Clinical features and management of primary biliary cirrhosis

Table 1 Epidemiology of primary biliary cirrhosis: Results from the most relevant studies[2–9]

Area	Patients (No.)	Prevalence (per million)	Incidence (per million/yr)	Age (yr)	Gender (M:F)
Europe (1984)	569	23	54	54	1:10
Northern Sweden (1990)	111	1511	13.3	55	1:6
North East England (1990)	347	1291	19	58	1:9
Ontario, Canada (1990)	225	22	3.3	59	1:13
Victoria, Australia (1995)	84	19	-	-	1:11
Newcastle, England (1997)	160	2401	22	66	1:10
Olmsted County, MN (2000)	46	4021	27	-	1:8
Victoria, Australia (2004)	249	511	-	61	1:9

¹Data include survey of laboratories for antimitochondrial antibodies.

Table 2 Modifications during time of the clinical spectrum of primary biliary cirrhosis at presentation[50–52]

	Sherlock 1973	James 1981	Nyberg 1989
	(n = 100)	(n = 93)	(n = 80)
Jaundice (%)	28	16	3
Pruritus (%)	57	14	26
Complications (%)	4	9	1
Asymptomatics (%)	11	61	70
Mean age (yr)	50	57	58

Table 3 Parameters independently associated with bad prognosis in different prognostic models based on a single point observation[16113119121–123]

Parameters	Yale	European	Mayo	Glasgow	Oslo	London
Increase in serum bilirubin	+	+	+	+	+	+
Decrease in serum albumin		+	+			+
Increase in PT (INR)			+
Advanced age	+	+	+	+		+
Hepatomegaly	+					+
Ascites, fluid retention			+	+		+
Esophageal varices						+
Gastrointestinal bleeding				+	+
Cirrhosis	+	+		+		+
Cholestatic picture at histology		+		+
Mallory bodies				+

Table 4 Pharmacological characteristics of the opiate antagonists investigated in clinical studies

	Pharmacological characteristics
Naloxone	Very short half life
	Intravenous continuous infusion
	Dose: 0.2-0.4 &mgr;g/kg per minute
Nalmefene	Longer half life
	Oral administration
	2 mg twice/d with a gradual increase until 20 mg twice/d
Naltrexone	Longer half life
	Oral administration
	50 mg/d
	(in two divided doses the first day and subsequently in a unique dose)

Table 5 Clinical management of metabolic bone disease associated with primary biliary cirrhosis

Clinical management	Efficacy
	Moderate efficacy	Mild efficacy, insufficient data
Prevention
1 Parenteral vitamin D3 supplementation	Indicated for all patients to prevent osteomalacic lesions
2 Calcium carbonate supplementation
Treatment
1 Estrogen		Few data but effective and safe
2 Etidronate		Conflicting data
		Indicated in case of concomitant corticosteroid administration
3 Alendronate		Few data but effective and safe
4 Calcitonin		Probably ineffective

Table 6 Efficacy and toxicity of the principal drugs investigated for the medical treatment of primary biliary cirrhosis

	Efficacy	Toxicity
D-penicillamine	-	+
Chlorambucil	+/-	+
Cyclosporine	+/-	+
Azathioprine	+/-	+
Methotrexate	+/-	+
Colchicine	+/-	-
Glucocorticoids	+/-	+/-
UDCA	+	-

Table 7 Randomized, double-blind, placebo-controlled trials on ursodeoxycholic acid administration to patients with primary biliary cirrhosis

First author	No. of patients	Study design and duration of follow up	UDCA effects on
			Pruritus	Histology	Survival
Poupon[191]	146	2 yr	Improved	Improved	No effect
Heathcote[192]	222	2 yr	No effect	Improved	No effect
Lindor[193]	180	Mean follow up: 2 yr	No effect	No effect	No effect
Combes[194]	151	2 yr	Improved	Improved (early stages)	No effect
Eriksson[195]	116	2 yr + 2 yr as open trial (UDCA)	No effect	No effect	No effect
Pares[196]	192	Mean follow up: 3.4 yr	Improved	Improved	No effect
Papatheodoritis[197]	86	Mean follow up 7.3 yr for UDCA 8.1 yr for controls	Not evaluated	No effect	No effect