What is the treatment for hepatomegaly and fatty infiltration (steatosis) of the liver?

From the Guidelines

Treatment for hepatomegaly and fatty liver disease should primarily focus on lifestyle modifications, including a hypocaloric diet and regular exercise, as recommended by the American Gastroenterological Association 1. The most effective approach is gradual weight loss through a balanced diet, aiming for 0.5-1 kg per week until reaching a healthy weight. Patients should follow a Mediterranean-style diet rich in fruits, vegetables, whole grains, and lean proteins while avoiding processed foods, sugary beverages, and alcohol.

• Key components of the diet include:
  • Minimizing saturated fatty acid intake specifically from red and processed meat
  • Limiting or eliminating consumption of commercially produced fructose
  • Targeting 1200–1500 kcal/d or a reduction of 500–1000 kcal/d from baseline for clinically significant weight loss
• Regular physical activity of at least 150 minutes per week of moderate-intensity exercise helps reduce liver fat and improve insulin sensitivity, as supported by the study 1. For patients with diabetes, tight glycemic control is crucial, often requiring medications like metformin or pioglitazone. Vitamin E may benefit non-diabetic patients with biopsy-proven non-alcoholic steatohepatitis, as suggested by the study 1. Management of concurrent conditions like hypertension and dyslipidemia is also important, as emphasized in the guidelines 1.
• These interventions work by reducing fat accumulation in the liver, decreasing inflammation, and improving insulin sensitivity, which collectively help reverse hepatomegaly and fatty infiltration while preventing progression to more severe liver disease. It is essential to note that the effect of other specific hypocaloric diets, such as low-carbohydrate/high-protein diets, meal replacement protocols, intermittent fasting, and vitamin supplementation, on histologic NAFLD end points have not been studied adequately to support their routine use in NAFLD-specific treatment, as stated in the study 1.

From the Research

Hepatomegaly and Fatty Infiltration of the Liver Treatment

• Hepatomegaly, or enlargement of the liver, can be caused by various conditions, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) 2, 3, 4.
• NAFLD is a continuum of liver abnormalities, ranging from simple steatosis to NASH, fibrosis, cirrhosis, and hepatocellular carcinoma 2.
• The treatment of NAFLD and NASH typically involves lifestyle modifications, such as weight loss, exercise, and a healthy diet 3, 4.
• Currently, there is no FDA-approved treatment for NAFLD and NASH, but several off-label medications are used to target disease risk factors, such as obesity and insulin resistance 4.
• Research is ongoing to investigate the beneficial effects of different drugs and phytochemicals in NASH, including antifibrotic drug candidates that target metabolic pathways, insulin resistance, hepatocyte death, and inflammatory cell recruitment 3.

Diagnostic Procedures

• Liver biopsy remains the gold standard for diagnosis of NAFLD, despite its limitations, such as sampling variability, invasive nature, and high cost 5.
• Non-invasive biomarkers, including serum markers and imaging modalities, are being developed to detect the presence of steatosis, NASH, or advanced fibrosis 5.
• Ultrasound is suggested as a first-line screening tool for defining steatosis in a selected population, while diagnosis of NAFLD requires exclusion of other chronic liver disease etiology or other steatosis causes 5.

Therapeutic Interventions

• Lifestyle modifications, such as weight loss, exercise, and a healthy diet, are the basis for prevention and treatment of NAFLD-associated fibrosis 3.
• Investigational drugs, such as the farnesoid X receptor agonist obeticholic acid, the pan-PPAR agonist lanifibranor, and the chemokine receptor CCR2/CCR5 inhibitor cenicriviroc, have shown promising results in the treatment of liver fibrosis 3.
• Combinatorial drug treatment and effective lifestyle changes may hold the greatest prospects for tackling NAFLD-associated fibrosis 3.