IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcohol-associated hepatitis.

BACKGROUND AND AIMS: Patients with severe alcohol-associated hepatitis (AH) have high mortality. Corticosteroids improve survival only for 30 days. We targeted inflammation, cellular injury, and gut leakiness in a randomized clinical trial comparing combination therapy to corticosteroids on 180-day survival. APPROACH AND RESULTS: Subjects with a clinical diagnosis of severe AH (Model for End-Stage Liver Disease [MELD] >20, Maddrey discriminant function [MDF] >32) were randomized to receive methylprednisolone (PRED; 28 days) or a combination of anakinra (14 days) plus pentoxifylline (28 days) plus zinc (COMB; 180 days). The primary endpoint was survival at 180 days. The study was designed in 2013, initiated in October 2014, and completed in March 2018. Five hundred patients were screened to randomize 104 subjects with a clinical diagnosis of AH with a MELD score >20. Fifty-three patients were randomized into the COMB and 50 to the PRED treatment; 1 dropped out of the study before randomization. Mean age was 45.3 ± 10.4 years; 60.6% were males, 92.3% White, and mean MELD 25.7 ± 3.9. Kaplan-Meier survival estimate at 180 days was 67.9% in COMB and 56% in PRED (HR = 0.69; p = 0.3001). Survival curves separated by 90 days (COMB, 69.8%; PRED, 58.0%; HR = 0.69; p = 0.28). Survival at 28 days was similar between the COMB (83.4%) and PRED groups (81.2%; HR = 0.91; p = 0.85). There were no unexpected serious adverse events, and incidence of infection was comparable between groups. MELD 20-25 and MELD >26 strata showed nonsignificant treatment effects in favor of COMB. CONCLUSIONS: A combination of anakinra, pentoxifylline plus zinc provides similar survival benefits compared to corticosteroid therapy in severe AH.

Acute Liver Failure (ALF) in Pregnancy: How Much Is Pregnancy Related?

BACKGROUND AND AIMS: Acute liver failure (ALF), characterized by sudden onset of coagulopathy (international normalized ratio [INR] ≥ 1.5) and encephalopathy, may occur during pregnancy either as a pregnancy-associated etiology or an unrelated and coincidental liver injury. The U.S. Acute Liver Failure Study Group, comprised of 33 tertiary care liver centers, has enrolled consecutive patients with ALF or acute liver injury (ALI; INR ≥ 2.0 with no encephalopathy), over two decades. APPROACH AND RESULTS: Etiologies, clinical features, and outcomes of 70 of 3,155 patients (2.2%) who developed ALF or ALI during pregnancy were reviewed to determine how many were pregnancy associated (pregnancy-associated liver disease; PAALD) and how many were attributed to other etiologies. Thirty-five of the 70 were considered PAALD, of whom nearly half were attributed to hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and half to acute fatty liver of pregnancy (AFLP), although, in some instances, the distinction was unclear. Virtually all with PAALD had been delivered before hepatology referral, mostly by cesarean section. Acetaminophen toxicity accounted for 21 (60% of the remaining cases), with the remainder resulting from a variety of other causes, but not including viral hepatitis A through E. Although recovery with delivery or supportive measures was possible in most cases, 11 of 70 (16%) required liver transplantation and 8 (11%) died. Swansea criteria to diagnose AFLP were met by all patients with PAALD and also by virtually all women with other forms of ALF. CONCLUSIONS: Only half of those with ALF during pregnancy appeared to have HELLP or AFLP. Morbidity and mortality for mother and fetus are strongly associated with etiology of liver failure.

Who Should Be Gluten-Free? A Review for the General Practitioner.

Historically, a gluten-free diet was recommended only for those with celiac disease or IgE-mediated wheat allergy. With changes in food allergy labeling in the United States and the publication of several best-selling books, gluten-related disorders have come to the forefront of popular culture. As a result, there has been a dramatic increase in the number of gluten-free diet followers, many for nontraditional reasons. As "going gluten-free" has become mainstream, it is imperative that health care providers acquire the knowledge to identify true gluten-related disorders to effectively counsel their patients and minimize potential complications from following such a restrictive diet.

The Association Between Artificial Sweeteners and Obesity.

PURPOSE OF REVIEW: The purpose of this paper is to review the epidemiology of obesity and the evolution of artificial sweeteners; to examine the latest research on the effects of artificial sweeteners on the host microbiome, the gut-brain axis, glucose homeostasis, and energy consumption; and to discuss how all of these changes ultimately contribute to obesity. RECENT FINDINGS: Although artificial sweeteners were developed as a sugar substitute to help reduce insulin resistance and obesity, data in both animal models and humans suggest that the effects of artificial sweeteners may contribute to metabolic syndrome and the obesity epidemic. Artificial sweeteners appear to change the host microbiome, lead to decreased satiety, and alter glucose homeostasis, and are associated with increased caloric consumption and weight gain. Artificial sweeteners are marketed as a healthy alternative to sugar and as a tool for weight loss. Data however suggests that the intended effects do not correlate with what is seen in clinical practice. Future research should focus on the newer plant-based sweeteners, incorporate extended study durations to determine the long-term effects of artificial sweetener consumption, and focus on changes in the microbiome, as that seems to be one of the main driving forces behind nutrient absorption and glucose metabolism.

Alcoholic hepatitis: current trends in management.

PURPOSE OF REVIEW: Alcohol consumption is increasing globally, as are complications of alcohol-related liver disease, including the most severe manifestation, alcoholic hepatitis. Despite the increased prevalence, many patients hospitalized with alcoholic hepatitis are either not diagnosed or inadequately treated leading to significant morbidity and high mortality rates. The purpose of this review is to discuss current challenges in the diagnosis and management of this frequently fatal condition. RECENT FINDINGS: Recent studies and meta-analyses have improved our understanding of both the evaluation and treatment of alcoholic hepatitis including the diagnostic criteria, appropriate use of glucocorticoids and other therapeutic modalities including novel disease-specific therapeutic agents and indications for considering liver transplantation. SUMMARY: Glucocorticoid therapy and enteral nutrition represent the best options for reducing short-term mortality in patients with the severe form of acute alcoholic hepatitis. The efficacy of other medications such as pentoxifylline as currently used does not support a role for use outside clinical trials. While the current management options for alcoholic hepatitis remain insufficient, improvements in diagnosis, determining prognosis and severity and the potential role of novel treatments provides encouragement that outcomes from this devastating condition will improve.

Alcoholic Hepatitis: Risk Factors, Pathogenesis, and Approach to Treatment.

BACKGROUND: Alcoholic hepatitis (AH) is an inflammatory disorder of the liver characterized clinically by jaundice, hepatomegaly, and abdominal pain, and histologically by macrovesicular steatosis and necroinflammation. METHODS: This clinical review will cover what is known about the pathogenesis, clinical presentation, current treatments, and novel therapies for AH. RESULTS: The pathogenesis and treatment of AH remain areas of active research. Although abstinence is the cornerstone of therapy for all stages of alcoholic liver disease, corticosteroids have shown modest short-term benefits in treatment of severe AH. CONCLUSIONS: Improved understanding of the pathogenesis of AH has expanded the range of potential treatments for this devastating disease. Several novel therapies are also currently in various stages of testing through clinical trials.

Hepatitis C virus therapy update 2013.

PURPOSE OF REVIEW: We review here the recent literature regarding hepatitis C virus (HCV) therapy through January 2013. We discuss current therapies, targets for new therapies, and what might be expected in this rapidly changing field. RECENT FINDINGS: Boceprevir-based and telaprevir-based triple therapy with pegylated interferon and ribavirin marked the beginning of a new era in HCV therapy for genotype 1 patients. New direct-acting antivirals (DAAs) are being developed and new antiviral drug targets are being explored. New combination treatment regimens are expected to emerge soon and there is hope for interferon-free regimens. SUMMARY: The standard of care for treatment of HCV genotype 1 changed dramatically with the approval of two new DAA drugs--telaprevir and boceprevir--for use in pegylated interferon-based and ribavirin-based triple therapy in mid-2011. Experience has shown improved response rates and treatment durations for many patients with genotype 1 HCV infection. However, persistent limitations to HCV treatment still exist for patients with prior treatment failure and comorbid conditions and patients on newer therapies suffer additional therapy-limiting side effects and drug-drug interactions. Genetic testing may provide some guidance but additional options for therapy are still needed for HCV. Many new drugs are currently under investigation and there is hope that effective and well tolerated interferon-free regimens may become a part of future therapy.

Quantitative analysis of the DNA distribution on cigarette butt filter paper.

The distribution of DNA on the filter paper of smoked cigarette butts was quantitatively mapped using real-time quantitative polymerase chain reaction. The filter papers from smoked cigarette butts collected from indoor and outdoor sources were sliced into equal pieces and the amount of DNA on each slice was determined. This study found that the cigarette butt filter papers sliced parallel to the seam of the cigarette had more uniformly distributed DNA on the slices and in most cases, there was enough DNA on each slice to obtain a complete DNA profile. The perpendicular slices had a less uniform pattern of distribution and some slices did not have enough DNA to obtain an interpretable DNA profile. Cigarette butts found indoors also had more DNA per cigarette on average than cigarette butts found outdoors.

Hepatitis C therapy update.

PURPOSE OF REVIEW: We review here the recent literature regarding hepatitis C treatment through January 2012. We discuss newly approved therapies and their clinical trial data and discuss what can be expected in this rapidly changing field. RECENT FINDINGS: Two new directly acting antiviral agents were approved in 2011 for use in hepatitis C treatment, bringing shortened treatment durations, and increased treatment success to some patients with genotype 1 hepatitis C. Additional drugs using different viral targets are in development to further improve response rates, tolerance, and increase access to therapy. SUMMARY: Telaprevir and boceprevir were approved in 2011 for use against genotype 1 hepatitis C, in combination with pegylated interferon and ribavirin. In most populations of genotype 1 patients, response rates are much improved but increased treatment related anemia has been seen. Additional options for therapy, including interferon-free regimens, are still needed and are under development.