ABSTRACT
New data concerning the management of autoimmune liver diseases have emerged since the last single-topic meeting sponsored by the Brazilian Society of Hepatology to draw recommendations about the diagnosis and treatment of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), overlap syndromes of AIH, PBC and PSC and specific complications and topics concerning AIH and cholestatic liver diseases. This manuscript updates those previous recommendations according to the best evidence available in the literature up to now. The same panel of experts that took part in the first consensus document reviewed all recommendations, which were subsequently scrutinized by all members of the Brazilian Society of Hepatology using a web-based approach. The new recommendations are presented herein.
Subject(s)
Autoimmune Diseases/diagnosis , Autoimmune Diseases/therapy , Liver Diseases/diagnosis , Liver Diseases/therapy , Cholangitis, Sclerosing/diagnosis , Cholangitis, Sclerosing/therapy , Disease Management , Hepatitis, Autoimmune/diagnosis , Hepatitis, Autoimmune/therapy , Humans , Liver Cirrhosis, Biliary/diagnosis , Liver Cirrhosis, Biliary/therapy , Societies, MedicalABSTRACT
OBJECTIVE: To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease. METHODS: A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA. RESULTS: High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36-4.29) and PBC/AID samples (3.89; 3.15-4.63) than in BN (2.43; 1.92-2.94) and BN/AID samples (2.52; 1.54-3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5-71.5 %) and PBC/AID samples (66.1 %; 54.4-77.8 %) than in BN samples (39.2 %; 30.9-37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118-8.019); high-titer IIF-AMA (OR 4.890; 2.319-10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924-46.060). CONCLUSION: The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals.
ABSTRACT
A doença sistêmica associada à IgG4 pode acometer virtualmente todos os órgãos, o que torna seu diagnóstico diferencial bastante abrangente. A pancreatite autoimune foi a primeira lesão orgânica a ser associada à IgG4 e, apenas em 2003, manifestações extrapancreáticas foram descritas. Portanto, é uma enfermidade relativamente nova e pouco conhecida de modo que se torna importante estudá-la. A colangite esclerosante associada à IgG4 está comumente associada à pancreatite autoimune, embora também possa ocorrer isoladamente ou em associação à lesão pancreática leve. Assim, pode ser difícil diferenciá-la da colangite esclerosante primária ou do colangiocarcinoma, a depender do padrão e do local onde ocorrem as estenoses. O acometimento renal é frequente nesta doença, e ocorre por nefrite tubulointersticial, acompanhada de alterações típicas nos exames de imagem, que mostram áreas heterogêneas e hipointensas no parênquima renal/ fato que não acontece em nefrites de outras etiologias. Relatamos, a seguir, o caso de um paciente com estenose do hepatocolédoco médio e suspeita de colangiocarcinoma, que posteriormente demonstrou acometimento de parótidas, pancreático, e renal, além de biliar, com níveis séricos elevados de IgG4.
Systemic disease associated with IgG4 can affect virtually every organ, which makes her very comprehensive differential diagnosis. Autoimmune Pancreatitis was the first organic lesion to be associated with IgG4, and only in 2003, extra-pancreatic manifestations have been described. Therefore, it is a relatively new disease and poorly known, so that it becomes important to study it. The IgG4 associated sclerosing cholangitis is commonly associated with autoimmune pancreatitis, although it can also occur in isolation or in association with mild pancreatic injury. Thus, it can be difficult to distinguish it from primary sclerosing cholangitis or cholangiocarcinoma, depending on the pattern and where the strictures occur. The renal involvement is common in this disease, and tubulointerstitial nephritis occurs, accompanied by typical changes in imaging studies that show heterogeneous and hypointense areas in the renal parenchyma, which did not happen in nephritis from other causes. The following describes the case of one patient with bile duct stenosis and medium suspected cholangiocarcinoma, which subsequently showed involvement of the parotid glands, pancreas, and kidney, and bladder, with elevated serum levels of IgG4.
