Referred patient with abnormal liver function tests (LFTs) are often asymptomatic and overweight (a little, at least). Assuming alcohol intake is not excessive, glucose intolerance/ diabetes and hypertriglyceridaemia need to be ruled out. Reactions to medications can raise suspicions but surprisingly, are unlikely as a major factor: statins are often blamed but are rarely responsible; more likely culprits are anti-inflammatories, anticonvulsants, and antibiotics.
Thinking of possibilities
Iron studies are important, to not miss haemochromatosis. However, ferritin, an acute phase reactant, commonly goes up with liver inflammation, even to levels of 1000, without implying iron overload. Transferrin saturation is the best indicator of haemochromatosis and the normal result here excludes the diagnosis.
Hep B surface antigen and Hep C antibodies should be checked, and an abdominal ultrasound to rule out overt pathology such as obstruction or secondaries. The presence or absence of fatty change on ultrasound is of little value in diagnosing NAFLD. Similarly, the ultrasound doesn’t confirm or refute cirrhosis.
Wilson’s disease is rare, so do not routinely test copper levels in adults unless there is some suggestion of neurological disturbance (including psychiatric issues).
Alpha-1-antitrypsin (AAT) deficiency can cause liver disease but patients are usually diagnosed because of pulmonary features. Measure AAT level in someone younger (< 25 years) or with more severe liver disease.
Anti-nuclear factor, anti-LKM and anti-mitochondrial ABs can suggest chronic active hepatitis or primary biliary sclerosis. I also check the INR. If prolonged, it points to a more serious derangement of liver function.
NAFLD outcomes
NAFLD runs a spectrum from non-alcoholic fatty liver (NAFL), which is relatively benign, to non-alcoholic steatohepatitis (NASH), which is associated with inflammation. Lifetime risk of NAFLD progressing to fibrosis is 36%, remaining stable 46%, and improving 21%; the risk is 2.5-fold higher with NASH compared to NAFL.
In addition, hepatocellular carcinoma (at least in European populations) is now more common in cirrhotic NAFLD patients than from end stage hepatitis B or C.
Risk factors for progression to fibrosis include older age, diabetes, hypertension, transaminase levels greater than twice normal (GGT doesn’t matter that much), and BMI greater than 28. Statins and coffee consumption seem to be protective. Metformin has not been shown to improve histological features of NASH; glitazones (e.g. pioglitazone) have, but the side effects (weight gain, fluid retention, bladder cancer) outweigh any potential benefit.
Weight loss remains the only therapy, which is both safe and proven to be effective.
Differentiating NAFL from NASH
It is important to differentiate NAFL from NASH. Liver biopsy is the ‘gold standard’ but has a significant morbidity (and mortality), so the search is on for non-invasive ways of separating the two.
The Hepascore is a locally validated calculation from a number of blood markers that predicts hepatic fibrosis and cirrhosis: a result below 0.5 makes fibrosis unlikely whereas a result above 0.80 gives a risk of cirrhosis of over 85%; it applies to patients with chronic hepatitis B and C, alcoholic liver disease and NAFLD and is best requested in patients where there is clinical concern, not everybody with a raised GGT.
Several imaging techniques have been studied. These include transient elastography, acoustic radiation force impulse imaging and magnetic resonance elastography (MRE), which seems the most promising, though costly. (Personally, I would happily pay for an MRI if it meant my liver didn’t need to have a needle stuck into it!)
The largest study in USA adults found no increase in mortality with either NAFL or NASH, though a smaller Swedish study did, most from cardiovascular disease rather than liver failure.
Control of lipids, blood pressure and diabetes thus remain cornerstones of therapy.
What to tell someone with a fatty liver?
Patients with a doubling of ALT, diabetes, or a raised ferritin should ideally abstain from alcohol and be aggressively encouraged to lose weight. But there is also a place for reassurance. Part of the liver’s job is to store fat. Ultrasound reports of fatty infiltration with minimal change in LFTs shouldn’t cause undue concern.
In this Case Report the most likely diagnosis is non-alcoholic fatty liver disease (NAFLD).
CASE REPORT
A 58 yo man presents for a check up. He is asymptomatic and has a history of hypertension and hyperlipidaemia. He takes perindopril and rosuvastatin. His BMI is 31.0. Blood results are:
Bilirubin 16 (< 16)
Alk Phos 215 (30 – 110)
GGT 250 (< 36)
ALT 100 (< 31)
Albumin 40 (36 – 48)
Fe 26 (11 – 27)
Transferrin 28 (20 – 45)
% sat 25% (15 – 55)
Ferritin 900 (30 – 300)
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