Pathologic Diagnosis of Nonalcoholic Fatty Liver Disease

Abstract

Context.— Nonalcoholic fatty liver disease (NAFLD) encompasses steatosis and steatohepatitis. The cause may be multifactorial, and diagnosis requires correlation with clinical information and laboratory results. Objective.— To provide an overview of the status of histology diagnosis of steatosis, steatohepatitis, and associated conditions. Data Sources.— A literature search was performed using the PubMed search engine. The terms ‘‘steatosis,'' ‘‘steatohepatitis,'' ‘‘nonalcoholic fatty liver disease (NAFLD),'' ‘‘nonalcoholic steatohepatitis (NASH),'' “alcoholic steatohepatitis (ASH),” ‘‘type 2 diabetes (T2DM),'' “cryptogenic cirrhosis,” “drug-induced liver injury (DILI),” “immune checkpoint inhibitor therapy,” and “COVID-19 and liver” were used. Conclusions.— Nonalcoholic fatty liver disease has become the most common chronic liver disease in the United States. NASH is the progressive form of nonalcoholic fatty liver disease. The hallmarks of steatohepatitis are steatosis, ballooned hepatocytes, and lobular inflammation. NASH and alcoholic steatohepatitis share similar histologic features, but some subtle differences may help their distinction. NASH is commonly seen in patients with metabolic dysfunction but can also be caused by other etiologies. Examples are medications including newly developed immune checkpoint inhibitors and viral infections such as coronavirus disease 2019 (COVID-19). NASH is also a common cause of cryptogenic cirrhosis but can be reversed. The results from recent clinical trials for NASH treatment are promising in reducing the severity of steatosis, ballooning, and fibrosis.

Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study

“…The new lifestyles derived from the lockdown have caused a statistically significant increase in obesity and overweight, which can be quantified with an increase in weight, BMI, percentage of fat mass, and abdominal perimeter as well as alterations in the lipid profile, simultaneously leading to a worsening of the obesity pandemic and an increase in metabolic pathologies [ 41 , 42 ] such as metabolic syndrome, insulin resistance in both the diabetic and non-diabetic individuals, and a greater risk of developing NAFLD [ 43 ], as seen in Table 2 and Table 3 , all of which affect the adult population worldwide [ 44 , 45 ], with metabolic syndrome representing the most frequent chronic liver disease in the United States [ 46 ].…”

Renal Transporter Alterations in Patients with Chronic Liver Diseases: Nonalcoholic Steatohepatitis, Alcohol-Associated, Viral Hepatitis, and Alcohol-Viral Combination

“…Although there have been several investigations of hepatic transporter alterations in CLD patients, resulting in the identification of dosing adjustments, there is nothing known regarding alterations of renal transporters in these patients (Droździk et al, 2020). The shortage of information is multifactorial, but the primary limitations include discrepancies in diagnosing CLD etiology, inaccuracy of kidney function assays to indicate renal biopsy evaluation, and invasiveness of biopsy procedures (Beben and Rifkin, 2015;Porrini et al, 2019;Younossi et al, 2019;Wieliczko et al, 2020;Lai et al, 2021). Combined, these limitations hinder clinical studies by restricting sample availability.…”

Exosomal microRNAs and Progression of Nonalcoholic Steatohepatitis (NASH)

“…Liver biopsy has been used as the golden standard for the diagnosis of NASH [ 2 , 3 , 4 , 5 , 6 ]. Although some advanced imaging techniques, such as MRI, could be helpful for the diagnosis of NASH, our recent clinical trial showed that changes in hepatic fat content measured by MRI do not predict treatment-induced histological improvement of steatohepatitis [ 3 ].…”

“…Although some advanced imaging techniques, such as MRI, could be helpful for the diagnosis of NASH, our recent clinical trial showed that changes in hepatic fat content measured by MRI do not predict treatment-induced histological improvement of steatohepatitis [ 3 ]. The histologic hallmarks of NASH are steatosis ( Figure 1 A), ballooned hepatocytes, and inflammation ( Figure 1 B) [ 2 , 7 ]. Steatosis is the simplest form of fatty liver disease characterized by the presence of fat droplets in hepatocytes without other abnormal findings.…”

“…Nonalcoholic fatty liver disease (NAFLD)/metabolic associated fatty liver disease (MAFLD) is becoming a public health problem worldwide [ 1 ]. Recent epidemiologic studies have shown that NAFLD has become the most common chronic liver disease in the United States, and it was estimated to have a prevalence of 34% in the general population based on screening using liver proton magnetic resonance spectroscopy [ 2 , 3 , 4 , 5 , 6 ]. Steatosis and steatohepatitis are the most common morphologic patterns of liver injury in patients with NAFLD, which are commonly seen in liver biopsy specimens from patients with obesity, diabetes, hyperlipidemia, hypertension, and the use of certain drugs.…”