Once ingested, most of the alcohol is metabolized in the liver by alcohol dehydrogenase to acetaldehyde. Two additional pathways of acetaldehyde generation are by microsomal ethanol oxidizing system (cytochrome P450 2E1) and catalase. Acetaldehyde can form adducts which can interfere with cellular function, leading to alcohol-induced liver injury. The variants of alcohol metabolizing genes encode enzymes with varied kinetic properties and result in the different rate of alcohol elimination and acetaldehyde generation. Allelic variants of these genes with higher enzymatic activity are believed to be able to modify susceptibility to alcohol-induced liver injury; however, the human studies on the association of these variants and alcohol-associated liver disease are inconclusive. In addition to acetaldehyde, the shift in the redox state during alcohol elimination may also link to other pathways resulting in activation of downstream signaling leading to liver injury.

MicroRNAs are small non-coding RNAs that range in length from 18 to 24 nucleotides. As one of the most extensively studied microRNAs, microRNA-21 (miR-21) is highly expressed in many mammalian cell types. It regulates multiple biological functions such as proliferation, differentiation, migration, and apoptosis. In this review, we summarized the mechanism of miR-21 in the pathogenesis of various liver diseases. While it is clear that miR-21 plays an important role in different types of liver diseases, its use as a diagnostic marker for specific liver disease or its therapeutic implication are not ready for prime time due to significant variability and heterogeneity in the expression of miR-21 in different types of liver diseases depending on the studies. Additional studies to further define miR-21 functions and its mechanism in association with each type of chronic liver diseases are needed before we can translate the bedside observations into clinical settings.

Alcoholic hepatitis (AH) is the most florid manifestation of alcoholic liver disease which accounts for significant morbidity, mortality, and financial burden. Aim of this study is to evaluate temporal trend of hospitalizations from AH and evaluate its financial impact. The National Inpatient Sample databases (from 2002 to 2010) which are collected as part of Healthcare Cost and Utilization Project by Agency for Healthcare Research and Quality were utilized. Individuals aged 21 years and older were included. The hospitalizations with primary diagnosis of AH were captured by ICD-9 codes. The national estimates of hospitalization were derived using sample weights provided by National Inpatient Sample. Simple linear regression method was used to assess trends in mortality and length of stay over time. We observed the increased in total cases of AH-related hospitalization from 249,884 (0.66% of total admission in 2002) to 326,403 (0.83% of total admission in 2010). The significant increase in the total admission rate was attributable mainly to the rise in inpatient hospitalization for secondary diagnosis of AH (0.48% in 2002 to 0.67% in 2010). Most of the AH-related hospitalization were males. Hepatic encephalopathy was found to be the most common admitting diagnosis for individuals hospitalized with secondary diagnosis of AH (8.9% in 2002 and 8.6% in 2010). There was a significant decrease in inpatient mortality for primary diagnosis of AH from 10.07% (in 2002) to 5.76% (in 2010) (absolute risk reduction: 4.3%). Average cost of hospitalization related to primary diagnosis of AH was $27,124 and $46,264 in 2002 and 2010, respectively. After adjusting for inflation, the additional cost of each hospitalization seemed to increase by 40.7% in 2010 compared with 2002 (additional cost per hospitalization $11,044 in 2010 compared with 2002). Federal (Medicare) or state (Medicaid) supported health insurance program are the main primary expected payers for these AH hospitalizations (∼25% to 29%). Despite increase in cost per hospitalization, length of stay for hospitalization due to primary diagnosis of AH was not observed to decrease substantially over time (6.7 d in 2002 to 6.1 d in 2010). AH-related hospitalization continued to increase during the study period, despite the decrease in the in-hospital mortality rate. Substantial increases in health care cost and utilization among hospitalized AH patients were observed.