Hepatitis E Virus Infection in the United States: Current Understanding of the Prevalence and Significance in the Liver Transplant Patient Population and Proposed Diagnostic and Treatment Strategies.

Hepatitis E virus (HEV), of the family Herpesviridae, is a virus that infects nearly 20 million people per year throughout the world. HEV is most commonly transmitted via the fecal-oral route and has long been described as a virus that afflicts only those in resource-poor countries. However, HEV has been detected in numerous animal carriers, various food sources, and even in human blood products in resource-rich regions of the world. HEV is of importance in the transplant patient population because of its ability to cause chronic viral infection in these patients can lead to graft loss and cirrhosis. In this review, we discuss the current knowledge of HEV as it pertains to the liver transplant patient population and discuss diagnosis and treatment of this infection.

Atrial fibrillation is highly prevalent yet undertreated in patients with biopsy-proven nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular disease. Atrial fibrillation is a prominent risk marker for underlying cardiovascular disease with a prevalence of 2% in patients <65 years old. Atrial fibrillation prevalence in NASH is unknown. We sought to assess the prevalence and impact of atrial fibrillation on healthcare utilization in NASH. METHODS: Patients were identified from a tertiary care centre Electronic Database from 2002 to 2015. International Classification of Diseases 9 (ICD9) codes identified comorbidities and atrial fibrillation. Descriptive statistics were used to compare characteristics between patients with NASH with and without atrial fibrillation. RESULTS: Of 9108 patients with ICD9 diagnosis of NASH, 215 (2.3%, mean age 57 years, 32% male) had biopsy-proven NASH. Atrial fibrillation prevalence was 4.6%. Patients with NASH and atrial fibrillation had a higher prevalence of heart failure (54.5% vs 8.8%, P < 0.001) and cerebrovascular (27.3% vs 2.0%, P < 0.001) or vascular disease (54.5% vs 13.2%, P = 0.002), compared to NASH without atrial fibrillation. All patients with NASH and atrial fibrillation had a CHA2DS2VASc score ≥2 indicating high stroke risk and need for anticoagulation. Eight of 10 patients were eligible for anticoagulation and 5 of 8 (62.5%) received appropriate therapy. CONCLUSION: Atrial fibrillation prevalence is two-fold higher in patients with NASH compared to the general population. Patients with NASH have a high risk of stroke; however, many do not receive appropriate guideline-directed therapy. Future studies are needed to identify whether guideline-based management of atrial fibrillation in NASH reduces cardiovascular morbidity and mortality.

A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score.

Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). CONCLUSION: The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979).

Clinical Features and Outcomes of Complementary and Alternative Medicine Induced Acute Liver Failure and Injury.

OBJECTIVES: The increasing use of complementary and alternative medicines (CAMs) has been associated with a rising incidence of CAM-induced drug-induced liver injury (DILI). The aim of this study was to examine the clinical features and outcomes among patients with acute liver failure (ALF) and acute liver injury (ALI) enrolled in the Acute Liver Failure Study Group database, comparing CAM-induced with prescription medicine (PM)-induced DILI. METHODS: A total of 2,626 hospitalized patients with ALF/ALI of any etiology were prospectively enrolled between 1998 and 2015 from 32 academic transplant centers. Only those with CAM or PM-induced ALI/ALF were selected for analysis. RESULTS: A total of 253 (9.6%) subjects were found to have idiosyncratic DILI, of which 41 (16.3%) were from CAM and 210 (83.7%) were due to PM. The fraction of DILI-ALF/ALI cases due to CAM increased from 1998-2007 to 2007-2015 (12.4 vs. 21.1%, P=0.047). There was no difference in the type of liver injury-hepatocellular, cholestatic, or mixed-between groups as determined by R score (P=0.26). PM-induced DILI showed higher serum alkaline phosphatase levels compared with the CAM group (median IU/L, 171 vs. 125, P=0.003). The CAM population had fewer comorbid conditions (1.0 vs. 2.0, P<0.005), higher transplantation rates (56 vs. 32%, P<0.005), and a lower ALF-specific 21-day transplant-free survival (17 vs. 34%, P=0.044). CONCLUSIONS: CAM-induced DILI is at least as severe in presentation as that observed due to PM with higher rates of transplantation and lower transplant-free survival in those who progress to ALF. This study highlights the increasing incidence of CAM-induced liver injury and emphasizes the importance of early referral and evaluation for liver transplantation when CAM-induced liver injury is suspected.

The utility of pulmonary function testing in predicting outcomes following liver transplantation.

Although pulmonary function tests (PFTs) are routinely performed in patients during the evaluation period before liver transplantation (LT), their utility in predicting post-LT mortality and morbidity outcomes is not known. The aim of this study was to determine the impact of obstructive and/or restrictive lung disease on post-LT outcomes. We conducted a retrospective analysis of patients who had pre-LT PFTs and underwent a subsequent LT (2007-2013). We used statistical analyses to determine independent associations between PFT parameters and outcomes (graft/patient survival, time on ventilator, and hospital/intensive care unit [ICU] length of stay [LOS]). A total of 415 LT recipients with available PFT data were included: 65% of patients had normal PFTs; 8% had obstructive lung disease; and 27% had restrictive lung disease. There was no difference in patient and graft survival between patients with normal, obstructive, and restrictive lung disease. However, restrictive lung disease was associated with longer post-LT time on ventilator and both ICU and hospital LOS (P < 0.05). More specific PFT parameters (diffusing capacity of the lungs for carbon monoxide, total lung capacity, and residual volume) were all significant predictors of ventilator time and both ICU and hospital LOS (P < 0.05). Although pre-LT PFT parameters may not predict post-LT mortality, restrictive abnormalities correlate with prolonged post-LT ventilation and LOS. Efforts to identify and minimize the impact of restrictive abnormalities on PFTs might improve such outcomes. Liver Transplantation 22 805-811 2016 AASLD.

A Clinical Decision Rule Based on the AST-to-Platelet Ratio Index Improves Adherence to Published Guidelines on the Management of Acute Variceal Bleeding.

BACKGROUND: Optimal management of acute upper gastrointestinal bleeding (UGIB) depends on identifying a variceal versus nonvariceal etiology. An objective measure predicting etiology could guide early management pending endoscopy. The AST-to-platelet ratio index (APRI) score has been studied as a marker of cirrhosis and portal hypertension, but has not been evaluated in the setting of acute UGIB. METHODS: In this single-center retrospective cohort study, we reviewed endoscopy reports and other data for patients with acute UGIB, and classified episodes as variceal bleeds or other. We assessed the diagnostic utility of the APRI score relative to other objective measures by Area Under the Receiver Operating Characteristic (AUROC) curve analysis. We constructed a clinical decision rule based on the APRI score, and assessed how it would have changed management. RESULTS: The APRI score performed well in predicting a variceal etiology of acute UGIB, with AUROC 0.89. We developed a clinical decision rule using an APRI score of 0.4 to guide early management of acute UGIB patients. Retroactively applying this to our cohort, adherence to published guidelines for administration of octreotide and antibiotics would have increased from 56% to 91%. CONCLUSIONS: The APRI score is an objective metric that helps predict a variceal etiology of acute UGIB. Using our proposed decision rule could improve adherence to guidelines on management of acute variceal bleeding. Although we were unable to demonstrate a survival benefit, improved adherence to evidence-based guidelines serves as a metric related to this most important outcome measure. Prospective study to validate these findings is indicated.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

Assessment of mental health in patients with chronic liver disease.

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Palliative care experience and perceived gaps in training among transplant hepatology fellows: A national survey.

Despite the likely benefits of palliative care (PC) for patients with cirrhosis, physician experiences and perspectives about best practices are variable. We aimed to assess PC experience and gaps in training among transplant hepatology fellows. We conducted a national survey of all transplant hepatology fellows enrolled in accredited fellowship programs during the 2020-2021 academic year. We assessed the frequency of PC provision and comfort with physical and psychological symptom management, psychosocial care, communication skills, advance care planning, and end-of-life care. A total of 45 of 56 (79%) of transplant hepatology fellows responded to the survey; 50% (n = 22) were female. Most trained at centers performing over 100 transplants per year (67%, n = 29) distributed evenly across geographic regions. Most fellows (69%, n = 31) had a PC or hospice care rotation during residency, and 42% (n = 19) of fellows received education in PC during transplant hepatology fellowship. Fellows reported feeling moderately to very comfortable with communication skills such as breaking bad news (93%, n = 41) and leading family meetings (75%, n = 33), but nearly one-third (30%, n = 13) reported feeling not very or not at all comfortable assessing and managing anxiety and depression (30%, n = 13) and spiritual distress (34%, n = 15). Nearly one-quarter (22%, n = 10) had never discussed or documented advance care plans during fellowship. Fellows wished to receive future instruction on the assessment and management of physical symptoms (68%, n = 30) and anxiety and depression (64%, n = 28). Conclusion: Our survey highlights gaps in PC experience and education during transplant hepatology fellowship, lack of comfort in managing psychological distress and advance care planning, and desire to improve skills, particularly in symptom management. Future studies should investigate how to enhance transplant hepatology competencies in these PC domains and whether this impacts clinical care, advance care planning, or patient experience.

Top Ten Tips Palliative Care Clinicians Should Know About End-Stage Liver Disease.

End-stage liver disease (ESLD) is an increasingly prevalent condition with high morbidity and mortality, especially for those ineligible for liver transplantation. Patients with ESLD, along with their family caregivers, have significant needs related to their quality of life, and there is increasing attention being paid to integration of palliative care (PC) principles into routine care throughout the disease spectrum. To provide upstream care for these patients and their family caregivers, it is essential for PC providers to understand their complex psychosocial and physical needs and to be aware of the unique challenges around medical decision making and end-of-life care for this patient population. This article, written by a team of liver and PC experts, shares 10 high-yield tips to help PC clinicians provide better care for patients with advanced liver disease.

Physical activity as a treatment of non-alcoholic fatty liver disease: A systematic review.

AIM: To review the effectiveness of exercise as a therapy for nonalcoholic fatty liver disease (NAFLD) and potential benefits in treating insulin resistance and atherosclerosis. METHODS: Medline (EBSCOhost) and PubMed were searched for English-language randomized controlled trials and prospective cohort studies in human adults aged ≥ 18 which investigated the various effects of exercise alone, a combination of exercise and diet, or exercise and diet coupled with behavioral modification on NAFLD from 2010 to Feburary 2015. RESULTS: Eighteen of 2298 available studies were chosen for critical review, which included 6925 patients. Nine (50%) studies were randomized controlled trials. Five (27.8%) studies utilized biopsy to examine the effects of physical activity on hepatic histology. The most commonly employed imaging modality to determine change in hepatic steatosis was hydrogen-magnetic resonance spectroscopy. Only two studies examined the effects of low impact physical activity for patients with significant mobility limitations and one compared the efficacy of aerobic and resistance exercise. No studies examined the exact duration of exercise required for hepatic and metabolic improvement in NAFLD. CONCLUSION: While exercise improved hepatic steatosis and underlying metabolic abnormalities in NAFLD, more studies are needed to define the most beneficial form and duration of exercise treatment.

SlimQuick™-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation.

Green tea extract is a popular ingredient in herbal weight loss supplements. There have been reports of hepatotoxicity associated with the use of dietary supplements, some of these cases lead to fatal outcomes. To our knowledge, we report the first case of fulminant hepatic failure requiring orthotopic liver transplantation caused by SlimQuick™ (Wellnx Life Sciences, Wilmington, DE), a widely available weight loss supplement containing green tea extract.