Page 212 - Medicine and Surgery

P1: KPE
BLUK007-05 BLUK007-Kendall May 25, 2005 8:52 Char Count= 0

208 Chapter 5: Hepatic, biliary and pancreatic systems

Table 5.6 Examples of drugs causing hepatotoxicity Clinical features
The illness may be asymptomatic with elevated liver en-
Acute hepatitis Isoniazid, rifampicin, methyldopa,
enalapril, ketoconazole, cytotoxic zymes. Patients may have an acute hepatitis or complica-
drugs tions of cirrhosis such as portal hypertension (e.g. bleed-
Acute hepatocyte Paracetamol, salicylates, ferrous ing oesophageal varices or hepatic encephalopathy).
necrosis sulphate
Fatty liver Methotrexate, tetracycline, sodium Investigations
valproate, amiodarone Diagnosis of chronic active hepatitis is made by liver
Granulomatous Hydralazine, allopurinol, biopsy, there is often a normochromic anaemia, raised
change carbamazepine
Cholestatic Sex hormones, chlorpromazine, bilirubin, moderately raised transaminases, alkaline
haloperidol, erythromycin, phosphatase and γ globulin levels. Autoantibodies that
flucloxacillin, cimetidine, ranitidine. may be detected include anti-smooth muscle antibodies,
Sclerosing cholangitis can be anti-nuclear antibodies, anti-mitochondrial antibodies,
caused by intra-arterial injection of anti-microsomal antibodies or anti-liver cystosol anti-
5-fluorodeoxyuridine.
Chronic active Methyldopa, fenofibrate, isoniazid bodies.
hepatitis
Chronic fibrosis Methotrexate, hypervitaminosis A, Management
and necrosis retinoids The condition may respond to immunosuppressant
Vascular change Oral contraceptive steroids, anabolic drugs, such as corticosteroids and azathioprine. In pa-
steroids, azathioprine, cytotoxic tients who develop end stage liver disease despite med-
drugs, alternative medicine such as ical treatment liver transplantation may be considered
Bush Tea
Liver tumours Oral contraceptive steroids, although hepatitis may recur in the transplanted organ.
androgens, (haemangioma, hepatic
adenomas, rarely hepatocellular Prognosis
carcinoma) Drug treatment may be withdrawn after 2 years of re-
mission, but relapse is common (60–80%). The risk of
hepatocellular carcinoma is low, in contrast to chronic
active hepatitis due to viral causes.
Prevalence
Most common cause of chronic active hepatitis in devel-
oped countries. Primary biliary cirrhosis (PBC)
Definition
Age
Ongoing autoimmune damage to the intralobular bile
10–30 and 40–60 years.
ducts causing liver failure.
Sex Incidence
F > M (6:1) 5per 100 000 population per annum.

Age
Aetiology/pathophysiology 20–80 years, mean age 50 years.
No autoimmune mechanism has yet been proven, al-
though high titres of autoantibodies are characteristic. Sex
Patients may have features that overlap with primary >90% female
biliary cirrhosis and primary sclerosing cholangitis. Au-
toimmune chronic hepatitis is also commonly associ- Aetiology
ated with other autoimmune disorders e.g. haemolytic Associated with other autoimmune disorders and also
anaemia, idiopathic thrombocytopenic purpura, type I HLA-DR8 haplotype. Antibodies to mitochondria are
diabetes mellitus, thyroiditis and ulcerative colitis (more present; however, their exact role in pathogenesis
often associated with primary sclerosing cholangitis). is unclear as titres do not correlate with disease.