Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis.

IMPORTANCE: No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH). OBJECTIVE: To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis. DESIGN, SETTING, AND PARTICIPANTS: In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021. EXPOSURES: Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care. MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework. RESULTS: A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2). CONCLUSIONS AND RELEVANCE: Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.

Impact of sleeve gastrectomy and Roux-en-Y gastric bypass on biopsy-proven non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome. Our aim was to study the long-term effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on NAFLD/NASH. METHODS: Between 2008 and 2015, 3813 patients had an intraoperative liver biopsy performed at the time of primary RYGB and SG at a single academic center. Utilizing strict inclusion criteria, 487 patients with biopsy-proven NAFLD who had abnormal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values (≥ 40 IU/L) at baseline were identified. Matching of SG to RYGB patients (1:4) was performed via logistic regression and propensity scores adjusting for clinical and liver histological characteristics. Changes in liver function tests (LFTs) at least 1 year after surgery were compared to baseline values and between the surgical groups. RESULTS: A total of 310 (weighted) patients (SG n = 62, and RYGB n = 248) with a median follow-up time of 4 years (range, 1-10) were included in the analysis. The distribution of covariates was well-balanced after propensity matching. In 84% of patients, LFT values normalized after bariatric surgery at the last follow-up time. The proportions of patients having normalized LFT values did not differ significantly between the SG and RYGB groups (82% vs. 84%, p = 0.66). The AST decreased from (SG: 49.1 ± 21.5 vs. RYGB: 49.3 ± 22.0, p = 0.93) at baseline to (SG: 28.0 ± 16.5 vs. RYGB: 26.5 ± 15.5, p = 0.33) at the last follow-up. Similarly, a significant reduction in ALT values from (SG: 61.7 ± 30.0 vs. RYGB 59.4 ± 24.9, p = 0.75) at baseline to (SG: 27.2 ± 21.5 vs. RYGB: 26.1 ± 19.2, p = 0.52) at the last follow-up was observed. CONCLUSIONS: In patients with biopsy-proven NAFLD/NASH, abnormal LFTs are normalized in most SG and RYGB patients by the end of the first postoperative year and remain normal until the last follow-up. This study also suggests that both bariatric procedures are similarly effective in improving liver function.

Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

GOALS: This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. BACKGROUND: The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). STUDY: We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. RESULTS: A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. CONCLUSIONS: Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

Sofosbuvir-based treatment is safe and effective in patients with chronic hepatitis C infection and end stage renal disease: a case series.

BACKGROUND & AIMS: Interferon and ribavirin-free regimens to treat chronic hepatitis C virus (HCV) infection in patients with end stage renal disease are not approved and represent an area of unmet clinical need. We report our experience on the safety and efficacy of sofosbuvir/simeprevir and sofosbuvir/ledipasvir therapy in patients on haemodialysis. METHODS: Patients with chronic HCV infection on haemodialysis were included in this study. Patients were started on either sofosbuvir/simeprevir or sofosbuvir/ledipasvir. Routine clinical and laboratory data were collected at baseline and during treatment. The primary outcome was sustained virological response at week 12 (SVR12). RESULTS: Eight patients with mean age 56.8 ± 20 years were included in this study. Seven were treatment naïve and one was a priori null responder to interferon-based therapy. Four patients were started on sofosbuvir/simeprevir and four on sofosbuvir/ledipasvir for 12 weeks. Therapy was well tolerated overall with nausea/vomiting, pruritus, headache and a 2 g/dl drop in haemoglobin developing in one patient each. No patient discontinued therapy because of side effects. Comparison of labs at baseline and nadir levels during treatment revealed no significant change in haemoglobin (10.8 ± 2.4 g/dl vs 10.3 ± 1.6 g/dl), platelet count (198 ± 164 k/µl vs 184.5 ± 162/µl) and bilirubin (0.3 ± 0.4 mg/dl vs 0.25 ± 0.15 mg/dl). Eight of eight patients had undetectable HCV RNA at the end of treatment. One patient was lost to follow up and the remaining seven achieved SVR12. CONCLUSION: Full dose sofosbuvir/simeprevir or sofosbuvir/ledipasvir therapy for HCV-infected patients with end stage renal disease was well tolerated with no discontinuation owing to side effects and no significant adverse events.

A guide to diagnosing and managing ascites in cirrhosis.

Combined serum and ascites fluid measurements point to the cause of ascites. For patients with modest edema, a reduced weight-loss target with diuresis may be acceptable.

Work up of fatty liver by primary care physicians, review.

Nonalcoholic fatty liver disease (NAFLD) is an overarching term that refers to abnormal deposition of lipids in the liver and is used to describe the spectrum of disease ranging from hepatic steatosis to nonalcoholic steatohepatitis to cirrhosis. NAFLD is the most common cause of chronic liver disease and the second most common cause of cirrhosis. Although the pathophysiology is not completely understood, there is a strong link between NAFLD and metabolic syndrome. This review focuses on the workup of NAFLD in the primary care setting, from differential diagnoses to assessing fibrosis via predictive models that use commonly used laboratory values, biomarkers, and imaging. The purpose of this review article is to provide a set of screening and diagnostic tools for all primary care physicians in order to better manage patients with NAFLD.

Role of platelet-albumin-bilirubin score in predicting re-bleeding after band ligation for acute variceal hemorrhage.

Platelet-albumin-bilirubin (PALBI) score was proposed by Roayaie et al with modification of previously studied albumin-bilirubin score to include platelet as an indicator of portal hypertension in 2015. Predictive value of this score was recently tested by Elshaarawy et al for re-bleeding in patients presenting with acute variceal hemorrhage. We did a similar study at our center (n = 170) to look at incidence of re-bleeding after band ligation defined as drop in 2 units of hemoglobin and witnessed melena or hematemesis within 2 wk of the procedure. We calculated PALBI scores for all patients based on lab values prior to the procedure. Of 25.3% had re-bleeding episodes, area under receiver operating characteristic curve for PALBI as predictor of re-bleeding was 0.601 (95% confidence interval: 0.502-0.699). PALBI score showed moderate accuracy at predicting re-bleeding in our population.

Hospital readmission following transjugular intrahepatic portosystemic shunt: a 14-year single-center experience.

BACKGROUND: Placement of a transjugular intrahepatic portosystemic shunt (TIPS) is a relatively common procedure used to treat complications of portal hypertension. However, only limited data exist regarding the hospital-readmission rate after TIPS placement and no studies have addressed the causes of hospital readmission. We therefore sought to identify the 30-day hospital-readmission rate after TIPS placement at our institution and to determine potential causes and predictors of readmission. METHODS: We reviewed our electronic medical-records system at our institution between 2004 and 2017 to identify patients who had undergone primary TIPS placement with polytetrafluoroethylene-covered stents and to determine the 30-day readmission rate among these patients. A series of univariable logistic-regression models were fit to assess potential predictors of 30-day readmission. RESULTS: A total of 566 patients were included in the analysis. The 30-day readmission rate after TIPS placement was 36%. The most common causes for readmission were confusion (48%), infection (15%), bleeding (11%), and fluid overload (7%). A higher Model for End-Stage Liver Disease (MELD) score corresponded with a higher rate of readmission (odds ratio associated with each 1-unit increase in MELD score: 1.06; 95% confidence interval: 1.02-1.09; P = 0.001). Other potential predictors, including indication for TIPS placement, were not significantly associated with a higher readmission rate. CONCLUSIONS: The 30-day readmission rate after TIPS placement with covered stents is high, with nearly half of these readmissions due to hepatic encephalopathy-a known complication of TIPS placement. Novel interventions to help reduce the TIPS readmission rate should be prioritized in future research.

Successful liver transplantation for acute sickle cell intrahepatic cholestasis: A case report and review of the literature.

BACKGROUND: Sickle cell hepatopathy (SCH) is an inclusive term referring to any liver dysfunction among patients with sickle cell disease. Acute sickle cell intrahepatic cholestasis is one of the rarest and most fatal presentations of SCH. We present the 23rd reported case of liver transplantation (LT) for SCH; a rare case of acute sickle cell intrahepatic cholestasis managed with LT from a hepatitis C virus (HCV) nucleic acid amplification test positive donor. CASE SUMMARY: A 29-year-old male with a past medical history of sickle cell disease presented with vaso-occlusive pain crisis. On examination, he had jaundice and a soft, non-tender abdomen. Initially he was alert and fully oriented; within 24 h he developed new-onset confusion. Laboratory evaluation was notable for hyperbilirubinemia, leukocytosis, anemia, thrombocytopenia, acute kidney injury and elevated international normalized ratio (INR). Imaging by ultrasound and computed tomography scan suggested a cirrhotic liver morphology with no evidence of biliary ductal dilatation. The patient was diagnosed with acute sickle cell intrahepatic cholestasis after excluding competing etiologies of acute liver injury. He underwent LT from an HCV nucleic acid amplification test positive donor 9 d after initial presentation. The liver explant was notable for widespread sinusoidal dilatation with innumerable clusters of sickled red blood cells and cholestasis. On postoperative day 3, HCV RNA was detectable in the patient's peripheral blood and anti-HCV therapy with glecaprevir/pibrentasvir was initiated on postoperative day 23. He subsequently achieved sustained virologic response after completing 3 mo of therapy and has been followed clinically for 12 mo post-transplant. CONCLUSION: This case highlights the utility of LT as a viable treatment option for acute sickle cell intrahepatic cholestasis.

Current management of Barrett esophagus and esophageal adenocarcinoma.

Barrett esophagus is found in 5% to 15% of patients with gastroesophageal reflux disease and is a precursor of esophageal adenocarcinoma, yet the condition often goes undiagnosed. Patients with reflux disease who are male, over age 50, or white, and who smoke or have central obesity or a family history of Barrett esophagus or esophageal adenocarcinoma, should undergo initial screening endoscopy and, if no dysplasia is noted, surveillance endoscopy every 3 to 5 years. Dysplasia is treated with endoscopic eradication by ablation, resection, or both. Chemoprotective agents are being studied to prevent progression to dysplasia in Barrett esophagus. The authors discuss current recommendations for screening and management.

Assessing liver fibrosis without biopsy in patients with HCV or NAFLD.

Staging of liver fibrosis is increasingly done using noninvasive methods, in some cases obviating the need for liver biopsy. Scores based on laboratory values and demographic variables have been developed and validated for assessing fibrosis in patients with hepatitis C virus (HCV) infection and nonalcoholic fatty liver disease (NAFLD), as have several imaging methods that measure shear-wave velocity, a reflection of fibrosis severity.

Endoscopic therapy for Barrett's esophagus and early esophageal cancer: Where do we go from here?

Since Barrett's esophagus is a precancerous condition, efforts have been made for its eradication by various ablative techniques. Initially, laser ablation was attempted in non-dysplastic Barrett's esophagus and subsequently, endoscopic ablation using photodynamic therapy was used in Barrett's patients with high-grade dysplasia who were poor surgical candidates. Since then, various ablative therapies have been developed with radiofrequency ablation having the best quality of evidence. Resection of dysplastic areas only without complete removal of entire Barrett's segment is associated with high risk of developing metachronous neoplasia. Hence, the current standard of management for Barrett's esophagus includes endoscopic mucosal resection of visible abnormalities followed by ablation to eradicate remaining Barrett's epithelium. Although endoscopic therapy cannot address regional lymph node metastases, such nodal involvement is present in only 1% to 2% of patients with intramucosal adenocarcinoma in Barrett esophagus and therefore is useful in intramucosal cancers. Post ablation surveillance is recommended as recurrence of intestinal metaplasia and dysplasia have been reported. This review includes a discussion of the technique, efficacy and complication rate of currently available ablation techniques such as radiofrequency ablation, cryotherapy, argon plasma coagulation and photodynamic therapy as well as endoscopic mucosal resection. A brief discussion of the emerging technique, endoscopic submucosal dissection is also included.

Patients with clinically metabolically healthy obesity are not necessarily healthy subclinically: further support for bariatric surgery in patients without metabolic disease?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized. OBJECTIVES: To determine the prevalence and characteristics of NAFLD in individuals with metabolically healthy obesity. SETTING: A tertiary, academic, referral hospital. METHODS: All patients who underwent bariatric surgery with intraoperative liver biopsy from 2008 to 2015 were identified. Patients with preoperative hypertension, dyslipidemia, or prediabetes/diabetes were excluded to identify a cohort of metabolically healthy obesity patients. Liver biopsy reports were reviewed to determine the prevalence of NAFLD. RESULTS: A total of 270 patients (7.0% of the total bariatric surgery patients) met the strict inclusion criteria for metabolically healthy obesity. The average age was 38 ± 10 years and the average body mass index was 47 ± 7 kg/m2. Abnormal alanine aminotransferase (>45 U/L) and asparate aminotransferase levels (>40 U/L) were observed in 28 (10.4%) and 18 (6.7%) patients, respectively. A total of 96 (35.5%) patients had NAFLD with NALFD Activity Scores 0 to 2 (n = 61), 3 to 4 (n = 25), and 5 to 8 (n = 10). A total of 62 (23%) patients had lobular inflammation, 23 (8.5%) had hepatocyte ballooning, 22 (8.2%) had steatohepatitis, and 12 (4.4%) had liver fibrosis. CONCLUSION: Even with the use of strict criteria to eliminate all patients with any metabolic problems, a significant proportion of metabolically healthy patients had unsuspected NAFLD. The need and clinical utility of routine screening of obese patients for fatty liver disease and the role of bariatric surgery in the management of NAFLD warrants further investigation.

A guide to managing acute liver failure.

Nearly 2,000 cases of acute liver failure occur each year in the United States. This disease carries a high mortality rate, and early recognition and transfer to a tertiary medical care center with transplant facilities is critical. This article reviews the definition, epidemiology, etiology, and management of acute liver failure.

Celiac disease: Managing a multisystem disorder.

Celiac disease is a multisystem autoimmune disorder that can cause symptoms involving the gastrointestinal tract and other organ systems such as the skin and bones. This paper reviews the pathogenesis, diagnosis, and management of celiac disease and associated diseases.

Impact of De Novo and Preexisting Inflammatory Bowel Disease on the Outcome of Orthotopic Liver Transplantation.

BACKGROUND: Diarrhea is a common problem in the setting of solid-organ transplantation, especially orthotopic liver transplant (OLT). De novo or preexisting inflammatory bowel disease (IBD) is one of the differential diagnoses. The aims of our study were to evaluate the frequency of de novo IBD in patients with OLT and to assess the impact of de novo IBD and preexisting IBD on the outcome of OLT. METHODS: This case-control study included all eligible patients who had OLT from January 2001 to December 2009. The study group included all patients who had a biopsy-proven diagnosis of IBD after their OLT (the de novo IBD group). The control groups included patients with existing IBD before OLT and those without IBD before and after OLT. The groups were matched based on their underlying diagnoses of end-stage liver disease. Univariate and multivariate analyses were performed. RESULTS: A total of 66 subjects were included in the study. The mean age was 45.4 ± 13.4 years, with 44 (66.7%) being male. Fifteen patients (23%) had de novo IBD, 21 (32%) had existing IBD before OLT, and 30 (45%) had no underlying IBD before or after OLT. There were no significant differences between the 2 IBD groups in any of the IBD characteristics, including IBD medications. Subjects without IBD were more likely to receive mycophenolate mofetil within 1 week of OLT than those in the de novo or preexisting IBD (70% versus 23% P = 0.018). Episodes of graft rejection were more commonly observed in subjects with preexisting IBD (52%) than de novo IBD (27%) or no IBD (20%) (P = 0.045). The rate of retransplantation was highest in the de novo IBD group followed by the preexisting IBD group and non-IBD group (20% versus 14% versus 0%; P = 0.029). Combined together, patients with IBD in the setting of OLT were more likely to be retransplanted than those without IBD (16.7% versus 0%, P = 0.045). In multivariate analysis, we found that patients with IBD were 6.7 (95% confidence interval, 1.9-23.9) times more likely to have an adverse outcome after liver transplant (P = 0.004), after adjusting for primary sclerosing cholangitis. CONCLUSIONS: De novo IBD can occur in patients after OLT. De novo IBD and preexisting IBD were found to be associated with a higher risk for graft failure, suggesting that early diagnosis and closer monitoring of the patients at risk are critical.

Bilirubin in coronary artery disease: Cytotoxic or protective?

Bilirubin has traditionally been considered a cytotoxic waste product. However, recent studies have shown bilirubin to have anti-oxidant, anti-inflammatory, vasodilatory, anti-apoptotic and anti-proliferative functions. These properties potentially confer bilirubin a new role of protection especially in coronary artery disease (CAD), which is a low grade inflammatory process exacerbated by oxidative stress. In fact, recent literature reports an inverse relationship between serum concentration of bilirubin and the presence of CAD. In this article, we review the current literature exploring the association between levels of bilirubin and risk of CAD. We conclude that current evidence is inconclusive regarding the protective effect of bilirubin on CAD. A causal relationship between low serum bilirubin level and increased risk of CAD is not currently established.