Updates in Endoscopic Bariatric and Metabolic Therapies.

The rising prevalence of obesity, and related morbidity and mortality, has necessitated the development of therapeutic weight loss strategies. Lifestyle modifications alone have only yielded modest benefit, and while bariatric surgery has shown significant short- and long-term results, only a minority of eligible patients end up receiving this treatment. Endoscopic bariatric and metabolic therapies (EBMTs) are a rapidly evolving field, which provides a less invasive middle ground treatment option for weight loss. Here we discuss the efficacy, as well as short- and long-term outcomes with restrictive, malabsorptive/metabolic and aspiration endoscopic techniques, and their effects on metabolic parameters.

Association between sustained virological response and clinical outcomes in patients with hepatitis C infection and hepatocellular carcinoma.

BACKGROUND: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC. METHODS: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts. RESULTS: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12). CONCLUSIONS: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment.

Primary care and referring physician perspectives on non-alcoholic fatty liver disease management: a nationwide survey.

INTRODUCTION: The optimal approach to screening and risk stratification for non-alcoholic fatty liver disease is challenging given disease burden and variable progression. The aim of this study was to assess primary care physician and referring physician practice patterns regarding non-alcoholic fatty liver disease. METHODS: An anonymous nationwide survey was administered to primary care physicians, endocrinologists, and cardiologists in a: (1) tertiary academic hospital, (2) community hospital, and (3) the American College of Physicians Insider Panel. Survey domains assessed non-alcoholic fatty liver disease knowledge, recommendations for screening, risk stratification, treatment, and referral patterns. RESULTS: A total of 440 providers completed the survey (35.2% completion rate; N = 82 academic hospital, N = 21 community hospital, N = 337 American College of Physicians). Half were male (51.7%), 78% from internal medicine, with 5% subspecialists. Providers were knowledgeable regarding prevalence and risk factors for non-alcoholic fatty liver disease. 58% would support screening for non-alcoholic fatty liver disease and used liver enzymes to do so. Only 22.5% used serum biomarkers and 23% used transient elastography for risk stratification. Primary reason for referral was advanced fibrosis/cirrhosis. 80% reported barriers to treating non-alcoholic fatty liver disease. There was no consistent diet recommended. CONCLUSION: In this nationwide survey, we demonstrated that while overall disease knowledge was good, there was an important disconnect between current guidelines and real-world clinical practice. There is also significant heterogeneity in practice patterns for first-line therapy of non-alcoholic fatty liver disease and the majority of provider's report barriers to treating non-alcoholic fatty liver disease. These findings highlight the potential role for reevaluating screening and risk stratification recommendations in primary care to better align with needs in that setting.

Marijuana use among adult liver transplant candidates and recipients.

BACKGROUND: Data regarding marijuana (MJ) use among liver transplant (LT) candidates are limited. We set out to determine the incidence and pre- and post-LT outcomes of adult LT candidates with a self-reported history of MJ use. METHODS: Baseline clinical characteristics, waitlist, and post-LT outcomes of adult LT candidates from January 2010 to March 2017 were compared. RESULTS: Among 2690 LT candidates, 630(23%) and 298(11%) reported a history of MJ use and use within the past 12 months, respectively. Although the proportion of MJ users increased over time(ß = .76, p = .03), the proportion listed and transplanted did not change. Listing for LT increased with male (OR 1.24, 95% CI 11.01-1.52), MELD score (OR 1.08, 95% CI 1.01-1.15), HCC (OR 1.83, 95% CI 1.39-2.41) but decreased among MJ users (OR 0.67, 95% CI 0.50-0.91, p = .01). The median time to listing was longer among MJ users compared to non-users (115 vs. 87 days, p < .0005). Post-LT survival was similar in 83 MJ users and 306 non-users. CONCLUSION: The proportion of MJ users among LT candidates is increasing. MJ users have a greater burden of psychosocial issues which may contribute to longer evaluations and lower rate of LT listing. Post-LT survival was not impacted by self-reported MJ use history.

Allopurinol hepatotoxicity is associated with human leukocyte antigen Class I alleles.

BACKGROUND/AIMS: Allopurinol can cause HLA class I-associated life-threatening severe skin reactions. However, HLA risk and association with clinical features in allopurinol hepatotoxicity are unknown. METHODS: Eleven of 17 patients with suspected allopurinol hepatotoxicity enrolled into the Drug-Induced Liver Injury Network were adjudicated as definite, highly likely, or probable. High-resolution HLA sequencing was undertaken in cases and compared with population and other DILI controls. RESULT: Median age was 60 years, 54% were male, and 63% African- American, 27% Caucasian, and 9% Hispanic. Patients presented at a median of 52 days after starting allopurinol, all were hospitalized and six were jaundiced. The median peak ALT, alkaline phosphatase, and total bilirubin were 525 U/L, 521 U/L, and 7.8 mg/dl, respectively, with a median R ratio of 2.7 at onset. During follow-up, nine patients were treated with corticosteroids including five of the six with suspected DRESS. Three patients died including two from liver failure at 38 and 45 days after onset, and the remaining eight recovered. Three HLA alleles were found to be overrepresented in allopurinol cases, particularly in African Americans: HLA-B*58:01, which has been previously linked to severe skin reactions, and HLA-B*53:01 and HLA-A*34:02, all of which are more frequently found in African Americans than European Americans or Latinos. CONCLUSIONS: Allopurinol hepatotoxicity is associated with systemic hypersensitivity, a short latency to onset, African-American race and three HLA risk alleles, HLA-B*58:01, HLA-B*53:01, and HLA-A*34:02-58:01 testing may help confirm a diagnosis of hepatotoxicity in allopurinol-treated patients.

Gender Disparities in Patients With Alcoholic Liver Disease Evaluated for Liver Transplantation.

BACKGROUND: The morbidity and mortality from alcohol-related liver disease (ALD) is increasing in the United States. However, little is known about gender differences in evaluation and listing for liver transplantation (LT) in patients with ALD. METHODS: This is a retrospective review of adult patients with ALD evaluated for LT at a single transplant center from January 1, 2010, to March 1, 2017. Univariate, multivariate, and time-series analyses were performed. RESULTS: Among the 949 patients with ALD evaluated, mean age was 53 years, 84% were Caucasian, and 33% were women. The median model for end-stage liver disease score was similar between the genders. Women were less likely to be listed for LT (10% versus 19%; P < 0.05). The proportion of women not listed due to active substance use was significantly higher versus men (42% versus 35%; P < 0.05), while the frequency of medical contraindications was comparable between the genders. During a median follow-up of 416 days (range: 0-2784), listed women with ALD were less likely to undergo transplantation (42% versus 47%; P < 0.05). CONCLUSIONS: Men with ALD were 95% more likely to be listed and 105% more likely to be transplanted compared to women with ALD. While men had more lifetime substance use and related consequences, women had more psychiatric comorbidities and were less likely to be listed due to active alcohol and opioid use. Early detection and effective treatment of psychiatric and substance use disorders in women with ALD may improve their transplant eligibility.

Incidence and Risks for Nonalcoholic Fatty Liver Disease and Steatohepatitis Post-liver Transplant: Systematic Review and Meta-analysis.

BACKGROUND: The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post-liver transplant (LT) remain poorly characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT. METHODS: MEDLINE via PubMed, Embase, Scopus, and CINAHL were searched for studies from 2000 to 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale. RESULTS: Seventeen studies representing 2378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of 2 studies that used imaging for outcome assessment. Seven studies evaluated occurrence of recurrent NAFLD/NASH, 3 evaluated de novo occurrence, and 7 evaluated both recurrent and de novo. In studies at generally high or moderate risk of bias, mean 1-, 3-, and ≥5-year incidence rates may be 59%, 57%, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; 53%, 57.4%, and 38% for recurrent NASH; and 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT body mass index (summarized odds ratio = 1.27) and hyperlipidemia were the most consistent predictors of outcomes. CONCLUSIONS: There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, whereas de novo NASH occurs rarely. NAFLD/NASH after LT is associated with metabolic risk factors.

Metronidazole-Induced Pancreatitis: Is There Underrecognition? A Case Report and Systematic Review of the Literature.

INTRODUCTION: Acute pancreatitis (AP) is the most common cause of gastroenterological hospitalization in the USA, with a mortality ranging from 5 to 20%. Up to 80% of cases are caused by cholelithiasis and alcohol abuse. Less common etiologies that need to be explored include hypertriglyceridemia, trauma, ERCP, infections, and drugs. A number of medications are known to cause acute pancreatitis, with 0.3-1.4% of all cases of pancreatitis being drug induced (DIP). Here, we present a case of metronidazole-induced acute pancreatitis. CASE SUMMARY: A 60-year-old female presented with constant severe epigastric pain associated with nausea, vomiting, and anorexia for one day. She had no past medical history of alcohol use or hypertriglyceridemia and was s/p cholecystectomy in the distant past. Symptoms had begun three days after starting metronidazole for Clostridium difficile colitis. Lipase was > 396, and CT abdomen revealed peripancreatic fat stranding. She was diagnosed with AP, metronidazole was suspected to be responsible and hence stopped, and supportive management initiated. Her symptoms improved rapidly, and pancreatic enzymes normalized within 2 days. Of note, she had had an episode of acute pancreatitis 3 years ago, also following metronidazole use, with resolution at discontinuation of the drug. She had concurrently been on omeprazole during both episodes. DISCUSSION: Metronidazole is a commonly used antibiotic and is infrequently reported as a cause of DIP. Our review suggests the possibility of a dose-response and duration-response effect between metronidazole use and occurrence of pancreatitis. The most common presenting symptom and sign was moderate to severe epigastric pain and tenderness, accompanied by nausea/vomiting. Symptoms usually start within 2-7 days of starting the medication and usually resolve 2-5 days after discontinuation of therapy and pancreatitis treatment. The most common causative dose was 1-1.5 g/day. Our review also supports findings by Norgaard et al. suggesting that concurrent use of omeprazole potentiates the risk of metronidazole-induced pancreatitis. CONCLUSION: Metronidazole is a commonly used antibiotic that may cause metronidazole-induced pancreatitis, especially if patients are concurrently taking PPIs. Awareness needs to be raised amongst clinicians regarding this association, in order to correctly identify etiology of pancreatitis and discontinue metronidazole promptly when suspected as the causative factor.

Impact of a Prohibitive Versus Restrictive Tobacco Policy on Liver Transplant Candidate Outcomes.

Tobacco use has been associated with poorer outcomes after liver transplantation (LT). Our study examined the effect on LT listing outcomes of a newly implemented policy prohibiting the use of all tobacco products compared with a prior restrictive policy. Medical records of consecutive adult patients evaluated for LT from January 2010 to July 2013 (era 1, n = 1344) and August 2013 to March 2017 (era 2, n = 1350) were reviewed. The proportion of LT candidates listed was the primary outcome. The mean age of the 2694 LT candidates was 54 ± 11 years, 60% were male, and the mean Model for End-Stage Liver Disease (MELD) score was 15 ± 7. Although the proportion of LT candidates who were smokers was significantly higher in era 2 (33% versus 23%; P < 0.005), the proportion of smokers listed for LT remained stable (13% versus 17%; P = 0.25). However, there were more smokers excluded for ongoing tobacco use in era 2 compared with era 1 (9.6% versus 4.4%; P = 0.001). Factors independently associated with LT listing included a diagnosis of hepatocellular carcinoma, being married, private insurance, absence of psychiatry comorbidity, and absence of tobacco, marijuana, or opiate use but evaluation during era 2 was not associated with LT listing. However, the median time to listing significantly increased over time, especially in smokers (from 65 to 122 days; P = 0.001), and this trend was independently associated with evaluation during era 2, a lower MELD score, not having children, and a lower level of education (P < 0.05). In conclusion, despite an increasing incidence of active smokers being referred for LT evaluation, the proportion of smoker candidates listed for LT was unchanged after instituting our prohibitive tobacco use policy. However, the time to get on the waiting list for smokers who were eventually listed was significantly longer due to the need to achieve complete tobacco cessation.

Evaluation of Dietary Approaches for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review.

Lifestyle interventions, namely optimizing nutrition and increasing physical activity, remain the cornerstone of therapy for non-alcoholic fatty liver disease (NAFLD), as this can lead to the significant improvement or resolution of disease. The optimal nutritional approach to treat NAFLD remains unclear. The aim of this systematic review is to evaluate the effectiveness of different nutritional patterns on hepatic, metabolic, and weight-loss endpoints. MEDLINE via PubMed, Embase, Scopus, and Google Scholar were searched. Randomized trials of dietary interventions alone for adults with NAFLD were selected. Two authors independently reviewed articles, to select eligible studies, and performed data abstraction. Six studies, representing 317 patients, were included. The participants had a median age of 46, mean body mass index (BMI) 31.5 and were 64.3% male. The mean study duration was 16.33 ± 8.62 weeks. Reduction in hepatic steatosis (HS) was statistically significant in 3/5 Mediterranean Diet (MD), one low-carbohydrate, one intermittent fasting (IF) and 1/2 low fat (LF) diet interventions. A total of 3/5 studies using MD, 1/2 LF interventions, and the one IF intervention demonstrated significant reductions in weight. In conclusion, there appears to be most data in support of MD-based interventions, though further randomized trials are needed to assess comparative effectiveness for NAFLD.

Tackling HCV-3 in Asia: Breakthroughs for Efficient and Cost-effective Treatment Strategies.

Hepatitis C virus (HCV) is known to cause chronic hepatitis C, and its sequelae of cirrhosis and hepatocellular carcinoma. Hepatitis C genotype 3 (HCV-3) in particular is notorious for causing accelerated liver fibrosis, cardiovascular, and metabolic effects, thus increasing morbidity and mortality. It is the commonest variant in Asian countries like India and Pakistan. It is also one of the hardest-to-treat genotypes, especially among treatment-experienced and cirrhotic patients. Due to limited health care affordability and accessibility in these areas, many patients remain untreated. Until recently, the established therapy for HCV had been a combination of pegylated interferon + ribavirin. However, it was only effective in about half of patients and had severe adverse effects; hence a more efficacious option needed to be found. Recent advances have led to the development of sofosbuvir, an NS5B inhibitor that is fast becoming the standard of care, in combination with other novel drugs. It was initially marketed at $1,000 per pill, a cost that was too high for most. Thus, it has not been utilized as a global therapy as yet. Formulation of effective interferon-free regimens is a huge milestone, and awareness needs to be raised regarding these new highly effective options in both the physician and the patient population. This article discusses the newest drugs and combinations that have been developed in the fight against HCV-3, as a treatment outline for HCV-3-dominant areas. It also highlights recent breakthroughs in cost reductions of these drugs and the effort to make them globally accessible. HOW TO CITE THIS ARTICLE: Saeed N, Gurakar A. Tackling HCV-3 in Asia: Breakthroughs for Efficient and Cost-effective Treatment Strategies. Euroasian J Hepato-Gastroenterol 2016;6(1):35-42.