking into account death as a competing risk) was 1.07 (95% CI, 1.05–1.08) and 1.38 (95% CI, 1.31–1.46), respectively.Conclusions.Liver stiffness is very accurate for predicting LRE in coinfected patients. Patients with an LS <12 kPa had a 98% probability of not developing LRE after a median follow-up of almost 6 years. Above the 12-kPa cutoff, the hazard of LRE increases proportionally with LS.

Direct Acting Antivirals in HIV- HCV Co-infection: A Community Based Retrospective Cohort Study

Introduction: Direct acting antivirals (DAA) has shown good response in HIV-chronic Hepatitis C co-infected patients. Studies have shown very good response among the patients in trial settings, but we have very limited information regarding the response in the community setting. Methods: A retrospective study was conducted to assess the efficacy of DAA among HIV- chronic HCV co-infected patients from 2013 January until December 2015. Electronic medial records from two community teaching hospitals were reviewed. End of treatment response (ETR) and sustained virologic response at 12 weeks (SVR 12) was analyzed. Results: Of the 154 patients with co-infection, 32 patients were treated with DAA's. Mean age of the patient was 56 years. Mean viral load at the start of treatment was 2231836. Out of 32 patients 44% were black, 16% White, 9% Hispanic, and 31% were others. Of these patients, 46.9% had HCV genotype 1a, 15.6% had genotype 1b, 3.1% had genotype 2, 6.3 % had genotype 3 and 28.9% had genotype 4. Sixty-six percent were treatment naive and 34.4% were treatment experienced. Of the naive group 80.9% were treated for 12 weeks and 19.1% were treated for 24 weeks. In treatment experienced group 82% were treated for 12 weeks and 18% were treated for 24 weeks. Of the study population 62.5% were non cirrhotic and 37.5% had cirrhosis. ETR revealed that 90.6% had undetectable viral load while 9.4% of the patient still had quantifiable viral loads (Chart 1). During evaluation for SVR 12, four patient had no documentation of SVR12, 23 of 28 (82%)patients (82%) had undetectable viral load and 5 (18%) had quantifiable viral load. Of those with quantifiable viral load, 1(3.1%) patient had breakthrough, 2 (6.3%) of the patient had relapse and 2 (6.3%) had partial response. Subgroup analysis showed no significant difference in SVR 12 among treatment experienced and treatment naive patients (p 0.36), between different genotype (p 0.71) and cirrhosis status (p 0.11). There was no statistically significant difference in treatment response among different treatment regimens of DAA (p 0.47). Adverse drug reactions experienced by the patients were as shown in chart 3.Figure 1Conclusion: Although newer DAA in recent trials have shown high SVR, in real world setting, SVR was found to be lower compared to the trial findings. Further studies are warranted to find out the reason behind lower response rate among the co-infected patients.Figure 2Figure 3

Safety and Efficacy of Sofosbuvir Based Regimens for Treatment of Chronic Hepatitis C Genotype 4: A Community Based Retrospective Cohort Study

Introduction: limited data exists on efficacy of short course therapy with peg interferon, ribavirin and sofosbuvir for chronic hepatitis C genotype 4 infection. We assessed the efficacy and tolerability of combination regimens involving sofosbuvir in patients infected with chronic hepatitis C genotype -4 in a retrospective cohort study. Methods: We retrospectively reviewed medical records of 37 patients with chronic hepatitis c genotype 4 treated between Jan 2013 to June 2015. Twenty-nine of the 37 patients were treated with Peg-Interferon 180mcg subcutaneously weekly with daily weight based ribavirin in combination with fixed dose sofosbuvir for 12 weeks. Three patients each received interferon free sofosbuvir + ribavirin and ledipasvir + sofosbuvir (Harvoni) regimens. Two patients were treated with simeprevir and sofosbuvir at standard doses. Results: Majority of the patients (N=33) were from Middle eastern or Egyptian origin. Eighty percent (N=30) were men and 19% (N=7) were women. Among all patients, 37% (N=14) were treatment experienced and 13% (N=5) had cirrhosis at baseline. Nine patients were co infected with human immunodeficiency virus. End of treatment was not recorded in one patient and sustained virologic response was not available for 4 patients. Two patients discontinued the treatment due to adverse reactions. Excluding patients, who discontinued treatment regimen and who don't have documented ETR and 12 week SVR rate, overall end of treatment response and sustained virologic response rate at 12 weeks post treatment were 100% (34/34) and 93.5% respectively (29/31). Hundred percent of the patients treated with interferon, ribavirin and sofosbuvir, attained 12 week sustained virologic response. One of the two patients who relapsed after treatment was treated with sofosbuvir and ribavirin and the other patient received simeprevir and sofosbuvir regimen. Most common adverse reactions were leukopenia (27%), followed by fatigue (21%), anemia (19%) and thrombocytopenia (16%). One patient developed severe skin reaction after 4 weeks of treatment and the other patient decompensated with esophageal variceal bleeding and both discontinued the treatment.Figure 1Figure 2Conclusion: Our results suggest that short course treatment with peg interferon, ribavirin with direct acting antiviral agent sofosbuvir still a suitable option for treating patients with chronic hepatitis C genotype 4 with excellent sustained virologic response and acceptable adverse events.

Results of Sofosbuvir Based Combination Therapy for Chronic Hepatitis C Cohort of Indian Patients in Real-Life Clinical Practice

Introduction: The introduction of Sofosbuvir(SOF), a direct acting antiviral (DAA), has revolutionized the treatment of chronic hepatitis C virus (HCV). Phase 3 clinical trials have demonstrated the efficacy and tolerability of Sofosbuvir-based regimens. This study was planned to observe whether excellent clinical trial results translate into real life clinical practice. Methods: This is a prospective, non-randomized observational study conducted in the Department of Gastroenterology at a tertiary care center in India, between April 2015 and December 2015. All consecutive treatment naive patients diagnosed with chronic hepatitis C (genotype 1-5) were included. Sofosbuvir was the only DAA available in India during this period and was used either as a part of triple drug regime (Pegylated interferon, Ribavirin, Sofosbuvir) or dual drug regime (Sofosbuvir and Ribavirin). Response to therapy was assessed at week 4 (Rapid Virological Response, RVR), week 12 or 24 (End of Treatment Response, ETR) and 12 weeks after cessation of therapy (Sustained Virological Response, SVR). Results: A total 947 patients were diagnosed with chronic HCV infection in our unit during the study period, of which 736 patients (77.1%) opted and completed anti viral treatment. Mean age of the patients was 45.1 years and the Male: Female ratio was 1.7:1. Genotype 3 (589/736, 80%) was the commonest followed by genotype 1 and 4 (106/736, 14.4%% and 36/736, 4.89 % respectively). Viral load was high (>600,000 IU/l) in 397/736 (53.9%); 335 patients (45.5%) had cirrhosis (of which 105 (31.4%) were decompensated) and 6 patients (0.8%) had hepatocellular carcinoma at presentation. Most of the patients with genotype 1,4,5 (n=135) were treated with triple drug regime for 12 weeks (10 patients with advanced liver disease were treated with sofosbuvir and ribavirin for 36 weeks). Patients with genotype 3 (n=589, 80%) were treated either with dual therapy for 24 weeks (n=405) or triple therapy for 12 weeks (n=184). SVR was achieved in 452/470 (96.2%) and there was no statistically significant difference in the SVR rates in different genotypes. Conclusion: SOF- based treatment regimens achieve high SVR rates in real life cohort of Indian patients with chronic hepatitis C infection. Patients with decompensated cirrhosis who were earlier ineligible to receive interferon-based protocols can also be considered for anti viral therapy.

Dual Treatment With Sofosbuvir Plus Ribavirin is as Effective as Triple Therapy With Pegylated Interferon Plus Sofosbuvir Plus Ribavirin in Predominant Genotype 3 Patients With Chronic Hepatitis C

Background and Aim Sofosbuvir (SOF) was the first directly acting antiviral made available for chronic hepatitis C (CHC) in India. We describe our “real life” experience of using SOF with ribavirin (RBV) with or without pegylated interferon (Peg-IFN) in predominant genotype 3 patients with CHC. Methods A total of 158 patients (men 99 [62.6%], mean age 40.3 ± 12.8 years) with CHC treated with dual therapy (SOF + RBV) for 24 weeks or triple therapy (Peg-IFN + SOF + RBV) for 12 weeks were included prospectively. Patients with co-infection, decompensated liver disease, and post-organ transplantation were excluded. Data were analysed for the preference of treatment regimen, end of treatment response (ETR), sustained virological response at 12 weeks, and side effects. Results Genotype 3 was the predominant genotype (105 [66.4%]) followed by genotype 1 (40 [25.3%]) and genotype 4 (13[8.2%]). Forty-eight (30.37%) patients had cirrhosis (LSM ≥ 13 kPa), and 30 (19%) were treatment experienced with Peg-IFN + RBV. A total of 103 (65.18%) patients received dual therapy, and 55 (34.81%) received triple therapy. Resentment to receive injections, inaccessibility to a facility, fear of injection or its side effects, and financial constraints were the reasons to refuse triple therapy. All patients in triple therapy group and all but two patients (98%) in the dual therapy group attained ETR. All those who achieved ETR achieved sustained virological response at 12 weeks in both groups. But for anemia in three patients (two in triple, one in dual therapy), there were no major side effects. Conclusions Most patients with CHC prefer an oral treatment with directly acting antivirals. Both oral and interferon-based regimens achieve high response rate.

COMPARISON OF HCV TREATMENT

Objectives: To analyze End of Treatment Response (ETR) and SustainedVirological Response (SVR) to HCV mono-infection in comparison with HCV/HBV co-infection.Study Design: Retrospective, multicenter study. Place and duration of study: The study wasconducted at Department of Biochemistry and Molecular Biology, Army Medical College incollaboration with Armed Forces Institute of Pathology (AFIP), Rawalpindi and was completed in12 months. Material and Methods: This study included two hundred and twelve HCV infectedpatients, treated with IFN-α-2b 6MU thrice weekly plus ribavirin 1000-1200 mg daily for 24 weeksduration. The subjects were divided into two groups of 152 HCV mono-infected and 60 HCV/HBVco-infected patients. Pretreatment biochemical factors, EVR and SVR were compared betweentwo groups. Results: There is no significant difference between the proportions of HCV monoinfectedversus HCV/HBV co-infected patients with ALT &amp; AST levels before interferon therapy.The analysis by intention to treat exhibit EVR of 75% and 60% among co-infected and monoinfectedpatients respectively (p = 0.038). Similarly, SVR of 50% and 45% was observed in HCV/HBV co-infected and mono-infected patients (p = 0.489). Conclusions: HCV/HBV co-infectedand HCV mono-infected patients had similar biochemical characteristics with significant lowerHCV-RNA titer in mono-infected patients. HCV/HBV co-infected patients showed higher EVRand SVR rates to interferon-alpha/ribavirin combination therapy as compare to mono-infectedpatients. The most possible factors responsible for favorable response rate in co-infectedpatients would be due to positive host immune reaction and reciprocal viral interaction.