Lower Sustained Virological Response Rates Research Articles

S1370 Delayed Clinical Follow Is Not Associated With Lower SVR Rates in an HCV-Infected Cohort in Mumbai, India

Introduction: Hepatitis C Virus (HCV) has a prevalence of 71 million cases worldwide. Regular follow-up can be challenging for patients in low middle income countries (LMIC) due to lack of access to healthcare facilities and transportation difficulties. Our aim was to determine if delayed vs regular follow up for patients being treated for HCV with direct acting antivirals (DAA) resulted in a difference in sustained virologic response (SVR). Methods: We conducted a retrospective cohort study of 149 patients in Mumbai, India who had received treatment for Hepatitis C from 2015 to 2021. All patients had confirmed HCV by PCR and were treated with direct acting antivirals (DAA) approved by the FDA equivalent in India. Patients were asked to present for follow up 12 weeks after end of treatment for SVR12 (sustained virologic response) testing. Results: 149 patients were included. 81 followed up on time (54%) and 68 did not (46%). The mean age at treatment in both groups was similar (51 vs 52, p = 0.29) while male/female distribution showed a significant difference (40% vs 54% male, 60% vs 46% female, p = 0.027). The most common genotype in the cohort was genotype 3 (52% vs 49%) and the second most common was genotype 1 (32% vs 20%). There was not a significant difference in genotypes between both groups (p = 1.0). History of hyperlipidemia (p = 0.12), thyroid disease (p = 0.20), and CKD (p = 0.16) did not show significant difference across both groups. On the other hand, diabetes (p = 0.026) and HTN (p < 0.01) were more prevalent in those who had delayed follow up. There was no significant difference in prior treatment experience between the two groups (p = 0.13). Change in AST and ALT from the initiation of treatment until SVR also did not show significant difference across both groups (p = 0.58, 0.38). Patients with advanced liver disease were more commonly seen in the group which did not have on-time follow up (p < 0.01). SVR was seen more in the group which did not follow up on time (94% vs 79%, p < 0.01). (Table) Conclusion: The likelihood of SVR was not impeded by delayed follow-up compared to regular follow-up in this cohort of infected patients. Further research is needed to determine if this is generalizable across different genotypes and geographic locations. Table 1. - Patients’ baseline clinical characteristics stratified against delayed vs regular follow-up Variable Overall (n=149) Delayed FU (n=68) Regular FU (n=81) P-value Age (mean ± SD) 52 ± 13 53 ± 13 51 ± 13 0.29 Sex (n, %) 0.10 Male 71 (48) 27 (40) 44 (54) Female 78 (52) 41 (60) 37 (46) Genotype (n, %) 1.0 1 46 (31) 20 (20) 26 (32) 2 1 (0.6) 0 (0) 1 (1.2) 3 75 (50) 33 (49) 42 (52) 4 4 (2.7) 2 (2.9) 2 (2.5) 5 1 (0.6) 0 (0) 1 (1.2) Not collected 22 (15) 13 (19) 9 (11) DM (n, %) 0.06 No 120 (81) 50 (74) 69 (85) Yes 29 (19) 18 (26) 12 (15) HTN (n, %) 0.03 No 96 (64) 37 (54) 59 (73) Yes 53 (36) 31 (46) 22 (27) HLD (n, %) 0.18 No 144 (97) 64 (94) 80 (99) Yes 5 (3) 4 (6) 1 (1) Thyroid Disease (n, %) 1.0 No 131 (88) 60 (88) 71 (88) Yes 18 (12) 8 (12) 10 (12) CKD (n, %) 0.38 No 137 (92) 61 (90) 76 (94) Yes 12 (8) 7 (10) 5 (6.2) Treatment Experience (n, %) 0.73 Naive 101 (68) 45 (66) 56 (69) Experienced 48 (32) 23 (34) 25 (31) Liver Status (n, %) 0.03 No Cirrhosis 56 (38) 26 (38) 30 (37) Comp Cirrhosis 68 (46) 25 (37) 43 (53) Decomp Cirrhosis 25 (17) 17 (25) 8 (10) SVR (n, %) < 0.01 No 21 (14) 4 (5.8) 17 (21) Yes 128 (86) 64 (94) 64 (79) Change in AST (mean ± SD) 35 ± 39 37 ± 38 33 ± 41 0.58 Change in ALT (mean ± SD) 42 ± 55 46 ± 64 37 ± 47 0.38

What Is the Optimal Bridging Therapy for Patients with Hepatitis C-associated Hepatocellular Carcinoma Awaiting Liver Transplant? An Analysis of the United States HCC Liver Transplantation Consortium

Introduction: Patients with hepatitis C (HCV)-associated hepatocellular carcinoma (HCC) often receive bridging therapy in the form of liver-directed therapy (LDT) while awaiting liver transplant (LT). The optimal modality of LDT, with respect to both cancer outcomes and response to direct-acting antiviral (DAA) therapy, remains unknown. Methods: The United States HCC Liver Transplantation Consortium was queried for patients with primary HCV-associated HCC within Milan criteria who completed DAA therapy and underwent LT. Primary outcomes were HCC recurrence-free survival (RFS) and overall survival (OS). Secondary outcome was sustained virologic response (SVR) as indicator of efficacy of DAA therapy. Results: Of 857 patients, 753 met inclusion criteria. LDT consisted of radiofrequency ablation (RFA,13.3%,N=100), transarterial chemoembolization (TACE,44.1%,N=332), yttrium-90 (Y90,4.8%,N=36), and stereotactic body radiation therapy (SBRT,2.9%,N=22). Eighty-one(10.8%) patients received no LDT and 182(24.2%) received multiple modalities. SBRT patients had the highest 5-year RFS(100%) followed by those receiving TACE(94%), Y90(91.4%), RFA(89.9%), and multiple therapies(88.2%) (p=0.048, Figure 1A). OS was higher among patients who received SBRT, but not statistically significant (p=0.685, Figure 1B). SVR rate was lower among radiation-based therapy groups (Y90 73.5%, SBRT 78.9%, others≥88%; p=0.046). Conclusions: In a homogeneous population of HCV-associated HCC patients within Milan criteria who received bridging therapy while awaiting LT, SBRT was associated with increased RFS and trended towards increased OS. However, radiation-based therapy was associated with decreased efficacy of DAA as measured by lower SVR rates. The optimal choice of bridging therapy to liver transplant must balance oncologic and virologic outcomes, but these findings seem to favor SBRT.

Acute reversible rhabdomyolysis during direct-acting antiviral hepatitis C virus treatment: a case report

IntroductionTreatment of hepatitis C infection has evolved dramatically since 2011. Previous conventional therapy with interferon and ribavirin used to have a low sustained virological response rate of less than 40%. In the new direct-acting antiviral therapy era, a sustained virological response can be achieved in more than 90% of cases.Case presentationWe report a rare case of severe reversible acute rhabdomyolysis in a 31-year-old Saudi male patient with very long-chain acyl-coenzyme A dehydrogenase deficiency and chronic hepatitis C infection. The patient was clinically asymptomatic with no signs of decompensated liver disease.The patient received new direct-acting antiviral agents: sofosbuvir and daclatasvir. Fourteen days after initiation of direct-acting antiviral agents, the patient was found to have asymptomatic rhabdomyolysis. His creatine kinase peaked at 2572 IU/l, and he was treated conservatively; the direct-acting antiviral agents were discontinued and within 7 days, the patient’s creatine kinase levels normalized.ConclusionThis case highlights possible direct-acting antiviral agent-induced rhabdomyolysis in a patient with very-long-chain acyl-CoA dehydrogenase deficiency, presumably through alteration of mitochondrial membrane potential. Further studies are required to assess the possible impact and associations.

Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs.

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.

Real-world experiences with direct-acting antiviral agents for chronic hepatitis C treatment.

As direct-acting antiviral (DAA) agents become more readily available for the treatment of chronic hepatitis C, it is important to understand real-world treatment experiences. In order to assess the effectiveness of DAA regimens and factors that influence sustained virologic response (SVR) rates in the Veterans Affairs healthcare system, we retrospectively identified veterans with chronic hepatitis C who were treated with DAAs from January 2014 to June 2015. We determined SVR rates and collected data on demographics, genotype (GT), previous interferon-based treatment, antiviral regimens, and co-morbidities (HIV, prior solid organ transplant, haemodialysis) for analysis. Of 15720 veterans, the majority were infected with genotype 1a (GT1a, 60.5%). Excluding the special populations, the overall cohort SVR rate was 92%. Compared to treatment-experienced patients, treatment-naïve patients had significantly higher SVR rates (90% vs 92%, P=.006). Subgroups associated with lower likelihood of achieving SVR-included African Americans (OR 0.79, 95% CI 0.69-0.91), GT3 (OR 0.65, CI 0.50-0.86), and cirrhosis (OR 0.91, CI 0.84-0.99) or decompensated cirrhosis (ascites: OR 0.78, CI 0.67-0.91, variceal bleed: OR 0.75, CI 0.57-0.99). The only treatment regimen independently associated with lower SVR rates was SOF+RBV+IFN (OR 0.65, CI 0.50-0.84). Special populations achieved high SVR rates: HIV 92%, haemodialysis 93%, liver transplant 96% and renal transplant 94%. In conclusion, overall SVR rates were comparable to those reported in clinical trials and carried over to historically more difficult-to-treat patients. Several patient- and treatment-related factors were identified as independent predictors of treatment failure and suggest subgroups to target for efforts to improve therapeutic strategies.

SUSTAINED VIROLOGIC RESPONSE RATE IN CHRONIC HEPATITIS C PATIENTS THROUGH DIRECT-ACTING ANTIVIRALS THERAPY.

In recent years the management of hepatitis C virus infection and the possibility of its eradication have been researched due to the importance that they represent in the health of the world population. Obtaining data that help to cope with this pathology improves the quality of life of those affected by it. The present study evaluated the effectiveness of direct-acting antiviral therapies provided by the Brazilian Ministry of Health in accordance to the Clinical Protocol and Therapeutic Guidelines of 2015. To evaluate the epidemiological profile of patients with chronic hepatitis C and the rate of sustained virologic response using direct-acting antivirals of all individuals that attended the referral service for the treatment of chronic hepatitis C at the Hospital of the Federal University of Rio Grande. This was an observational, retrospective/prospective study with all patients with chronic hepatitis C who had their treatments available from December 2015 to August 2017 according to the criteria of the Clinical Protocol and Therapeutic Guidelines of 2015. In the first phase, the clinical and demographic variables of all individuals enrolled in a treatment for hepatitis C were selected and collected from the Reference Service database. In the second phase, treatment data were collected. The outcome variable, sustained virologic response, was defined as an undetectable viral load on the blood test three months after the end of treatment. The descriptive and bivariate analyzes were performed with Pearson's chi-square and Fisher's Exact test, adopting a P value ≤0.05 in the SPSS 20 software. Of the 252 participants in the study, 228 (90.5%) had a sustained virologic response, 55.2% were male with an average age of 58.6 years (SD±9.1). Genotype 1 was the most prevalent, observed in 54.4% of the participants, and 87.4% of the patients had moderate/advanced hepatic fibrosis. After the statistical analysis, it was observed that the individuals with genotype 3 and moderate/advanced hepatic fibrosis had lower sustained virologic response rate (P=0.05 and P=0.04, respectively). It was observed that the use of direct-acting antivirals, in comparison to previous therapeutic regimens, increases the sustained virologic response, reaching all patients with mild fibrosis. This study provides information that helps in the hepatitis C treatment by showing that prescribing early treatment for patients without hepatic fibrosis and/or genotype 3 virus could increase therapeutic effectiveness.

2501 A Rare Case of Sofosbuvir/Velpatasvir/Voxilaprevir Failure in a Patient With Hepatitis C Virus Infection and Previously Undiagnosed Hepatocellular Carcinoma

INTRODUCTION: The advent of direct acting antiviral (DAA) agents has revolutionized the treatment for chronic hepatitis C virus (HCV) infection with greater than 95% success rate. In 2017, a combination of sofosbuvir, velpatasvir, and voxilaprevir (sof-vel-vox) was approved after clinical trials demonstrated a 97-100% sustained virological response (SVR) rate in patients who had failed a previous NS5A inhibitor regimen. We present a rare case of treatment failure with sof-vel-vox in a non-cirrhotic patient with previously undiagnosed hepatocellular carcinoma (HCC). CASE DESCRIPTION/METHODS: The patient is a 68-year-old African-American male with a history of HCV-G1b infection who had previously failed treatment with a 12-week regimen of sofosbuvir/ledipasvir. He was subsequently retreated with 12 weeks of sof-vel-vox. He had an end of treatment response but had a viral relapse at 3 months post-treatment. He denied hepatitis exposure in the interim and repeat genotyping was G1b. He was compliant with his medications. He was referred to Hepatology for salvage treatment options. Prior labs and images did not show evidence of cirrhosis and he did not have a history of hepatic decompensations. Combined HIV Ab/Ag and Hepatitis B Core Ab were negative. A Fibrosure test revealed F3 fibrosis but unfortunately, he did not undergo HCC surveillance. At our initial evaluation a contrast MRI was ordered and revealed a 4.6 cm right lobe enhancing lesion with delayed washout consistent with HCC. Resection was not possible due to the location of the lesion, so he underwent locoregional therapy and is currently listed for liver transplantation with MELD exception. DISCUSSION: Treatment failure with sof-vel-vox is a rare event. Underlying HCC is known to be associated with lower SVR rates in patients treated with DAAs. Some have surmised a protection from eradication due to immunologic changes in cancer patients. We hypothesize that the presence of HCC was the most likely factor for this treatment failure. With sof-vel-vox as the last available option in the treatment paradigm, failure of this regimen in previous NS5A treated patients leads to a situation where there is not an available proven treatment regimen for salvage therapy. As such, we suggest that patients being considered for sof-vel-vox have “up to date” advanced imaging of the liver even in the absence of documented cirrhosis. If treatment failure does occur, one should consider the possibility of an underlying diagnosis of HCC.

Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis

The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.

Effectiveness of Direct-Acting Antiviral Therapy in Patients With Human Immunodeficiency Virus-Hepatitis C Virus Coinfection in Routine Clinical Care: A Multicenter Study.

BackgroundDirect-acting antiviral (DAA) therapy have been shown to be highly successful in clinical trials and observational studies, but less is known about treatment success in patients with a high burden of comorbid conditions, including mental health and substance use disorders. We evaluated DAA effectiveness across a broad spectrum of patients with human immunodeficiency virus (HIV)–hepatitis C virus (HCV) coinfection in routine clinical care, including those with psychosocial comorbid conditions.MethodsThe primary end point was sustained virologic response (SVR), defined as HCV RNA not detected or <25 IU/mL ≥10 weeks after treatment. We calculated SVR rates and 95% confidence intervals (CIs) in a modified intent-to-treat analysis. We repeated this analysis after multiply imputing missing SVR values.ResultsAmong 642 DAA-treated patients, 536 had SVR assessments. The median age was 55 years; 79% were men, 59% black, and 32% white. Cirrhosis (fibrosis-4 index>3.25) was present in 24%, and 17% were interferon treatment experienced; 96% had genotype 1 infection and 432 (81%) had received ledipasvir-sofosbuvir. SVR occurred in 96.5% (95% CI, 94.5%–97.9%). Patients who were black, treatment experienced, or cirrhotic all had SVR rates >95%. Patients with depression and/or anxiety, psychotic disorder, illicit drug use, or alcohol use disorder also had high SVR rates, ranging from 95.4% to 96.8%. The only factor associated with lower SVR rate was early discontinuation (77.8%; 95% CI, 52.4%–93.6%). Similar results were seen in multiply imputed data sets.ConclusionsOur study represents a large multicenter examination of DAA therapy in HIV/HCV-coinfected patients. The broad treatment success we observed across this diverse group of patients with significant comorbid conditions is highly affirming and argues for widespread implementation of DAA therapy.

Predictive factors of hepatitis C virus eradication after interferon-free therapy in HIV coinfection.

Real-life cohorts have shown that the effectiveness of all-oral, direct-acting antivirals (DAA) for HCV treatment is > 90%. We aimed to explore the predictive factors of DAA success in HIV coinfection. This is an observational prospective study within the cohort "VIH-DOC", Madrid, Spain. HIV/HCV-coinfected patients were included if they had been treated with DAAs between 9 January 2015 and 31 August 2016. The sustained virological response (SVR) was analysed in the intention-to-treat population. Binary logistic regression was used to study the impact of cirrhosis, anti-HCV therapy experience and the IL28B polymorphism on SVR, besides factors with a p value < 0.15 from the univariate analysis. DAA were prescribed to 423 patients. SVR was confirmed in 92.9%. The univariate analysis showed higher proportion of patients with SVR among those with DAA adherence ≥ 95% (difference + 10.3%, 95% CI 3.5-19.6) and a baseline CD4+ cell count ≥ 200/μL (difference + 14.7%, 95% CI 4.1-31.0). Logistic regression evinced that both DAA adherence and baseline CD4+ cell counts predicted the SVR (OR 3.9, 95% CI 1.8-8.8, and OR 5.2, 95% CI 1.9-13.9, respectively). Moreover, men who reported having sex with other men (MSM) were less likely to achieve SVR (OR 4.2, 95% CI 1.1-16.1). Among MSM, three of three patients without SVR were suspected to have experienced HCV reinfection. DAA for HCV in HIV-coinfected patients is highly effective. DAA adherence ≥ 95% and a baseline CD4+ count ≥ 200/μL predicted a higher probability of SVR. A lower rate of SVR was found in MSM, presumably due to a higher frequency of HCV reinfection.

Assessment of efficacy and safety of PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C

Patients with chronic hepatitis C‐associated liver disease are of an older age in southern Taiwan. PEGylated interferon‐based therapy could reduce the risk of cirrhosis and hepatocellular carcinoma and improve survival. We assessed the efficacy and safety of combination therapy with PEGylated interferon plus ribavirin in elderly patients with chronic hepatitis C. A total of 88 consecutive patients with chronic hepatitis C treated with combination therapy were analyzed retrospectively to identify factors associated with a sustained virological response (SVR). These patients were divided into two groups according to age: elderly patients ≧ 60 years (n = 43) and patients 50 to 59 years (n = 45). We compared baseline characteristics, adherence 80/80/80, dose modification, discontinuation, and adverse events profiles between these two groups. We further compared virological response rates stratified by genotype. The factors associated with an SVR were determined by total patients and different age groups. In the intent‐to‐treat analysis, the SVR rate was 61.8%. The SVR rate of elderly patients tended to be superior to that of total patients. Patients aged ≧ 60 years had a higher proportion of concomitant chronic disease, dose modification, clinical events with anorexia, depression, leucopenia, and anemia than those aged 50 to 59 years. Total patients with genotype 1 tended to have a lower SVR rate than nongenotype 1 (P = 0.067). Total patients with nongenotype 1 had a significantly higher rapid virological response (RVR) rate than genotype 1 (P = 0.009). In patients aged ≧ 60 years, the relapse rate of genotype 1 was higher than that of nongenotype 1 (P = 0.034). After stratification by HCV genotype 1, high viral load, and achievement of an RVR, the SVR rates remained similar between the two groups. The most strongly predictive factors of an SVR of total patients were the achievement of an RVR (OR: 49.744; 95% CI: 6.979‐354.574; P &lt; 0.001), followed by breakthrough (OR: 0.018; 95% CI: 0.002‐0.195; P = 0.001). The factor mostly predictive of an SVR in age ≧ 60 years group was achievement of an RVR (OR: 12.779; 1.430‐114.180; P = 0.023). Elderly patients had a greater frequency of adverse events. Genotype 1 is independently associated with lower SVR and RVR rates and high relapse rates. Attainment of an RVR is the most powerful predictor of SVR in elderly patients.

Effectiveness of ledipasvir/lofosbuvir plus ribavarin regimen in hepatitis C virus genotype 3 infection in patients with or without cirrhosis

Background: In last few years direct-acting antiviral agents (DAAs) showed high efficacy in chronic hepatitis C treatment. One of them Ledipasvir/Sofosbuvir demonstrated almost 100% cure rate on specific genotypes. But the question of HCV 3 genotype patients’ treatment with Ledipasvir/Sofosbuvir is still under debate (due to the variable data). This study evaluates the efficacy of Ledipasvir/Sofosbuvir plus ribavirin regimen on HCV genotype 3 patients with/without cirrhosis. Has been conducted retrospective analysis of patients with HCV 3 genotype involved in the national hepatitis C elimination program of Georgia. The patients with or without cirrhosis were treated for 24 or 12 weeks respectively. Methods & Materials: The data of 1136 patients were analyzed who underwent treated in 2016-2017; in whom sustained virological response (SVR) was assessed 12 to 24 weeks after treatment. Most of them were non-cirrhotic 91.73% (1042) and 8.27% (94) had cirrhosis. Results: Overall SVR rate was 98.5% (1120 individuals); only 1.41% (16 patients) relapsed. SVR rate in non-cirrhotic patients was 98.8% (1030); in cirrhotic patients the same index was 95.7% (90). Conclusion: Ledipasvir/Sofosbuvir combination presented high cure rate in HCV genotype 3 patients, especially in non-cirrhotic patients; but the low rate of SVR in cirrhotic patients may be disputed due to the relatively low number of patients. Further research is recommended to make the relevant conclusion on the efficiency of ledipasvir/sofosbuvir in genotype 3 patients, especially in cirrhotic patients involving more number of patients.

Direct-Acting Antiviral Therapy for Hepatitis C Infection in a Large Immigrant Community.

Hepatitis C treatment has rapidly evolved with the arrival of direct-acting antiviral therapy. Sustained virologic response (SVR) rates in clinical trials are high but it is unknown how this translates to the immigrant community. Data from December 2013 to September 2015 was collected from a Midwest academic and community practice with a large immigrant population. There were 802 patients with an overall SVR rate of 88%. Ledipasvir/sofosbuvir was associated with favorable response among genotype 1 and 4 patients compared to other regimens (p < 0.001 and p = 0.05). Factors associated with treatment failure included advanced liver disease, male gender, East African/Middle Eastern ethnicity, and non-compliance. Patients with genotype 4 had lower SVR rates than other genotypes (58% vs. 89%, p < 0.001), particularly among East Africans (40% vs. 82% for other ethnicities). Our SVR rate for genotype 4 infection is lower than clinical trials and may be related to cultural, biologic and socioeconomic factors.

INTERLEUKIN 28B GENE POLYMORPHISMS AS A PREDICTOR OF TREATMENT RESPONSE IN EGYPTIANS WITH CHRONIC HEPATITIS C.

Egypt has the highest prevalence of HCV all over the world with 9% countrywide and up to 42% in certain rural areas. Combined PEG-IFN and ribavirin is still the only standard of care treatment in spite of its side effects, high costs and low sustained virological response rates. Hence, this provides a compelling reason for the identification of biomarker predictors of disease response to treatment. Aim of the work: This study is designed to identify IL28B gene polymorphisms in patients with chronic hepatitis C genotype 4 who received standard of care therapy to highlight its impact on response to treatment. Location of study: Viral Hepatitis Treatment Center at Al-Ahrar Hospital, Sharkia Governorate. and Biochemistry Departments of Faculty of Medicine, Zagazig University. Methods: Case control study on 124 patients with chronic hepatitis C who finished their treatment with standard of care therapy ( pegylated interferon and ribavirin). Sixty two patients were non responders to SOC therapy (case group) and 62 other patients were responders (control group). In addition to the chemical, laboratory data and histological parameters that were taken from their files, blood samples were taken at the time of study for detection of SNPs for rs8099917 by PCR-RFLP technique. Results: The TT homozygous of rs8099917 genotype was detected in 54 (43.54%) of overall HCV patients, 42 of them (67.74%) achieved SVR. The GT heterozygous was detected in 48 (38.71%) of HCV patients, SVR was achieved in 9 (14.52%) of them. While, the GG genotype was found in 22 patients and 11 of them only (17.74%) were responders. Multiple regression analysis identified IL28 B SNP genotype as the single independent predictor of response to SOC therapy. Conclusion: These data suggest that host genetics may be useful for the prediction of treatment outcomes and that IL28B SNP genotype is an important predictive biomarker for SVR in patients with HCV genotypes 4

HCV mono-infected and HIV/HCV co-infected individuals treated with direct-acting antivirals: to what extent do they differ?

BackgroundDirect-acting antiviral (DAA)-based treatment of hepatitis C virus (HCV) has been associated with high sustained virological response (SVR) rates and good tolerability in randomized clinical trials. This study was performed to assess the safety and effectiveness of DAAs in both HCV mono-infected and HIV/HCV co-infected patients. MethodsAll consecutive HCV-infected patients, including HIV/HCV co-infected patients, receiving DAA-based treatment from February 2015 to September 2016 at the study clinic were included. Clinical, virological, and biochemical data were retrieved. The primary end-point was the SVR12 (HCV RNA undetectable 12 weeks after the end of treatment) is commonly used worldwide. The secondary end-point was the safety profile of DAAs during the treatment period. ResultsA total of 382 patients were included; 62 were HIV/HCV co-infected. Cirrhosis was found in 256 patients (67.4%). SVR12 was achieved in 365/382 (95.5%) individuals (58/62 HIV/HCV co-infected, 93.5%) in the intention-to-treat (ITT) analysis. A platelet count <90×109/l (odds ratio (OR) 4.12, 95% confidence interval (CI) 1.5–11.3, p=0.006), HCV genotype 3 infection (OR 5.49, 95% CI 1.9–15.7, p=0.002), liver stiffness >20kPa (OR 3.05, 95% CI 1.03–8.96, p=0.04), and Model for End-Stage Liver Disease (MELD) score >10 (OR 5.27, 95% CI 1.16–23.8, p=0.03) were associated with lower SVR rates. On multivariate analysis, only genotype 3 infection remained a negative predictor of SVR (OR 21.6, 95% CI 3.81–123, p=0.001). Treatment discontinuation was observed in 10 subjects. Severe adverse events (SAEs) occurred in 17 patients (4.5%). ConclusionsHigh SVR12 rates were observed in both HCV mono-infected and HIV/HCV co-infected individuals. Overall, DAA-based treatment was safe and there were no differences in terms of SAEs and treatment discontinuation between the two groups.

Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review.

Rapid improvements in hepatitis C virus (HCV) therapy have led to the approval of multiple oral direct-acting antiviral (DAA) regimens by the U.S. Food and Drug Administration (FDA) for treatment of chronic HCV infection. To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection. MEDLINE and EMBASE from inception through 1 November 2016. 42 English-language studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs. Two investigators abstracted data on study design, patient characteristics, and virologic and safety outcomes sequentially and assessed quality independently. Six DAA regimens showed high sustained virologic response (SVR) rates (>95%) in patients with HCV genotype 1 infection without cirrhosis, including those with HIV co-infection. Effective treatments for HCV genotype 3 infection are limited (2 DAA regimens). Patients with hepatic decompensation, particularly those with Child-Turcotte-Pugh class C disease, had lower SVR rates (78% to 87%) than other populations. The addition of ribavirin was associated with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were low (<10% in the general population); regimens that included ribavirin had more mild or moderate adverse events than those without. Twenty-three studies had moderate risk of bias (10 were open-label single-group trials, 11 had limited information on concealment of the allocation scheme, and 5 had selective outcome reporting). All but 1 of the studies were industry-funded. Heterogeneity of interventions precluded pooling. Multiple oral DAA regimens show high rates of safety, tolerability, and efficacy for treatment of HCV genotype 1 infection, particularly among persons without cirrhosis. Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42014009711).

Effectiveness of All-Oral Antiviral Regimens in 996 Human Immunodeficiency Virus/Hepatitis C Virus Genotype 1–Coinfected Patients Treated in Routine Practice

Large cohorts are needed to assess human immunodeficiency virus (HIV)/hepatitis C virus (HCV) real-world treatment outcomes. We examined the effectiveness of ledipasvir/sofosbuvir with or without ribavirin (LDV/SOF ± RBV) and ombitasvir/ paritaprevir/ritonavir plus dasabuvir (OPrD) ± RBV in HIV/HCV genotype 1 (GT1)-coinfected patients initiating HCV therapy in clinical practice. Observational intent-to-treat cohort analysis using the Veterans Affairs Clinical Case Registry to identify HIV/HCV GT1-coinfected veterans initiating 12 weeks of LDV/SOF ± RBV or OPrD ± RBV. Multivariate models of sustained virologic response (SVR) included age, race, cirrhosis, proton pump inhibitor (PPI) prescription, prior HCV treatment, body mass index, genotype subtype, and HCV treatment regimen. Nine hundred ninety-six HIV/HCV GT1-coinfected veterans initiated therapy: 757 LDV/SOF, 138 LDV/SOF + RBV, 28 OPrD, and 73 OPrD + RBV. Overall SVR was 90.9% (823/905); LDV/SOF 92.1% (631/685), LDV/SOF + RBV 86.3% (113/131), OPrD 88.9% (24/27), and OPrD + RBV 88.7% (55/62). SVR was 85.9% (176/205) and 92.4% (647/700) in those with and without cirrhosis (P = .006). SVR was similar between African Americans (90.5% [546/603]) and all others (91.7% [277/302]). PPI use with LDV/SOF ± RBV did not affect SVR (89.7% [131/146] with PPI and 91.5% [613/670] without PPI). Cirrhosis was predictive of reduced SVR (0.51 [95% confidence interval {CI}, .31-.87]; P = .01). Median creatinine change did not differ among patients receiving LDV/SOF and tenofovir disoproxil fumarate (TDF) without a protease inhibitor (PI) (0.18 [interquartile range {IQR}, 0.08-0.30]; n = 372), LDV/SOF and TDF/PI (0.17 [IQR, 0.04-0.30]; n = 100), and LDV/SOF without TDF (0.15 [IQR, 0.00-0.30]; n = 423). SVR rates in HIV/HCV GT1-coinfected patients were high. African American race or PPI use with LDV/SOF ± RBV was not associated with lower SVR rates, but cirrhosis was. Renal function did not worsen on LDV/SOF regimens with TDF.

Study of the Efficacy of Triple Therapy of Sofosbuvir, Pegylated INFalpha 2a and Ribavirin in Treatment of Chronic Hepatitis C Patients Genotype 4 with High Fibrosis

Purpose: The aim is evaluation of the efficacy of triple therapy of sofosbuvir, pegylated INFalpha 2a and ribavirin in treatment of chronic hepatitis C (CHC) patients genotype 4 who have high fibrosis. Materials and Methods: Fifty HCV patients with high fibrosis (F3 & F4) were included in the study. Results: SVR rate was 54%; non-responders rate was 12% and relapsers rate was 34%. When comparing SVR between F3 group patients and F4 group, it was 88% and 66% respectively, which means that SVR was higher in the F3 group. Conclusion: Triple therapy including pegylated INFalpha 2a is not an ideal therapy in treatment of CHC patients genotype 4 with cirrhosis because of low sustained virological response rates and high incidence of side effects.

Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV–HCV co-infected patients: final results of the Spanish BOC HIV–HCV Study

Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

Lower SVR Rates in Treatment Experienced Cirrhotic Veterans for Hepatitis C Genotype 1

Introduction: Newer therapies for hepatitis C virus (HCV) genotype 1 produce high rates of sustained virologic response (SVR) in the general population. Not known is whether these therapies translate to a veteran population, with high HCV prevalence, and pleomorphic epidemiological environments such as alcohol, tobacco, obesity, homelessness, and substance abuse. This study assessed the SVR in such a population. Methods: A retrospective study was performed on all patients treated for HCV genotype 1 infection during the 2015 federal fiscal year at VA Loma Linda Health Care System (VALLHCS). Patients received 8, 12, or 24 weeks of daily therapy with ledipasvir-sofosbuvir (LDV/SOF) or ombitasvir-paritaprevirritonavir with dasabuvir (OPRD) with or without ribavirin (RBV) according to AASLD guidelines. All patients were evaluated for sustained virologic response at 12 weeks (SVR12) by serum quantitative PCR. Results: Ninety-seven patients were reviewed of which 55% received LDV/SOF, and 45% received OPRD therapy. Demographic analysis revealed that ninty-eight percent of patients were male, mean age 62, of which 25% were black, and 11% were Hispanic. Sixty-one percent had cirrhosis, 35% were treatment experienced, and 75% had HCV genotype 1a infection. All patients achieved virologic response during therapy, reaching an undetectable viral load by PCR. SVR12 was achieved in 93% of all patients (95% confidence interval [CI], 86-96). SVR12 was achieved in 100% of non-cirrhotic patients who received LDV/SOF+/-RBV (95% CI, 85-100), 94% of non-cirrhotic patients who received OPRD+/-RBV (95% CI, 72-99), 84% of cirrhotic patients who received LDV/SOF+/-RBV (95% CI, 67-93), and 96% of cirrhotic patients who received OPRD (95% CI, 82-99). The lowest SVR12 rate of 71% was observed in the treatment-experienced cirrhosis group who received LDV/SOF+RBV. The most common adverse effects included fatigue, headache, insomnia, and nausea.Figure 1Conclusion: New oral therapies for chronic HCV genotype 1 infections are effective in VA healthcare system patients with SVR12 rates comparable to the general population, except in treatment experienced cirrhotics. This group achieved a lower SVR12. Factors contributing may be the pleomorphic demographics of the VA population, which is pending further analysis.