Faculty Bibliography

Hepatitis E virus (HEV), of the family Herpeviridae, is a virus which infects nearly 20 million people per year throughout the world. HEV is most commonly transmitted via the fecal-oral route and has long been described as a virus which afflicts only those in resource-poor countries. However, HEV has been detected in numerous animal carriers, various food sources, and even in human blood products in resource-rich regions of the world. HEV is of importance in the transplant patient population, for its ability to cause chronic viral infection in these patients can lead to graft loss and cirrhosis. In this review, we discuss the current knowledge of HEV as it pertains to the liver transplant patient population and discuss diagnosis and treatment of this infection.

BACKGROUND & AIMS/OBJECTIVE:Patients with hepatitis C virus (HCV) infections who achieve a sustained virologic response (SVR) to treatment have improved patient-reported outcomes (PROs). We compared post-treatment PRO scores between patients with chronic HCV infection who did and did not achieve an SVR to treatment. METHODS:Patients who completed treatment in clinical trials were enrolled in 2 registries, depending on the treatment outcome (#NCT01457755, #NCT01457768), from 2016-2017 in 17 countries in North America, Europe, and Asia-Pacific region. PRO scores (a 0-100 scale) were collected at pre-treatment (baseline); the last day of treatment; the post-treatment week 12 follow-up visit (in patients with SVR only); the registry baseline; and on registry weeks 12, 24, 36, 48, and 96 (the non-SVR registry) or every 24 weeks until week 96 (SVR registry), using the short form-36 (SF-36) instrument. RESULTS:Our analysis included 4234 patients with an SVR and 242 without an SVR from whom pre-treatment PRO data were available (mean age, 54±10 years; 63% male; 65% enrolled in the United States; 17% with cirrhosis; 12% with HIV coinfection). Upon registry enrollment, patients with an SVR had significant increases in all PRO scores compared with pre-treatment baseline levels (all P<.05). Patients without an SVR had mean reductions of ≤9.2 points in PRO scores while followed on the registry (P<.05 for 4-8 of 8 PRO domains measured by the SF-36). In contrast, patients with an SVR had sustained increases in PRO scores (mean increase of ≤7.0 points) while on the registry. In multivariate analysis, achieving an SVR was independently associated with superior scores in all SF-36 domains at all registry time points (beta from +4.8 to +15.9 points, all P≤.01). CONCLUSIONS:In a follow-up analysis of participants in clinical trials, we found that those with an SVR to treatment for HCV infection had significant increases in well-being, based on PRO scores. Patients without an SVR had decreasing PRO scores over the follow-up period.

BACKGROUND:The causative relationship between clearance of infection and long-term health-related quality of life (HRQL) improvements in patients with hepatitis C virus (HCV) has been generally accepted. The aim is to assess long-term HRQL trends in HCV patients who did not achieve sustained virologic response (SVR) after treatment with direct-acting antivirals. METHODS:HCV patients who completed treatment in clinical trials and did not achieve SVR were enrolled in a long-term registry (#NCT01457768). HRQL scores were prospectively collected using Short Form-36 instrument (SF-36; 8 HRQL domains and 2 summary scores). RESULTS:242 patients were included: 54±8 years, 85% male, 38% cirrhosis. Before treatment, patients' HRQL scores were similar to the general population norms (all one-sided p>0.05) followed by significant decreases by the end of treatment (-3.4 to -6.2 points, p<0.05 for 5/8 HRQL domains and Mental Summary). By the time subjects entered the registry, all but one mean HRQL scores had returned to pre-treatment levels (p>0.05). During subsequent periods in the registry, patients experienced further HRQL decrements: up to -9.2 points, p<0.05 for all HRQL domains, at week 24; up to -8.3 points, p<0.05 for 5/8 HRQL domains, at week 48. Although these HRQL decrements were observed regardless of cirrhosis status, they were more pronounced in patients with cirrhosis (p<0.05 for 3/8 HRQL domains). CONCLUSIONS:Patients who did not achieve SVR after treatment experience worsening of HRQL scores in long-term follow-up. Re-treatment of these patients will be important not only to improve their clinical outcomes but also their quality of life.

Background: Standard of care nucleos(t)ide analogs (Nrtl) are effective in chronic HBV (CHB) infection, but achieve low rates of sustained responses off therapy. The combination of the HBV Core Inhibitor ABI-H0731 (731) with a Nrtl has demonstrated potent antiviral activity in prior clinical studies and is being evaluated in a long-term treatment study.
Method(s): Studies ABI-H0731-201 and ABI-H0731-202 were 24-wk double-blind, placebo (Pbo)-controlled studies in CHB patients (pts). After 24 wks of treatment, pts could enter the open-label extension study ABI-H0731-211 and receive 731+Nrtl for up to an additional 52 wks. The study diagram summarizes study design, patient flow and monitored parameters. This interim report summarizes data for HBeAg+ pts only.
Result(s): Final Wk 24 results confirmed greater mean Iog10 declines in HBV DNA (5.27 vs 3.99; p=0.017) and RNA (2.34 vs 0.61; p<0.001) are achieved with 731+ETV vs ETV in Study 202. By Wk 24 in Study 201, the proportion of pts on 731+Nrtl vs Nrtl achieving DNA "TND" was 69% vs 0% (p<0.001), and the proportion of pts achieving RNA <35 U/mL whose baseline RNA > 35 U/mL was 52% vs 0% (p=0.0013) respectively. There are 64 HBeAg+ pts currently on treatment in Study 211, having received an overall treatment duration of >32 wks. Among the 27 HBeAg+ pts receiving 731+Nrtl in Study 201, 41% (11/27) have now achieved DNA TND along with RNA <35 U/mL and HBeAg <1 lU/mL At their last timepoint, Study 202 (Rx naive) pts now in Study 211 (n=22) have demonstrated mean DNA and RNA declines of 6.1 and 3.0 logs, respectively, with observed mean log changes of >0.6 for HBeAg (11 pts >0.5, 4 pts >1.0), >0.8 log for HBcrAg (7 pts >1.0, 3 pts >2.0) and >0.4 log for HBsAg (7 pts >0.5, 3 pts >1.0). When, administered in combination with Nrtl for up to 1 year, 731 has been well-tolerated, with only mild/moderate adverse events and lab abnormalities, and only a single discontinuation due to a Grade 1 rash.
Conclusion(s): ABI-H0731 continues to exhibit a favorable safety and tolerability profile in pts treated for up to 1 yr. The combination of 731+Nrtl results in faster, deeper declines in HBV DNA and RNA than Nrtl alone, as well as subsequent declines in the surrogate markers of cccDNA (pgRNA, HBeAg and HBcrAg) predictive of cccDNA pool depletion, and HBsAg. The emergent data supports the continued development of ABI-H0731. Updated safety and efficacy data will be presented

The development of bacterial endocarditis as a result of endoscopic interventions within the gastrointestinal tract is exceedingly rare. Antibiotic prophylaxis for endoscopic procedures is generally not warranted, except for certain high-risk patients. Double-balloon enteroscopy (DBE) is a common endoscopic procedure for evaluation of the small bowel. Bacterial endocarditis secondary to DBE has not been previously described. We describe the first case of enterococcal endocarditis attributed to DBE in a patient with a history of stage 1 primary biliary cholangitis.