The future of autoimmune liver diseases – Understanding pathogenesis and improving morbidity and mortality

Abstract

Autoimmune liver diseases (AILD), namely autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are rare diseases. These days, patients with PBC almost never require liver transplantation. When treated early with ursodeoxycholic acid patients have a normal life expectancy if the disease is diagnosed at an early stage and the patients respond to treatment. Patients with AIH often go into remission with first‐line therapy including corticosteroids alone or in combination with azathioprine. Nevertheless, about one quarter of patients already developed cirrhosis at diagnosis. Those who do not respond to first line standard of care (SOC) have significant liver‐related morbidity and mortality. No approved second‐ or third‐line treatments are available and the drugs are selected based on limited case series and personal experience. Larger trials are needed to develop efficient therapies for difficult‐to‐treat AIH patients. No treatment has been found to alter the natural course of disease in patients with PSC except for liver transplantation. Identifying PSC patients at risk of developing cholangiocarcinoma (CCA) is another unmet need. Current research in all AILD including AIH, PBC and PSC, focuses on improving our understanding of the underlying disease process and identifying new therapeutic targets to decrease morbidity and mortality.

Gut Microbiota and Liver Interaction through Immune System Cross-Talk: A Comprehensive Review at the Time of the SARS-CoV-2 Pandemic

“…Autoimmune hepatic diseases include several pathological entities, named autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), characterized by antibody formation to self-antigens. These diseases do not have a selective hepatic manifestation but are systemic with phenotypic diversity and grading [81].…”

Gastrointestinal involvement of primary skin diseases

“…Autoimmune liver diseases, which include mainly autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis, are often associated with extrahepatic autoimmune manifestations. 97,98 The association of autoimmune hepatitis with vitiligo is well known, 99 while the presence of autoimmune thyroid diseases seems to play a role. Associations with alopecia areata, psoriasis and pyoderma gangrenosum have also been described.…”

“…98 Primary biliary cholangitis, formerly called primary biliary cirrhosis, involves the small and medium intrahepatic bile ducts predominantly in women at a median age of 50 years. 97,98 In addition to pruritus, butterfly sign on the upper back, xanthomatoses and skin hyperpigmentation, a possible association with vitiligo, psoriasis and amicrobial pustulosis of the folds remains to be confirmed. 98 Primary sclerosing cholangitis is a rare chronic progressive inflammation and fibrosis of medium to large intra-and extrahepatic bile ducts, affecting more men than women in the middle ages.…”

“…98 Primary sclerosing cholangitis is a rare chronic progressive inflammation and fibrosis of medium to large intra-and extrahepatic bile ducts, affecting more men than women in the middle ages. 97,98 Due to a strong association with inflammatory bowel disease, the attribution of the concurrence with pyoderma gangrenosum, erythema nodosum and psoriasis is difficult to determine. 98 Further studies are required to understand the associations between vitiligo and autoimmune atrophic gastritis or coeliac disease in terms of autoimmune pathogenesis.…”

“…In addition to pruritus, butterfly sign on the upper back, xanthomatoses and skin hyperpigmentation, a possible association with vitiligo, psoriasis and amicrobial pustulosis of the folds remains to be confirmed 98 . Primary sclerosing cholangitis is a rare chronic progressive inflammation and fibrosis of medium to large intra‐ and extrahepatic bile ducts, affecting more men than women in the middle ages 97,98 . Due to a strong association with inflammatory bowel disease, the attribution of the concurrence with pyoderma gangrenosum, erythema nodosum and psoriasis is difficult to determine 98 .…”