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.

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.

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.

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. (Hepatology 2020;72:1366-1377). A cute liver failure (ALF) is a rare condition, affecting approximately 2,000-3,000 patients annually in the United States. (1) ALF occurring in pregnancy is associated with significant maternal and fetal morbidity and mortality. (2,3) Certain liver conditions that lead to ALF, such as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and acute fatty liver of pregnancy (AFLP), are limited solely to pregnant women, occur during the third trimester, and can be classified as pregnancy-associated acute liver diseases (PAALDs). (4-6) In the obstetrical literature, diagnostic criteria for AFLP, known as the Swansea criteria, have been proposed as a means to distinguish AFLP from other causes of liver dysfunction, including HELLP, but these have not been extensively validated. (7,8) Not all ALF that occurs during pregnancy is directly related to the pregnancy itself. For example, certain viruses occur relatively frequently in the reproductive years; likewise, pregnant women may be more susceptible to

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.