Autoimmune liver disease for the non-specialistBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b3305 (Published 08 September 2009) Cite this as: BMJ 2009;339:b3305
All rapid responses
We read the practical review on autoimmune liver disease (1) and
considered of interest to emphasize the diverse forms of presentation of
autoimmune hepatitis (AIH). This progressive liver disease of unknown
etiology may be associated with immune-mediated disorders. Genetic
predisposition, triggering factors such as viral infections or drugs, and
altered immunoregulation are implicated in its pathogenesis (2-4).
Methotrexate (MTX), a folic acid antagonist, improves symptoms minimizing
joint damage in rheumatoid arthritis (RA) (4). We describe the first RA
patient receiving MTX who developed severe AIH resolved with
A 57-year-old man with RA diagnosed in December-2000 received MTX, 15
mg weekly. On July-03 he presented with asthenia, jaundice, weight lost
and liver tests (LFT) alterations: prothrombine time (PT) 15 sec, albumin
3.2 g/dl, total bilirubin (TB) 3.3 mg/dl, AST 1242 IU/l, ALT 1715 IU/l,
gamma-GT 196 IU/l and alkaline phosphatase 167 IU/l. He was hospitalized
with probable toxic hepatitis, remaining asymptomatic although LFT
worsened (TB 6.8 mg/dl, AST 1175 UI/l, PT 17 sec and albumin 2.9 g/d).
Serology showed 1/160 ANA positivity ( previously negative),
gammaglobulin 2.1 g/dl and IgG 1890. Biopsy found typical AIH:
architectural distortion caused by perivenular and lobular confluent and
bridging necrosis, portal tracts enlargement by intense inflammatory
plasma cells infiltrate , foci of interface hepatitis, marked liver-cell
damage within parenchyma with regenerative changes, and intra-acinar
necrosis with plasma cells infiltration (Figure). Diagnostic score >7
denoted definite AIH (6). Metilprednisone (80 mg/day) was initiated: at
day 3 a decrease of transaminases (AST 216 UI/l, ALT 644 IU/l) and TB (4.3
mg/dl) appeared, with PT (13 sec) and albumin (3.3) improvement. On
tapering corticosteroids, at month 5 LFT normalized: TB 0.6 mg/dl, AST
26 UI/l, ALT 38 UI/l, PT 12 sec, albumin 3.5 mg/dl, gammaglobulin 1.7 g/dl
and IgG 1670. After 6 years follow-up, LFT persist normal.
Liver involvement in RA is usually slight (7). Our patient received
MTX for RA and developed severe liver damage. The damage induced by MTX
range from steatosis to cirrhosis, being acute inflammation and necrosis
rare (8). MTX causes liver folate depletion and, although its relationship
with hepatic damage has not been established, folinic acid supplementation
reduces AST/ALT levels. LFT changes and autoimmunity alterations
(previously absent) occurred in this patient, and histology diagnosed
AIH. As AIH appeared during MTX course and a successful corticosteroids
response was attained, this hepatic autoreactivity could be more probably
related to MTX than just a manifestation of RA. This case highlights
that breakdown of immune tolerance by drugs may trigger liver
autoreactivity (9-11), that difficulties in establishing a diagnosis of
AIH instead of toxic damage exist, and that rapid corticosteroids
therapy is effective.
Ricardo Moreno-Otero M.D., María Trapero-Marugán M.D. and Luisa
Digestive Diseases Service and Centro de Investigación Biomédica en
Red (CIBEREHD), Instituto De salud Carlos III, Madrid, Spain.
Hospital Universitario de La Princesa, Universidad Autónoma de
Madrid, Madrid, Spain.
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Patient consent obtained.
Competing interests: No competing interests