Connective Tissue Diseases and the Liver

Abstract

Connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, and scleroderma are systemic disorders that may have an autoimmune basis. The system manifestations vary, and there is frequent overlap among the syndromes. Liver involvement in patients with connective tissue diseases has been well documented but is generally considered rare. Although advanced liver disease with cirrhosis and liver failure is rare in patients with connective tissue diseases, clinical and biochemical evidence of associated liver abnormalities is common. Previous treatment with potentially hepatotoxic drugs or coincident viral hepatitis has usually been implicated as the main causes of liver disease in patients with connective tissue diseases. However, even after careful exclusion of these etiologies, the question remains whether to classify the patient as having a primary liver disease with associated autoimmune, clinical, and laboratory features or as having liver disease as a manifestation of generalized connective tissue disease. The main example of this pathogenetic dilemma is autoimmune hepatitis and SLE-associated hepatitis, which have been regarded as two different entities, although they have features in common of autoimmune syndromes. Several clinical and histopathologic features have been used to discriminate autoimmune hepatitis from SLE, a relevant diagnostic exercise because complications and therapy are quite different. Although hepatic steatosis and abnormal results on biochemical liver function tests are the most common hepatic abnormalities associated with connective tissue diseases, other less frequent abnormalities have been noted, such as nodular regenerative hyperplasia, portal vein obliteration and portal hypertension, features of primary biliary cirrhosis, and rarely portal fibrosis with abnormal lobular architecture. Vascular disorders of the liver also have been described, such as Budd-Chiari syndrome. Histologic assessment may reveal a variety of subclinical liver diseases. The aim of this contribution is to review the current published data regarding liver involvement in connective tissue diseases.

CD8-positive T Cell-induced Liver Damage was Found in a Patient with Polymyositis

“…On the other hand, a variety of histological findings of liver including non-specific reactive hepatitis are found in patients with collagen disease (2,7). In the present case, liver histology showed mild perivascular infiltration by CD8 T cells, which were uncommon in AIH.…”

Liver Cirrhosis Due to Autoimmune Hepatitis Combined with Systemic Sclerosis

“…The disorder is characterized by three features: tissue fibrosis, vessel vasculopathy, and an autoimmune response associated with specific autoantibodies. 7 Although up to 90% of patients with SSc have been estimated to have gastrointestinal involvement, 8 liver disease has been reported only rarely in these cases. In a review of 727 patients with scleroderma, only eight (1.1%) had hepatic involvement.…”

Circadian Disorganization in Experimental Arthritis

“…Although it initially presents as a symmetrical polyarticular synovitis with prominent hand involvement, rheumatoid arthritis has multiple potential systemic manifestations. Fever, weight loss, and cachexia can be part of the first symptoms, while splenomegaly, vasculitis, neutropenia and amyloidosis are some of the disease's complications which may occur in patients with long-standing disease [1,3,4].…”

“…Since rheumatoid arthritis is frequently accompanied by other known autoimmune or autoimmune-associated disorders (e.g., systemic lupus erythematosus, Hashimoto's thyroiditis) that are themselves characterized by autoantibody production [3,4], a generalized autoimmune susceptibility in affected individuals is suspected. Also regarded as supporting an autoimmune etiology for rheumatoid arthritis is the fact that treatment regimens usually include drugs that directly target the immune system, like glucocorticoids, methotrexate, azathioprine or cyclophosphamide [5,6].…”