Faculty Bibliography

Introduction: TAF is a new prodrug of tenofovir with improved safety profile compared to tenofovir disoproxil fumarate (TDF).
Objective(s): To assess real-world experience with TAF for HBV patients of Asian race in US Clinical Practice. Methodology: This study includes 212 of 1078 TRIO HBV registry patients in care at 10 centers and representing 17 US states. Patients were self-reported Asian race, initiated TAF after Nov 2016, and received >= 6 months TAF with follow up to 18 months.
Result(s): Population characteristics. Country of origin 49% China, 27% South Korea, 7% Viet Nam, 17% from 13 other Asian countries, median age 53 years, BMI 24.0 kg/m2, 58% male, 23% HBeAg positive, 18% osteopenia/osteoporosis, and 6% FIB-4>3.25. 200/212 (94%) TAF patients switched from TDF (182/200, 91%), entecavir (15/200, 8%), or other therapies (3/200, 2%). Median TAF duration was 12 months as of data collection. Paired comparisons. HBV DNA suppression (<2000 IU/ml) increased from 94% patients at baseline to 99% after 6 or 12 months TAF (n = 206, p = 0.006). Mean eGFR increased 4% from baseline 86.5 to 90.1 ml/min after 6 months TAF (n = 179, p<0.001) and 5% from 86.2 to 90.6 ml/min after 12 months TAF (n = 120, p<0.001). Normal ALT (<=29 U/L females, <= 35 U/L males) increased from 73% patients at baseline to 86% after 6 months TAF (n = 185, p = 0.002) and from 70% at baseline to 87% after 12 months TAF (n = 126, p = 0.001).
Conclusion(s): In US, clinical experience with TAF for Asian patients indicates effective HBV suppression and improved renal function and ALT normalization

BACKGROUND:Necrolytic acral erythema (NAE) is a rare dermatological disorder, which is associated with hepatitis C virus (HCV) infection or zinc deficiency. It is characterized by erythematous or violaceous lesions occurring primarily in the lower extremities. The treatment includes systemic steroids and oral zinc supplementation. We report a case of NAE in a 66-year-old human immunodeficiency virus (HIV)/HCV co-infected woman with NAE. NAE is rarely reported in co-infected patients and the exact mechanisms of pathogenesis are still unclear. CASE SUMMARY/METHODS:A 66-year-old HIV/HCV co-infected female patient presented with painless, non-pruritic rash of extremities for one week and underwent extensive work-up for possible rheumatologic disorders including vasculitis and cryoglobulinemia. Punch skin biopsies of right and left thigh revealed thickened parakeratotic stratum corneum most consistent with NAE. Patient was started on prednisone and zinc supplementation with resolution of the lesions and improvement of rash. CONCLUSION/CONCLUSIONS:Clinicians should maintain high clinical suspicion for early recognition of NAE in patients with rash and HCV.

Background: TAF provides similar efficacy to tenofovir disoproxil fumarate (TDF) but with an improved safety profile particularly for renal injury and bone loss. Here, we evaluate clinical characteristics for patients switching to TAF during the first year of availability in US. Methods: TRIO has developed a national HBV network consisting of 7 academic and 4 community-based centers serving 17 US States to understand real-world HBV treatment. This study started Nov 2016 and is planning to enroll 1000 patients. HBV data is obtained retrospectively from patient records and then followed for 2 years through an electronic registry. To assess early TAF adoption, data are presented for 320 patients who switched nucleos(t)ide (NUC) therapy Nov 2016 to Oct 2017 or who did not switch but were followed during the same period. Results: Treatment for 320 patients at enrollment: 227 (71%) TDF, 72 (23%) entecavir (ETV), 12 (4%) TDF + emtricitabine (FTC), 10/375 (3%) lamivudine (3TC), and 2/375 (1%) adefovir dipivoxil (ADV). Of 320, 156 (49%) switched NUCs to: 144/156 (92%) TAF, 5/156 (3%) TDF, 3/156 (2%) 3TC, 2/156 (1%) ETV + TDF, 1/156 (1%) ETV, and 1/156 (1%) 3TC + TDF. Physician-provided reasons for switching to TAF included: 83/144 (58%) safety concerns or side effects, 46/144 (32%) physician preference, and 7/144 (5%) lack of efficacy. TAF switchers previously received: 131/144 (91%) TDF, 8/144 (6%) ETV, 4/144 (3%) TDF + FTC, and 1/144 (1%) ADV. TAF switchers did not significantly differ from the non-switchers for demographics, select comorbidities, HBeAg status, HBV DNA, nor degree of fibrosis [TABLE]. In the non-switch group, 7/164 (4.3%) patients had eGFR <60 ml/min vs 12/122 (9.8%) for TAF switchers; however, these results were not significantly different. Within the TAF switch group, from the time of enrollment to the date of switch, 52/122 (43%) patients had a 14% mean eGFR reduction. Bone density scans were available for 102/320 (32%) patients. A Z score of-1 or less indicating bone disease was recorded for 62, of which 40/62 (65%) switched to TAF. Conclusion: In the first year after TAF approval, almost 50% of study patients switched to TAF, predominantly for safety concerns or physician preference. For some who switched, renal (43%) and bone changes (65% of those tested) were shown. Many patients who did not switch had similar bone and renal findings. Further follow up will evaluate prospective criteria for switch strategies. (Figure Presented)

Background: Few studies have evaluated the treatment landscape of chronic HBV in the US, where estimates range from 850,000 to 2.2 million people living with HBV. TRIO analytics has developed a national HBV network consisting of 7 academic and 4 community-based centers serving 17 States in the US, with the goal of understanding the realworld treatment of HBV in US clinical practice. We report here the demographic and clinical characteristics of this large cohort at enrollment. Methods: This is an observational, retrospective and prospective study of HBV patients which started in Nov 2016 and is planning to enroll 1000 patients and follow them for up to 2 years. At enrollment HBV data are retrospectively obtained from patient records through an electronic registry which collects patient demographics, treatment experience, disease characteristics, comorbidities, and lab measures. Results: 884 patients have been enrolled and data are available for this analysis on 601 patients. Select characteristics are shown in the TABLE. The majority were Asian and 8% were African or African-American. Mean age was 51 years and over 75% were HBeAg negative. Any evidence of fibrosis (measured by Fib-4 > 1.45) was 29% and cirrhosis (Fib-4 > 3.25) was 5%. At enrollment 540 patients (90%) were on treatment: 363/540 (67%) tenofovir disoproxil fumarate (TDF), 129/540 (24%) entecavir (ETV), 24/540 (4%) TDF + emtricitabine (FTC), 12/540 (2%) lamivudine (3TC), 9/540 (2%) initiated tenofovir alafenamide (TAF), and 3/540 (1%) adefovir dipivoxil (ADV). Overall 32 of 540 (6%) treated patients had viral loads >=2000 IU/ml at entry. Providerreported reasons for non-treatment of 61 patients were: 51/61 (84%) lack of clinical indication (HBeAg-/Ab+, normal liver function, and/or undetected viral load), 5/61 (8%) patient refusal, and 5/61 (8%) reason unspecified. Comorbidities of interest for risk of renal disease included hypertension (25%), diabetes (12%), and overall 51% had evidence of eGFR < 90 ml/min which was more common in treated patients. Conclusion: The HBV population in this US cohort is older, HBeAg negative, predominantly non-advanced liver disease and with significant co-morbidities. Current treatment is dominated by TDF and ETV with a high level of virological suppression. Full enrollment and prospective data over 2 years is ongoing. (Table Presented)

Objective The primary study objective is to determine which measures of depression are associated with early discontinuation of hepatitis C virus infection treatment and to determine which measure best characterizes the depression that develops during treatment. Methods Seventy-eight treatment-naïve subjects who initiated pegylated interferon/ribavirin treatment for hepatitis C virus infection were included. Baseline depression was assessed with the Structured Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the Hamilton Depression Rating Scale, and the Beck Depression Inventory-II. The latter two measures were repeated at treatment weeks 12 and 24. Results Depression scores, as measured by the three instruments, lacked adequate consistency. Baseline depression as measured by the Beck Depression Inventory-II, but not by the other scales, was associated with early treatment discontinuation at weeks 12 and 24. Changes in depression during treatment were restricted to somatic symptoms. Of those who completed treatment, those who were not depressed at baseline tended to demonstrate significant depression increases during treatment. Conclusion The Beck Depression Inventory-II is recommended to assess depression prior to hepatitis C virus infection treatment. Somatic symptoms of depression should be monitored during treatment. Baseline depression as measured by the Beck Depression Inventory-II was associated with early treatment discontinuation. The Beck Depression Inventory-II, Structured Interview for DSM-IV, and Hamilton Depression Rating Scale yielded results that were not consistent with each other in this sample. Future research should focus on standardizing depression assessment in medically ill populations to identify measures that predict treatment discontinuation.

AIM/OBJECTIVE:To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed. METHODS:Outcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir). RESULTS:/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22). CONCLUSION/CONCLUSIONS:The SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.

The human immunodeficiency virus (HIV), hepatitis C virus (HCV), and the treatment of HCV with pegylated interferon and ribavirin (IFN/RBV) have been associated with neurocognitive and psychiatric abnormalities. The goal of this research was to prospectively evaluate neurocognitive functioning among a group of HCV mono-infected and HIV/HCV co-infected patients during the first 24 weeks of IFN/RBV treatment while accounting for practice effects, normal variations in change over time, and variations in IFN/RBV treatment exposure. Forty-four HCV mono-infected and 30 HIV/HCV co-infected patients were enrolled in a prospective study of patients beginning on IFN/RBV for chronic HCV infection. Patients were administered a depression inventory, a measure of fatigue, a structured psychiatric interview, and a neurocognitive battery at baseline and 24 weeks after initiation of treatment. Analyses were conducted to explore possible associations between neurocognitive functioning and the following: HIV/HCV co-infection vs. HCV mono-infection, IFN and RBV treatment exposure, psychiatric status, liver disease stage, and other medical characteristics. At baseline, there were no significant differences between the two groups' neuropsychiatric or neurocognitive function other than the mono-infected group had significantly higher reports of fatigue (p = 0.033). Over the course of 24 weeks of treatment after controlling for practice effects, the HIV/HCV co-infected patients experienced significantly greater declines in memory (t(56) = 2.14, p = 0.037) and global neurocognitive functioning (t(53) = 2.28, p = 0.027). In a well-characterized sample of mono-infected and co-infected patients, it appears that persons with HIV/HCV co-infection are potentially more vulnerable to neurocognitive sequalae during HCV treatment.

AIM/OBJECTIVE:To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection. METHODS:The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included. Rates of sustained virological response - the absence of a detectable serum HCV RNA 12 wk after the end of treatment [sustained virological response (SVR) 12] - were calculated on an intention-to-treat basis. Costs were calculated from the payer's perspective using Medicare/Medicaid fees and Redbook Wholesale Acquisition Costs. Patient-related factors associated with SVR12 were identified using multivariable logistic regression. RESULTS:SVR12 rates were as follows: 86% (95%CI: 80%-91%) among 178 patients on SMV/SOF ± RBV; 62% (95%CI: 55%-68%) among 234 patients on SOF/RBV; and 78% (95%CI: 68%-86%) among 96 patients on SOF/PEG/RBV. Mean costs-per-SVR12 were $174442 (standard deviation: ± $18588) for SMV/SOF ± RBV; $223003 (± $77946) for SOF/RBV; and $126496 (± $31052) for SOF/PEG/RBV. Among patients on SMV/SOF ± RBV, SVR12 was less likely in patients previously treated with a protease inhibitor [odds ratio (OR): 0.20, 95%CI: 0.06-0.56]. Higher bilirubin (OR: 0.47, 95%CI: 0.30-0.69) reduced the likelihood of SVR12 among patients on SOF/RBV, while FIB-4 score ≥ 3.25 reduced the likelihood of SVR12 (OR: 0.18, 95%CI: 0.05-0.59) among those on SOF/PEG/RBV. CONCLUSION/CONCLUSIONS:SVR12 rates for SMV and/or SOF-based regimens in a diverse real-world population are comparable to those in clinical trials. Treatment failure accounts for 27% of costs.

AIM: To determine the factors associated with regimen selection from currently available direct-acting antivirals (DAAs) in the treatment of genotype (GT) 1 HCV. METHODS: Data were collected from providers and specialty pharmacies through Trio Health's disease management program. Patients (n=2300) who initiated therapy for GT1 HCV from Jul to Dec 2016 were included. Variables identified as significantly associated with treatment selection through chi-square testing (p=0.1) were subsequently assessed via stepwise logistic regression. Multicollinearity between variables was assessed followed by exclusion of the variable with smaller effect on model prediction. RESULTS: 3 regimens accounted for 97% (2234/2300) of initiated treatment: 79% (1823) ledipasvir/sofosbuvir (LDV/SOF) +/-ribavirin (RBV), 11% (261) elbasvir/grazoprevir (EBR/GZR) +/-RBV, and 7% (150) sofosbuvir/velpatasvir (SOF/VEL) +/-RBV. Variables identified as significantly associated with regimen selection are indicated in the TABLE. Factors found not to be significantly associated include baseline viral load, HIV, anxiety, and payer type. NS5A resistance testing was not assessed due to small sample of patients who had resistance testing at baseline. Baseline eGFR <30 ml/min was most impactful in the selection model and was negatively associated with LDV/SOF (OR=0.025) and positively favored EBR/GZR (OR=47.449). Treatment naive (TN) favored LDV/SOF (OR=2.176) and was negatively associated with EBR/GZR (OR=0.649) and SOF/VEL (OR=0.344). Baseline platelets <=100K/mcl was negatively associated with LDV/SOF (OR=0.535) and positively with SOF/VEL (OR= 2.654). SUMMARY: Based on usage patterns in the real world, LDV/SOF is the preferred regimen in GT1 patients. In patients with severe renal impairment, EBR/GZR is preferred, and SOF/VEL is preferred for patients who previously failed treatment and/or have baseline platelet counts >100K/mcl (Table presented)