The article delves into nonalcoholic fatty liver disease (NAFLD), detailing its definition, epidemiological trends, histological progression, and contemporary management approaches encompassing lifestyle modifications and pharmacotherapy.

Definition

The "Nonalcoholic Fatty Liver Disease" (NAFLD) was defined by the American Association for the Study of Liver Disease (AASLD) in 2018, and their subsequent update in 2023, as an overarching term encompassing a condition in which a minimum of 5% of hepatocytes (liver cells) exhibit macrovesicular steatosis, without any identifiable alternative cause for this accumulation of fat in the liver.

These alternative causes may include substantial alcohol intake, medication usage, malnutrition, or rare genetic disorders [1,2]. In contrast, the European Association for the Study of Liver Disease (EASL) defines NAFLD as the excessive buildup of fat in the liver, often associated with insulin resistance (IR).

The diagnosis of NAFLD is typically established by the presence of steatosis (accumulation of fat) in more than 5% of hepatocytes, a determination that can be made through histological analysis or magnetic resonance imaging.

To diagnose NAFLD, secondary causes of steatosis must be ruled out, and individuals with daily alcohol consumption exceeding 30 grams for men and 20 grams for women are excluded from this diagnosis [3].

Epidemiology

1. NAFLD has emerged as the most prevalent liver disorder globally, affecting approximately 25% of the global population [4,5].
2. This escalating prevalence of NAFLD closely correlates with the increasing rates of obesity and metabolic comorbidities [6]. Remarkably, NAFLD can be found in approximately 90% of obese individuals, 60% of diabetics, and even 20% of individuals with normal weight [7-9].
3. As of 2017, NAFLD has become the second most common reason for liver transplantation in both the United States and Europe [11]. Projections indicate that the prevalence of NAFLD is expected to steadily rise to 33.5% by 2030, with around 27% of these cases progressing to NASH [6].
4. Consequently, the incidence of hepatic decompensation, Hepatocellular Carcinoma (HCC), and NASH cirrhosis-related mortality are also anticipated to increase two- to threefold by 2030 [6].
5. The histological spectrum of NAFLD ranges from simple steatosis (non-alcoholic fatty liver-NAFL), steatohepatitis with or without fibrosis ( non-alcoholic steatohepatitis – NASH), cirrhosis and hepatocellular carcinoma (HCC).

Current management of NAFLD

Adequate management of metabolic co-morbidities including diabetes, hypertension, dyslipidemia and obesity is paramount and may lead to liver-related benefits.

Statins if indicated from cardiovascular viewpoints are safe in the presence of raised transamineses and have been associated with improved insulin resistance and decreased risk of HCC in NAFLD patients.

1. Lifestyle interventions

Including dietary calorie restrictions and exercise targeting weight loss is the cornerstone in the management of NAFLD. Achieving a weight loss of ≥ 7% of the body weight leads to improvement of all features of liver histology, and of ≥10% of body weight leads to improvement of fibrosis [1-3].

A 1200-1600 calories restricted diet (30% reduction in the daily calorie intake) with preferable consumption of a Mediterranean diet is advised.

A daily exercise of 30-45 minutes per day (150-200 min per week) of moderate intensity (achieving 70% of the maximum heart rate) leads to improvement of NASH histology.

2. Pharmacotherapy

Currently, only two drugs ie Pioglitazone and Vitamin E are recommended by the international guidelines for the treatment of biopsy-proven NASH [1-3]. A third drug, Saroglitazar has been approved for patients with NASH only in India.

Several other drugs like metformin and ursodeoxycholic acid have been tried but are not recommended due to the lack of demonstrable benefit on liver histology.

1. Vitamin E 

1. Vitamin E is an anti-oxidant and in dosage of 800 IU/day in two divided doses has been shown to decrease hepatic steatosis, inflammation, and ballooning with improvement in NAFLD activity score (NAS) and NASH – resolution in the PIVENS trial.
2. It is considered in biopsy-proven non-diabetic NASH, although there is concern about increased risk of prostate cancer.
3. Concerns regarding the increased all-cause mortality with Vitamin E have been disapproved in a large meta-analysis.

2. Pioglitazone

1. Pioglitazone is a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist with an established anti-diabetic effect and has been shown to reduce steatosis, and hepatic transaminase level and improve histology.
2. It is recommended in a dose of 30 mg/day in biopsy-proven both diabetic and non-diabetic NASH. However, there are concerns about weight gain, risk of bladder cancer and an unsubstantiated cardiac risk.

3. Saroglitazar 

1. Saroglitazar is a dual PPAR agonist with a predominant PPAR-alpha effect and moderate PPAR-gamma effect. Thus it is helpful in dyslipidemia and insulin resistance, without being associated with typical glitazone side effects.
2. Saroglitazar in a dose of 4mg/day was approved by the Drug Controller General of India in March 2020 for use in NAFLD with comorbidities (obesity, diabetes mellitus, dyslipidemia or metabolic syndrome) or NASH with F-F3 fibrosis.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Vishal Bodh is an Associate Professor, in the Department of Gastroenterology at  AIMSS-Chamiana, Shimla.