Clinical Presentation and Gene Expression of Acute Alcohol‐Induced Microvesicular Steatosis Mimicking Alcoholic Hepatitis

Abstract

Acute alcoholic microvesicular steatosis (MIC) may complicate heavy alcohol intake and present as alcoholic hepatitis (AH) syndrome. However, detailed clinical, biological, and histologic data associated with MIC are scarce. We compared the clinical presentation, histologic features, and hepatic transcriptomic of patients presenting with AH due to either MIC or severe alcoholic steatohepatitis (ASH). In this case‐control study, patients who drank heavily (>100 g/day) with the AH syndrome were included either in the MIC group (>50% severe microvesicular steatosis, no inflammation) or in the severe ASH group (polynuclear neutrophil infiltration, macrosteatosis, ballooned hepatocytes). All patients received standard supportive care plus steroids for those with severe ASH and were followed up for 3 months. Whole‐liver transcriptome profiling was performed on liver snap‐frozen biopsies. Compared to ASH (n = 24, mean age 49.3 years), patients in the MIC group (n = 12, mean age 49.1 years) had a higher reported alcohol intake (P < 0.01), lower Model for End‐Stage Liver Disease score (P < 0.05), lower hepatic venous pressure gradient (P < 0.01), higher alanine aminotransferase (P < 0.02) and gamma‐glutamyltransferase (P < 0.001), higher triglycerides (P < 0.001) and total cholesterol (P < 0.002), but similar bilirubin levels (P = 0.54). At histology, patients with MIC had a lower fibrotic stage compared to those with ASH (P < 0.001). A higher density of megamitochondria was seen in MIC compared to ASH (P < 0.05). During follow‐up, death or transplantation occurred in 4/12 (33%) patients with MIC and 7/24 (29%) patients with severe ASH. Differential hepatic gene expression in MIC compared to ASH included down‐regulation of genes related to inflammation and fibrosis and up‐regulation of genes involved in lipid metabolism and mitochondrial function. Conclusion: MIC is an acute, noninflammatory, potentially severe alcoholic liver injury mimicking ASH, is associated with a lower fibrosis stage, and has a distinct gene expression profile.

A case of coexistent acute severe alcoholic and Q fever hepatitis: The useful contribution of repeated liver biopsies

“…In our case, liver biopsy was able to determine the coexistence of both steatohepatitis lesions (steatosis, polynuclear rich in lammation, ballooned hepatocytes) and histological alterations that were highly suggestive of acute C. burnetii infection [7,2]. This was a clinically relevant observation with regards to the indication for corticosteroids in severe ASH, as relying on clinical and biological criteria alone may lead to misclassi ication and the inappropriate use of steroids with potentially adverse consequences [9,10]. In the present case, the very elevated serum level of CRP was a inding incongruent with suspicion of ASH, suggesting the coexistence of an acute infection.…”

“…The indication to perform a liver biopsy when a severe form of alcoholic hepatitis is suspected on clinical and biological grounds is still a matter of debate [8]. However, histological demonstration of an alternative diagnosis (in up to approximately 20% of suspected cases [9,10] avoids the inappropriate and potentially hazardous administration of corticosteroids in patients with advanced liver failure and a high risk of infections [11].…”

Letter: the value of quality liver biopsy before initiation of corticosteroids for severe alcoholic hepatitis

“…2 During 3 years, out of 162 patients with suspected severe AH in whom a liver biopsy was performed, 13 patients had a definite diagnosis of MIC, corresponding to 8% of our population. 2 The clinical presentation is in fact quite similar, especially the elevated bilirubin level (Table 1). Biological differences exist between the two groups (higher transaminases, triglycerides and cholesterol levels) but biopsy remains the test of choice to discriminate between the two entities (Table 1).…”

“…We would like to put forward our view, particularly following a recent publication from our group. 2 In our recent study, we describe a category of patients who present as (clinical) severe AH but whose histological diagnosis demonstrates a less common illness, namely acute alcohol-induced microvesicular steatosis (MIC). 2 During 3 years, out of 162 patients with suspected severe AH in whom a liver biopsy was performed, 13 patients had a definite diagnosis of MIC, corresponding to 8% of our population.…”

“…2 In our recent study, we describe a category of patients who present as (clinical) severe AH but whose histological diagnosis demonstrates a less common illness, namely acute alcohol-induced microvesicular steatosis (MIC). 2 During 3 years, out of 162 patients with suspected severe AH in whom a liver biopsy was performed, 13 patients had a definite diagnosis of MIC, corresponding to 8% of our population. 2 The clinical presentation is in fact quite similar, especially the elevated bilirubin level (Table 1).…”