Nonalcoholic fatty liver disease is associated with worse intestinal complications in patients hospitalized for Clostridioides difficile infection

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)has become the leading cause of chronic liver disease with increasing prevalence worldwide.Clostridioides difficile infection(CDI)remains the most common cause of nosocomial diarrhea in developed countries.AIM To assess the impact of NAFLD on the outcomes of hospitalized patients with CDI.METHODS This study was a retrospective cohort study.The Nationwide Inpatient Sample database was used to identify a total of 7239 adults admitted as inpatients with a primary diagnosis of CDI and coexisting NAFLD diagnosis from 2010 to 2014 using ICD-9 codes.Patients with CDI and coexisting NAFLD were compared to those with CDI and coexisting alcoholic liver disease(ALD)and viral liver disease(VLD),individually.Primary outcomes included mortality,length of stay,and total hospitalization charges.Secondary outcomes were in-hospital complications.Multivariate regression was used for outcome analysis after adjusting for possible confounders.RESULTS CDI with NAFLD was independently associated with lower rates of acute respiratory failure(2.7%vs 4.2%,P<0.01;2.7%vs 4.2%,P<0.05),shorter length of stay(days)(5.75±0.16 vs 6.77±0.15,P<0.001;5.75±0.16 vs 6.84±0.23,P<0.001),and lower hospitalization charges(dollars)(38150.34±1757.01 vs 46326.72±1809.82,P<0.001;38150.34±1757.01 vs 44641.74±1660.66,P<0.001)when compared to CDI with VLD and CDI with ALD,respectively.CDI with NAFLD was associated with a lower rate of acute kidney injury(13.0%vs 17.2%,P<0.01),but a higher rate of intestinal perforation(P<0.01)when compared to VLD.A lower rate of mortality(0.8%vs 2.7%,P<0.05)but a higher rate of intestinal obstruction(4.6%vs 2.2%,P=0.001)was also observed when comparing CDI with NAFLD to ALD.CONCLUSION Hospitalized CDI patients with NAFLD had more intestinal complications compared to CDI patients with VLD and ALD.Gut microbiota dysbiosis may contribute to the pathogenesis of intestinal complications.

Mechanisms of hepatocellular carcinoma progression

Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.