Lethargy in a patient with cirrhosis.

Accepted 12 January 1996 In December 1983, a 53-year old Chinese woman presented with a one-year history of generalised pruritus. Various members of her family, extending over four generations, had autoimmunne thyroid disorders. On examination, she had bilateral xanthelasmata but no stigmata of chronic liver disease nor jaundice. Her liver was just palpable but she had neither splenomegaly nor ascites. Serum bilirubin was 7 jumol/l, total alkaline phosphatase 710 IU/1, aspartate transaminase 98 IU/1, alanine transaminase 108 IU/1 and albumin 39 g/l. Erythrocyte sedimentation rate was 110 mm/h and her total cholesterol was 6.1 mmol/l. Serum IgM level was elevated at 404 mg/dl (normal range: 100 206) but IgG and IgA levels were both within normal limits. Antinuclear factor and anti-smooth muscle antibody were both negative but antimitochondrial antibody was positive. A liver biopsy was done (figures 1, 2). She was started on a gradually increasing dose of penicillamine and attained a maximum dose of 600 mg/day in just over six months. Because of her strong family history of autoimmune thyroid disorders, her thyroid status was checked. She was clinically and biochemically euthyroid but antimicrosomal antibody and antithyroglobulin were detected at titres of 1 in 1600 and 1 in 20, respectively. About a year after the onset of illness, she was started on cholestyramine as her itching had persisted. Her serum bilirubin had by now risen to 30 imol/ but her alkaline phosphatase, aspartate transaminase and alanine transaminase were 313, 115 and > 108 IU/1, respectively. Six months later, her pruritus had improved remarkably but she noticed gradual onset weakness in both upper limbs over a six-week period and blurring of vision. These symptoms tended to worsen towards the evening. She complained of diplopia on looking to the left but this was not present on formal testing. A diagnosis was made and she was treated medically. Her weakness gradually improved and within a year, she was off treatment. Four years after the initial diagnosis she presented with lethargy, palpitations and weight loss of about 8 kg in 10 months despite a normal appetite. In January 1990 she complained of eye irritation. Ursodeoxycholic acid was started five years after her initial presentation. It has been 12 years since she first presented and she remains relatively well with a serum bilirubin of 25 ,umol/l, total alkaline phosphatase 441 IU/1, aspartate transaminase 114 IU/1, alanine transaminase 130 IU/1, albumin 36 g/l and a total cholesterol of 10.6 mmol/l.