Velpatasvir and Early Virological Results

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worsened, improved, no change" and performed Chi-square/Exact test to compare between responders and non-responders. Results: We identified a total of 447 eligible patients, 193 (44%) were females, and the average age was 58 years. 95% of patients achieved SVR (n= 426). The mean change in creatinine (post treatment minus at initiation, lower value indicates improvement) for the responders was 0.02 (standard deviation 0.18) and was 0.11 among non-responders (standard deviation 0.21) and the difference was statistically significant (Two Sample T-test p-value=0.0499). GFR was > 60 at treatment initiation and follow-up among 75% of the non-responders and 87% of the responders; GFR worsened among 20% of the non-responders and 7% of the responders. However, the difference was not statistically significant (exact p-value=0.1532). Conclusion: Patients who achieved SVR were more likely to experience stable renal function and less likely to have worsening renal function compared with those who did not achieve SVR. There was a small, statistically none significant, increase in the GFR in those who achieved SVR.

RISK OF HEPATOCARCINOGENESIS AFTER ERADICATION OF HEPATITIS C VIRUS BY DIRECT ACTING ANTIVIRALS Yasunori Kawaguchi, Taiga Otsuka, Wataru Yoshioka, Shotaro Noge, Hirokazu Takahashi, Yuichiro Eguchi, Iwata Ozaki, Michiaki Okada, Kimihiko Yanagita, Toshikazu Kohira, Yasushi Ide, Tsutomu Yasutake, Hiroaki Kawasoe, Toshihiko Mizuta Background and aims: The risk of developing hepatocellular carcinoma (HCC) among patients with sustained virologic response (SVR) to interferon (IFN)-free direct acting antivirals (DAAs) therapy remains unclear. The aim of this study was to evaluate whether eradication of hepatitis C virus (HCV) by IFN-free regimens reduces hepatocarcinogenesis as efficiently as IFN-based regimens. Methods: We analyzed 143 patients with SVR by IFN-based therapy (PEG/RBV/TLV, n=83; PEG/RBV/SMV, 59; PEG/RBV/VAN, 1) and 417 patients with SVR by IFN-free therapy (DCV/ASV, n=215; SOF/LDV, 119; SOF/RBV, 70; OMV/PTV/r, 1; DCV/ ASV/BMS791325, 6; MK5172/MK8742, 6) using Cox's proportional hazards models to calculate the hazard ratio (HR) and 95% confidence interval (CI) for risk factors associated with HCC development. Results: After a median follow-up of 7.2 months, 42 patients developed HCC. Multivariate analysis showed that history of HCC (HR: 11.5, 95% CI: 5.424.8, p<0.001), IFN-free therapy (HR: 3.3, 95% CI: 1.4-8.0, p=0.009), habitual drinker (HR: 2.5, 95% CI: 1.2-5.4, p=0.02), diabetes (HR: 4.5, 95% CI: 2.3-8.8, p<0.001), and albumin ≤4.0 g/dL (HR: 2.9, 95% CI: 1.2-6.7, p=0.016) were independently associated with HCC development. In subgroup analysis, 13 of 419 patients without history of HCC developed HCC, and IFN-free therapy (HR: 6.0, 95% CI: 1.1-33.2, p=0.042) was the only independent factor among this group. Twenty-nine of 69 patients with history of HCC developed tumor recurrence, and habitual drinker (HR: 2.7, 95% CI: 1.2-6.1, p=0.02), diabetes (HR: 4.8, 95% CI: 2.0-11.4, p<0.001), and albumin ≤4.0 g/dL (HR: 3.0, 95% CI: 1.1-8.1, p=0.034) were independent factors. Conclusions: Eradication of HCV by IFN-free DAA regimens did not reduce HCC development compared with IFN-based regimens, especially in patients without history of HCC. Patients with history of HCC still had a significantly high risk of tumor recurrence after SVR. Among this subgroup, diabetes, habitual drinker, and serum albumin levels were risk factors for HCC recurrence. For these reasons, all patients with SVR by IFN-free DAA regimens should be closely monitored during and after antiviral therapy.

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BACKGROUND & AIMS: Up to 3.9 million people in the United States may suffer from chronic hepatitis C infection. While safe and effective therapies now exist, the majority of these patients remain untreated due to numerous barriers including identification of candidates and initiation of timely treatment. At our center, prescription of these medications is limited to health care providers trained in the treatment of hepatitis C virus (HCV). We present a novel model for expanding access to hepatitis C care for patients with advanced liver disease. METHODS: We identified candidate patients through our HCV Clinical Case Registry (CCR) and patients scheduled for future liver clinic appointments (Figure 1). The HCV CCR is a national population-based archive which can be used to identify chronically HCV-infected patients. Once identified, patients were then established in the liver clinic and all subjects were given sofosbuvir (400 mg, once daily), velpatasvir (100 mg, once daily), ± ribavirin (600-1200 mg/day) in divided doses for 12 weeks. Patients with major medical comorbidities, psychiatric diseases, alcohol, or recent substance use disorders were not excluded. The primary endpoint was establishment of HCV therapy and early clinical follow up. RESULTS: Characteristics of 32 actively enrolled patients included 47% treatment-experienced and 53% treatment-naïve patients. Psychiatric illness and history of substance use were present in 66% and 38% of patients, respectively. All patients had major medical comorbidities, which included diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, arrhythmias, obstructive sleep apnea, and obesity. The average FIB-4 score was 4.62. Proton-pump inhibitors were continued in 22% of enrollees during their course of treatment. Beta-blockers were continued in 44% of patients in the study. Cirrhosis was determined by either imaging or biopsy in 47% of patients with esophageal varices present in 25%. Of 23 patients who had completed 4 weeks, 100% had either HCV RNA which was undetected or detected < 15 IU/ml. Those patients with HCV RNA detected < 15 IU/ ml, all became undetectable except for 1 patient who discontinued therapy. Two patients incarcerated during their course of treatment have completed 4 to 8 weeks. CONCLUSIONS: Prescreening the HCV CCR is a successful model to improve access to HCV therapy. This model improves identification and linkage to care for patients in need of HCV therapies. In patients identified through our model, our preliminary data show that treatment with sofosbuvir/velpatasvir ± ribavirin leads to early virological response in 94% of veterans with HCV genotype 2 and 3 infection, NS5a resistance, significant fibrosis or cirrhosis, and multiple medical and/or psychiatric comorbidities, regardless of their treatment history.

Sa1531 EFFICACY AND SAFETY OF SOFOSBUVIR AND DACLATASVIR FOR 8 WEEKS IN TREATMENT-NAÏVE NON-CIRRHOTIC PATIENTS WITH CHRONIC HCV GENOTYPE 3 INFECTION Christophe Hezode, Vincent Leroy, Isabelle Rosa, Jean-Michel Pawlotsky, Victor de Ledinghen, Jean-Pierre Bronowicki Background and Aims: HCV GT 3 is the second most common GT worldwide. For noncirrhotic patients with HCV GT 3 infection, the EASL and AASLD/IDSA guidelines recommend treatment with the IFN- and RBV-free regimen of DCV + SOF for 12 weeks, according to the results of the ALLY-3 phase 3 study, in which this patient group achieved a 96% SVR12 rate. The objective of this pilot study was to investigate the efficacy and safety of 8 weeks of DCV + SOF in treatment-naïve patients with HCV GT 3 infection without cirrhosis. Methods: This ongoing pilot study is a multicenter, open label, single arm trial that enrolled treatment-naïve GT-3 patients without cirrhosis. Key exclusion criteria included the presence of cirrhosis, as determined by either a FibroScan score ≥12.5 kPa or a FibroTest score of ≥0.75, and baseline HCV RNA level >6,000,000 IU/mL. The regimen was DCV 60 mg and SOF 400 mg once daily for 8 weeks. Efficacy was calculated as the percent of patients achieving SVR12 (HCV RNA
Sa1532 IMPACT OF ACHIEVING SUSTAINED VIROLOGIC RESPONSE ON RENAL FUNCTION IN HCV PATIENTS Krishna V. Venkata, Mohamed G. Shoreibah, Jie zhang, Vishnu Kommineni, Jordan Orr, Ahmed A. Elkafrawy, Omar Massoud Objective/Background: It is estimated that 10-20% of all HCV-infected patients have some degree of kidney disease. HCV may accelerate the progression of kidney disease. We hypothesized that patients who responded to their HCV treatment were more likely to experience improvement or stable renal function compared to those who did not. Methods: We conducted a large retrospective cohort study to compare changes in renal function among HCV patients who achieved sustained virologic response (SVR) and those who did not. Patients who received HCV treatment, had follow up for at least 3 months after completing treatment, had documented viral load at 3 months after treatment, and had renal function tests at the initiation of treatment and 3-6 months after completing treatment, were included in the study. The outcomes were changes in GFR and in Creatinine, which were measured at treatment initiation and again at 3-6 months after. We calculated the difference in Creatinine, examined its distribution among responders and non-responders, and used T-test to compare the difference between the two groups. GFR values were documented numerically if they were <= 60 and as ">60" based on the lab reports. As a result, we classified individuals as follows based on their GFR at treatment initiated and follow-up: "> 60 at both times,

Figure 1. Screening and treatment algorithm for managing and treating veteran patients with chronic HCV infection, genotypes 2 & 3 with significant fibrosis or cirrhosis.

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AASLD Abstracts

AASLD Abstracts

CHRONIC HEPATITIS C WITH SIGNIFICANT FIBROSIS & CIRRHOSIS: IMPROVED PATIENT ACCESS TO TREATMENT WITH SOFOSBUVIR/ VELPATASVIR AND EARLY VIROLOGICAL RESULTS Ariel W. Aday, Geri Brown

treatment. Results: Of the 35 patients included in the study, 30 had SVR, 2 had relapse (1 CC, 1 CG), 1 (CG) had liver transplantation and 2 (CC) died before SVR. The remaining 30 patients had SVR (16 CC, 11 CG, 3 GG). The demographic and baseline clinical characteristics of the 30 patients were similar except patients with rs738409 CC genotype had a higher mean body-mass index (BMI) (35 vs 29, p = 0.03). Patients with CC genotype had an average baseline CPT score 8.6 and MELD score of 13 while those with CG/GG genotype had an average baseline CPT score of 7.6 and MELD score of 14. Of the 16 patients with CC genotype, 13 patients (81%) had improved CPT score and 8 patients (50%) had improved MELD score by at least 1 point while none of them had worsened CPT or MELD score. Of the 14 patients with CG/GG genotype, 5 (36%) had improved CPT score and 4 (29%) had improved MELD score by at least 1 point, while 3 (21%) of the patients had worsened CPT score and 4 (29%) of them have worsened MELD score by at least 1 point. The CG/GG genotype was associated with a 1.7 (95% CI: 0.7 - 2.7) point higher delta CPT score and 2.3 (95% CI: 0.2 - 4.4) point higher delta MELD score in multivariable linear regression adjusting for confounders. In terms of CPT components, those with CG/GG genotype had a slower recovery of encephalopathy, ascites and bilirubin. Conclusion: Our study showed that rs738409 CG/GG genotype can identify a subgroup of patients with decompensated HCV cirrhosis that have suboptimal clinical recovery despite SVR. Our results will help target patients for liver transplant evaluation based on individual genetic risk factors

Sa1536 TREATMENT UPTAKE AND REAL WORLD EFFECTIVENESS OF SOFOSBUVIR/LEDIPASVIR AND PARITAPREVIR/RITONAVIR/OMBITASVIR/ DASABUVIR AMONG HCV-INFECTED PERSONS WITH CHRONIC KIDNEY DISEASE Mohamad Alkadi, Yanjie Ren, Amy Puenpatom, Ritesh Kumar, Jean Marie Arduino, Abdul-Badi Abou-Samra, Adeel Butt

AASLD Abstracts

Table 1. Baseline characteristics of enrollees.

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Background: HCV infected persons have a higher burden of comorbidities, including advanced chronic kidney disease (CKD). Patients with CKD are often excluded from treatment due to various reasons. We evaluated factors associated with treatment initiation of HCV/ CKD patients and determined SVR rates in patients who were treated with the sofosbuvir/ ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens. Methods: We identified patients in the ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) database determined by eGFR, who were treated with the above regimens. We excluded those with HIV, positive HBsAg, and those with missing data to determine CKD stage or SVR rate. We determined SVR rates for HCV genotype 1 (GT1) infected persons >12 weeks after completion of treatment, by CKD stage, HCV subtype and presence of cirrhosis at baseline. We used logistic regression analysis to determine the factors associated with treatment uptake with SOF/LDV or PrOD regimens with or without ribavirin (RBV). Results: Among 76,513 HCV-infected persons with CKD, the treatment uptake of SOF/LDV and PrOD was low (8.8%, N =6,715). Persons with more advanced CKD were significantly less likely to initiate treatment (OR 0.28 for CKD stage 4-5; 0.66 for CKD stage 3; comparison group eGFR >60 mL/min/1.73m2). Male sex, non-GT1 HCV, non-cirrhotics, and presence of comorbidities (diabetes, cardiovascular disease, alcohol abuse and moderate-severe anemia) were negatively associated with treatment initiation with SOF/LDV or PrOD. Among 2,875 HCV genotype-1 infected persons who completed a course of treatment with SOF/LDV or PrOD, 2,712 (94.3%) had eGFR >60 mL/min/1.73m2, 145 (5%) had CKD stage 3, and only 18 (0.6%) had CKD stages 4-5. Among those with eGFR >60 mL/min/1.73m2, SVR rates ranged from 83-100% regardless of HCV subtype (1a or 1b), presence of cirrhosis or use of ribavirin. Among the 18 patients with CKD stage 4-5, SVR rate was 100%. Conclusions: Relatively small number of patients with CKD stage 3-5 was initiated on treatment with a SOF/LDV or PrOD based regimen. Factors associated with non-initiation of treatment included having advanced CKD, non-GT1 HCV, male sex and specific comorbidities such as diabetes, CVD, alcohol abuse and anemia. In the small group of advanced CKD patients who were treated, SVR rates were high. There is an unmet need in advanced CKD patients within the VA that are awaiting treatment despite the approval of SOF/LDV and PrOD regimens.

IMPACT OF DIRECT ACTING ANTIVIRALS ON HCV-RELATED HCC WAITLIST REGISTRATIONS AND RISING HCC INCIDENCE IN NATIONAL LIVER TRANSPLANT REGISTRY Chiranjeevi Gadiparthi, Osama Siddique, Rosann Cholankeril, Eric R. Yoo, Muhammad Ali Khan, Ryan B. Perumpail, Menghan Hu, George Cholankeril, Aijaz Ahmed Background and Aims: Major advances in the treatment of chronic hepatitis C virus (HCV) have been made since the introduction of direct-acting antiviral (DAA) agents with sustained virological response exceeding above 90%. However, there has been conflicting evidence regarding the risk of hepatocellular carcinoma (HCC) following successful DAA therapy. Our aim was to evaluate the short-term impact of DAA agents on HCV-related HCC waitlist registrants in a national registry. Methods: Using the United Network for Organ Sharing (UNOS) database, we compared HCV-related HCC and HCV non-HCC waitlist registrants 18 months before (pre-DAA: May 2012 to October 2013) and after (post-DAA: January 2014 to June 2015) the Food and Drug Administration approval of DAA agents (November to December 2012). Comparisons between groups utilized Chi-square tests for categorical variables and Mann-Whitney test for continuous variables. All statistical analyses were performed using SAS 9.4. Results: Compared to the pre-DAA era, there was a higher number (pre-DAA, n = 2,675 vs post-DAA, n = 2,958) and proportion of overall (old and new) HCV-related HCC waitlist registrants in the post-DAA era (pre-DAA n = 25.2% vs postDAA = 30.2%, P < 0.01). There were 3,819 new or initial HCV-related HCC waitlist registrants within the pre-DAA and post-DAA eras. The number of new HCV-related HCC registrations increased 39.1% in the post-DAA era (pre-DAA, n = 1,841 vs post-DAA, n = 2,561) with month-to-month trends demonstrated in Figure 1. In addition to this rise in HCV-related HCC waitlist registrations, the number of new HCV non-HCC waitlist registrations declined 20.8% from the pre-DAA to the post-DAA era (pre-DAA era n=3,525 vs postDAA era, n=2,811). A significantly higher proportion of new HCV waitlist registrants had concurrent HCC in the post-DAA era (pre-DAA = 34.3% vs post-DAA = 43.6%, P < .01) as depicted in Figure 2. Furthermore, the likelihood of new HCV waitlist registrants having concurrent HCC was higher in the post-DAA era (OR 1.29, 95% CI: 1.19-1.40, P < 0.01) Conclusion Our short-term results demonstrate that there was a significant rise in HCVrelated HCC waitlist registrations and a decline in the number of HCV non-HCC waitlist registrations in the post-DAA era following the introduction of DAA regimen. While this increase in HCV-related HCC waitlist registrations may suggest a causal relationship with DAA therapy, further long-term follow-up is needed.

Sa1535 RS738409 SNP OF PNPLA3 GENE PREDICTS CLINICAL RECOVERY IN PATIENTS WITH DECOMPENSATED HEPATITIS C CIRRHOSIS AFTER ATTAINING SUSTAINED VIROLOGICAL RESPONSE Anusha Vittal, Steven A. Weinman, Jie Zhao, Shweta chakraborthy, Melissa Whitener, Ryan M. Taylor, Jody C. Olson, Brian Bridges, Mojtaba S. Olyaee, Melissa Laycock, Timothy Schmitt Introduction: Direct-acting antiviral (DAA) agents provide a virologic cure for most patients with Hepatitis C virus (HCV) cirrhosis. Although patients with compensated cirrhosis generally do well after achieving SVR, patients with decompensated cirrhosis experience a variety of outcomes. Aim: We hypothesize that the genetic risks for steatosis, namely the Rs738409 Single Nucleotide Polymorphism (SNP) of Patatin-like Phospholipase Domain Containing 3 (PNPLA3) gene, predicts clinical recovery in patients with decompensated HCV cirrhosis after SVR. Methods: This prospective cohort study conducted at the University of Kansas Medical Center included patients with Child-Pugh (CPT) Class B or C cirrhosis due to HCV infection who underwent interferon-free DAA therapy. Exclusion criteria were: active alcohol consumption ≥12 drinks per week; HIV or HBV co-infection; other causes of cirrhosis; history of hepatocellular carcinoma; history of liver transplantation prior to DAA treatment; and failure to achieve SVR with DAA treatment. We collected DNA from each patient using a cheek swab. The primary outcomes were changes in CPT score and Model for End-Stage Liver Disease (MELD) score from before DAA treatment to 12 weeks after the end of

AASLD Abstracts

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