Epidemiology & Definitions
NAFLD
- Affects 1/3 of adults in the United States
- Between 1998 and 2012, NHANES data showed a 68% increase of NAFLD prevalence (Ruhl & Everhart, 2015).
- is expected to become the leading reason for liver transplantation within the next two decades (Zezos & Renner, 2015)
- considered the liver manifestation of metabolic syndrome
- Obese and diabetic patients have the highest prevalence. Rates in obese patients can be as high as 90%.
- has two categories: Nonalcohlic fatty liver (NAFL) and Nonalcoholic steatohepatitis (NASH).
NAFL
- steatosis that occurs in the presence of metabolic risk factors and the absence of alcohol abuse
- Inflammation and fibrosis ARE NOT present
- not usually associated with increased morbidity/mortality, but patients should be monitored for impaired glucose tolerance/Type 2 Diabetes Mellitus if not already present
- generally benign unless patients move over into NASH category
NASH
- steatosis as in NAFL, but with inflammation and fibrosis.
- occurs in an estimated 20% of those with NAFLD and is the more concerning form (Spengler & Loomba, 2015)
- Up to 20% of patients with NASH can develop cirrhosis and Hepato Cellular Carcinoma (Nones et al., 2017; Stal, 2015).
- associated with increased morbidity/mortality from liver complications and cardiovascular disease.
- Presence of fibrosis can only be graded using biopsy but there are noninvasive methods to estimate the amount of fibrosis (see diagnosis module). The Kleiner scale (Kleiner et al., 2005) is used to grade biopsy results. 0 = no fibrosis 1 = mild fibrosis 2 = moderate fibrosis 3 =advanced fibrosis 4 = cirrhosis .
- NASH progresses through each fibrosis stage at a rate of one stage every 7.7 years (Calzadilla-Bertot & Adams, 2016).
Pathophysiology
- NAFLD is a spectrum of disease.
- hard to predict who will stay in benign NAFL stage and who will progress to NASH – genetics influences much of this pathophysiology is complex and still incompletely understood.
- Poor diet, high caloric intake, high fructose/sucrose intake, and changes in intestinal flora are all proposed mechanisms that can lead to cell injury and inflammation in NAFLD (Byrne, 2015).
- genetics partially involved – PNPLA3 gene
- NAFLD is also associated with several chronic conditions including cardiovascular disease and chronic kidney disease (Byrne, 2015).
- Even though persons with NASH have an increased risk of liver related mortality compared to non-NASH counterparts, Cardiovascular disease (CVD), not liver failure, is the leading cause of mortality in individuals with both NAFL and NASH. Compared to patients without NAFLD, patients with NAFLD experience more elevations in triglycerides and very low density lipoproteins as well as decreases in high density lipoproteins (Chatrath, Vuppalanchi, & Chalasani, 2012). NAFLD also predisposes patients to hypertension.
- Some people can develop “nonobese NAFLD” or Lean NAFLD. This is particularly true of Asian patients who exhibit overweight complications at a lower BMI compared to their non-Asian counterparts. In fact, experts recommend a BMI greater than or equal to 25 kg/m2 constitutes obesity in Asians (whereas non-Asians are not categorized as obese until a BMI of 30 kg/m2 ) (Aby & Saab, 2017).
- Alcoholic fatty liver disease and Non-alcoholic fatty liver disease can present in similar fashions (elevated ALT/AST, steatosis on ultrasound). Collecting a good history is key in differentiating the two (see diagnosis module).
- Research suggests that there is a probable link between NAFLD and Chronic Kidney Disease, though research is still examining the extent of this association and the mechanism is not fully understood (Marcuccilli & Chonchol, 2016; Musso et al., 2016).
- NAFLD is prevalent in patients with COPD, though it is too early to conclude if there is a shared pathophysiologic mechanism or more than chance association (Lonardo, Nascimbeni, & Ponz de Leon, 2017; Viglino et al., 2017)
Case Study – Epidemiology/Pathophysiology
A 45 year old Asian male presents to your clinic to establish care. His weight is 155 lbs and his height is 5 ft 3 inches. He is taking metformin 500mg BID for metabolic syndrome diagnosed 3 years ago (HgB A1C was 6.0) and he also uses a CPAP for sleep apnea diagnosed 5 years ago. He recently underwent a cardiac stent a year ago for 85% occlusion of the left anterior descending artery. He saw a hepatologist six months ago for elevated AST/ALT (AST= 35/ALT=62) and underwent biopsy which showed steatosis with inflammation and stage 1 liver fibrosis. His hepatologist wants to see him back in 3 years and recommended healthy diet and exercise and close management of his metabolic comorbidities. You checked his AST/ALT today and found them to be 25 IU/I and 32 IU/I respectively. Calculate his BMI and describe the pathophysiology involved for this patient.