Non-Alcoholic Fatty Liver Disease (Burns 3/25/2020)

Thanks to Dr. Autumn Burnes for being such a wonderful and flexible first presenter on our new Virtual Social Distancing Zoom Grand Rounds at SSRRH. It was really nice to take 45 minutes to think about something other than COVID-19. We had over 35 attendees. . .Thanks to everyone who tuned in!

The topic was Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH).

NAFLD: histologic evidence of an accumulation of fat in hepatocytes (steatosis)
NASH: the presence of NAFLD plus liver cell injury and death, and accumulation of inflammatory cells

Some shocking stats:

• 25% of US adults are affected by NAFLD 

  

  (NEJM 2017, https://www.nejm.org/doi/full/10.1056/NEJMra1503519)

• 5% have NASH
• NASH is among the top 3 indications for liver transplant and will likely surpass Hepatitis C and Alcohol cirrhosis in the coming years
• 70% of Type 2 diabetics have NAFLD (!!)

MOST COMMON risk factors include metabolic syndrome: abdominal obesity, impaired glucose tolerance/diabetes, hypertension, dyslipidemia

LESS COMMON risk factors include nutritional syndromes, drugs and toxins, inherited metabolic diseases, and pregnancy-related factors:

• TPN, rapid weight loss, jejunoileal bypass
• EtOH, corticosteroids, tamoxifen, amiodarone, methotrexate, industrial solvents
• Lipodystrophy, abetalipoproteinemia, Wilson's
• Acute fatty liver of pregnancy, HELLP 

NAFLD is a diagnosis of exclusion.

You should consider other causes of chronic liver disease, including (but not limited to): chronic viral hepatitis, hemachromatosis, autoimmune liver disease, alpha1antitrypsin deficinecy, Wilson's disease, drug induced liver disease)

NAFLD (by AASLD criteria):

1. Hepatic steatosis by imaging or histology [>5% hepatocytes, +ballooning/hepatocyte injury for NASH]
2. No significant alcohol consumption [>1 drink/day for F and 2 drinks/day M]
3. No competing etiologies for hepatic steatosis
4. No coexisting causes of chronic liver disease
5. Liver biopsy is gold standard

What is our primary care role ?

Consider using this AAFP approach to elevated liver enzymes in your primary care practice (this is a picture of Figure 1 from AAFP 2017 article, entire article can be found here: https://www.aafp.org/afp/2017/1201/p709.html)

(AAFP 2017)

It's frustrating and scary to not have much to offer patients who already have cirrhosis from NASH, so can we intervene sooner?

We don't have great tools to distinguish those who will go onto develop NASH from the large population that has NAFLD. But we know that risk of progression is multifactorial including genetic factors, epigenetic factors, and environmental (e.g. shift work, gut microbiome, toxins).

Here are two risk calculators (links should work):
NAFLD Fibrosis Score (Age, BMI, IGT/DM, AST, ALT, platelet count, albumin)
Fibrosis- 4 (Fib-4) Index for Liver Fibrosis (Age, AST, ALT, platelet count)

Routine screening for NASH is currently NOT recommended (by AASLD, USPSTF, or NICE guidelines) BUT we should have a high index of suspicion, particularly in our Type 2 diabetic patients, and we might consider either using the Fib-4 calculator to risk stratify OR send for elastography (specialized ultrasound).

However, for those of you who are looking for screening guidelines, here is a paradigm for HIGH risk patients:

There are evolving pharmacologic treatment options, including:

• Thiazolidinediones (pioglitazone), even in patients without diabetes  (some possible benefit in the PIVENS trial)
• GLP-1 agonists (very small study LEAN trial, too early to know)
• Vitamin E  (800 IU/day, recommended by AASLD only in biopsy-proven NASH)
• Keep taking statin if it is indicated (despite hepatotoxicity)
• (Metformin has NO benefit)

Mortality in NAFLD:

• Cardiovascular disease is the most common cause of death in patients with NAFLD, independent of other metabolic comorbidities. 
• we should treat CVD proactively
• Cancer
• Liver-related death
• Increased all-cause mortality