Shari S. Rogal

Effect of addition of statins to antiviral therapy in hepatitis C virus-infected persons: Results from ERCHIVES.

3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) have been variably noted to affect hepatitis C virus (HCV) treatment response, fibrosis progression, and hepatocellular carcinoma (HCC) incidence, with some having a more potent effect than others. We sought to determine the impact of adding statins to antiviral therapy upon sustained virological response (SVR) rates, fibrosis progression, and HCC development among HCV‐infected persons using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), an established, longitudinal, national cohort of HCV‐infected veterans. Within ERCHIVES, we identified those who received HCV treatment and a follow‐up of >24 months after treatment completion. We excluded those with human immunodeficiency virus coinfection, hepatitis B surface antigen positivity, cirrhosis, and HCC at baseline. Our main outcomes were liver fibrosis progression measured by FIB‐4 scores, SVR rates, and incident HCC (iHCC). Among 7,248 eligible subjects, 46% received statin therapy. Statin use was significantly associated with attaining SVR (39.2% vs. 33.3%; P < 0.01), decreased cirrhosis development (17.3% vs. 25.2%; P < 0.001), and decreased iHCC (1.2% vs. 2.6%; P < 0.01). Statins remained significantly associated with increased odds of SVR (odds ratio = 1.44; 95% confidence interval [CI] = 1.29, 1.61), but lower fibrosis progression rate, lower risk of progression to cirrhosis (hazard ratio [HR] = 0.56; 95% CI = −0.50, 0.63), and of incident HCC (HR = 0.51; 95% CI = 0.34, 0.76) after adjusting for other relevant clinical factors. Conclusions: Statin use was associated with improved virological response (VR) rates to antiviral therapy and decreased progression of liver fibrosis and incidence of HCC among a large cohort of HCV‐positive Veterans. These data support the use of statins in patients with HCV. (Hepatology 2015) Hepatology 2015;62:365–374

Pretransplant depression, antidepressant use, and outcomes of orthotopic liver transplantation.

Depression is a common problem among patients awaiting organ transplantation, but little is known about the impact of depression and its treatment on the outcomes of liver transplantation. In this retrospective cohort analysis, we studied all patients over 18 years of age who underwent liver transplantation during a 5‐year period (2004‐2008) at a single center. Among 179 recipients, 65 patients had depression, as defined by a health care provider assessment, before transplantation. Depression was defined as past or active depression or an adjustment disorder. The associations between pretransplant depression and various outcomes (time to death, graft failure, first acute cellular rejection episode, first infection, and first rehospitalization) were assessed. In the entire sample, more patients with depression required posttransplant psychiatric care (37% versus 18%); the adjusted hazard ratio was 2.28 (1.27‐4.11). The rates of other outcomes, including hospital readmission, acute cellular rejection, graft failure, mortality, and infection, were similar for patients with depression and patients without depression. Among those with depression, patients on antidepressants at the time of transplantation had acute cellular rejection less frequently than those not taking antidepressants (13% versus 40%); the adjusted hazard ratio was 0.14 (0.03‐0.62). The rates of other outcomes were similar between these 2 groups. These data indicate that depression affects posttransplant psychiatric morbidity but not other medical outcomes of liver transplantation. Pharmacological treatment of depression may significantly reduce the incidence of acute cellular rejection in patients undergoing liver transplantation. However, future prospective studies of mental health and liver transplantation are required to definitively assess the effects of antidepressant medications on medical outcomes. Liver Transpl, 2011.

Early Treatment of Depressive Symptoms and Long‐Term Survival After Liver Transplantation

While depression after liver transplantation (LTX) is associated with decreased survival, the effects of treating depression remain unknown. We assessed a previously described, prospective cohort of 167 patients transplanted for alcohol‐related liver disease from 1998 to 2003. Depressive symptoms were measured with the Beck Depression Inventory serially throughout the first posttransplant year. Adequacy of antidepressant treatment was measured with the Antidepressant Treatment History Form. Using Cox‐proportional Hazards modeling, survival times were assessed for recipients with no depression versus depression with adequate medications versus depression with inadequate medications. Seventy‐two recipients had depressive symptoms in the first posttransplant year. Of these, 43% (n = 31) received adequate pharmacotherapy and 57% (n = 41) received inadequate (n = 7) or no pharmacotherapy (n = 34). After a median follow‐up time of 9.5 years, 32% of the inadequately treated depressed group survived versus 52% of the adequately treated group and 56% of the nondepressed group (p = 0.006). Compared to the nondepressed group, those with adequately treated depression had no significant difference in survival. However, recipients with depression and inadequate pharmacotherapy had decreased survival times compared to nondepressed recipients (HR for death = 2.44, 95% CI = 1.45, 4.11), controlling for other known confounders. The factor most strongly linked to long‐term mortality after liver transplantation in this cohort was untreated depression.

Relationship Between Detection of Adenomas by Flexible Sigmoidoscopy and Interval Distal Colorectal Cancer

BACKGROUND & AIMS Low rates of adenoma detection by colonoscopy have been associated with increased rates of interval colorectal cancer. We evaluated the relationship between the rate of adenoma detection by flexible sigmoidoscopy and interval distal colorectal cancer. METHODS We analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer screening trial, which used flexible sigmoidoscopy as a colorectal cancer screening modality (46,835 subjects; 66,711 examinations by 93 examiners). An adenoma detection rate was defined for each examiner as the number of examinations that identified adenomas (confirmed by pathology analysis) divided by the total number of screening examinations. Interval cancers were defined as cancers presumed detectable but not detected, which was based on the stage at diagnosis and the elapsed time from screening to diagnosis. RESULTS The Prostate, Lung, Colorectal, and Ovarian Cancer study identified 32 interval distal cancers. The incidence of interval cancer for individuals screened by examiners in the lowest quartile of distal adenoma detection (2.0%-7.2%) was 9.0/10,000 examinations, whereas the incidence of interval cancers was lower among individuals whose examiners were in higher quartiles of adenoma detection, ranging from 3.0 to 5.4/10,000 examinations. The odds of interval distal cancer were significantly increased for patients of examiners in the lowest quartile of distal adenoma detection (<7.2%), with an adjusted odds ratio of 2.4 (95% confidence interval, 1.1-5.0; P = .02). CONCLUSIONS Lower levels of adenoma detection by flexible sigmoidoscopy increase the risk for interval distal cancer. Detection of distal adenomas is a marker of the performance quality of flexible sigmoidoscopy.

Risk factors for frequent readmissions and barriers to transplantation in patients with cirrhosis.

Background Hospital readmission rate is receiving increasing regulatory scrutiny. Patients with cirrhosis have high hospital readmissions rates but the relationship between frequent readmissions and barriers to transplantation remains unexplored. The goal of this study was to determine risk factors for frequent readmissions among patients with cirrhosis and identify barriers to transplantation in this population. Methods We retrospectively reviewed medical records of 587 patients with a confirmed diagnosis of cirrhosis admitted to a large tertiary care center between May 1, 2008 and May 1, 2009. Demographics, clinical factors, and outcomes were recorded. Multivariate logistic regression was performed to identify risk factors for high readmission rates. Transplant-related factors were assessed for patients in the high readmission group. Results The 587 patients included in the study had 1557 admissions during the study period. A subset of 87 (15%) patients with 5 or more admissions accounted for 672 (43%) admissions. The factors associated with frequent admissions were non-white race (OR = 2.45, p = 0.01), diabetes (OR = 2.04, p = 0.01), higher Model for End-Stage Liver Disease (MELD) score (OR = 35.10, p<0.0001 for MELD>30) and younger age (OR = 0.98, p = 0.02). Among the 87 patients with ≥5 admissions, only 14 (16%) underwent liver transplantation during the study period. Substance abuse, medical co-morbidities, and low (<15) MELD scores were barriers to transplantation in this group. Conclusions A small group of patients with cirrhosis account for a disproportionately high number of hospital admissions. Interventions targeting this high-risk group may decrease frequent hospital readmissions and increase access to transplantation.

Cost‐effectiveness of new antiviral regimens for treatment‐naïve U.S. veterans with hepatitis C

Recently approved, interferon‐free medication regimens for treating hepatitis C are highly effective, but extremely costly. We aimed to identify cost‐effective strategies for managing treatment‐naïve U.S. veterans with new hepatitis C medication regimens. We developed a Markov model with 1‐year cycle length for a cohort of 60‐year‐old veterans with untreated genotype 1 hepatitis C seeking treatment in a typical year. We compared using sofosbuvir/ledipasvir or ombitasvir/ritonavir/paritaprevir/dasabuvir to treat: (1) any patient seeking treatment; (2) only patients with advanced fibrosis or cirrhosis; or (3) patients with advanced disease first and healthier patients 1 year later. The previous standard of care, sofosbuvir/simeprevir or sofosbuvir/pegylated interferon/ribavirin, was included for comparison. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die. Complications were less likely after sustained virological response. We calculated the incremental cost per quality‐adjusted life year (QALY) and varied model inputs in one‐way and probabilistic sensitivity analyses. We used the Veterans Health Administration perspective with a lifetime time horizon and 3% annual discounting. Treating any patient with ombitasvir‐based therapy was the preferred strategy (

Economic and Public Health Impacts of Policies Restricting Access to Hepatitis C Treatment for Medicaid Patients

35,560; 14.0 QALYs). All other strategies were dominated (greater costs/QALY gained than more effective strategies). Varying treatment efficacy, price, and/or duration changed the preferred strategy. In probabilistic sensitivity analysis, treating any patient with ombitasvir‐based therapy was cost‐effective in 70% of iterations at a

Inflammation, Psychiatric Symptoms, and Opioid Use Are Associated With Pain and Disability in Patients With Cirrhosis

50,000/QALY threshold and 65% of iterations at a

Healthcare utilization in chronic liver disease: the importance of pain and prescription opioid use

100,000/QALY threshold. Conclusion: Managing any treatment‐naïve genotype 1 hepatitis C patient with ombitasvir‐based therapy is the most economically efficient strategy, although price and efficacy can impact cost‐effectiveness. It is economically unfavorable to restrict treatment to patients with advanced disease or use a staged treatment strategy. (Hepatology 2016;63:428–436)

Rapid improvement in post-infectious gastroparesis symptoms with mirtazapine.

BACKGROUND Interferon-free hepatitis C treatment regimens are effective but very costly. The cost-effectiveness, budget, and public health impacts of current Medicaid treatment policies restricting treatment to patients with advanced disease remain unknown. OBJECTIVES To evaluate the cost-effectiveness of current Medicaid policies restricting hepatitis C treatment to patients with advanced disease compared with a strategy providing unrestricted access to hepatitis C treatment, assess the budget and public health impact of each strategy, and estimate the feasibility and long-term effects of increased access to treatment for patients with hepatitis C. METHODS Using a Markov model, we compared two strategies for 45- to 55-year-old Medicaid beneficiaries: 1) Current Practice-only advanced disease is treated before Medicare eligibility and 2) Full Access-both early-stage and advanced disease are treated before Medicare eligibility. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die each year. Morbidity was reduced after successful treatment. We calculated the incremental cost-effectiveness ratio and compared the costs and public health effects of each strategy from the perspective of Medicare alone as well as the Centers for Medicare & Medicaid Services perspective. We varied model inputs in one-way and probabilistic sensitivity analyses. RESULTS Full Access was less costly and more effective than Current Practice for all cohorts and perspectives, with differences in cost ranging from