Multicenter, Double-Blind, Randomized Trial of Emricasan in Hepatitis C-Treated Liver Transplant Recipients With Residual Fibrosis or Cirrhosis.

Despite achieving sustained virologic response (SVR) to hepatitis C virus (HCV) therapy, there remains a post liver transplantation population with advanced fibrosis/cirrhosis. Emricasan is an orally active, pan-caspase inhibitor that suppresses apoptosis and inflammation, potentially decreasing hepatic inflammation and fibrosis. We aimed to determine the safety and efficacy of emricasan (IDN-6556-07) in a double-blind, randomized, placebo-controlled, multicenter study in reducing or preventing the progression of hepatic fibrosis in HCV liver transplant recipients with residual fibrosis or cirrhosis after achieving SVR. A total of 64 participants were randomly assigned to receive 25 mg twice daily of emricasan or placebo in a 2:1 ratio for 24 months. 41 participants were randomly assigned to emricasan and 23 to placebo; 32 participants in the emricasan group (78.0%) and 19 who took a placebo (82.6%) completed the study. There was no difference in the primary endpoint (Ishak fibrosis stages F2-F5, improvement in fibrosis or stability; Ishak fibrosis stage F6, improvement) between the emricasan (77.1%) and placebo groups (74.1%); P = NS. There was no difference between the emricasan (54.5%) and placebo (60.7%) arms in the rate of fibrosis improvement alone. However, those in the prespecified F3 to F5 subgroup had higher rates of stability or improvement in fibrosis in the emricasan group (95.2%) compared with placebo (54.6%) (P = 0.01). The tolerability and safety profiles were similar in both groups. In conclusion, overall stability in the Ishak fibrosis stage was similar between emricasan and placebo groups at 24 months. However, there was improvement and/or stability in fibrosis stage in the prespecified F3 to F5 subgroup with emricasan versus placebo, suggesting that patients with moderate fibrosis may benefit with emricasan.

Fluoroscopy Time During Endoscopic Retrograde Cholangiopancreatography Performed for Children and Adolescents is Significantly Higher With Low-volume Endoscopists.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a fluoroscopy and endoscopy-based procedure important for diagnosis and management of pediatric pancreaticobiliary disorders. Patient, procedure, endoscopist, and facility characteristics have been shown to influence ERCP complexity and procedure outcomes as well as fluoroscopy utilization in adults; however, the extent to which this is true in pediatric patients remains under-studied and there are minimal data regarding fluoroscopy utilization in pediatric ERCP. METHODS: We retrospectively analyzed ERCPs performed on patients <18 years of age at our tertiary care children's hospital from 2002 to 2017 using our institution's paper and electronic medical record system along with a prospectively maintained radiation exposure database. Procedure complexity was graded using the Stanford Fluoroscopy Complexity Score and the American Society of Gastrointestinal Endoscopy Complexity scale. High-volume endoscopists (HVE) were defined as having a cumulative annual ERCP volume >100 and low-volume endoscopists (LVE) as <100 (pediatric + adult) ERCPs/year. RESULTS: Three hundred eighty-five ERCPs performed on 321 patients were included in this analysis. The mean patient age was 13.4 years (+/- 4.2 years), 77% were index ERCPs (native ampullas), and 81% were performed with therapeutic intent (87% for biliary indication and 13% for pancreatic indication). Fluoroscopy times (FTs) varied between procedures and providers. Median FT was 4.85 (+/- 2.68) minutes. Endoscopist annual ERCP volume was the strongest predictor of FT (P < 0.001). In addition to endoscopist volume, procedure-specific predictors of increased FT included pancreatic indication for the procedure, biliary or pancreatic duct stricture, patient age <4 years or >16 years at the time of ERCP (P < 0.01 for each), and native ampulla. ERCP complexity rating based on the Stanford Fluoroscopy Complexity Score correlated with FT. CONCLUSIONS: Radiation exposure is higher than desirable for pediatric ERCP and varies with endoscopist as well as patient and procedure-specific factors. HVE perform ERCP with lower FT relative to LVE even though HVE procedure complexity was higher. The Stanford Fluoroscopy Score predicted FT for pediatric ERCP, but the ASGE ERCP complexity scale did not. Adaptation and refinement of pediatric-specific ERCP complexity scales including factors, such as patient size and age and indications/interventions more consistent with those encountered in pediatrics could be beneficial.

Hepatitis B in Pregnant Women and their Infants.

Chronic hepatitis B is a global health problem affecting approximately 350 million to 400 million individuals worldwide, and mother to child transmission remains the major mode of transmission. Approximately 50% of chronically infected individuals acquire infection, either perinatally or early in childhood, predominantly in areas where hepatitis B virus (HBV) is endemic. Management of HBV in pregnancy presents a unique set of challenges. All infants born of hepatitis B surface antigen-positive mothers should receive postexposure immune prophylaxis with hepatitis B immunoglobulin and HBV vaccination within 24 hours of birth and need close follow-up for the first few years of life.

Use of Transarterial Chemoembolization (TACE) and Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: US Regional Analysis of the GIDEON Registry.

BACKGROUND: Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of Treatment with Sorafenib (GIDEON) is a worldwide, prospective, non-interventional study to evaluate the safety of sorafenib in a variety of patient subsets. METHODS: Eligible patients had unresectable hepatocellular carcinoma for whom the decision had been made to treat with sorafenib. Treatment strategies were instituted at the physician's discretion. Patient and disease characteristics, treatment practices, incidences of adverse events (AEs), and overall survival were collected. RESULTS: In the United States, 563 patients were evaluable for safety. Subgroup analysis was performed for patients who underwent transarterial chemoembolization (TACE) prior to the initiation of sorafenib (group A, n=158), after the initiation of sorafenib only (group B, n=29), both (group C, n=38), or did not undergo TACE (n=318). Patient demographics were similar across the groups. In group A, 29% had Child-Pugh score B or C at diagnosis, and 19% had Barcelona Clinic Liver Cancer tumor stage C or D. In group B, 48% had Child-Pugh score B or C at study entry, and 31% had BCLC stage C or D. The majority of patients in all groups initially received full-dose sorafenib. Incidences of grade ≥3 drug-related AEs were 30%, 17%, and 16% in groups A, B, and C, respectively, and 22% in patients who did not undergo TACE. No new safety signals emerged. CONCLUSIONS: The results from GIDEON reaffirm that sorafenib can be safely used in the context of TACE.

Retreatment of chronic hepatitis C virus infection.

Despite advances in antiviral therapy for chronic hepatitis C, approximately half of patients undergoing initial treatment fail to achieve a sustained virologic response (SVR), thus prompting consideration of retreatment with alternative regimens. The decision to re-treat should be based on the severity of liver disease, as well as the presence of clinical and virologic predictors of a successful outcome of additional therapy. Retreatment of patients who were prior nonresponders to interferon monotherapy with interferon plus ribavirin results in SVR rates of 13% to 15%, which can be increased to 25% to 40% if peginterferon plus ribavirin is used. Retreatment of patients who were prior nonresponders to interferon plus ribavirin with peginterferon plus ribavirin unfortunately achieves SVR rates of approximately 10%. The growing number of patients who have been treated and have failed initial therapy highlights the need for the development of more efficacious antiviral agents for the treatment of chronic hepatitis C.

Chronic hepatitis C in the state prison system: insights into the problems and possible solutions.

The prevalence of chronic hepatitis C virus (HCV) within the correctional system is estimated to be 10-20-times greater than that which is reported in the general population. High-risk behavioral patterns probably account for the greater estimates in this population. Recent observations of more than 780 patient-inmates infected with HCV within the California Department of Corrections suggest a very high prevalence of advanced fibrosis in this population. Observational studies performed in Texas have shown that the rates of chronic liver disease-related deaths have increased significantly between 1989 and 2003, especially among Hispanic patient-inmates. Viral hepatitis accounts for a significant number of these chronic liver disease-related deaths. Identification of high-risk patient-inmates infected with HCV, as well as appropriation of funds for their treatment, should result in a decreased rate of liver-related complications. This should translate into reduced morbidity and cost to correctional institutions, as well as to improved public health and safety.

Impact of a designated hepatology nurse on the clinical course and quality of life of patients treated with rebetron therapy for chronic hepatitis C.

A two- to three-fold increase in mortality from hepatitis C is predicted in the next 10-20 years as the largest cohort of patients age. More qualified providers are needed to care for this population. The objective of this study was to assess the impact of a hepatology nurse practitioner as compared to care by a physician on the quality of life and treatment outcomes of patients with chronic hepatitis C. Seventy-five patients with chronic hepatitis C were assigned to either a nurse practitioner or physician and asked to complete a SF-36 Health Survey quarterly to measure their perceived quality of life.Two-sided t-tests comparing the quality of life scores in the physician and nurse practitioner groups at weeks 1, 12, and 24 were calculated using SPSS version 12.0 (Chicago, IL). Although marginal differences between physicians and nurse practitioners were noted for physical function at week 1, bodily pain at week 12, and role physical at week 24 by the patients, no statistically significant differences were observed overall in the quality of life scores reported by the patients according to healthcare provider. The treatment outcome data for the nurse practitioner groups showed 12/25 (48%) of patients with genotype 1 achieved a sustained virologic response as did 13/22 (59%) of patients with genotype 2 or 3. In the physician groups, 11/27 (41%) of patients with genotype 1 achieved a sustained virologic response as did 14/23 (61%) of patients with genotype 2 or 3. These results suggest nurse practitioners can provide effective care to the chronic hepatitis C population.