If the standard liver test panel is abnormal
Capsule Summary: If the standard liver test panel [i] is abnormal go straight to the Standard Liver Etiology Panel (below), regardless of duration and magnitude of the abnormality. Authority: British Society of Gastroenterology Guideline 2018 [ii].
Background: Some current US guidelines still advocate repeat testing and different approaches for mild and moderate increases and duration of abnormality [iii]. The British Society of Gastroenterology has determined that these many rules are confusing in primary care and patients are falling through the cracks. A simplified bright line rule makes it easier to detect patients who require specialist referral early: If the standard liver test panel i is abnormal go straight to the Standard Liver Etiology Panel (below), regardless of duration and magnitude of the abnormality.
The Standard Liver Disease Etiology Panel
|The Standard Liver Etiology Panel should be ordered if the standard liver test panel shows abnormalities. It consists of:
The burden of liver disease is quickly rising, mostly due to the obesity epidemic. For example, the prevalence of decompensated cirrhosis in the US from non-alcoholic fatty liver disease is projected to increase by 180% from 2015 to 2030 (from 134,000 to 376,000 cases) [iv].
Somehow patients with abnormal liver blood tests are falling through the cracks. About half of patients who eventually are diagnosed by somebody with end-stage liver disease – without a prior diagnosis of liver disease – were previously noted to have abnormal liver blood tests in their medical record suggesting that this was not further investigated [v].
It is quite underappreciated that the most common causes of abnormal liver blood tests resulting in end-stage chronic liver disease —namely non-alcoholic fatty liver disease, alcohol-related liver disease and hepatitis C — are frequently associated with only mild or moderate liver blood test abnormalities.
When to obtain a standard liver blood test panel?
The standard panel: bilirubin, albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT), together with a full blood count if not already performed within the previous 12 months
- Non-specific symptoms
- Evidence of chronic liver disease
- High risk for developing liver disease
- Preexisting autoimmune diseases
- Inflammatory Bowel Disease
- Use of hepatotoxic drugs
- Examples: carbamazepine, methyldopa, minocycline, macrolide antibiotics, nitrofurantoin, statins, sulfonamides, terbinafine, chlorpromazine and methotrexate.
- Family history of liver disease
- Suspicion of viral hepatitis
- Obesity and type 2 diabetes
If the standard liver blood test panel is abnormal, what’s next?
Obtain the Standard Liver Etiology Panel (box above). For the rationale in detail, see the guideline ii.
When to refer?
Marked abnormalities, acute disease, ill-appearing
If patients have marked abnormalities of liver blood tests, synthetic failure (high INR), and/or suspicious clinical symptoms/signs, an urgent consultation with a hepatologist or gastroenterologist with an interest in liver disease, if necessary, by phone, is recommended.
Mild to moderate abnormalities
If the Standard Liver Etiology Panel shows an abnormality, items on the Extended Liver Disease Etiology Panel can be ordered based on the abnormality found, but specialist referral is also an option. If the Standard Liver Etiology Panel shows no clear cause, the entire Extended Liver Disease Etiology Panel (below) may be ordered, however, at this stage specialist referral will be chosen by many primary care providers.
Liver etiology panels for patients with non-acute abnormal liver blood tests
|Standard Liver Etiology Panel||Extended Liver Etiology Panel|
|Viral hepatitis||Hepatitis B surface antigen AND hepatitis C antibody (with follow-on PCR if positive)||Anti-HBc and anti-HBs hepatitis B DNA quantification of hepatitis delta in high-prevalence areas|
|Iron overload||Ferritin AND transferrin saturation||Hemochromatosis gene testing|
|Autoimmune liver disease
|Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins||Anti-LKM antibody and celiac antibodies
(consider ANCA in the presence of cholestatic liver blood tests)
|Metabolic liver disease||Alpha-1-antitrypsin level; thyroid function tests; ceruloplasmin (age >3 and <40 years) ± urinary copper collection|
ANCA, antineutrophil cytoplasmic antibodies; LKM, liver kidney miscrosome; PCR, polymerase chain reaction; PSC, primary sclerosing cholangitis. Source: Guidelines on the management of abnormal liver blood tests ii.
NASH and NAFLD
The topic it without the scope of this post, and will be a topic of a future post.
Dr. Klaus Gottlieb, with office hours in San Luis Obispo, CA, and Templeton, CA, has a special interest in liver disease. For appointments, follow this link.
[i] The standard panel: bilirubin, albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT), together with a full blood count if not already performed within the previous 12 months
[ii] Newsome PN, Cramb R, Davison SM, Dillon JF, Foulerton M, Godfrey EM, Hall R, Harrower U, Hudson M, Langford A, Mackie A. Guidelines on the management of abnormal liver blood tests. Gut. 2017 Nov 9:gutjnl-2017.
[iii] Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. The American journal of gastroenterology. 2017 Jan;112(1):18.
[iv] Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2017 Aug 12.
[v] Williams R, Aspinall R, Bellis M, et al. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet 2014;384:1953–97