User:Pal Manickam

Non Alcoholic Fatty Liver Disease (NAFLD)

Definition:

A condition where liver is accumulated with fat and usually associated with metabolic conditions. Risk factors for NAFLD included obesity, diabetes and dyslipidemia. During the last decade NAFLD has reached epidemic proportions even in pediatric population.

Categories:

NAFLD is sub categorixed into non alcoholic fatty liver (NAFL) and non alcoholic steatohepatosis (NASH). NAFL has just fat accumulation whereas NASH has fat as well as inflammation of the liver tissues.

Prevalence of NAFLD:

Prevalence varies widely and it depends on age, sex and race of the population. Studies show that men are at highest risk for NAFLD, 31% in men Vs 16% in women. Compared to non-Hispanic whites, Hispanics have higher prevalence of NAFLD.

Who are at High Risk: People with the following conditions are at high risk to develop NAFLD,

       Obesity, Type 2 diabetes mellitus, Dyslipidemia, Metabolic syndrome,  Polycystic ovary syndrome,

Hypothyroidism, Obstructive Sleep apnea, Hypopituitarism, Hypogonadism, Pancreato-duodenal resection.

When to Obtain a Liver Biopsy in Patients with NAFLD?

Liver biopsy will be needed when the diagnosis of liver disease is uncertain and other causes need to be ruled out.

Is there a screening test?!

Due to the increased morbidity and mortality, a screening test if present will be helpful. But, in most cases liver function will be normal and cannot be a good sensitive test. USG of liver will give more helpful information about the liver but it is expensive making screening test less affordable. SO, high risk patients are offered USG of liver.

                         Management of NAFLD

Initial step - Making the diagnosis:

1 Diagnosis of NAFLD requires that (a) there is hepatic steatosis by imaging or histology, (b) there is no significant alcohol consumption, (c) there are no other causes for hepatic steatosis, and (d) there are no co-existing causes for chronic liver disease.

2 Exclude other causes of hepatic steatosis like significant alcohol consumption, hepatitis C, medications, parenteral nutrition, Wilson’s disease, and severe malnutrition, other chronic liver disease including hemochromatosis, autoimmune liver disease and chronic viral hepatitis.

3 Liver biopsy is the gold standard for characterizing liver histology in patients with NAFLD. Due to procedural risk, cost, it should be performed in those who would benefit the most from diagnostic, therapeutic guidance, and prognostic perspectives.

Treatment:

            Treatment of  NAFLD includes treating liver disease as well as the associated metabolic co-morbidities 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. Lifestyle modification will reduce aminotransferases and improve hepatic steatosis when measured by ultrasound. Exercise programs consisted of 2–3 sessions a week of

30 – 60 minutes over a period of 6 to 12 weeks and showed liver fat content diminished without a significant change in body weight.

Effect of exercise and diet on NAFLD:

             Multiple studies have shown that Weight loss generally reduces hepatic steatosis evidenced by USG/imaging studies. It can be done by low caloric diet alone or with increased physical activity. Loss of at least 3–5% of body weight appears 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.

Role of metformin in NASH:

Few sudies have shown that metformin might help NASH and decrease aminotranferase levels. However, a pen label study found that Metformin has no significant effect on liver histology and is not recommended as a specific treatment for liver disease in adults with NASH.

Pioglitazone and NASH:

         Pioglitazone can be used to treat steatohepatitis in patients with biopsy-proven NASH. But, the caveat in the study which showed the benfit is that majority of the patients who took pioglitazone for NASH were non- diabetic and that long term safety and efficacy of this drug in patients

with NASH is not established.

Oxidative stress and Vitamin E:

         Oxidative stress has been long considered a mechanism of hepatic injury. hence, Vitamin E administered at daily dose of 800 IU/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. However, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.

Other treatment considerations for NASH:

            Statins can be used to treat dyslipidemia in patients with NAFLD and NASH. Until RCTs with histological endpoints prove their efficacy,

statins should not be used to specifically treat NASH.

            Ursodeoxy cholic acid is not recommended for the treatment of NAFLD or NASH.

            Omega-3 fatty acids is not recommended 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.

            Patients with NAFLD should not consume heavy amounts of alcohol.

            Foregut bariatric surgery is not contraindicated in otherwise eligible obese individuals with NAFLD or NASH (but with- out established cirrhosis).

            Patients with NASH cirrhosis should be screened for gastroesophageal varices according to the AASLD/ACG practice guidelines. Patients with NASH cirrhosis should be considered for HCC screening according to the AASLD/ACG practice guidelines. Do need to repeat liver biopsy in patients with NAFL or NASH.

To see a Specialist:

           Patients with steatohepatitis on liver biopsy be followed by a hepatologist. Patients with nonalcoholic fatty liver without steatohepatitis can be followed by a primary care physician, provided the diagnosis is clear.

            Patients who develop cirrhosis and have complications (eg, ascites, variceal bleeding) or a model for end-stage liver disease (MELD) score ≥10 will be referred for a liver transplantation evaluation.