Non-Alcoholic Fatty Liver Disease : Summary of the Guidelines

  Non-Alcoholic Fatty Liver Disease: Summary of the Guidelines

Prof. Dr. Mona Ahmed Amin

Professor of Internal Medicine & Hepatology

Cairo University

The definition of nonalcoholic fatty liver disease (NAFLD) requires that (a) there is evidence of hepatic steatosis, either by imaging or by histology and (b) there are no causes for secondary hepatic fat accumulation such as significant alcohol consumption, use of steatogenic medication or hereditary disorders

The histologic spectrum of NAFLD spans from generally benign, bland steatosis ( NAFL ) to steatosis with evidence of hepatocellular inflammation and damage (nonalcoholic steatohepatitis, or NASH), which may be complicated by progressive fibrosis and cirrhosis.

NAFLD is more frequent among people with diabetes (50%) and obesity (76%), and it is almost universal among diabetic people who are morbidly obese. Patients with NAFLD have increased overall mortality compared to matched control populations, the most common cause of death in patients with NAFLD, NAFL and NASH is cardiovascular disease, and patients with NASH (but not NAFL) have an increased liver-related mortality rate.

Diagnosis of NASH :

Most patients are suspected to have NAFLD because of characteristic appearance on hepatic ultrasonography and/or elevation of liver enzymes. Ultrasonographic examination for bright hepatic echotexture (compared with kidney and/or spleen), deep attenuation and vascular blunting[1] has adequate threshold for the detection of steatosis when more than 33% of hepatocytes contain fat, as shown by liver histology.

Computerized tomography (CT) scan and magnetic resonance imaging (MRI) are alternative imaging techniques for diagnosing fatty liver.

In patients with unsuspected hepatic steatosis detected on imaging who lack any liver-related symptoms or signs and have normal liver biochemistries, it is reasonable to assess for metabolic risk factors (e.g., obesity, glucose intolerance, dyslipidemia)

and alternate causes for hepatic steatosis such as significant alcohol consumption or medications.

In patients with unsuspected hepatic steatosis detected on imaging who are asymptomatic and have normal liver biochemistries, a liver biopsy cannot

be recommended.

When to obtain a liver biopsy in patients with NAFLD?

Liver biopsy remains the gold standard for characterizing liver histology in patients with NAFLD. However, it is expensive and carries some morbidity and very rare mortality risk. Th us, it should be performed in those who would benefit the most from diagnostic, therapeutic guidance, and prognostic perspectives.

1- live biopsy should be should be considered in patients with nafld who are at increased risk to have steatohepatitis and advanced fibrosis.

2- the presence of metabolic syndrome and the nafld fibrosis scoremay be used for identfying patients who are at risk for steatohepatitis and advanced fibrosis.

3 - liver biopsy should be considered in patients with suspected nafld in whom competing etiologies for hepatic steatosis and coexisting chronic liver diseases cannot be excluded without a liver biopsy

The management of patients with NAFLD consists of treating liver disease as well as the associated metabolic comorbidities such as obesity, hyperlipidemia, insulin resistance, and T2DM. As patients with NAFLD without steatohepatitis have excellent prognosis from a liver standpoint, treatments aimed at improving liver disease should be limited to those with NASH .

- Weight loss generally reduces hepatic steatosis, achieved either by hypocaloric diet alone or in conjunction with increased physical activity.

- Loss of at least 3 – 5 % of body weight appears necessary to improve steatosis, but a greater weight loss (up to 10 % ) may be needed to improve necroinflammation.

- Exercise alone in adults with NAFLD may reduce hepatic steatosis but its ability to improve other aspects of liver histology remains unknown.

- Metformin has no significant effect on liver histology and is not recommended as a specific treatment for liver disease in adults with NASH.

- Pioglitazone can be used to treat steatohepatitis in patients with biopsy-proven NASH. However, it should be noted that the majority of the patients who participated in clinical trials that investigated pioglitazone for NASH were non-diabetic and that long-term safety and efficacy of pioglitazone in patients with NASH is not established.

- Vitamin E ( ᾳ-tocopherol) administered at daily dose of 800 I U / day improves liver histology in non-diabetic adults with biopsy-proven NASH and therefore it should be considered as a first-line pharmacotherapy for this patient population. Until further data

supporting its effectiveness become available, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver

biopsy, NASH cirrhosis, or cryptogenic cirrhosis.

- UDCA is not recommended for the treatment of NAFLD or NASH.

- It is premature to recommend omega-3 fatty acids for the specific treatment of NAFLD or NASH but they may be considered as the first-line agents to treat hypertriglyceridemia in patients with NAFLD.

- Foregut bariatric surgery is not contraindicated in otherwise eligible obese individuals with NAFLD or NASH (but without established cirrhosis). The type, safety, and efficacy of foregut bariatric surgery in otherwise eligible obese individuals with established cirrhosis due to NAFLD are not established. It is premature to consider foregut bariatric surgery as an established option to specifically treat NASH.

- Given the lack of evidence to show that patients with NAFLD and NASH are at increased risk for serious drug-induced liver injury from statins, statins can be used to treat dyslipidemia in patients with NAFLD and NASH. Until RCTs with histological end points prove their efficacy, statins should not be used to specifically treat NASH.

REFERENCES

1- Chalasani N, MD, FACG1 , Zobair Younossi , MD, FACG2 , et al : The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the , American Gastroenterological Association . Am J Gastroenterol 2012; 107: 811– 826

2- Chalasani N, MD, FACG1, Zobair Younossi, MD, FACG2 Joel E. Lavine, MD, et al : The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the , American Gastroenterological Association . HEPATOLOGY 2012 ; Vol. 55, No. 6: 2005-2023