Trends in Hospitalizations for Clostridioides difficile Infection in End-Stage Liver Disease, 2005-2014.

BACKGROUND: Data on the current estimates of the disease burden of Clostridioides difficile (C. difficile) infection in the setting of end-stage liver disease (ESLD) are emerging. AIMS: We examined the recent trends and predictors of hospitalizations and in-hospital mortality from C. difficile infection among hospitalizations with ESLD in the USA. METHODS: We performed a retrospective analysis using the National Inpatient Sample, 2005-2014. We defined ESLD and C. difficile infection using the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable logistic regression was used to determine the risk factors that impacted hospitalization and mortality. RESULTS: The prevalence of coding for C. difficile infection in decompensated cirrhosis increased from 1.3% in 2005 to 2.7% in 2014, with an annual rate of 7.8%. In hospitalizations with hepatocellular carcinoma, C. difficile infection increased steadily from 1.0 to 1.7% with an annual incremental rate of 6.4%. Among hospitalizations with ESLD, each passing 2-year period, increasing age, female, higher Charlson index, accompanying infection, hepatorenal syndrome, and ascites were associated with C. difficile infection. Although C. difficile infection was an independent predictor of in-hospital mortality during hospitalization with decompensated cirrhosis (odds ratio 1.53, 95% confidence interval 1.44-1.63), the proportion of in-hospital mortality during hospitalization with C. difficile infection and decompensated cirrhosis decreased from 15.4% in 2005 to 11.1% in 2014, with an annual rate of - 3.1% (95% CI - 5.7% to - 0.3%). CONCLUSIONS: While the prevalence of C. difficile infection in hospitalized patients with ESLD increased approximately twofold, the in-hospital mortality decreased significantly during the past decade.

Diet quality and its association with nonalcoholic fatty liver disease and all-cause and cause-specific mortality.

BACKGROUND & AIMS: Healthy diet has been recommended for nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent mortality. We aim to assess the impact of quality of diet on NAFLD and mortality in subjects with and without NAFLD. METHODS: We performed cohort study using the Third National Health and Nutrition Examination Survey from 1988 to 1994 and linked mortality data through 2015. We used the Healthy Eating Index (HEI) scores to define diet quality, with higher HEI scores (Q4) indicating better adherence to dietary recommendations. NAFLD was defined as ultrasonographic hepatic steatosis. RESULTS: Multivariate analysis showed that subjects with higher diet quality were inversely associated with NAFLD in a dose-dependent manner. During the median follow-up of 23 years, having a higher diet quality was associated with reduction in risk of all-cause mortality in the age, sex, Race/ethnicity-adjusted hazard ratio (HR) (Q4, HR: 0.60, 95% CI: 0.52-0.68) and the multivariate model (Q4, HR: 0.81, 95% CI: 0.71-0.92). Higher diet quality was associated with a lower risk for all-cause mortality in subjects without NAFLD; however, this protective association with diet quality was not noted in those with NAFLD. Furthermore, a high diet quality was associated with a lower risk for cancer-related mortality in the total population and among those without NAFLD. This association was not noted in those with NAFLD. CONCLUSIONS: High diet quality was inversely associated with NAFLD and was positively associated with a lower risk for cancer-related and all-cause mortality in those without NAFLD.

Chronic Liver Disease and Silymarin: A Biochemical and Clinical Review.

Chronic liver disease (CLD) is an under-recognized epidemic that continues to increase in prevalence and is a major health concern. Silymarin, the active compound of Silybum marianum (Milk thistle), has historically been used in CLD. A significant barrier to silymarin use is its poor bioavailability. Attempts at improving the bioavailability of silymarin have led to a better understanding of formulation methods, pharmacokinetics, dosing, and associated drug interactions. Clinically, silymarin exerts its hepatoprotective effects through antioxidative, antifibrotic, anti-inflammatory, antitoxin, and anticancerous mechanisms of actions. Despite the use of silymarin being extensively studied in alcoholic liver disease, metabolic-associated fatty liver disease, viral hepatitis, and drug-induced liver injury, the overall efficacy of silymarin remains unclear and more research is warranted to better elucidate the role of silymarin in CLD, specifically regarding its anti-inflammatory effects. Here, we review the current biochemical and clinical evidence regarding silymarin in CLD.

Depression is associated with non-alcoholic fatty liver disease among adults in the United States.

BACKGROUND: Currently, the relationship between depression and non-alcoholic fatty liver disease (NAFLD) is not clearly defined. AIM: To determine whether depression is associated with NAFLD and NAFLD-related advanced fibrosis in a large population sample. METHODS: We performed a cross-sectional analysis using the 2007-2016 National Health and Nutrition Examination Survey database among adults (20 years or older) in the United States (US). Depression and functional impairment due to depression were assessed with the Patient Health Questionnaire (PHQ-9). NAFLD was defined by utilising the US fatty liver index (USFLI), hepatic steatosis index (HSI) and the fatty liver index (FLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD were defined by Fibrosis-4 score. RESULTS: Of the 10 484 subjects (mean age 47.0 years; 48.8% men), the prevalence of depression and functional impairment due to depression was higher in subjects with NAFLD than in those without. Compared to subjects without depression, those with depression were 1.6-2.2-fold more likely to have NAFLD. In our multivariate analyses, depression_med was associated with increased risk of NAFLD using USFLI (odds ratio [OR] 1.48 95% confidence interval [CI] 1.17-1.87), HSI (OR 1.51 95% CI 1.04-2.19) and FLI (OR 2.01 95% CI 1.65-2.48), respectively. The addition of diabetes, obesity and lipid profile to the model reduced the ORs for depression, but the significance persisted. Depression was not associated with NAFLD-related advanced fibrosis. CONCLUSIONS: In a nationally representative sample of US adults, depression was independently associated with NAFLD.

Treatment of inoperable hepatocellular carcinoma with immunotherapy.

In the USA, mortality associated with hepatocellular carcinoma (HCC) continues to rise. Globally, HCC is the third most common cause of cancer-related death. In early stages of HCC, hepatic resection or liver transplantation are the preferred treatment options with a high probability of recurrence-free postoperative course. However, ineffective screening of chronic liver diseases in high-risk populations, poor linkage to care and suboptimal HCC surveillance has led to increasing rates of late-stage HCC at clinical presentation or diagnosis amenable only to palliative and experimental treatment options. Our case is a 66-year-old man with chronic hepatitis C virus infection complicated by cirrhosis and inoperable HCC which was non-responsive to selective intrahepatic trans-arterial chemoembolisation by interventional radiology. Therefore, he was treated with nivolumab immunotherapy and demonstrated normalisation of previously elevated alpha-fetoprotein levels suggestive of at least a partial response to immunotherapy. No adverse events related to nivolumab immunotherapy were encountered.

Trends in hospitalizations for chronic liver disease-related liver failure in the United States, 2005-2014.

BACKGROUND & AIMS: Current estimates of the population-based disease burden of liver failure or end-stage liver disease (ESLD) are lacking. We investigated recent trends in hospitalizations and in-hospital mortality among patients with ESLD in the United States (US). METHODS: A retrospective analysis was performed utilizing the National Inpatient Sample from 2005 to 2014. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma (HCC), criteria obtained from the International Classification of Diseases, Ninth Revision. Nationwide rates of hospitalization and in-hospital mortality were analysed from 2005 to 2014. RESULTS: Hospitalization rates for decompensated cirrhosis during this period increased from 105.3/100 000 persons to 159.9/100 000 persons. In terms of HCC, hospitalization rates increased from 13.6/100 000 to 22.1/100 000. In patients with non-alcoholic fatty liver disease (NAFLD)-related decompensated cirrhosis, the hospitalization rate increased from 13.4/100 000 to 32.1/100 000 with an annual incremental increase of 10.6%, a magnitude twofold higher than other aetiologies. The proportion of NAFLD among hospitalizations with ESLD steadily increased from 12.7% to 20.1% for decompensated cirrhosis while the proportion of chronic hepatitis C (HCV) and alcoholic liver disease (ALD) declined (from 29.3% to 27.6% for HCV; from 39.0% to 37.4% for ALD). Although the overall in-hospital mortality rates for ESLD declined during the study, mortality rates for NAFLD-related decompensated cirrhosis showed no significant change. CONCLUSIONS: Among aetiologies of chronic liver disease, NAFLD demonstrated the fastest growing rate of hospitalizations in non-HCC patients with ESLD in the US. Our study highlights the need for a focus on NAFLD-related hospitalizations and its impact on resource utilization.

Elevated urinary bisphenol A levels are associated with non-alcoholic fatty liver disease among adults in the United States.

BACKGROUND AND AIMS: The relationship between bisphenol A (BPA) and non-alcoholic fatty liver disease (NAFLD) is undefined. We studied the impact of BPA on NAFLD. METHODS: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014 among adults in the United States (US). NAFLD was diagnosed using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver diseases. The first sample using HSI consisted of 7605 adults. The second sample using USFLI consisted of 3631 participants with availability of fasting data. RESULTS: Of the first 7605 participants (mean age 47 years, 48.4% male), the prevalence of NAFLD and abnormally elevated alanine aminotransferase (ALT) levels was correlated with urinary BPA levels (P < 0.05). Compared to the reference group with lowest quartile of urinary BPA levels, those with the third and fourth quartiles were 81% and 53% more likely to develop NAFLD defined by HSI. In a multivariate model, the ORs for NAFLD in the third and fourth quartiles were 1.69 (95% CI 1.39-2.04) and 1.44 (95% CI 1.19-1.76) respectively (P for trend <0.001). In the second sample using USFLI, high BPA levels (fourth quartile) remained an independent predictor of NAFLD (OR 1.44, 95% CI 1.05-1.98, P for trend = 0.012). CONCLUSIONS: High levels of urinary BPA were associated with NAFLD in a nationally representative sample of adults in the US. The pathophysiology remains unclear and warrants further investigation.

Kratom-Induced Cholestatic Liver Injury and Its Conservative Management.

Drug-induced liver injury (DILI) is a common cause of hepatotoxicity associated with prescription-based and over-the-counter exposure to medications and herbal supplements. Use of unapproved and inadequately tested herbal supplements can cause DILI. Therefore, thorough history-taking on exposure to herbal supplements must be an integral part of clinical evaluation of DILI. Kratom is an herbal supplement or remedy that has been known for its analgesic effects and has also been used for self-treatment of opiate withdrawals. A 52-year-old man was seen for evaluation of yellow discoloration of the eyes and skin. He reported taking kratom for right shoulder strain for at least a couple of months. On workup, his total bilirubin was noted to be 23.2 mg/dL, which peaked at 28.9 mg/dL. He was noted to have mild elevation of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Extensive laboratory tests were ordered and known causes of chronic liver disease ruled out. Magnetic resonance imaging of the abdomen was unremarkable without stigmata of portal hypertension or signs of chronic liver disease. He demonstrated no evidence of coagulopathy or hepatic encephalopathy during his illness. He underwent liver biopsy, which demonstrated histologic evidence of acute cholestatic hepatitis highly suspicious of DILI. He was advised to avoid kratom or other herbal supplements in future and prescribed ursodeoxycholic acid with significant improvement in his liver chemistries. Kratom is associated with significant liver enzymes derangements leading to DILI. Kratom is not approved for use in the United States and should be avoided.

Race/ethnicity-based temporal changes in prevalence of NAFLD-related advanced fibrosis in the United States, 2005-2016.

BACKGROUND AND AIM: Advanced fibrosis associated with nonalcoholic fatty liver disease (NAFLD) has been reported to have a higher risk of hepatic and non-hepatic mortality. We aim to study the recent trends in the prevalence of NAFLD-related advanced fibrosis in a large population sample. METHODS: Cross-sectional data from 28,739 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016 were utilized. NAFLD was defined using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD was determined by the NAFLD fibrosis score, FIB-4 score, and aspartate aminotransferase-to-platelet ratio index. RESULTS: The prevalence of NAFLD-related advanced fibrosis increased from 2.6% [95% confidence interval (CI) 2.1-3.1] in 2005-2008 and 4.4% (95% CI 3.7-5.1) in 2009-2012, to 5.0% (95% CI 4.2-5.9) in 2013-2016 using HSI as the NAFLD prediction model; and from 3.3% (95% CI 2.5-4.5) in 2005-2008 and 6.4% (95% CI 3.7-5.1) in 2009-2012, to 6.8% (95% 5.3-8.7) in 2013-2016 using USFLI (p < 0.01). A similar trend was observed in entire NHANES cohort regardless of NAFLD status. While the prevalence of advanced fibrosis increased steadily in non-Hispanic whites through the duration of the study, it leveled off during 2013-2016 in non-Hispanic blacks. CONCLUSIONS: Prevalence of advanced fibrosis associated with NAFLD increased steadily from 2005 to 2016. More importantly, race/ethnicity-based temporal differences were noted in the prevalence of NAFLD-related advanced fibrosis during the study.

Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States.

The pathogenetic pathways leading to increasing prevalence of advanced fibrosis in the setting of nonalcoholic fatty liver disease (NAFLD) and resulting in higher rates of liver-related and cardiovascular morbidity and mortality in the United States are multifactorial.1 The negative health impact of "low-normal" thyroid function, which is defined as a higher level of thyroid-stimulating hormone (TSH) within the euthyroid reference range, may be comparable with overt and subclinical hypothyroidism.2-4 We reported a strong association between biopsy-proven advanced fibrosis in NAFLD with increasing TSH levels in a dose-dependent manner even within the euthyroid reference range.5 To generalize our findings across all ethnicities, we examined the association of both low-normal thyroid function and subclinical hypothyroidism with advanced fibrosis in the US general population.