Aylin Tansel

Efficacy of Psychosocial Interventions in Inducing and Maintaining Alcohol Abstinence in Patients With Chronic Liver Disease: A Systematic Review

BACKGROUND & AIMS We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), motivational interviewing, supportive therapy, and psychoeducation either alone or in combination in the intervention group and general health education or treatment as usual in the control group. All studies of induction of abstinence (4 RCTs and 6 observational studies) reported an increase in abstinence among participants in the intervention and control groups. Only an integrated therapy that combined CBT and motivational enhancement therapy with comprehensive medical care, delivered during a period of 2 years, produced a significant increase in abstinence (74% increase in intervention group vs 48% increase in control group, P = .02), which was reported in 1 RCT. All studies of maintenance of abstinence (1 RCT and 2 observational studies) observed recidivism in the intervention and control groups. Only an integrated therapy that combined medical care with CBT produced a significantly smaller rate of recidivism (32.7% in integrated CBT group vs 75% in control group, P = .03), which was reported from 1 observational study. However, data were not collected for more than 2 years on outcomes of patients with CLD and AUD. CONCLUSIONS In a systematic analysis of studies of interventions to induce or maintain alcohol abstinence in patients with CLD and AUD, integrated combination psychotherapy with CBT, motivational enhancement therapy, and comprehensive medical care increased alcohol abstinence. No psychosocial intervention was successful in maintaining abstinence, but an integrated therapy with CBT and medical care appears to reduce recidivism.

Trends in 30-Day and 1-Year Mortality Among Patients Hospitalized With Cirrhosis From 2004 to 2013

Objectives:Recent data suggest decreasing in-patient mortality in patients hospitalized with cirrhosis. We sought to determine if improvements in short-term outcomes for patients with cirrhosis are associated with changes in longer-term outcomes.Methods:We examined temporal trends in 30 days and 1-year postdischarge mortality among patients hospitalized with cirrhosis at any of the 126 Veterans Administration hospitals from 2004 and 2013. We adjusted for a range of demographic, liver disease severity, and comorbidity-related factors to account for differences in patient cohorts over time.Results:We identified 109,358 unique patients who were hospitalized with cirrhosis between 2004 and 2013. In-hospital mortality decreased from 11.4 to 7.6%, whereas 1-year mortality decreased from 34.5 to 33.2%. Over a third of out-of-hospital deaths occurred within the first 30 days after discharge; 30-day mortality increased from 9.3 to 10.1%. After adjusting for patient factors, the odds of in-hospital mortality in 2013 were 30% lower (adjusted odds ratio (OR)=0.70, 95% confidence interval (CI), 0.64–0.78), 1-year mortality were 13% lower (adjusted OR=0.87, 95% CI=0.82–0.93), whereas the 30-day mortality were 10% higher than 2004 (adjusted OR=1.10, 95% CI=0.99–1.21), although the latter did not reach statistical significance.Conclusions:In patients admitted with cirrhosis, reduction in in-hospital mortality was associated with less marked reduction in 1-year mortality, and an unchanged, if not higher, 30-day mortality following discharge. Our data suggest that some of the burden of mortality in cirrhosis has shifted from in-hospital to the immediate postdischarge period.

Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis

BACKGROUND & AIMS Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase‐1) in feces are widely used to identify patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic accuracy of this test, an ELISA, is not clear. We performed a systematic review and meta‐analysis to determine the accuracy of measurement of fecal elastase‐1 in detection of EPI. METHODS We searched PubMed, Embase, and reference lists for articles through November 2016 describing studies that compared fecal level of elastase‐1 with results from a reference standard, direct method (secretin stimulation test), or indirect method (measurement of fecal fat) for detection of EPI. Sensitivity and specificity values were pooled statistically using bivariate diagnostic meta–analysis. RESULTS We included total of 428 cases of EPI and 673 individuals without EPI (controls), from 14 studies, in the meta‐analysis. The assay for elastase‐1, compared to secretin stimulation test, identified patients with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI, 0.58–0.89) and specificity value of 0.88 (95% CI, 0.78–0.93). In an analysis of 345 cases of EPI and 312 controls, from 6 studies, the fecal elastase‐1 assay identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI, 0.79–0.99) and specificity value of 0.88 (95% CI, 0.59–0.97), compared to quantitative fecal fat estimation. In patients with low pre–test probability of EPI (5%), the fecal elastase‐1 assay would have a false‐negative rate of 1.1% and a false‐positive rate of 11%, indicating a high yield in ruling out EPI but not in detection of EPI. In contrast, in patients with high pre‐test probability of EPI (40%), approximately 10% of patients with EPI would be missed (false negatives). CONCLUSIONS In a systematic review and meta‐analysis of studies that compared fecal level of elastase‐1 for detection of EPI, we found that normal level of elastase‐1 (above 200 mcg/g) can rule out EPI in patients with a low probability of this disorder (such as those with irritable bowel syndrome with diarrhea). However, in these patients, an abnormal level of elastase‐1 (below 200 mcg/g) has a high false‐positive rate.

Incidence and Determinants of Hepatocellular Carcinoma in Autoimmune Hepatitis: A Systematic Review and Meta-analysis

Background & Aims The risk of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is unclear. We conducted a systematic review and meta‐analysis of the incidence of HCC and associated risk factors among patients with AIH. Methods We searched PubMed, Embase, and reference lists from relevant articles through June 2016 to identify cohort studies that examined the incidence of HCC in patients with AIH. We used random effects models to estimate pooled incidence rates overall and in subgroup of patients with cirrhosis. The between‐study heterogeneity was assessed using I2 statistic. Results A total of 25 studies (20 papers and 5 abstracts), including 6528 patients, met the eligibility criteria. The median cohort size was 170 patients with AIH (range, 25–1721 patients), followed for a median of 8.0 years (range, 3.3–16.0 years). The pooled incidence rate for HCC in patients with AIH was 3.06 per 1000 patient‐years (95% confidence interval, 2.22–4.23; I2 = 51.5%; P = .002). The pooled incidence of HCC in patients with cirrhosis at AIH diagnosis was 10.07 per 1000 patient‐years (95% confidence interval, 6.89–14.70; I2 = 48.8%; P = .015). In addition, 92 of 93 patients who had HCC had evidence of cirrhosis before or at the time of their HCC diagnosis. The risk of HCC seems to be lower in patients with AIH and cirrhosis than that reported for patients with cirrhosis from hepatitis B, hepatitis C, or primary biliary cholangitis. Conclusions Based on the increased risked of HCC shown in this meta‐analysis, there may be a role for HCC surveillance in patients with AIH and cirrhosis.

Risk and Predictors of Variceal Bleeding in Cirrhosis Patients Receiving Primary Prophylaxis With Non-Selective Beta-Blockers.

OBJECTIVES:Prior studies have demonstrated the efficacy of non-selective beta-blockers (NSBB) in preventing first variceal bleeding in patients with cirrhosis. However, little is known about the overall effectiveness of NSBB in routine clinical care.METHODS:We conducted a retrospective cohort study of cirrhotic patients without prior bleeding who initiated a NSBB (propranolol, nadolol) at any Veterans Administration facility between 2008 and 2013. The primary outcome was variceal bleeding within 12 months. We conducted Cox-proportional hazards analyses to identify demographic, clinical, and NSBB-related (type of NSBB, mean dose, dose change, and heart rate response) factors associated with variceal bleeding.RESULTS:Of 5,775 patients, 678 (11.7%) developed variceal bleeding. Mean daily dose of NSBB was <40 mg in 58.8%, 18.1% had either upward or downward titration in NSBB dose, and 9.8% had hemodynamic response. Patients who were younger, with ascites, greater medical comorbidity, and higher MELD (Model for end-stage liver disease) scores had a higher risk of variceal bleeding. Patients on a higher daily dose (>60 vs. <40 mg, adjusted hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.51–0.81), who had either upward or downward dose titration (adjusted HR 0.69; 95% CI: 0.52–0.90 and 0.64; 95% CI 0.45–0.90, respectively), and those who achieved hemodynamic response (adjusted HR 0.75; 95% CI=0.57–1.0) had lower risk.CONCLUSIONS:Approximately 12% of patients bled while being on NSBB for primary prophylaxis. A higher NSBB dose and dose titration were protective; yet most patients did not have the NSBB dose titrated to the recommended levels. Our data highlight the need for careful monitoring of cirrhotic patients on NSBB.

Factors That Contribute to Indeterminate Results From the QuantiFERON-TB Gold In-Tube Test in Patients With Inflammatory Bowel Disease

Background & Aims The QuantiFERON‐Tuberculosis Gold In‐Tube (QFT‐GIT) (QIAGEN Group, Hilden, Germany) test is widely used to screen for latent Mycobacterium tuberculosis infection in patients with inflammatory bowel diseases (IBD) before treatment with a tumor necrosis factor antagonist. The test frequently produces indeterminate results, prompting additional testing. We evaluated factors associated with indeterminate results from the QFT‐GIT test among patients with IBD. Methods We conducted a case–control study among eligible adults with QFT‐GIT test results and a concomitant diagnosis of IBD receiving care at a tertiary referral center from 2011 through 2013. We compared patients with IBD with indeterminate and determinate (positive or negative) results from the QFT‐GIT test. We collected data on patient demographics, clinical features, laboratory parameters, and medication use from medical charts. We calculated odds ratios (OR) and 95% CIs using multivariate logistic regression models. Results A total of 400 patients with IBD (265 Crohn’s disease and 135 ulcerative colitis) were included in the final analyses. Indeterminate results were noted in 11.5% of patients. At the time of testing, a higher proportion of patients with indeterminate results from the QFT‐GIT test were on systemic corticosteroid therapy (60.9% vs 30.5% of patients with conclusive test results; P < .001), had levels of C‐reactive protein above 0.8 mg (62.2% vs 39.9% of patients with clear test results; P = .005), had an erythrocyte sedimentation rate above 15 mm/h (55.6% vs 35.8% of patients with clear test results; P = .01), had serum levels of albumin below 3.5 g/dL (33.3% vs 6.3% of patients with clear test results; P < .001), and had low levels of hemoglobin (52.2% vs 28.3% of patients with clear test results; P = .001). In multivariable analysis, corticosteroid use (adjusted OR, 2.92; 95% CI, 1.44–5.88; P = .003) and serum levels of albumin below 3.5 g/dL (adjusted OR, 3.62; 95% CI, 1.36–9.60; P = .009) were independently associated with increased risk of indeterminate QFT‐GIT test results. We did not identify a dose‐related effect with corticosteroid therapy and the odds of indeterminate QFT‐GIT test results. Conclusions In a case–control study of patients with IBD, we associated systemic corticosteroid therapy and low levels of albumin with an increased likelihood of having indeterminate QFT‐GIT test result.

Use of Hy’s Law, R Criteria, and nR Criteria to Predict Acute Liver Failure or Transplantation in Patients With Drug-Induced Liver Injury

Dear Editor: We read with great interest the article by Robles-Diaz et al regarding the use of Professor Hyman Zimmerman’s law (Hy’s law) and a proposal to use a modified algorithm to predict liver failure in druginduced liver injury patients. This innovative study used the Spanish Drug-Induced Liver Injury registry to take advantage of current methods for the prediction of liver failure. We feel, however, that there is a need for clarification regarding the formulas for the ratio (R) and new ratio (nR) values that were employed. The R ratio is a method for classifying liver disease as hepatocellular, cholestatic, or mixed injury pattern. However, we believe that the formulas for R and nR as published in the article by Robles-Diaz et al can be misleading to clinicians as described:

Su1079 Changes in the Incidence and Prevalence of Cirrhosis in the National Veterans Administration Over a Decade: 2002-2012

BACKGROUND: Cirrhosis is associated with a high morbidity and mortality, and is a risk factor for hepatocellular carcinoma. Yet there is limited information regarding the burden of cirrhosis from population-based studies in the U.S. We aimed to determine the annual incidence and prevalence of cirrhosis as well as time trends in the underlying etiology in a national veterans cohort. METHODS: Using the Veterans Administration Corporate Data Warehouse, we calculated the time trends in the annual incidence and prevalence of overall cirrhosis and decompensated cirrhosis between 2002 and 2012. In addition to the overall trends, we also examined the time trends by subgroups based on the underlying etiology for liver disease. We defined cirrhosis on the basis of previously validated ICD-9 code based algorithms. We used direct standardization method to adjust the time trends for changing age of the cohort (where 2002 VA population used as standard), and used joinpoint regression models to determine the magnitude of these time trends (by calculating average annual percentage change (AAPC)). RESULTS: The age-adjusted incidence rates of cirrhosis per 100 persons slightly increased from 0.22 (95% CI 0.21-0.22) in 2002 to 0.23 in 2012 (95% CI 0.23-0.24). The average annual percentage change (AAPC) in the age-adjusted incidence was 1.76% (p<0.05). The age-adjusted prevalence of cirrhosis per 100 persons increased steeply (AAPC=6.75%) from 0.62 (95% CI 0.61-0.63) in 2002 to 1.27 (95% CI 1.26-1.28) in 2010 and then the rate of increase slowed (AAPC=1.69%) between 2010-2012 to 1.36 (95% CI 1.35-1.37) in 2012. The prevalence of decompensated cirrhosis increased in parallel (0.46 in 2002 to 0.72 in 2012 per 100 persons). There were 68,760 and 41,780 patients with a diagnosis of cirrhosis and decompensated cirrhosis, respectively, who received care in VA facilities in 2012. Figures 1 and 2 shows the trends in overall incidence and prevalence of cirrhosis by etiology. HCV was the leading underlying etiology. In 2002, 47% of prevalent cirrhosis cases had HCV; this proportion increased to 53% in 2012. The proportion of cirrhosis patients with alcohol as the underlying etiology fell slightly from 29.8% in 2002 to 26.1% in 2012, whereas those with HBV remained stable at 0.9% to 1.2%. CONCLUSION: The prevalence of cirrhosis and decompensated cirrhosis has increased significantly over the last decade, and the trend is still upwards. Most patients with cirrhosis have underlying HCV, and successful diffusion of treatment may change the future trajectory of cirrhosis burden. Yet, given the existing and large burden of cirrhosis (and its complications), clinicians and healthcare system need to develop strategies targeted to provide timely and effective care to this high-risk patient population.