Peppermint oil (PO) has intrinsic properties that may benefit patients with irritable bowel syndrome (IBS) symptoms. The study objective was to determine the effect of peppermint oil in the treatment of the IBS. We systematically searched MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (Cochrane CENTRAL), ClinicalTrials.gov, EMBASE (Ovid), and Web of Science for randomized controlled trials (RCTs) of PO for IBS. We appraised the eligible studies by the Cochrane risk of bias tool. We performed random-effects meta-analysis on primary outcomes including global improvement in IBS symptoms and abdominal pain. A PRISMA-compliant study protocol is registered in PROSPERO Register [2016, CRD42016050917]. Twelve randomized trials with 835 patients were included. For global symptom improvement, the risk ratio (RR) from seven RCTs for the effect of PO (n = 253) versus placebo (n = 254) on global symptoms was 2.39 [95% confidence interval (CI): 1.93, 2.97], I2 = 0%, z = 7.93 (p < 0.00001). Regarding abdominal pain, the RR from six RCTs for the effect of PO (n = 278) versus placebo (n = 278) was 1.78 [95% CI: 1.43, 2.20], I2 = 0%, z = 5.23 (p < 0.00001). Overall, there were no differences in the reported adverse effects: PO (32 events, 344 total, 9.3%) versus placebo (20 events, 327 total, 6.1%) for eight RCTs; RR 1.40 [95% CI: 0.87, 2.26] I2 = 0%, z = 1.39 (p = 0.16). The number needed to treat with PO to prevent one patient from having persistent symptoms was three for global symptoms and four for abdominal pain. In the most comprehensive meta-analysis to date, PO was shown to be a safe and effective therapy for pain and global symptoms in adults with IBS.

Hepatitis C virus infection has been the most common etiology in HCC‐related liver transplantation (LT). Since 2014, direct‐acting antivirals (DAAs) have dramatically improved HCV cure. We aimed to study the changing pattern of etiologies and impact in outcome in HCC‐related LT according to HCV treatment‐era through retrospective analysis of the Scientific Registry of Transplant Recipients (SRTR) database (1987‐2017). A total of 27 855 HCC‐related liver transplants were performed (median age 59 years, 77% male). In the DAA era (2014‐2017) there has been a 14.6% decrease in LT for HCV‐related HCC; however, HCV remains the most common etiology in 50% of cases. In the same era, there has been a 50% increase in LT for NAFLD‐related HCC. Overall survival was significantly worse for HCV‐related HCC compared to NAFLD‐related HCC during pre‐DAA era (2002‐2013; P = .031), but these differences disappeared in the DAA era. In addition, HCV patients had a significant improvement in survival when comparing the DAA era with IFN era (P < .001). Independent predictors of survival were significantly different in the pre‐DAA era (HCV, AFP, diabetes) than in the DAA era (tumor size). HCV‐related HCC continues to be the main indication for LT in the DAA era, but patients’ survival has significantly improved and is comparable to that of NAFLD‐related HCC.

Liver injury is commonly seen in coronavirus disease 2019 (COVID-19); however, the mechanism behind liver injury, particularly in patients with severe and critical COVID-19, remains unclear, and the clinical course is poorly described. We conducted a single-center retrospective cohort study of consecutive patients hospitalized with severe and critical COVID-19 with or without liver injury and who underwent immunologic testing (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-1β). Liver injury was defined as peak aminotransferases ≥3 times the upper limit of normal (40 U/L) or ≥120 U/L. Patients with liver injury were compared to those who had normal aminotransferases throughout the hospital course. We studied 176 patients: 109 with liver injury and 67 controls. Patients with liver injury were more likely to be men (71.6% vs. 37.3%, P < 0.001). Peak inflammatory markers and IL-6 were higher in the liver injury group: C-reactive protein (CRP), 247 vs. 168 mg/L, P < 0.001; lactate dehydrogenase (LDH), 706 vs. 421 U/L; ferritin, 2,973 vs. 751 ng/mL, P < 0.001; IL-6, 121.0 vs. 71.8 pg/mL, P < 0.001. There was no difference in the levels of IL-8, TNF-α, and IL-1β. The liver injury group had a longer length of stay in the hospital and more severe COVID-19 despite having less diabetes and chronic kidney disease. Conclusion: An exaggerated hyperinflammatory response (cytokine storm) characterized by significantly elevated CRP, LDH, ferritin, and IL-6 levels and increasing severity of COVID-19 appears to be associated with the occurrence of liver injury in patients with severe/critical COVID-19.

Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholic hepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End-stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care. Severe AH is associated with significant mortality. Currently, there is no ideal medical treatment for this condition. Besides alcohol cessation, corticosteroids have been used with conflicting results and are associated with an inherent risk of infection. Overall steroids have shown short term benefit when compared to placebo, but they have no obvious long term benefits. Pentoxifylline does not improve survival in patients with severe AH and is no longer recommended based on the results of the STOPAH (Steroid Or Pentoxifylline for Alcoholic Hepatitis) trial. Anti-tumor necrosis factor (TNF) agents are associated with increased risk of life threatening infections and death. Currently, early stage trials are underway, mainly targeting novel pathways based on disease pathogenesis, including modulation of innate immune system, inhibition of gut-liver axis and cell death pathways, and activation of transcription factor farnesyl X receptor (FXR). Future treatment may lie in human induced pluripotent stem cell (iPSC) technology, which is currently under investigation for the study of pathogenesis, drug discovery, and stem cell transplantation. Liver transplantation has been reported with good results in highly selected patients but is controversial due to limited organ supply.

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is one of the most common etiologies of liver transplantation (LT) in the United States. We investigated regional trends in waitlist candidates, LT rates, and recipient survival among patients with NASH. METHODS: Using the United Network for Organ Sharing database by Organ Procurement and Transplantation Network regions, we investigated waitlist registration, LT rates, and survival for NASH between January 2004 and December 2019. RESULTS: The absolute number and percentage of total LT performed for NASH increased substantially in all Organ Procurement and Transplantation Network regions. In 2019, region 11 had the highest percentage of NASH-related LT with 31.4% followed by region 10 (25.3%) and region 8 (23.1%). Between 2015 and 2019, region 5 had the highest rising percentage in LT for NASH at 208%, followed by region 1 (194%) and region 4 (183%). The proportion of NASH hepatocellular carcinoma (NASH-HCC) was the highest in region 9 at 37.7% and lowest in region 10 (19.2%), region 3 (20.6%), and region 11 (20.8%). In multivariate analysis, diabetes (HR 1.18, P < 0.001), dialysis before LT (hazard ratio [HR] 1.53, P < 0.001), HCC (HR 1.19, P < 0.00), portal vein thrombosis (HR 1.24, P < 0.001), donor age (HR 1.026, P = 0.03), and recipient age (HR 1.24, P = <0.001) were associated with worse survival. DISCUSSION: LT for patients with NASH has dramatically increased across all regions since 2004, but with substantial heterogeneity among regions in the proportion with HCC and post-LT survival. Identifying contributing factors to these regional differences is warranted.