Primary Biliary Cirrhosis (PBC) Flashcards
PBC
Primary biliary cirrhosis (now increasingly referred to as primary biliary cholangitis) is a chronic liver disorder typically seen in middle-aged females (female:male ratio of 9:1). The aetiology is not fully understood although it is thought to be an autoimmune condition. Interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis which may eventually progress to cirrhosis. The classic presentation is itching in a middle-aged woman
M Rule
IgM
Middle aged F
anti-mitochondrial antibodies (M2 subtype)
PBC - Associations
Associations Sjogren's syndrome (seen in up to 80% of patients) rheumatoid arthritis systemic sclerosis thyroid disease
PBC - Diagnosis
Diagnosis
anti-mitochondrial antibodies (AMA) M2 subtype are present in 98% of patients and are highly specific
smooth muscle antibodies in 30% of patients
raised serum IgM
PBC - Mx
Management pruritus: cholestyramine fat-soluble vitamin supplementation ursodeoxycholic acid liver transplantation e.g. if bilirubin > 100 (PBC is a major indication) - recurrence in graft can occur but is not usually a problem
PBC and RA: Example Question
A 45-year-old woman is reviewed in rheumatology clinic. She has rheumatoid arthritis and has been on methotrexate for many years. Over the past 6 months her LFTs have become abnormal.
Bilirubin 13 µmol/l ALP 179 u/l ALT 63 u/l γGT 101 u/l Albumin 31 g/l
Which blood test will help determine the underlying pathology?
Ferritin Anti-LKM antibody Anti-smooth muscle antibody > Anti-mitochondrial antibody Alpha fetoprotein
Primary biliary cirrhosis (PBC) is a chronic cholestatic, autoimmune liver disease . There is progressive inflammatory destruction of the intrahepatic bile ducts. It is more common in middle-aged females. Autoimmune diseases such as Sjögrens syndrome, systemic sclerosis, autoimmune thyroiditis and rheumatoid arthritis, are frequently found to co-exist with PBC. Diagnosis is aided by autoantibody detection (anti-mitochondrial antibodies).
The blood tests suggest a more cholestatic picture, which is in keeping with PBC. She also has a past medical history (rheumatoid arthritis) that would suggest concomitant PBC. Her blood tests are not in keeping with haemochromatosis, which would affect the ALT more than the ALP. She also has no risk factors for developing HCC and, that often doesn’t affect liver function tests until advanced disease.
PBC Mx - Example Question
A 40-year-old man is referred by his GP to the outpatient department with a 4 month history of tiredness and itching. He currently sleeps excessively during the daytime and reports he is having trouble concentrating at work, where he is an auditor. The itching becomes worse when he is in hotter climates and if he sleeps with a blanket over him. His past medical history includes asthma and dry eyes. His regular medications include beclometasone and antihistamine that he takes for the itching. He is not allergic to any medication and there is no family history of any known conditions. He does not smoke and drinks 5-10 units of alcohol per week.
Examination reveals mild jaundice of the sclera and scratch marks over his upper torso and arms. On examination of his abdomen, he has a slightly enlarged spleen and liver, both by 1cm.
Blood tests reveal raised bilirubin and alkaline phosphatase (ALP). Autoantibody screening reveals antimitochondrial antibodies (AMA) and antinuclear bodies (ANA) both being present.
What is the most appropriate management to help control his symptoms?
Hydroxyzine Cetirizine Hydrochloride > Ursodeoxycholic acid Fexofenadine Corticosteroid therapy
The most likely diagnosis in this case is primary biliary cirrhosis, as evidenced by the patients severe tiredness, itching and positive autoantibodies. The ratio of male:female is around 1:9, however it is important to remember this disease does affect men as well. Treatments are aimed at alleviation of symptoms and at slowing the disease, although liver transplant can offer a cure. Ursodeoxycholic acid has been shown to slow progression of the disease and improve the symptoms of jaundice.
PBC - Clinical Fx
Clinical features
early: may be asymptomatic (e.g. raised ALP on routine LFTs) or fatigue, pruritus
cholestatic jaundice
hyperpigmentation, especially over pressure points
xanthelasmas, xanthomata
also: clubbing, hepatosplenomegaly
late: may progress to liver failure
PBC Cx
Complications
malabsorption: osteomalacia, coagulopathy
sicca syndrome occurs in 70% of cases
portal hypertension: ascites, variceal haemorrhage
hepatocellular cancer (20-fold increased risk)
PBC - Diagnosis: Example Question
A 40-year-old woman with a background of Sjogren’s syndrome presents with fatigue and itchy skin. She has not been commenced on any new medications or travelled recently. On examination, she is found to have a palpable liver edge. Further investigations reveal the following results:
Bilirubin 22 µmol/l
ALP 400 u/l
ALT 35 u/l
Anti-mitochondrial antibodies positive, anti-smooth muscle antibodies negative
Anti-HBs positive, HBsAg negative, HBcAg negative
Hepatitis C negative
What is the most likely diagnosis?
> Primary biliary cirrhosis Primary sclerosing cholangitis Autoimmune hepatitis Acute Hepatitis B infection Hepatitis B carrier
Given the fact that she is a middle-aged woman, with a background of Sjogren’s and a positive antimitochondrial antibody test, the best answer is primary biliary cirrhosis.
Negative anti-smooth muscle antibodies make autoimmune hepatitis less likely. Primary sclerosing cholangitis is frequently associated with ulcerative colitis and does not fit the clinical picture here. Her hepatitis B results indicate previous vaccination and not an infection or carrier status.
PBC Diagnosis - Example Question
A 48-year-old female who was diagnosed with type 2 diabetes mellitus six months ago presents with fatigue. She had a long standing history of obesity and a recent high cholesterol level of 6.5 mmol/l.
She doesnt smoke, and drinks alcohol on special occasions only. She has one sister who has Graves’ disease.
The only abnormality noted on the examination is a soft yellow plaque on the eyelids bilaterally.
The following investigations had been ordered:
Hb 13 g/dl Platelets 175 * 10^9/l WBC 5 * 10^9/l MCV 80 fl MCH 0.4 fmol/cell MCHC 20 mmol/l Na+ 135 mmol/l K+ 4 mmol/l Creatinine 80 µmol/l Urea 3 mmol/l ESR 40 mm/hr Alkaline phosphatase 300 IU/l Gamma glutamyl transpeptidase 100 IU/l Alanine transaminase 60 IU/l Aspartate transaminase 15 IU/l Bilirubin 10 µmol/l Serum albumin 40 g/l Serum cholesterol 7 mmol/l
What is the most useful additional investigation to reach a diagnosis?
Immunoglobulin level Liver biopsy > Antimitochondrial antibodies (AMA) Viral screening Abdominal ultrasound
This lady has primary biliary cirrhosis (PBC) as evidenced by the history of fatigue, elevated liver enzymes, xanthelasma, history of autoimmune disease in the family, raised ESR, and the elevated cholesterol level.
Synthetic functions of the liver wouldnt be deranged until late in the disease process and usually indicate a poor prognosis. The same applies to jaundice.
AMA is present in 95% of cases and is highly specific for PBC. When combined with a clinical history fitting the diagnosis no additional tests need to be made.
Liver biopsy is increasingly losing support as a diagnostic tool for the following reasons:
- The high value and the specificity of AMA
- The changes in the liver are focal
Serum IgM is elevated in pure PBC but its neither sensitive nor specific. It is useful in cases where doubt exists. There is nothing in the history or the clinical examination to suggest that this lady is at an increased risk of viral hepatitis. Abdominal ultrasound would help to exclude obstructive duct lesions. However it would not be as valuable in diagnosing PBC as AMA.
PBC - Cholestyramine: Example Question
A 50-year-old woman presents with a 12-month history of fatigue and pruritus. She has a history of rheumatoid arthritis which was diagnosed 4 years ago and has been quiescent. Aside from a flare-up of her rheumatoid arthritis 2 years ago requiring a course of steroids, she has never been on any disease modifying drugs. Her present medications include naproxen 500mg BD and omeprazole 20mg OD.
On examination, there is evidence of scratch marks and icteric sclera. There is some fullness in the right upper quadrant of her abdomen on palpation.
Her blood tests are:
Hb 105 g/l Na+ 137 mmol/l Bilirubin 56 µmol/l Platelets 190 * 109/l K+ 4.2 mmol/l ALP 210 u/l WBC 9 * 109/l Urea 2.6 mmol/l ALT 60 u/l Neuts 6.5 * 109/l Creatinine 77 µmol/l γGT 80 u/l Lymphs 1.4 * 109/l Albumin 32 g/l Eosin 0.2 * 109/l
Her antibody screen reveals:
ANA Positive at 1:160 titre
ANCA Negative
AMA Positive at 1:40 titre
ASMA Negative
What drug can be used to provide symptomatic relief for the patient’s pruritus?
Ursodeoxycholic acid Desferrioxamine Prednisolone > Cholestyramine Pentoxifylline
This patient has primary biliary cirrhosis (PBC). Patients with PBC is classically a middle aged woman and has a history of other autoimmune diseases, rheumatoid arthritis in this case. Antimitochondrial antibodies (AMA) are present in up to 95% of patients and a proportion of patients with PBC also have detectable antinuclear antibodies (ANA).
Symptoms of fatigue and pruritus are common in patients with PBC and in some cases can be extremely debilitating. Cholestyramine is used first line to sequestrate bile acid salts in the enteric lumen and to provide relief for the patient’s pruritus. Other drugs such as colestipol or rifampicin can also be used. Ursodeoxycholic acid is used to slow the progression of the disease and patients on this medication have shown biochemical and histological improvement.
