Arun B. Jesudian

Impact of depressive symptoms and hepatic encephalopathy on health-related quality of life in cirrhotic hepatitis C patients

Depression, common in chronic medical conditions, and hepatic encephalopathy (HE), a reversible neuropsychiatric syndrome due to liver dysfunction, are associated with impaired health-related quality of life (HRQOL) in cirrhosis and hepatitis C (HCV). This study investigated the impact of depression and HE on HRQOL in cirrhotic patients with HCV. A convenience sample of 43 ambulatory patients, with varying degrees of cirrhosis secondary to HCV, was prospectively enrolled in this study. Participants were assessed for any current depressive, fatigue, and daytime sleepiness symptoms and underwent a psychometric evaluation to determine the presence of HE symptoms. Participants reported current HRQOL on general health and liver disease-specific questionnaires. Diagnosis and current health status were confirmed via medical records. The associations between disease severity, depressive symptoms, HE, fatigue, and daytime sleepiness were measured. Predictors of HRQOL in this sample were determined. Depressive symptoms (70xa0%) and HE (77xa0%) were highly prevalent in this sample, with 58xa0% actively experiencing both conditions at the time of study participation. A significant positive association was found between depressive symptoms and HE severity (Pxa0=xa0.05). Depressive symptoms were significantly associated with fatigue (Pxa0<xa0.001), daytime sleepiness (Pxa0<xa0.001), general HRQOL (Pxa0<xa0.001), and disease-specific HRQOL (Pxa0<xa0.001). HE was significantly associated with fatigue (Pxa0=xa0.02), general HRQOL (Pxa0<xa0.001), and disease-specific HRQOL (Pxa0<xa0.001). Depressive symptoms and HE were significant predictors of reduced HRQOL (Pxa0<xa0.001), with depressive symptoms alone accounting for 58.8xa0% of the variance. Depressive symptoms and HE accounted for 68.0xa0% of the variance. Findings suggest a possible pathophysiological link between depression and HE in cirrhosis, and potentially a wider-reaching benefit of treating minimal and overt HE than previously appreciated.

Optimal treatment with telaprevir for chronic HCV infection.

Telaprevir is a recently approved direct‐acting antiviral against hepatitis C virus (HCV) that works through inhibition of the NS3/4A serine protease inhibitor.Phase 2b and 3 studies have shown marked increase in sustained virological response rates in both treatment‐ naïve and treatment‐experienced patients with HCV genotype 1 treated with a telaprevir‐containing regimen compared with pegylated interferon (PEG‐IFN) and ribavirin alone. The most commonly observed side effects of telaprevir therapy are anaemia to a greater degree than that observed with PEG‐IFN/ribavirin alone; eczematous rash, which can be severe in a minority of patients; and anorectal discomfort.

Association Between Cirrhosis and Stroke in a Nationally Representative Cohort

Importance Cirrhosis is associated with hemorrhagic and thrombotic extrahepatic complications. The risk of cerebrovascular complications is less well understood. Objective To investigate the association between cirrhosis and various stroke types. Design, Setting, and Participants We performed a retrospective cohort study using inpatient and outpatient Medicare claims data from January 1, 2008, through December 31, 2014, for a random 5% sample of 1 618 059 Medicare beneficiaries older than 66 years. Exposures Cirrhosis, as defined by a validated diagnosis code algorithm. Main Outcomes and Measures The primary outcome was stroke, and secondary outcomes were ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage as defined by validated diagnosis code algorithms. Results Among 1 618 059 beneficiaries, 15 586 patients (1.0%) had cirrhosis (mean [SD] age, 74.1 [6.9] years; 7263 [46.6%] female). During a mean (SD) of 4.3 (1.9) years of follow-up, 77 268 patients were hospitalized with a stroke. The incidence of stroke was 2.17% (95% CI, 1.99%-2.36%) per year in patients with cirrhosis and 1.11% (95% CI, 1.10%-1.11%) per year in patients without cirrhosis. After adjustment for demographic characteristics and stroke risk factors, patients with cirrhosis had a higher risk of stroke (hazard ratio [HR], 1.4; 95% CI, 1.3-1.5). The magnitude of association appeared to be higher for intracerebral hemorrhage (HR, 1.9; 95% CI, 1.5-2.4) and subarachnoid hemorrhage (HR, 2.4; 95% CI, 1.7-3.5) than for ischemic stroke (HR, 1.3; 95% CI, 1.2-1.5). Conclusions and Relevance In a nationally representative sample of Medicare beneficiaries, cirrhosis was associated with an increased risk of stroke, particularly hemorrhagic stroke. A potential explanation of these findings implicates the mixed coagulopathy observed in cirrhosis.

Acute alcoholic hepatitis as indication for liver transplantation.

Purpose of reviewUntil recently, severe acute alcoholic hepatitis that is refractory to medical therapy was a disease with extremely high mortality and no viable treatment options. A landmark trial of early liver transplantation in highly selected patients demonstrated a clear survival benefit and favorable posttransplant outcomes. Since then, new findings regarding medical therapy for alcoholic hepatitis, outcomes of early transplant, and ethical considerations as well as public perception of this intervention have been published. Recent findingsGlucocorticoids remain the best initial medical therapy for severe acute alcoholic hepatitis, but liver transplantation can be an acceptable and effective therapy for those who fail to respond to steroids. Recurrence of harmful drinking is a valid concern, and has been observed in long-term follow-up of patients transplanted for alcoholic liver disease. Public perception of early liver transplant for severe acute alcoholic hepatitis is overall positive. SummaryLiver transplantation for refractory severe acute alcoholic hepatitis is a life-saving intervention and should be judiciously employed in highly selected individuals who are at low risk of recidivism.

High prevalence of colon adenomas in end‐stage kidney disease patients on hemodialysis undergoing renal transplant evaluation

The aim of this study was to determine whether patients with end‐stage kidney disease (ESKD) on hemodialysis (HD) undergoing kidney transplant evaluation are at higher risk for colonic neoplasia than the general population. This is a retrospective cohort study of patients with ESKD who underwent a first screening colonoscopy while undergoing kidney transplant evaluation. Data were collected on the prevalence of adenomatous polyps and advanced adenomas in 70 patients with ESKD and 70 controls, undergoing their first screening colonoscopy, matched for age, gender, and endoscopist. At the time of the colonoscopy, an average time on HD was 3.2 ± 2.9 yr. The prevalence of adenomatous polyps was significantly higher in ESKD on HD (54.3% vs. 32.9%, p = 0.008) than in controls. In a multivariate analysis controlling for other factors, ESKD on HD remained a risk factor for the presence of adenomas (OR 3.06, 95% CI 1.21, 7.73). No colonoscopy‐related complications were reported in the patients with ESKD on HD. We demonstrate a significantly higher prevalence of adenomatous polyps in patients with ESKD undergoing a first screening colonoscopy as part of kidney transplant evaluation. In addition, colonoscopy can be safely performed in this population.

Donor Factors Including Donor Risk Index Predict Fibrosis Progression, Allograft Loss, and Patient Survival following Liver Transplantation for Hepatitis C Virus

BACKGROUNDnThe utilization of liver transplantation (LT) is limited by the availability of suitable organs. This study aimed to assess the impact of the donor risk index (DRI) and other donor characteristics on fibrosis progression, graft, and patient survival in hepatitis C virus (HCV)-infected LT recipients.nnnMETHODSnHCV-infected LT recipients who had at least 2 post-LT protocol liver biopsy specimens available were included. Hazard ratio for bivariate analysis was computed using Cox proportional hazard regression analysis.nnnRESULTSnOf 312 recipients, 26.6% died over a median follow-up of 58.5 months (95% CI: 46.5-67.3). Fourteen patients underwent re-transplantation. Mean time to graft failure was 84.3 months, median follow-up: 59 months, 95% CI (48.2, 68.3). DRI >1.5 was significantly associated with patient and graft survival (Pxa0=xa00.04). Of the subset of 104 individuals who underwent histological analysis, 67.3% progressed to ≥F2. On multivariate analysis, significant donor-specific predictors of fibrosis progression were: donor age >50 years and DRI >1.7.nnnCONCLUSIONSn(1) Fibrosis progression in HCV-infected LT recipients is strongly associated with donor characteristics, specifically donor age and DRI. (2) DRI, an objective measure of donor quality, appears to correlate both with rate of histological progression and overall patient/graft survival.

Cirrhotic Patients Have Worse Bowel Preparation at Screening Colonoscopy than Chronic Liver Disease Patients without Cirrhosis

BACKGROUNDnCirrhosis has been shown in small studies to be a predictor of suboptimal bowel preparation at screening colonoscopy. It has yet to be established whether patients with chronic liver disease in the absence of cirrhosis experience equally poor colon cleansing. Intestinal dysmotility related to cirrhosis might impair bowel preparation in this population more than those with chronic liver disease without cirrhosis.nnnOBJECTIVEnThis study compared the quality of bowel preparation in cirrhotic and non-cirrhotic patients with chronic liver disease and determined whether this influenced polyp detection rate.nnnMETHODSnA retrospective study of patients with chronic liver disease, both cirrhotic and non-cirrhotic, who underwent screening colonoscopy was performed. Patient characteristics, concomitant medication use, adequacy of bowel preparation, and the total number and types of polyps found were compared between cirrhotic and non-cirrhotic groups.nnnRESULTSn330 patients fulfilled inclusion criteria; 36% (nxa0=xa0120) were cirrhotic. Cirrhotic patients had significantly worse bowel preparation scores compared with non-cirrhotics (mean 3.4xa0±xa01.1 vs. 3.7xa0±xa00.9, Pxa0=xa00.003). Worse bowel preparation scores in cirrhotics vs. non-cirrhotics persisted despite controlling for age, sex, and concomitant diabetes mellitus (DM) (Pxa0=xa00.0027). Among the cirrhotics, 48% had the lowest preparation scores compared with 30% of non-cirrhotics. No difference in polyp detection rate was found between cirrhotics and non-cirrhotics. Severity of cirrhosis as assessed by the MELD score did not predict worse bowel preparation.nnnCONCLUSIONSnCirrhotics have significantly worse bowel preparation scores compared to non-cirrhotics with chronic liver disease. No correlation between MELD score and bowel preparation score was observed in the cirrhotic cohort.

Delayed calcineurin inhibitor introduction and renal outcomes in liver transplant recipients receiving basiliximab induction.

To investigate the impact of delayed calcineurin inhibitor (CNI) initiation in liver transplant recipients (LTR) with peri‐operative renal insufficiency receiving basiliximab induction, we compared renal outcomes of LTR stratified by the degree of achieved post‐operative renal recovery (RR) prior to CNI initiation.

Cost-Effectiveness of Early Insertion of Transjugular Intrahepatic Portosystemic Shunts for Recurrent Ascites

Background & Aims Treatment options for recurrent ascites resulting from decompensated cirrhosis include serial large‐volume paracentesis and albumin infusion (LVP+A) or insertion of a transjugular intrahepatic portosystemic shunt (TIPS). Insertion of TIPSs with covered stents during early stages of ascites (early TIPS, defined as 2 LVPs within the past 3 weeks and <6 LVPs in the prior 3 months) significantly improves chances of survival and reduces complications of cirrhosis compared with LVP+A. However, it is not clear if TIPS insertion is cost effective in these patients. Methods We developed a Markov model using the payer perspective for a hypothetical cohort of patients with cirrhosis with recurrent ascites receiving early TIPSs or LVP+A using data from publications and national databases collected from 2012 to 2018. Projected outcomes included quality‐adjusted life‐year (QALY), costs (2017 US dollars), and incremental cost‐effectiveness ratios (ICERs;

Advances in the treatment of hepatitis C virus infection.

/QALY). Sensitivity analyses (1‐way, 2‐way, and probabilistic) were conducted. ICERs less than