Liver autoantibody Screen/ Liver Kidney Stomach (LKS) Screen

This test is a screen for autoimmune liver disease with the ability to detect smooth muscle, LC1 and LKM antibodies, seen in autoimmune hepatitis, and mitochondrial antibodies (AMA), seen in primary biliary cholangitis (PBC). Gastric parietal cell antibodies can also be detected (see GPCA).

PBC is a chronic T cell mediated autoimmune cholestatic disease featuring granulomatous destruction of biliary epithelial cells resulting in cholestasis, fibrosis and end stage liver disease. It is most commonly found in women around 50 years old. Symptoms include bone and joint aches, hyperlipidaemia, fatigue, pruritus, abdominal pain and dry eyes and mouth. PBC is characterised by raised alkaline phosphatase (ALP) and polyclonal IgM. Around 90% of PBC patients have AMA. Nine different AMA specificities have been described (M1-M9), of which the M2 antibodies directed against the 2-oxo-acid dehydrogenase complex (PDC-E2, OGDC-E2, BCOADC-E2) are most clinically relevant. Some PBC patients are positive for PBC-specific ANA only (gp210, PML, SP100) and these patients may have more rapidly progressive disease refractory to standard treatment. The 2018 British Society for Gastroenterology/UK-PBC Guidelines state that the presence of AMA at titres >1/40 or presence of PBC-specific ANA plus evidence of cholestatic liver biochemistry (repeatedly raised ALP and gamma-glutamyl transferase (GGT)) is sufficient for a diagnosis of PBC.

Positive AMA in the absence of abnormal liver function tests or symptoms has uncertain clinical significance (low titre AMA have been reported in 0.5% of the healthy population), current recommendations are to repeat LFT annually in these patients.

Autoimmune hepatitis is a chronic, inflammatory liver disease which, if untreated, often leads to cirrhosis and liver failure. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (ASP) are persistently raised, usually with hyperglobulinaemia. Common presenting symptoms include fatigue, anorexia, nausea, joint pain and weight loss although 25% of patients are asymptomatic at diagnosis. The diagnosis of AIH is based on the presence of autoantibodies, elevated IgG, typical histology and a negative viral hepatitis screen. AIH type 1 is seen in adults and associated with smooth muscle antibodies (80%), which react against a variety of cytoskeletal filaments (filamentous-actin (F-actin), vimentin, desmin, cytokeratin, and tubulin). F-actin antibodies at high titre are strongly associated with AIH type 1. AIH type I is also associated with ANA (60%) and SLA/LP antibody (15%). Juvenile onset type 2 AIH is associated with LKM1 (directed against the cytochrome P45 II D6) and LC-1 (targeting formiminotransferase cyclodeaminsae) antibodies.

There is no known molecular target for around 30% of ANA positive AIH patients and therefore ANA (hep2) immunofluorescence remains the gold standard for their detection. Additionally a small proportion of AIH 1 patients are solely positive for SLA antibody which is difficult to detect by LKS IIF. Where there is high suspicion of AIH but a negative SMA and ANA please contact the laboratory to add on the liver immunoblot to screen for SLA antibody.

This test is performed by indirect immunofluorescence (IIF) on mouse liver/kidney/stomach tissue. Positive samples are then confirmed by liver antibody immunoblot to confirm mitochondrial antibody specificity and screen for SLA in AIH.

Suspected autoimmune liver disease (AIH, PBC)
Unexplained deranged liver function tests
Unexplained fatigue/pruritus/right upper quadrant discomfort/dry eyes

Negative