Continuous renal replacement therapy in critically ill patients with acute on chronic liver failure and acute kidney injury: A retrospective cohort study
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BACKGROUND: Incident acute kidney injury (AKI) in critically ill patients with acute on chronic liver failure (ACLF) is associated with poor prognosis. The role of continuous renal replacement therapy (CRRT) is not well established for patients with ACLF and AKI. MATERIALS AND METHODS: We conducted a retrospective cohort study to examine clinical outcomes in 66 patients with ACLF and AKI requiring CRRT. RESULTS: All-cause hospital mortality was 89.4%. Five (7.6%) patients were listed for liver transplantation, of whom 1 (1.5%) was eventually subjected to transplantation. Etiology of AKI included type 1 hepatorenal syndrome (HRS) with or without some degree of acute tubular necrosis (ATN) in 20 (30.3%) patients, and primarily ATN in 46 (69.7%) patients. When evaluated at the time of CRRT initiation, Child-Pugh-Turcotte (CPT) and Model for End-stage Liver Disease (MELD) (area under the receiver operating characteristics curve (AUROC) 0.67 for both) had fair performance for prediction of mortality, whereas Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure (CLIF)-SOFA performed better for the prediction of mortality (AUROC 0.87 for both). SOFA and CLIF-SOFA also performed well when determined at the time of ICU admission (AUROC 0.86 and 0.85, respectively). Etiology of liver disease or AKI did not influence prognosis. CONCLUSION: Critically ill patients with ACLF and AKI requiring CRRT have poor hospital survival, even with provision of extracorporeal support therapy. SOFA and CLIF-SOFA are good prognostic tools of mortality in this susceptible population.

Long term outcomes of patients transplanted for hepatocellular carcinoma with human immunodeficiency virus infection.

BACKGROUND: We aimed to study outcomes in HIV + patients with HCC in the US following Liver Transplantation (LT) using the UNOS dataset. METHODS: The database was queried from 2003 to 2016 for patients undergoing LT with HCC, HIV+, and HCC/HIV+. RESULTS: Out of 17,397 LT performed for HCC during the study period, 113 were transplanted for HCC with HIV infection (91 isolated livers). Patients transplanted for HCC/HIV+ were younger (55.54 ± 5.89 vs 58.80 ± 7.37, p < 0.001), had lower total bilirubin (1.20 vs 1.60, p = 0.042) significantly lower BMI (25.35 ± 4.43 vs 28.39 ± 5.17, p < 0.001) and were more likely to be co-infected with HBV (25.3% vs 8.2% p < 0.001) than those transplanted for HCC alone. HCC/HIV + patients were found to have a 3.8 fold increased risk of peri-operative mortality at 90 days after matching. HCC/HIV + recipients had 54% decreased long-term survival within the HCC cohort. Our initial analysis of overall graft and patient survival found significant differences between HCC/HIV and HCC/HIV + recipients. However, these variances were lost after case-matching. Recurrence and disease free survival were similar in HCC alone vs HCC/HIV + recipients. CONCLUSIONS: Our analysis suggests that excellent outcomes can be achieved in selected patients with HCC/HIV+.

Heart transplantation in cardiac amyloidosis.

"Cardiac amyloidosis" is the term commonly used to reflect the deposition of abnormal protein amyloid in the heart. This process can result from several different forms, most commonly from light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, which in turn can represent wild-type (ATTRwt) or genetic form. Regardless of the origin, cardiac involvement is usually associated with poor prognosis, especially in AL amyloidosis. Although several treatment options, including chemotherapy, exist for different forms of the disease, cardiac transplantation is increasingly considered. However, high mortality on the transplantation list, typical for patients with amyloidosis, and suboptimal post-transplant outcomes are major issues. We are reviewing the literature and summarizing pros and cons of listing patients with amyloidosis for cardiac or combine organ transplant, appropriate work-up, and intermediate and long-term outcomes. Both AL and ATTR amyloidosis are included in this review.

Liver transplantation for fibrolamellar hepatocellular carcinoma: A national perspective.

BACKGROUND: Fibrolamellar Hepatocellular Carcinoma (FL-HCC) is a rare primary liver tumor that usually presents in younger patients without underlying liver disease. METHODS: We queried the United Network of Organ Sharing (UNOS) database between October 1988 and January 2013 to evaluate outcomes in patients with FL-HCC undergoing liver transplantation in the United States compared to patients with conventional Hepatocellular Carcinoma (HCC). RESULTS: Sixty-three patients were identified (57% female, mean age 30 years). Only one patient (2%) had an associated Hepatitis C Virus. Mean Model for End-Stage Liver Disease (MELD) score at the time of transplantation was 11.3. Mean waiting time was 325 days and mean cold ischemic time was 6 hr. Overall survival of FL-HCC patients at 1, 3, and 5 years was 96%, 80%, and 48% as compared to HCC patients whose rates were 89%, 77%, and 68%. Six patients had tumor recurrence (10%). The Cox Model demonstrated that MELD and cold ischemic time are the strongest predictors of overall survival in FL-HCC patients. Age and wait time were not associated with poor patient survival in this series. CONCLUSIONS: Good results can be obtained in selected patients transplanted for FL-HCC. FL-HCC patients had similar survival compared to those transplanted for HCC. J. Surg. Oncol. 2017;115:319-323. © 2016 Wiley Periodicals, Inc.

Racial Differences in the Prevalence of Celiac Disease in the US Population: National Health and Nutrition Examination Survey (NHANES) 2009-2012.

AIM: To provide an estimate of the prevalence of celiac disease by race/ethnic origin in large sample of US population. METHODS: Data from the 2009-2010 and 2011-2012 NHANES were combined and analyzed. The NHANES is a nationally representative survey with oversampling of certain minorities. Sample-based frequencies were reported and weighted frequencies were used to estimate prevalence. RESULTS: A total of 14,701 participants were checked for tissue transglutaminase (tTG) and endomysial (EMA) IgA antibodies. Seventy-four participants had positive tTG and/or EMA corresponding to prevalence of 0.79 % (95 % CI 0.54-1.04 %). Non-Hispanic white were more likely to be positive for both compared with other races (72.0 vs 31.7 %; p = 0.010) and less likely to be weakly positive for tTG but positive for EMA (3.6 vs 26.4 %; p = 0.03). The prevalence of positive serology according to race was as follows: 1.08 % (95 % CI 0.70-1.45 %) in non-Hispanic white, 0.23 % (95 % CI 0.03-0.43 %) in Mexican, 0.22 % (95 % CI 0.01-0.44 %) in non-Hispanic black, 0.38 % (95 % CI 0.00-0.89 %) in "other Hispanic," and 0.15 % (95 % CI 0.00-0.34 %) in other races including multiracial and undeterminable in non-Hispanic Asian due to the presence of only one positive EMA test. 0.9 % of the NHANES sample participants followed gluten-free diet. Of this group of participants, 85 % were never diagnosed with celiac disease and 99 % of them had negative celiac disease serology. CONCLUSIONS: Potentially 0.79 % of the general US population demonstrate serologic evidence of celiac disease autoimmunity. The prevalence is 4-8 times higher among non-Hispanic white compared with other races. Close to 1 % of the population is electively following gluten-free diet despite having little evidence of the disease.

Transcatheter interventions for valvular heart diseases in liver cirrhosis patients.

There is an increasing prevalence of patients who have both liver cirrhosis (LC) and severe valvular heart disease. This combination typically poses prohibitive risk for liver transplantation. LC related malnourishment, hypoalbuminemia and hyperdynamic circulation places patients with severe LC at higher rates for significant bleeding and/or thrombosis, as well as infectious and renal complications, after either surgical or transcatheter valvular interventions. Although there remains scarce comparative evidence, the preponderance of data suggest that percutaneous strategies are preferred over surgical ones. A multidisciplinary team is ideal for identifying those patients with LC who would benefit from transcatheter valvular heart interventions.

Management of Acute Coronary Syndrome in Patients with Liver Cirrhosis.

Liver cirrhosis (LC) is becoming increasingly common among patients presenting with acute coronary syndromes (ACS) and is associated with significant cardiovascular morbidity and mortality. Management of such patients is complicated by LC related complications. Literature is scarce on the safety of antithrombotic regimens and invasive strategies for ACS in patients with LC, especially those undergoing liver transplant evaluation. Recently there has been evidence that cirrhosis is an independent risk factor for adverse outcomes in ACS. As patients with LC are generally excluded from large randomized trials, definitive guidelines for the management of ACS in this particular cohort are lacking. Many antithrombotic drugs require either hepatic activation or clearance; hence, an accurate assessment of hepatic function is required prior to initiation and dose adjustment. Despite a demonstrated survival benefit of optimal medical therapy and invasive revascularization techniques in LC patients with ACS, both strategies are currently underutilized in this population. This review aims to present currently available data and provide a practical, clinically oriented approach for the management of ACS in LC. Randomized clinical trials in LC patients with ACS are the need of the hour to further refine their management for favorable outcomes.

The efficacy of endoscopic therapy for pancreas divisum: a meta-analysis.

BACKGROUND: The purpose of this study was to perform a meta-analysis assessing the efficacy and predictors of success of endoscopic therapy in the management of patients with pancreas divisum. METHODS: An electronic database search (PubMed and ScienceDirect) was performed for relevant studies. Studies were selected based on predefined criteria and data were extracted on patient population, follow up, endotherapy methods, success rates and complication rates. A random-effect model was used to pool the effect size across studies. Heterogeneity testing and publication bias assessment were performed. Multivariate regression analysis was performed to identify predictors of successful endoscopic therapy. RESULTS: Of 381 articles reviewed, 23 studies with 874 patients met the inclusion criteria. All were case series with suboptimal quality. Endoscopic therapy included minor papilla sphincterotomy, minor papilla sphincteroplasty and dorsal duct stenting. Mean follow-up duration was 37 months. The rate of "improvement" as defined by authors after endoscopic therapy varied significantly across studies, ranging from 31-96%: 589/874 patients were reported to have improved, corresponding to a pooled efficacy rate of 67.5% (95% confidence interval [CI] 0.610-0.734; P=0.0001). The pooled rate of pancreatitis after endoscopic retrograde cholangiopancreatography was 10.1% (95%CI 0.084-0.124; 2-sided P=0.0001). On subgroup analysis, patients with recurrent acute pancreatitis had better endoscopic outcomes (pooled efficacy rate 76%, 95%CI 0.712-0.803, P=0.0001). Dorsal duct stenting and longer follow up were the only parameters predictive of successful endotherapy. Significant heterogeneity was observed within and across studies. CONCLUSIONS: Endoscopic efficacy in pancreas divisum is estimated at 67.5%. Available studies are of poor quality with significant heterogeneity. Comparative studies with rigorous methodology are needed.

Liver Transplantation for the Treatment of Complicated Iatrogenic Biliary Injuries: A National Review from the UNOS Data Set.

BACKGROUND: Liver transplantation (LT) is rarely indicated in the management of iatrogenic bile duct injuries (IBDI), but occasionally, it becomes the only remaining therapy. The purpose of this study is to evaluate potential complications of IBDI and their impact on perioperative mortality, graft, and patient survival after LT. METHODS: The United Network for Organ Sharing database was queried for all LT performed in the United States between 1994 and 2014. Of the 101 238 liver transplants performed, 61 were related to IBDI. We performed a case matched analysis in a 5:1 ratio. RESULTS: The median age for patients with IBDI was 50.16 ± 11.7 years with a mean Model End-Stage Liver Disease score of 22.6 ± 9.8. Patients receiving LT for IBDI were more likely women (54.1%, P = 0.001), had lower incidence of hepatitis C virus infection (4.9%, P = 0.001) and longer cold ischemic time (P = 0.001). The mean body mass index was 25.5 ± 5.2 in patients transplanted for IBDI. IBDI was recognized as the strongest independent predictor associated with eightfold increased risk of early graft loss (P = 0.001; odds ratio, 8.4) and a 2.9-fold increased risk of 30-day mortality after LT in a case matched analysis (P = 0.03). CONCLUSIONS: IBDI is an uncommon but challenging indication for LT. These patients have significantly increased rates of early graft loss. IBDI is an independent factor related to increased risk of perioperative death after LT. Further studies are needed to determine the causes of perioperative complications and identify potential modifiable factors to improve outcomes in patients undergoing transplantation for IBDI.

Hepatic encephalopathy for the hospitalist.

The care of patients with advanced liver disease is often complicated by episodes of acute decline in alertness and cognition, termed hepatic encephalopathy (HE). Hospitalists must be familiar with HE, as it is a common reason for hospitalization in this population and is associated with significantly increased mortality. This narrative review addresses common issues related to diagnosis and classification, precipitants, inpatient management, and transitions of care for patients with HE. The initial presentation can be variable, and HE remains a clinical diagnosis. The spectrum of HE manifestations spans from mild, subclinical cognitive deficits to overt coma. The West Haven scoring system is the most widely used classification system for HE. Various metabolic insults may precipitate HE, and providers must specifically seek to rule out infection and bleeding in cirrhotic patients presenting with altered cognition. This is consistent with the 4-pronged approach of the American Association for the Study of Liver Disease practice guidelines. Patients with HE are typically treated primarily with nonabsorbable disaccharide laxatives, often with adjunctive rifaximin. The evidence for these agents is discussed, and available support for other treatment options is presented. Management issues relevant to general hospitalists include those related to acute pain management, decisional capacity, and HE following transjugular intrahepatic portosystemic shunt placement. These issues are examined individually. Successfully transitioning patients recovering from HE to outpatient care requires open communication with multiple role players including patients, caregivers, and outpatient providers. Journal of Hospital Medicine 2016;11:591-594. © 2016 Society of Hospital Medicine.

Tipping the Scales: Liver Transplant Outcomes of the Super Obese.

OBJECTIVE: We aim to study outcomes in liver transplant recipients with body mass index (BMI) ≥50 using the United Network for Organ Sharing (UNOS) database. METHODS: We reviewed patients undergoing liver transplantation recorded in the UNOS database from 1988 to 2013. Of 104,250 liver transplant procedures, 123 were performed on super obese patients. RESULTS: Sixty-four percent of the super obese patients are female (64 %) and had a mean age 47 years (20-71). The mean BMI was 53.5 (50-72.86) and 16 % had diabetes. The mean Model for End-Stage Disease (MELD) score at transplant was 29.1 (6-53). It was found that BMI ≥50 increased 1.6-fold the risk of death within 30 days after liver transplantation. Graft failure was increased by 52 % and overall mortality was by 62 %. A 1:1 propensity score-matched analysis demonstrated that patients with BMI <50 have significantly better graft and overall patient survival than the super obese. CONCLUSIONS: Overall, our data shows that BMI ≥50 is an independent predictor of perioperative mortality and graft and overall patient survival. Further studies are necessary to better understand predictors of outcomes in super obese patients.

Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: A meta-analysis.

BACKGROUND AND AIM: Fenofibrate is a potential novel therapy for primary biliary cirrhosis (PBC). We performed a systematic review and a meta-analysis of studies of fenofibrate in PBC. METHODS: Electronic database search was performed for relevant studies. A search of abstracts presented in the main scientific meetings in the field and articles in press was also performed. Random effect model was used to pool the effect size across studies for changes in alkaline phosphatase, GGT, bilirubin and IgM levels before and after treatment and the overall rate of complete response to fenofibrate therapy. RESULTS: Six studies with 102 patients met the inclusion criteria. All studies were case series and in all, patients who had no or incomplete response to UDCA had fenofibrate added at a dose of 100-200mg daily. Treatment duration ranged from 8-100weeks. Treatment with fenofibrate was associated with a significant decrease in alkaline phosphatase (-114IU/L, 95% CI: -152 to -76, P<0.0001); a significant decrease in GGT level (-92IU/L, 95% CI: -149 to -43; P=0.0004); significant decrease in total bilirubin (-0.11mg/dL, 95% CI: -0.18 to -0.08; P=0.0008); and a significant decrease in IgM level (-88mg/dL, 95% CI: -119 to -58; P<0.0001). The complete response rate was 69% (95% CI: 53-82%) with an odds ratio of 82.8 (95% CI: 21.6-317.2; P=0.024) while on fenofibrate. CONCLUSIONS: Fenofibrate at doses of 100-200mg daily appears to be effective adjunctive therapy in PBC patients who had no or incomplete response to UDCA. There is a critical need for larger scale randomized trials to determine its effect on liver-related morbidity and mortality (or progression towards end-stage disease).

Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active ulcerative colitis: a meta-analysis.

BACKGROUND: VSL#3 is a probiotic mix preparation reported to be effective in the treatment of mild to moderately active ulcerative colitis. We aimed to perform a systematic review of the literature and a meta-analysis of studies on its efficacy. METHODS: The searched databases included PubMed, Scopus, and ScienceDirect. The Mantel-Haenszel method was used to pool the effect- ize across studies, and the odds ratios (ORs) and 95% confidence intervals (CIs) of experiencing a specific outcome were calculated. RESULTS: Five studies with 441 patients were identified. The pooled remission rate was 49.4% (95% CI, 42.7-56.1). Only 3 low risk of bias studies with 319 patients met the inclusion criteria for further analysis. A total of 162 patients received 3.6 × 10 CFU/d VSL#3, and 157 patients received placebo. A total of 95% of patients received concomitant therapies with 5-ASA and/or immunomodulators. The Ulcerative Colitis Disease Activity Index was used to define response and remission. A >50% decrease in the Ulcerative Colitis Disease Activity Index was achieved in 44.6% of the VSL#3-treated patients versus 25.1% of the patients given placebo (P = 0008; OR, 2.793; 95% CI, 1.375-5.676; number needed to treat = 4-5). The response rate was 53.4% in VSL#3-treated patients versus 29.3% in patients given placebo (P < 0001; OR, 3.03; 95% CI, 1.89-4.83; number needed to treat = 3-4). The remission rate was 43.8% in VSL#3-treated patients versus 24.8% in patients given placebo (P = 0007; OR, 2.4; 95% CI, 1.48-3.88; number needed to treat = 4-5). No serious side effects were reported. CONCLUSIONS: VSL#3, when added to conventional therapy at a daily dose of 3.6 × 10 CFU/d, is safe and more effective than conventional therapy alone in achieving higher response and remission rates in mild to moderately active ulcerative colitis.

Hepatotoxicity Secondary to Chemotherapy.

The difficult problem faced by multiple generation of practicing physicians is determining the cause of abnormal liver function tests in cancer patients on chemotherapy. Hepatotoxicity from chemotherapy occurs frequently from an unpredictable or idiosyncratic reaction. Despite remarkable advances in our understanding of the mechanisms of action, pharmacodynamics, and interrelationships between the liver and chemotherapy, the underlying etiology of hepatic toxicity for various agents remains unexplained. Here, we present a concise review of the broad differential diagnosis for abnormal liver function tests (LFTs) in oncology patients.