Citations

Background and Aims Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post‐transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine‐topiramate, naltrexone‐bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). Approach and Results While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine‐topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. Conclusions The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co‐morbidities, and concomitant medications.

Abstract Background Obesity is commonly observed in patients with cirrhosis, especially with the increasing prevalence of non-alcoholic steatohepatitis (NASH). Bariatric surgery has been avoided in these patients given concerns about increased perioperative risk; therefore, data are lacking regarding long-term outcomes. In this study, we aimed to evaluate the long-term outcomes of patients with cirrhosis who underwent bariatric surgery. Methods We reviewed the charts of adult patients with compensated cirrhosis who underwent bariatric surgery after they were prospectively enrolled between February 23, 2009 and November 9, 2011, and followed in a pilot study for evaluation of bariatric surgery outcomes. Only patients with more than 4 years of follow-up were included in the analysis. Data regarding their liver disease, metabolic status, and survival were collected. A descriptive analysis was performed. Results The cohort consisted of 10 patients, of whom 7 were females. The median post-surgical follow-up was 8.7 years (± 1.4 years). All patients had biopsy-proven NASH; two patients had concurrent, untreated hepatitis C infection. During the observation period, there was a mean weight loss of 24 kg (19.2% of total body weight pre surgery, P < 0.001) and only one patient regained weight to the baseline pre-surgical measurement. One patient who was not eligible for transplant developed hepatic encephalopathy 3 years after surgery and later died. The remainder of the patients did not have any hepatic decompensation, cardiovascular event, or mortality. Except for one patient with Gilbert syndrome, bilirubin was normal in all patients at last follow-up. Conclusions Bariatric surgery in patients with compensated cirrhosis can lead to sustained weight loss and stable hepatic function on long-term follow-up.

Background. The role of MZ phenotype of α 1 antitrypsin (α1AT) deficiency as a potential cofactor in advanced liver disease arising from other primary causes is not widely understood. In the general population, MZ phenotype accounts for 2%–4% in Europe and 2%–7.1% in North America. The aim of this study was to determine the prevalence of the MZ phenotype among various causes of cirrhosis in the United States in the modern era and its impact on pulmonary function before and after liver transplantation. Methods. This retrospective study included adult patients with cirrhosis who underwent liver transplantation at Mayo Clinic. Participants’ data including pathogenesis of cirrhosis, model for end-stage liver disease-Na score, α1AT phenotype, liver decompensation events, and pulmonary outcomes was determined by retrospective review of the liver transplantation database. Results. One hundred thirty of 1341 adult patients with cirrhosis (9.7%) were α1AT MZ carriers. When comparing the distribution of protease inhibitor (PI) MZ among different pathogenesis, the prevalence of MZ was significantly increased in nonalcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), and cryptogenic cirrhosis compared with other causes. Thirty-seven of 171 with NASH (22%), 37 of 187 with ALD (20%), and 9 of 39 with cryptogenic cirrhosis (23.1%) were identified as PI MZ, while in other subgroups; we detected 18 of 320 with viral hepatitis, and 11 of 339 with primary biliary cholangitis/primary sclerosing cholangitis. Also, MZ patients were more likely to develop preoperative chronic obstructive lung disease, and postoperative pulmonary hypertension and pulmonary embolism than MM patients. Conclusions. The rates of preoperative and postoperative pulmonary complications were found to be higher in PI MZ patients than in PI MM patients. The MZ phenotype was significantly enriched in NASH, ALD, and cryptogenic cirrhosis.

Background and Aims Alcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as biomarkers for many diseases and are also implicated in the pathogenesis of AH. Therefore, we investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects. Approach and Results EVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end‐stage liver disease (ESLD) attributed to cholestatic liver diseases and nonalcoholic steatohepatitis, decompensated alcohol‐associated cirrhosis (AC), and AH. Sphingolipids were quantified by tandem mass spectroscopy. The median plasma EV concentration was significantly higher in AH subjects (5.38 × 1011/mL) compared to healthy controls (4.38 × 1010/mL; P < 0.0001), heavy drinkers (1.28 × 1011/mL; P < 0.0001), ESLD (5.35 × 1010/mL; P < 0.0001), and decompensated AC (9.2 × 1010/mL; P < 0.0001) disease controls. Among AH subjects, EV concentration correlated with Model for End‐Stage Liver Disease score. When EV counts were dichotomized at the median, survival probability for AH subjects at 90 days was 63.0% in the high‐EV group and 90.0% in the low‐EV group (log‐rank P value = 0.015). Interestingly, EV sphingolipid cargo was significantly enriched in AH when compared to healthy controls, heavy drinkers, ESLD, and decompensated AC (P = 0.0001). Multiple sphingolipids demonstrated good diagnostic and prognostic performance as biomarkers for AH. Conclusions Circulating EV concentration and sphingolipid cargo signature can be used in the diagnosis and differentiation of AH from heavy drinkers, decompensated AC, and other etiologies of ESLD and predict 90‐day survival permitting dynamic risk profiling.

Machine learning (ML) utilizes artificial intelligence to generate predictive models efficiently and more effectively than conventional methods through detection of hidden patterns within large data sets. With this in mind, there are several areas within hepatology where these methods can be applied. In this review, we examine the literature pertaining to machine learning in hepatology and liver transplant medicine. We provide an overview of the strengths and limitations of ML tools and their potential applications to both clinical and molecular data in hepatology. ML has been applied to various types of data in liver disease research, including clinical, demographic, molecular, radiological, and pathological data. We anticipate that use of ML tools to generate predictive algorithms will change the face of clinical practice in hepatology and transplantation. This review will provide readers with the opportunity to learn about the ML tools available and potential applications to questions of interest in hepatology.