NON ALCOHOLIC FATTY LIVER

- This is a spectrum of disorders characterized mainly by macrovesicular hepatic steatosis

- as a spectrum, the disease is comprise of mild fatty liver to a more severe form of NASH or even cirrhosis
- very important to exclude significant alcohol consumption
- NAFLD can lead to cirrhosis
- unfortunately, there is no Philippine data on the prevalence of NAFLD
- prevalence in neighboring countries range from 5 30%
- Etiology:
- Acquired metabolic disorders
- diabetes mellitus, dyslipidemia, kwashiorkor, marasmus, obesity, starvation
- DM, dyslipidemia and obesity are 3 most common causes of NAFLD
- cytotoxic or cytostatic drugs
- methotrexate, tetracycline, puromycin, azaserine,, azacitidine, l-asparaginase
- other drugs
- amiodarone, estrogens, glucocorticoids, tamoxifen
- metals
- inborn errors of metabolism
- abetalipoproteinemia, galactosemia, glycogen storage disease, Wilson disease
- surgical procedures
- biliopancreatic diversion, gastric bypass, extensive small bowel resection
- miscellaneous conditions
- inflammatory bowel disease, severe anemia, total parenteral nutrition

- Classification:
- Primary associated with metabolic syndrome
- obesity, diabetes, hypertriglyceridemia, hypertension
- Secondary fatty liver diseases with a proximate cause
- severe weith loss, total parenteral nutrition, iatrogenic, refeeding syndrome

- prevalence of NAFLD is increased in high risk population like those with DM, obesity and dyslipidemia

- Pathophysiology (theory)
- First hit fat accumulation in the liver occurs due to insulin resistance
- second hit cell injury and seatohepatitis occurs due to toxins, oxidative stress, drugs.
- This leads to morphological changes, inflammation and fibrosis or cirrhosis

Symptoms
- varies, depending on the spectrum of disease
- none to vague RUQ pains, fatigue, malaise
Signs
- there may be signs of chronic liver disease like hepatomegaly, splenomegaly, spider angioma,
ascites, etc

Laboratory
- elevations in ALT, AST with AST/ALT ratio <1 compared to alcoholic (>2)
- elevations in ALP, serum ferritin, transferrin saturation
- may have normal bilirubins, albumin
- ANA is low titer

Imaging
- Ultrasound hyperechoic or increased echogenicity consistent with steatosis
- CT scan hypodensity compared to spleen
- MRI fat appears bright on T1-weighted imaging

Histopathology
- resembles alcohol induced liver disease
- steatosis (>5% fats)
- steatohepatitis (steatosis with parenchymal inflammation
- may or may not have focal necrosis
- varying degress of fibrosis including cirrhosis
- lobular inflammation is the hallmark of NASH
- steatosis more severe in NASH than alcohol hepatitis
- perisinusoidal fibrosis is most common
- risk of cirrhosis increased in obese patients

Diagnosis
- based on clinical and histologic data
- exclude other liver disease
- exclude alcohol (20-40 gm/day)
- liver biopsy will not affect management
- best prognostic indicator is histology
- non-invasive markers of fibrosis
- fibrotest is a panel of blood test
- clinical fibrosis scoring
- NAFLD fibrosis (age, BMI, hyperglycemia, AST/ALT ratio, platelet count, albumin)
- BARD
- APRI
- elastography
- fibroscan will quantify liver stiffness and estimate fibrosis

Natural history
- unknown due to lack of studies
- generally benign if without necrosis or fibrosis
- can lead to cirrhosis, liver failure or hepatocellular carcinoma
- 20% of NASH will lead to cirrhosis of which 30-40% can have liver related deaths

Treatment
- depends on predisposing or risk factors
- avoid toxin
- exercise and diet
- anti diabetic agents of insulin sensitizing agents
- lipid lowering agents
- anti oxidants
- iron reduction by phlebotomy
- inflammatory mediators
- bariatric surgery
- liver transplant