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Chapter 5: Disorders of the liver 209

Environmental triggers suggested include enterobacte- ducts. Raised cholesterol and raised total IgM are also
ria suchas E. coli. found.

Pathophysiology Management
Chronic inflammation of the small intrahepatic bile Supportive treatment involves ursodeoxycholic acid
ducts leads to cholestasis and destruction of bile ducts. (which helps the pruritus), calcium and vitamin sup-
This leads on to portal tract fibrosis and cirrhosis. Duct plementation, management of complications such as
epithelium in the pancreas, salivary and lacrimal glands varices, hyperlipidaemia. The disease may recur after
are also affected. liver transplantation.

Prognosis
Clinical features
Up to half of patients are asymptomatic at diagnosis. Pa- Asymptomatic patients may have a normal life ex-
pectancy. In symptomatic patients advancing age, hep-
tients may complain of fatigue and pruritus, followed
atomegaly, high bilirubin, low albumin and cirrhosis
some months later by jaundice. Any sign of liver disease
correlate with shortened survival (5–7 years in severe
may be present, such as clubbing, hepatomegaly, spider
disease).
naevi, xanthomata. Asymptomatic patients are discov-
ered through abnormal biochemical findings or during
investigation of another autoimmune disorder such as Primary sclerosing cholangitis (PSC)
thyroiditis.
Definition
Macroscopy/microscopy A disease of unknown aetiology in which chronic in-
Throughout the disease, copper accumulates due to the flammation of the bile ducts leads to stricture formation
chronic cholestasis. and progressive obstructive jaundice.
Stage I: Lymphocytic infiltration of small bile ducts

Age
and portal tracts with occasional granuloma forma-
Peak 25–40 years.
tion.
Stage II: More widespread inflammation in the peri-

Sex
portal parenchyma, leading to loss of bile ducts.
M > F
Stage III: Fibrous septa extend between triads and

form fibrous bridges (bridging necrosis).
Aetiology
Stage IV: Cirrhosis with absent bile ducts, scarring,

The cause is unknown but there is a strong associa-
distorted architecture and nodular regeneration.
tion with HLA haplotype (HLA-B8, DR-3, DR-2 and
DR-52a). There is also a strong association with inflam-
Complications
matory bowel disease, which is present in 60–75%, but
Oesophagealvarices,osteoporosis,osteomalacia,pan-

may be asymptomatic. Also associated with HIV infec-
creatic hyposecretion, renal tubular acidosis (possibly
tion.
copper induced).
Increased risk of hepatocellular carcinoma and breast Pathophysiology

cancer. Chronic inflammation of the intra- and extra-hepatic
Associated with many other disorders, such as bile ducts leads to fibrosis and short strictures form

Sj¨ ogren’s, hypothyroidism, systemic lupus erythe- which obstruct the passage of bile. Chronic obstruc-
matosus, scleroderma, dermatomyositis. tion leads to jaundice and cirrhosis develops over about
10 years.
Investigations
Definitive diagnosis is made on liver biopsy. Anti- Clinical features
mitochondrial antibodies (AMA) are present in >99%. Patients usually present with progressive jaundice and
Raised alkaline phosphatase suggests damage to bile pruritus or ascending cholangitis.