Primary Biliary Cirrhosis

The one I always mix up with PSC.


Primary Biliary Cirrhosis (PBC)

Definition: liver disease where interlobular bile ducts are damaged by chronic autoimmune granulomatous inflammation causing cholestasis which may lead to fibrosis, cirrhosis and portal hypertension.

Aetiology/ risk factors:

Cause:

-autoimmune aetiology likely

-unknown environmental triggers + genetic predisposition (e.g. IL12A locus) leading to loss of immune tolerance to self-mitochondrial proteins. Antimitochondrial antibodies (AMA) are the hallmark of PBC = autoimmune response directed against bile duct epithelial cells.

Risk factors:

-positive family history (seen in 1-6%)

-many UTIs

-smoking

-past pregnancy

-other autoimmune diseases e.g. Sjogren’s syndrome

-use of nail polish/ hair dye (weird…)

Epidemiology: prevalence is approx. ≤ 4/100,000

About 9x more common in females

Typical age at presentation is about 50 years

Symptoms:

-often asymptomatic

May present with:

-lethargy, sleepiness

-pruritus (itching)

-weight loss

-RUQ abdominal discomfort (rarely)

Which may be followed, years later, by

-jaundice

and other features of liver decompensation e.g. ascites, variceal bleeds

Associated conditions e.g. Sjogren’s syndrome– dry eyes and dry mouth

Signs:

-may show no signs early on

-jaundice

-scratch marks (from itching)

-skin hyperpigmentation

-xanthomata- deposition of yellowish cholesterol-rich material that can appear anywhere in the body (secondary to hypercholesteraemia)

Image result for xanthomata

-xanthelasma- xanthomata around the eyes

Image result for xanthelasma

 

-hepatosplenomegaly

-Signs of complications e.g. liver cirrhosis- spider naevi, palmar erythema, ascites, clubbing

Image result for spider naevi

Spider Naevi

Image result for palmar erythema

Palmar erythema (red hands)

Image result for ascites

Ascites

Investigations:

Bloods-

LFTs- ↑Alkaline phosphatase, GGT, mild transaminases. Later stages- Bilirubin & ↓albumin, prothrombin time

Serology- increased immunoglobulins, especially ↑IgM 

AMA +ve (anti-mitochondrial antibody)- 98% are AMA M2 subtype +ve

Other autoantibodies may occur in low titres

TSH (associated autoimmune thyroid disease) & Cholesterol are elevated or normal (hence the fatty xanthomata, the liver and bile are important in cholesterol metabolism)

Ca, Phosphate, 25-hydroxyvitamin D

Ultrasound- excludes extrahepatic cholestasis and obstruction (e.g. by gallstones or strictures)

Liver biopsy- not usually needed (unless drug-induced cholestasis or hepatic sarcoidosis need excluding)

Shows granulomas around intrapehatic bile ducts +/- cirrhosis (fibrosis and regenerating nodules of hepatocytes), and destruction of the intrahepatic bile ducts.

Image result for granuloma liver pbc

A granuloma  is a focal collection of inflammatory cells at sites of tissue infection and includes activated macrophages (epithelioid cells), Langhans’ giant cells, and lymphocytes. 

Management:

-No curative treatment with management focusing on symptom control

COLESTYRAMINE (4-8g/24h PO) for pruritus. (Naltrexone and rifampicin may also help).

Osteoporosis prevention/treatment e.g. Calcium and Vitamin D supplementation, bisphosphonates, exercise programme, periodic DXA scans.

-Fat soluble vitamin prophylaxis: vitamin A, D and K

-Consider high dose URSODEOXYCHOLIC ACID. If baseline bilirubin >24μmol/L, it may improve survival and delay transplant. (= hydrophilic bile acid which may decrease the toxicity or improve elimination of retained bile acids.)

-Regular monitoring of LFTs, ultrasound and AFP (increase risk of hepatocellular carcinoma)

⇒Liver transplant is the mainstay for end-stage disease or intractable pruritus.

Complications:

-liver cirrhosis and associated complications:

-jaundice

-encephalopathy

-ascites

-variceal bleeding

-hepatocellular carcinoma- so check AFP tumour marker twice yearly

-osteoporosis

-hyperlipidaemia (due to cholestasis)

-malabsorption of fat-soluble vitamins (K, A, D, E) due to cholestasis and decreased bilirubin in gut results in:

-osteomalacia (vitamin D deficiency)

-coagulopathy (vitamin K deficiency- required for production of factors 2, 7, 9, 10)

Prognosis: histological recurrence in the graft post-transplant is ∼17% after 5 years. Although graft failure can occur as a result of recurrence, it is rare and unpredictable.

Once jaundice develops, survival is less than 2 years without transplantation.

References: Cheese & Onion, Rapid Medicine
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