Hypercholesterolemia After COVID-19: Time to Include Lipoprotein X Among the Differential Diagnoses.

Background: Lipoprotein X (LpX) is an abnormal lipoprotein composed of phospholipids, free cholesterol, and albumin. Its overaccumulation is an infrequent cause of hyperlipidemia, which oftentimes presents in patients with cholestatic liver disease. The aim is to present the first 2 cases of patients with post-COVID cholangiopathy and LpX overaccumulation. Case Report: We present 2 female patients (ie, a 34-year-old [patient 1] and a 56-year-old [patient 2]), who had complicated courses of COVID-19, requiring prolonged mechanical ventilation (>4 weeks). One month after discharge, patient 1 presented with abdominal pain. Patient 2 had gangrenous cholecystitis and later developed recurrent elevation of alkaline phosphatase and bilirubin. Both patients were diagnosed with cholestatic liver disease. During outpatient follow-up both patients were found to have elevated plasma low-density lipoprotein cholesterol (LDL-C) in routine lipid panels (723 mg/dL and 1389 mg/dL, respectively). Both patients underwent various treatments for elevated LDL-C before referral to endocrinology. Patients were diagnosed with LpX overaccumulation from post-COVID-19 cholangiopathy. In both patients, LDL-C fluctuations seen in routine lipid panels (affected by LpX levels) were tightly correlated with changes in alkaline phosphate and bilirubin. Discussion: Our patients represent the first report of LpX overaccumulation in patients with post-COVID-19 cholangiopathy. Whether LpX accumulation is only the result of liver dysfunction, or COVID-19 infection plays a direct role in elevated LpX levels is still unknown. Conclusion: In patients with complicated courses of COVID-19, LpX overaccumulation should be considered when a routine lipid panel shows significant LDL-C elevations. Awareness among health care providers regarding LpX is important to avoid unnecessary workup and treatment.

Bedside Live-View Capsule Endoscopy in Evaluation of Overt Obscure Gastrointestinal Bleeding: A Pilot Point-of-Care Study.

BACKGROUND: Capsule endoscopy (CE) is an emerging tool in the diagnosis and management of occult bleeding and overt obscure gastrointestinal bleeding (OOGIB). Maximizing the efficiency of CE can lead to rapid bleeding localization and shorter time to therapy. We investigated whether a trained registered nurse (RN) can accurately interpret bleeding by observing the CE findings in real time by measuring inter-observer agreement between RN and physician interpretation. METHODS: We conducted a prospective study of patients admitted for OOGIB who underwent live-view capsule endoscopy (LVCE) between December 2016 and November 2017. A matched control group who underwent standard CE was obtained through retrospective review. An RN received a 2-day training program for CE interpretation. RN bedside interpretation for bleeding was followed by interpretation by 2 gastrointestinal physicians blinded to LVCE findings. Outcomes were compared between groups using t-tests and χ2 tests. Cohen's kappa measured the agreement between the physicians and the RN. RESULTS: Ten subjects were in the LVCE group, and 12 subjects were in the standard-of-care group. The agreement between the physicians and the RN was 9/10 (90%), with a kappa of 0.73 (95% CI: 0.26-1.00; p = 0.016). Patients in the LVCE group had shorter duration to physician interpretation (0.6 vs. 0.7 days [p = 0.50]), shorter duration to endoscopy (1.8 days vs. 3 days [p = 0.240]), and shorter length of stay (8.1 vs. 11.4 days [p = 0.26]) compared to the standard-of-care group. CONCLUSION: This study utilizing an RN for LVCE interpretation found inter-observer agreement between RN and physician findings. Larger studies are needed to assess whether this RN-physician team approach can translate to improved outcomes.

Perioperative Transjugular Intrahepatic Portosystemic Shunt Is Associated With Decreased Postoperative Complications in Decompensated Cirrhotics Undergoing Abdominal Surgery.

BACKGROUND: Operative risk in patients with cirrhosis is related to the severity of liver disease and nature of procedure. Pre and postoperative portal decompression via transjugular intrahepatic portosystemic shunt (TIPS) are logical approaches to facilitate surgery and improve postoperative outcomes. We compared postoperative outcomes of decompensated cirrhotics undergoing abdominal surgery either with or without perioperative TIPS placement. METHODS: We performed a retrospective review of 41 decompensated cirrhotic patients who had abdominal surgery from 2010-2019 at the University of Alabama at Birmingham. Patients were stratified based on having received either perioperative TIPS or no TIPS. Demographics, laboratory data, perioperative TIPS status and postoperative complications were compared between the 2 groups using Fisher exact test and Student 2 sample t-test. RESULTS: Group 1 consisted of 28 patients who had TIPS procedure, with 21 being preoperative and 7 being postoperative. Group 2 had 13 patients who had abdominal surgery without TIPS. When compared to those with perioperative TIPS, patients without TIPS had a significantly increased incidence of postoperative ascites (33% vs 77%, P = .0026), infection (18% vs 54%, P = .028), and acute kidney injury (AKI) (14% vs 46%, P = .0485). Additionally, postoperative Model of End Stage Liver Disease Sodium score was significantly higher in patients without TIPS (22 ± 4.74) when compared to those who had TIPS (17.14 ± 5.48) (P = .009). DISCUSSION: Perioperative TIPS placement in decompensated cirrhotics was associated with decreased postoperative ascites, infection, and AKI when compared to those without TIPS. Further studies are needed to validate our findings.

Vedolizumab Therapy in Refractory Microscopic Colitis: A Single Center Case Series.

Microscopic colitis (MC) is a disease characterized by chronic watery diarrhea secondary to colonic inflammation. Endoscopically, the mucosa is usually normal but biopsies show characteristic histologic findings.1.

Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and affects approximately one third of adults in the United States. The disease is becoming a global epidemic as a result of the rising rates of obesity and metabolic disease. Emerging data suggest weight loss of ≥10% overall body weight is beneficial in resolving steatosis and reversing fibrosis. Prospective trials comparing various diets are limited by lack of sufficient power as well as pre- and post-treatment histopathology, and therefore no specific diet is recommended at this time. In this narrative review we examine the pathophysiology behind specific macronutrient components that can either promote or reverse NAFLD to help inform more specific dietary recommendations. Overall, the data supports reducing saturated fat, refined carbohydrates, and red and processed meats in the diet, and increasing the consumption of plant-based foods. Diets that incorporate these recommendations include plant-based diets such as the Dietary Approaches to Stop Hypertension, Mediterranean, vegetarian, and vegan diets.

Model for End-Stage Liver Disease Score Predicts Development of First Episode of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis.

OBJECTIVE: To examine whether baseline model for end-stage liver disease (MELD) score in patients with cirrhosis and ascites predicts the future development of first spontaneous bacterial peritonitis (SBP) episode. METHODS: A retrospective case-control study was performed at three academic centers to select patients admitted with first SBP episode (cases) and those with ascites admitted for decompensation without SBP (controls). Medical records from these centers were reviewed between January 1, 2008, and December 31, 2013. Cases and controls were matched (1:2) for age, sex, and race. Conditional logistic recession models were built to determine whether baseline MELD score (within a month before hospitalization) predicts first SBP episode. RESULTS: Of 697 patients (308, 230, and 159 from centers A, B, and C, respectively), cases and controls were matched in 94%, 89%, and 100% at three respective centers. In the pooled sample, probability of SBP was 11%, 31%, 71%, and 93% at baseline MELD scores less than or equal to 10, from 11 to 20, from 21 to 30, and greater than 30, respectively. Compared with MELD score less than or equal to 10, patients with MELD scores from 11 to 20, 21 to 30, and greater than 30 had six- (3- to 11-), 29- (12- to 69-), and 115- (22- to 598-) folds (95% CI) risk of SBP, respectively. Based on different MELD score cutoff points, MELD score greater than 17 was most accurate in predicting SBP occurrence. Analyzing 315 patients (152 cases) with available data on ascitic fluid protein level controlling for age, sex, and center, MELD score but not ascitic fluid protein associated with first SBP episode with respective odds ratios of 1.20 (1.14 to 1.26) and 0.88 (0.70 to 1.11). CONCLUSION: Baseline MELD score predicts first SBP episode in patients with cirrhosis and ascites.

Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review.

Hepatocellular carcinoma (HCC) is a leading cause of liver-related death worldwide. Hepatitis C virus (HCV) infection is a major cause of advanced hepatic fibrosis and cirrhosis, with significantly increased risk for development of HCC. The morbidity and mortality of HCV-related HCC remains high, as rates of HCV cirrhosis continue to increase. The long-term goal of antiviral therapy for chronic HCV is to reduce complications from cirrhosis, including HCC. The advent of new direct-acting antivirals with high rates of virological clearance has revolutionized cure of HCV infection. While the development of HCC in HCV patients who achieve disease sustained virologic response is reduced, these patients remain at risk for HCC, particularly those patients with advanced fibrosis and cirrhosis. This review outlines the epidemiology of HCC in chronic HCV, various mechanisms, risk factors and pathophysiology that contribute to this disease process, screening recommendations, and the available data on the impact of new direct-acting antiviral treatment on the development on HCC.

Biomarkers of Renal Injury in Cirrhosis: Association with Acute Kidney Injury and Recovery after Liver Transplantation.

BACKGROUND: To define urine or serum biomarkers in predicting renal function recovery after liver transplantation (LT). METHODS: Adults listed for LT (February 2011-July 2014) and with modified diet for renal disease-6 (MDRD-6) <60 mL/min provided urine/blood samples at baseline and serially until LT for biomarkers in serum (pg/mL) and urine (pg/mg creatinine). RESULTS: Of 271 LT listed patients (mean age 57 years, 63% males, median listing MELD 17.5), 1 year acute kidney injury (AKI) probability was 49%, with odds of 1.3-, 3.0-, 4.6-, and 8.5-fold times for listing MELD 16-20, 21-25, 26-30, and >30, compared to MELD <16. Thirty-seven people died over 1 year from the time of listing, with twofold increased odds with AKI. Among 67 patients with MDRD <60, only urinary epidermal growth factor was different comparing AKI (increase in serum creatinine ≥0.3 mg/dL from baseline within past 3 months) vs. no AKI (2,254 vs. 4,253, p = 0.003). Differences between acute tubular necrosis (ATN) and hepatorenal syndrome could not be ascertained for a small sample of 3 patients with ATN. Analyzing 15 of 43 receiving LT and MDRD-6 <30 prior to LT, biomarkers were not different comparing 5 patients recovering renal function (MDRD-6 >50 mL/min) at 6 months vs. 10 without recovery. CONCLUSIONS: AKI is common among LT listed patients, with a negative impact on transplant-free survival. Serum and urine biomarkers are not associated with the recovery of renal function after LT. Multicenter studies are suggested to (a) develop strategies to reduce the development of AKI and (b) derive novel biomarkers for use in accurately predicting renal recovery after LT.

Text messaging approach improves weight loss in patients with nonalcoholic fatty liver disease: A randomized study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease. The only effective treatment is 7%-10% weight loss. Mobile technology is increasingly used in weight management. This study was performed to evaluate the effects of text messaging intervention on weight loss in patients with NAFLD. METHODS: Thirty well-defined NAFLD patients (mean age 52 years, 67% females, mean BMI 38) were randomized 1:1 to control group: counselling on healthy diet and exercise, or intervention group: text messages in addition to healthy life style counselling. NAFLD text messaging program sent weekly messages for 22 weeks on healthy life style education. Primary outcome was change in weight. Secondary outcomes were changes in liver enzymes and lipid profile. RESULTS: Intervention group lost an average of 6.9 lbs. (P = .03) compared to gain of 1.8 lbs. in the control group (P = .45). Intervention group also showed a decrease in ALT level (-12.5 IU/L, P = .035) and improvement in serum triglycerides (-28 mg/dL, P = .048). There were no changes in the control group on serum ALT level (-6.1 IU/L, P = .46) and on serum triglycerides (-20.3 mg/dL P = .27). Using one-way analysis of variance, change in outcomes in intervention group compared to control group was significant for weight (P = .02) and BMI (P = .02). CONCLUSIONS: Text messaging on healthy life style is associated with reduction in weight in NAFLD patients. Larger studies are suggested to examine benefits on liver histology, and assess long-term impact of this approach in patients with NAFLD.

Ammonia level at admission predicts in-hospital mortality for patients with alcoholic hepatitis.

OBJECTIVE: Alcoholic hepatitis (AH), a unique clinical syndrome among patients with chronic and active alcohol use, is associated with high short-term mortality. An elevated ammonia level is associated with mortality in patients with acute liver failure; however, its impact in AH has not been well-studied. METHODS: A retrospective study was performed on patients admitted to a tertiary-care hospital with the discharge diagnosis of AH. Patients meeting criteria for AH were included in the final data analysis. Multivariate logistic regression models were built to examine the impact of serum ammonia in predicting in-hospital mortality (IHM) and 30-day mortality (TDM). Subgroup analysis was also performed, which was limited to patients who had hepatic encephalopathy. RESULTS: Of the 105 AH patients included, 26 (25%) died during the initial hospitalization. Among the 79 patients who survived initial hospitalization, 30 (39%) died within 30 days. Information about ammonia levels at admission was available for 82 patients. Of these, 25 patients had IHM and significantly higher ammonia level (97 vs. 69 µmol/L, P < 0.01). Among the 57 who survived hospitalization, ammonia levels were not significantly different (71 vs. 67 µmol/L, P = 0.69) in patients with and without TDM. The addition of ammonia to the multivariate regression models including age, sex, cirrhosis, treatment and model for end-stage liver disease (MELD) score improved the C statistics for IHM from 0.708 to 0.801 and for TDM from 0.756 to 0.766, respectively. These results were identical, even when limited to patients with hepatic encephalopathy. CONCLUSION: AH patients with elevated ammonia levels at admission have higher IHM; however, they do not seem to play a significant role in 30-day mortality for patients who survived hospitalization.

Use of automated irrigation pumps improves quality of bowel preparation for colonoscopy.

AIM: To evaluate the effectiveness of automated irrigation pumps (AIPs) in improving the quality of the bowel preparation and the yield of colonoscopy. METHODS: A retrospective observational study was conducted at a single medical center. Outpatient colonoscopies performed during a 4-mo time period when AIPs were not in use, were compared to colonoscopies performed during control period. The main outcomes measured were quality of bowel preparation, procedures aborted due to poor preparation, recommendations to repeat at short interval due to sub-optimal bowel preparation and adenoma detection rates. RESULTS: One thousand and thirty-seven colonoscopies were included. A higher proportion of cases did not achieve a satisfactory bowel preparation when AIPs were not used (24.4% vs 10.3%, P < 0.01). The number of procedures aborted due to inadequate preparation was not significantly different, however a repeat procedure at a short interval was recommended in a higher proportion of cases when AIPs were not used (21.3% vs 6.9%, P < 0.01). Good or excellent preparation was 2.91 (95%CI: 2.04-4.15) times more likely when AIPs were used. Detection of polyps and adenomas was not significantly different. CONCLUSION: AIP use during colonoscopy results in a higher proportion of colonic preparation rated as satisfactory, although polyp detection rate is not significantly affected. Recommendations for repeat colonoscopy at shorter interval significantly decrease with the use of AIPs. This study supports the use of the irrigation pumps in endoscopy units to improve the quality of colonoscopy.

Autoimmune Markers Do Not Impact Clinical Presentation or Natural History of Steatohepatitis-Related Liver Disease.

BACKGROUND AND AIM: Autoimmune (AI) markers are reported in patients with steatohepatitis-related liver disease. However, their clinical significance is unclear. METHODS: Charts of patients due to alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD) were stratified for antinuclear antigen (ANA > 1:80), antismooth muscle antibody (ASMA > 1:40), or antimitochondrial antibody (AMA > 1:20). Study outcomes were patient survival and complications of liver disease. RESULTS: Of 607 patients (401 NAFLD), information about AI markers was available for 398 (mean age 50 ± 15 year; 52% males; median body mass index (BMI) 38; 44% diabetic; 62% nonalcoholic steatohepatitis (NASH) as type of steatohepatitis; median MELD score 9). A total of 78 (19.6%) patients were positive for AI markers without differences for ALD versus NAFLD, cirrhosis versus no cirrhosis, and NASH versus no NASH. There were no differences for age, gender, BMI, cirrhosis at presentation, MELD score, endoscopic findings, and histology based on AI markers. Serum ALT was higher among patients with AI markers (65 ± 46 vs. 59 ± 66 IU/l; P = 0.048). Data remained unchanged on analyzing NAFLD patients. None of the 11 ANA-positive patients (1:640 in 4) showed findings of AI hepatitis. Biopsy in three AMA-positive patients showed mild bile duct damage in one patient. On median follow-up of about 3 years, there were no differences in liver disease outcomes (ascites, encephalopathy, variceal bleeding), hepatocellular carcinoma, transplantation, and survival. CONCLUSIONS: Autoimmune markers are frequently present in steatohepatitis-related liver disease patients. Their presence is an epiphenomenon without histological changes of autoimmune hepatitis. Further, their presence does not impact clinical presentation and follow-up outcomes.

Regorafenib: an evidence-based review of its potential in patients with advanced liver cancer.

Hepatocellular carcinoma (HCC) is the second-most common cause of cancer-related death in the world. In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options. Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC. Over the last 5 years, several other medications have been tested in Phase III trials. However, they have not shown any added benefit over sorafenib. Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models. After its safety and pharmacological properties was studied in Phase I trials, a Phase II study evaluating the role of Regorafenib in patients with advanced HCC who progressed on sorafenib therapy demonstrated efficacy and a manageable safety profile. A Phase III trial is ongoing, and its result will help us better evaluate the role of Regorafenib in patients with advanced HCC.