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Key Clinical Updates in Primary Biliary Cholangitis
Obeticholic acid, a farnesoid X receptor agonist, can cause serious liver injury in patients with advanced cirrhosis, and its use in these patients has been restricted by the FDA.
Lleo A et al. Lancet. [PMID: 33308474]
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ESSENTIALS OF DIAGNOSIS
Occurs in middle-aged women.
Often asymptomatic.
Elevation of alkaline phosphatase, positive antimitochondrial antibodies, elevated IgM, increased cholesterol.
Characteristic liver biopsy.
In later stages, can present with fatigue, jaundice, features of cirrhosis, xanthelasmas, xanthomas, steatorrhea.
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GENERAL CONSIDERATIONS
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PBC is a chronic disease of the liver characterized by autoimmune destruction of small intrahepatic bile ducts and cholestasis. The designation “primary biliary cholangitis” has replaced “primary biliary cirrhosis” because many patients do not have cirrhosis. The disease is insidious in onset, occurs usually in women aged 40–60 years, and is often detected by the chance finding of elevated alkaline phosphatase levels. Estimated incidence and prevalence rates in the United States are 4.5 and 65.4 per 100,000, respectively, in women, and 0.7 and 12.1 per 100,000, respectively, in men. These rates may be increasing. The frequency of the disease among first-degree relatives of affected persons is 1.3–6%, the risk is increased in second- and third-degree relatives, and the concordance rate in identical twins is high. PBC is associated with HLA DRB1*08 and DQB1 as well as the IL12A and IL12RB2 genes, which encode interleukin-12alpha and interleukin 12 receptor beta2, respectively, and IRF5-TNPO3, which encodes interferon regulatory factor 5-transportin 3. The disease may be associated with Sjögren syndrome, autoimmune thyroid disease, Raynaud syndrome, systemic sclerosis (scleroderma), hypothyroidism, and celiac disease; all patients with PBC should be screened for these conditions. Infection with Novosphingobium aromaticivorans or Chlamydophila pneumoniae may trigger or cause PBC. Other triggers, including viruses (such as human betaretrovirus), lactobacillus vaccination to prevent recurrent vaginitis, and xenobiotics, are also suspected. X-chromosome monosomy may be a predisposing factor. A history of UTIs (caused by E coli or Lactobacillus delbrueckii) and smoking, and possibly use of hormone replacement therapy and hair dye, are risk factors, and clustering of cases in time and space argues for a causative role of environmental agents.
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A. Symptoms and Signs
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Many patients are asymptomatic for years. The onset of clinical illness is insidious and is heralded by fatigue (excessive daytime somnolence) and pruritus, which appears to be mediated by enzyme autotaxin and its product lysophosphatidic acid, as well as Mas-related G protein coupled receptor X4. With progression, physical examination reveals hepatosplenomegaly. Xanthomatous lesions may occur in the skin (eFigure 16–35) and tendons and around the eyelids. Jaundice, steatorrhea, and signs of portal hypertension are late findings, although occasional patients have esophageal varices despite an early histologic stage. Autonomic dysfunction, including orthostatic hypotension and associated fatigue and cognitive dysfunction, appear to be common. The risk of low bone density, osteoporosis, ...