Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

Abstract

Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as “lupus hepatitis”. In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis.

Keywords: Systemic lupus erythematosus, Lupus hepatitis, Esteatosis, Regenerative nodular hyperplasia, Hepatitis C, Autoimmune hepatitis, Hepatotoxicity, Nonsteroidal anti-inflammatory drugs, Methotrexate

Core tip: The existence of liver disease associated with lupus itself, or increased susceptibility to concomitant liver diseases, either autoimmune or non-autoimmune ones, is still somewhat controversial, and difficult to diagnose. Data in the literature are scarce, and often based on case reports or clinical studies with limited patient size or histological evidence. The pros and cons to support the existence of such pathological entities, and the still preliminary studies on the mechanisms involved, are critically discussed here. We concluded that liver is often a target of systemic lupus erythematosus, and biochemical liver tests should be systematically carried out in these patients.