Infliximab-induced autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an inflammatory disorder of the liver with a wide spectrum of disease presentation, from asymptomatic elevations in liver-associated enzymes to acute liver failure. AIH is classically associated with elevated immunoglobulins and autoantibodies, although approximately 20% of patients with features of AIH lack circulating antibodies. Recently, tumour necrosis factor alpha inhibitors have been implicated in several cases of drug-induced AIH which impact treatment regimens for patients with inflammatory bowel disease (IBD). We present a case of infliximab-induced seronegative AIH responding to budesonide therapy with successful alteration of IBD treatment regimen to vedolizumab.

Occult HBV Infection: A Case Series at a Military Treatment Facility.

Occult HBV infection (OBI) is defined as the presence of detectable hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg) negative individuals. Rarely, OBI is attributed to mutant HBV that cannot be detected by commercial assays, but most cases occur in the setting of chronic hepatitis B, particularly infection with wild-type viruses associated with strong HBV suppression. OBI is a high-risk diagnosis as it is associated with multiple complications: HBV reactivation in immunocompromised states, transmission of HBV, progression of liver disease, and hepatocellular carcinoma. The diagnosis is also easy to overlook, as the negative HBsAg in such cases can be falsely reassuring. This case series describes four male patients (mean age 51) who were diagnosed with OBI in the same military treatment facility between February 2018 and October 2018. Two of the four patients were active duty service members at the time of diagnosis. These patients had variable clinical presentations and outcomes. This case series illustrates the clinical significance of OBI and the importance of screening for OBI in HBsAg negative patients with signs of chronic or severe hepatic inflammation. It also prompts an intriguing question regarding the prevalence of both HBV and OBI in the United States military and whether or not routine screening for HBV should be implemented in this population. Further study is warranted to determine if adding HBV core antibody to a universally employed screening regimen would be beneficial.

Memantine-Induced Liver Injury With Probable Causality as Assessed Using the Roussel Uclaf Causality Assessment Method (RUCAM).

Presentations of drug-induced liver injury (DILI) are highly variable. Although biochemical evidence of cholestasis is common, the extent of aminotransferase elevations and patterns of liver injury vary. Patients may be asymptomatic, and many cases may never be diagnosed. We describe a case of memantine-induced hepatotoxicity in an elderly patient with Alzheimer's dementia, with probable causality for drug-induced liver injury, as assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) score.

Jaundice in a Service member Returning From Taiwan; Diagnostic Challenges in a Case of Acute Hepatitis E.

When the evaluation of newly elevated liver enzymes is unrevealing, a common diagnosis of exclusion is drug-induced liver injury. A 39-year-old active duty service member who presented with jaundice after returning from a mission in Thailand was found to have an acute hepatitis and developing acute liver failure. He was ultimately diagnosed with acute hepatitis E, but his diagnosis was initially confounded by multiple exposures to supplements known to cause drug-induced liver injury. This case illustrates the importance of broadened serologic testing in patients with acute liver injury returning from countries endemic with hepatitis E and also highlights the challenges in diagnosis of acute hepatitis E with currently available testing.

Nonalcoholic Steatohepatitis and Endpoints in Clinical Trials.

Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development. The complex molecular mechanisms leading to NASH and the long duration of time to develop complications of disease are challenges to developing meaningful clinical endpoints. Because of these challenges, surrogate endpoints that are linked to all-cause mortality, liver-related death, and complications of cirrhosis are much more likely to be beneficial in the majority of patients.

Hepatitis C eradication with sofosbuvir leads to significant metabolic changes.

AIM: To assess the effect of sofosbuvir (SOF) based regimens on glycemic and lipid control. METHODS: This is a retrospective analysis of hepatitis C virus (HCV)-infected patients treated and cured with a SOF regimen [SOF/ribavirin/interferon, SOF/simeprevir, or SOF/ledipasvir (LDV) ± ribavirin] from January 2014 to March 2015. Patients with hemoglobin A1C (HbA1C) and lipid panels within six months before and six months after therapy were identified and included in our study. Due to the known hemolytic effect of ribavirin, HbA1C was obtained a minimum of three months post-treatment for the patients treated with a ribavirin regimen. Medical history, demographics, HCV genotype, pre-therapy RNA, and liver biopsies were included in our analysis. The patients who started a new medication or had an adjustment of baseline medical management for hyperlipidemia or diabetes mellitus (DM) were excluded from our analysis. RESULTS: Two hundred and thirty-four patients were reviewed, of which 60 patients met inclusion criteria. Sixty-three point three percent were male, 26.7% were Caucasian, 41.7% were African American and 91.7% were infected with hepatitis C genotype 1. Mean age was 60.6 ± 6.7 years. Thirty-nine patients had HbA1C checked before and after treatment, of which 22 had the diagnosis of DM type 2. HbA1C significantly decreased with treatment of HCV (pretreatment 6.66% ± 0.95% vs post-treatment 6.14% ± 0.65%, P < 0.005). Those treated with SOF/LDV had a lower HbA1C response than those treated with other regimens (0.26% ± 0.53% vs 0.71% ± 0.83%, P = 0.070). Fifty-two patients had pre- and post-treatment lipid panels; there was a significant increase in low-density lipoprotein (LDL) and total cholesterol (TC) after treatment (LDL: 99.5 ± 28.9 mg/dL vs 128.3 ± 34.9 mg/dL, P < 0.001; TC: 171.6 ± 32.5 mg/dL vs 199.7 ± 40.0 mg/dL, P < 0.001). Pre-treatment body-mass index (BMI) did not differ from post-treatment BMI (P = 0.684). CONCLUSION: Eradication of HCV with a SOF regimen resulted in a significant drop in HbA1C and an increase in LDL and TC post therapy.

Randomized, controlled pilot study comparing large-volume paracentesis using wall suction and traditional glass vacuum bottle methods.

OBJECTIVES: Large-volume paracentesis (LVP) can be time and labor intensive depending on the amount of ascites removed and the method of drainage. Wall suction has been adopted as the preferred method of drainage at many centers, though the safety and benefits of this technique have not been formally evaluated. The primary objective of this study was to define the cost and time savings of wall suction over the traditional glass vacuum bottle method for ascites drainage. The secondary objective was to compare the safety profile and patient satisfaction using these two techniques. METHODS: We conducted a randomized, controlled pilot study of the wall suction versus vacuum bottle methods for LVP in hospitalized patients. All LVPs were performed under ultrasound guidance by a single proceduralist. Patients with at least 4 liters removed received 25% intravenous albumin, 8 g/liter fluid removed. Demographic, clinical characteristics, and procedure details were recorded. Laboratory and hemodynamic data were recorded for 24 h prior to and 24-48 h post LVP. An electronic chart review was conducted to evaluate procedure-related complications. Data were compared using Fisher's exact test, t test, or Mann-Whitney U test. RESULTS: Thirty-four patients were randomized to wall suction at 200 mmHg (n = 17) or glass vacuum bottle drainage (n = 17). Wall suction was significantly faster and less costly than vacuum bottle drainage (7 versus 15 min, p = 0.002; $4.59 versus $12.73, p < 0.001). There were no differences in outcomes at 24 and 48 h post LVP, or at 60-day follow up. CONCLUSION: Performing LVP using wall suction resulted in significantly shorter procedure time and supply cost savings. There were no differences in outcomes between the groups, suggesting equivalent safety, though larger studies powered to detect small differences are needed. Given its efficiency, convenience, and cost effectiveness, wall suction may be a superior method of ascites drainage for LVP.

Review of treatment options for nonalcoholic fatty liver disease.

Although the future of NAFLD and NASH treatment has many promising agents, clinicians are currently faced with limited options with an emphasis on lifestyle modification. Figs. 1 and 2 summarize current practices for the diagnosis and treatment of NAFLD with the understanding that each patient's treatment must be customized to their comorbidities, exercise tolerance, and willingness to comply with therapy.

Nutrition in cirrhosis and chronic liver disease.

Nutrition has not been a primary focus of many medical conditions despite its importance in the development and the severity of these diseases. This is certainly the case with nutrition and end-stage liver disease despite the well-established association of nutritional deficiencies and increased rates of complications and mortality in cirrhosis. This review provides an overview of nutrition in chronic liver disease with an emphasis on its pathogenesis as well as ways to assess nutritional status and intervene in an effort to improve nutrition.

Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is now recognized as part of the metabolic syndrome, and is specifically related to obesity and insulin resistance. Lifestyle modification is advocated for the treatment of NAFLD, but few studies have evaluated its impact on liver histology. The purpose of this study was to investigate which, if any, specific diet and exercise recommendations are associated with histopathologic changes. METHODS: A total of 56 participants were randomly assigned to 1 of 4 lifestyle modification subgroups for 6 months: standard care, low-fat diet and moderate exercise, moderate-fat/low-processed-carbohydrate diet and moderate exercise, or moderate exercise only. All subjects had biopsy-proven NAFLD, to include nonalcoholic steatohepatitis (NASH), and received a repeat 6-month biopsy to detect histopathologic changes. Other measures included blood assay of liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), fasting glucose, serum insulin, lipid panel, body weight, dietary intake, fat mass, and fitness level. RESULTS: Among the 41 participants who completed the study (88% with NASH), a significant change was found in pre- to post-NAFLD activity score in the group as a whole (p < 0.001) with no difference detected between subgroups (p = 0.31). Our results confirm that lifestyle modification is effective in improving NAFLD and NASH. CONCLUSIONS: Regardless of intervention group, lifestyle modification improved liver histology, as verified by repeat biopsy, after a 6-month intervention. This study reinforces the importance of lifestyle modification as the primary treatment strategy for patients with NAFLD.

NAFLD: Predictive value of ALT levels for NASH and advanced fibrosis.

With expanding waistlines, the prevalence of NAFLD has burgeoned to become the leading cause of chronic liver disease in the USA. A subset of patients with NAFLD meet criteria for NASH with its inherent risk of progression to cirrhosis. Verma et al. addressed the utility of alanine aminotransferase levels for predicting NASH or advanced fibrosis to decide who would benefit from the definitive test of liver biopsy.

Killing two birds with one stone: screening for chronic hepatitis C at the time of colonoscopy in the baby boomer cohort.

Colonoscopy is a well-accepted colon cancer screening modality that is recommended by the United States Multi-Society Task Force on all individuals greater than 50 years of age. Chronic hepatitis C (CHC) is a common cause of chronic liver disease with notably increased rates of infection in individuals born between 1945 and 1965. The Centers for Disease Control recently recommended all individuals of this "Baby Boomer" cohort undergo one time screening for CHC. As gastroenterologists interface with these patients for screening colonoscopy, this represents a unique opportunity to complete this screening and identify CHC patients at risk for advanced liver disease.

Vitamin D and nonalcoholic fatty liver disease (NAFLD): is it more than just an association?

Vitamin D is a secosteroid with known effects on calcium homeostasis that has recently been shown to have other significant functions regarding immune modulation, cell differentiation and proliferation, and the inflammatory response. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency (VDD) has become more evident in Western populations. Concomitantly, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. NAFLD and VDD are often found together, and while this is not unexpected, given their similar associations with obesity and sedentary lifestyle, a growing body of evidence points to a closely linked and potentially causative relationship between VDD and NAFLD. The epidemiologic association between VDD and NAFLD as well as the role of VDD in the pathogenesis of NAFLD and the available evidence on the clinical utility of vitamin D replacement in NAFLD populations are discussed.

Physical activity: an essential component of lifestyle modification in NAFLD.

NAFLD encompasses a spectrum of liver diseases pertaining to fat accumulation in the liver in the absence of significant alcohol consumption. NASH is the most clinically relevant subset of NAFLD, and patients with NASH have an increased risk of progression to cirrhosis or developing liver cancer. No pharmacotherapy is currently approved for NAFLD, and lifestyle modification via diet and exercise is most commonly recommended. The optimal physical activity regimen in terms of both effectiveness and compliance remains to be determined and is the focus of this Review.