The management of autoimmunity in patients with cholestatic liver diseases

Abstract

Cholestatic liver diseases are rare diseases that often lead to cirrhosis and its consequent complications. In addition to liver-related morbidity, patients with cholestatic liver diseases often suffer from autoimmune diseases that affect several organs and tissues. The robust and efficient data collection and collaboration between hepatologists and rheumatologists have led to significant advancements in understanding the relationship between the cholestatic liver diseases and associated autoimmune diseases. In this paper, we discuss the cholestatic liver diseases (primary biliary cirrhosis, primary sclerosing cholangitis and immunoglobulin G4 associated cholangitis) and associated autoimmune diseases.

KEYWORDS:

• antimitochondrial antibody
• autoimmune
• IgG4-associated cholangitis
• primary biliary cirrhosis
• primary sclerosing cholangitis

Financial & competing interest disclosures

KD Lindor is an unpaid advisor for Lumena Pharmaceuticals and Intercept Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and immunoglobulin G4-related sclerosing cholangitis (IAC) are commonly associated with autoimmune disorders.

• Sjogren’s syndrome (SS) is the autoimmune disorder that is most associated with PBC. Patients often complain of dry eyes and/or dry mouth. Anti-Ro/SSA and anti-La/SSB autoantibodies are frequently detected in patients with PBC and SS. Biopsy of the affected glands might be required to confirm the diagnosis of SS.

• In patients with PBC and PSC, the presence of markedly elevated serum transaminases, particularly alanine aminotransferase, should raise the suspicion for autoimmune hepatitis, and should be further investigated. Serology (immunoglobulins, anti-smooth muscle antibodies, antinuclear antibodies, anti-liver/kidney microsomal-1 antibodies) and liver biopsy are both necessary for further evaluation.

• Ulcerative colitis (UC) is very common among the PSC population. Patients with UC often present with persistent bloody diarrhea, rectal urgency or tenesmus. Colonoscopy (or Sigmoidoscopy) is needed to confirm the diagnosis. Characteristic colonoscopic findings include loss of the typical vascular pattern, granularity, friability and ulceration. Biopsy of the affected areas in the colon might be helpful to distinguish UC from infectious colitis. Patients with both UC and PSC are at higher risk for hepatobiliary and colon neoplasm than patients with either disease alone; therefore, these patients should be carefully monitored.

• Autoimmune pancreatitis (AIP) is commonly associated with IAC. Diffuse or segmental enlargement of the pancreas on imaging, elevated serum immunoglobulin G subclass and lymphocytic infiltration of the pancreas characterize AIP. AIP and IAC respond very well to treatment with corticosteroids.

• In patients with PBC and PSC, the presence of the fatigue, cold intolerance, malaise, appetite problems, mood disturbance, diarrhea/constipation and menstrual cycle irregularities should prompt further workup to exclude thyroid dysfunction.

• Thickening of the skin of the fingers and esophageal dysmotility in patients with PBC suggest systemic sclerosis. Serological tests such as screening for anti-centromere antibodies, anti-topoisomerase I antibodies (anti-topo I), anti-RNA polymerases antibodies and anti-Scleroderma 70 antibodies (anti-Scl-70) are needed to confirm the diagnosis.

• Celiac disease is a common disease in western society, and is associated with PBC. Diarrhea, bloating, anemia and vitamin deficiencies are the common clinical features of celiac disease. It is characterized serologically by the presence of anti-tissue transglutaminase antibodies and anti-endomysial antibodies and histologically by intestinal villous atrophy, crypt hyperplasia and presence of intraepithelial lymphocytes.

• Ursodeoxycholic acid does not affect the clinical course of arthritis, Raynaud’s, hypothyroidism and SS in PBC patients.

Notes

AIH: Autoimmune hepatitis; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AMA: Antimitochondrial antibody; ASMA: Anti-smooth muscle antibody; GGTP: Gamma glutamyl transpeptidase; PBC: Primary biliary cirrhosis; ULN: Upper limit of normal.