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AIH-PSC Overlap 25% of patients with AIH have PSC. The complex is of AIH on serology but PSC on cholangio - Written by Dr Sebastian Zeki 10% PBC may have AIH variant-can develop before, during or after diagnosis Types Histology of autoimmune hepatitis, serology of PBC : Clinical course as per type 1 AIH Histology of PBC but no AMA, and generally with antinuclear antibodies (ANA) +/-smooth muscle antibodies (SMA). (AKA immune cholangiopathy, autoimmune cholangiopathy, immune cholangitis, and autoimmune cholangitis, AMA-negative PBC. Subtypes 1. AMA +ve or AMA -ve patients with ANA-PBC-related antibodies 2. AMA -ve patients with non-PBC-related ANAs 3.Patients with autoimmune hepatitis-related antibodies with serum PBC markers Clinical Implications: AIH superimposed upon PBC more likely to develop esophageal varices, GI bleeding, ascites, and liver failure compared with more classical PBC Reasons to suspect AIH PSC overlap Pruritus. Chronic ulcerative colitis (in16 % with AIH). Bile duct abnormalities on histology (eg. portal edema, cholestasis, and fibrous or obliterative cholangitis). Cholestatic laboratory changes (ALP>2xULN). The patient has no response to corticosteroid therapy. An abnormal cholangiogram (in up to 42 % of AIH and UC). High levels of IgG, circulating ANA or SMA (titer >1:40), and moderate to severe interface hepatitis on liver biopsy Evolution from AIH to PSC has also been described. Compared to PSC, AIH-PSC younger at presentation (mean age 21 v 32) had higher aminotransferases, serum Ig’s and prevalence of autoantibodies. Diagnosis of Autoimmune Hepatitis
ALKM-1 occur +/-ALC-1 (LC1) antibodies or rarely ANA. ALC-1 antibodies can occur alone Anti SLA/LP are common Treat as ryptogenic chronic hepatitis or cryptogenic cirrhosis. A therapeutic response to antiinflammatory therapy may be the only indication that autoimmune hepatitis is the underlying disease in these patients. Most common Type 1 diabetes Autoimmune thyroid disease, Vitiligo. Also assoc with a syndrome of vitiligo, nail dystrophy, and alopecia, and with autoimmune polyglandular syndrome type I. Most common Thyroiditis Graves' disease Ulcerative colitis (16%) Rheumatoid arthritis. Also: uveitis, celiac disease, pernicious anemia, Sjögren's syndrome, mixed connective tissue disease, Weber- Christian panniculitis and CREST syndrome. Extrahepatic manifestations of autoimmune hepatitis Both types 10 % have coeliac disease Extrahepatic manifestations assoc with HLA-DR4 HLA alleles that seem to confer susceptibility to autoimmune hepatitis is associated with resistance to ulcerative colitis. Rash/ arthralgia/ anorexia Autoimmune association in 30% 80% female
>50
20-30
Ab -ve AIH Autoantibodies
Organ- specific Ab’s Possible Common Autoantigen Unknown CYP2D6 HLA B8, DR3, DR4 DR7,B14,DR3,C4A-Q0 Age Adult Child Fulminant Onset Possible Possible Low IgA No Possible Prog to cirrhosis 36% 82% Steroid response Yes Yes Extrahepatic anti SLA/LP LKM1 Asiaglycoprotein recep Liver cytosol 1 Smooth muscle Nucleus Actin pANCA 3
2
1
Diagnostic Criteria -ALT is raised- reliably reflects hepatic inflammation. -IgG is 1.5x normal. -SMA, ANA or LKM1 is >1:80. -Histology shows interface hepatitis with or without lobular hepatitis or bridging necrosis in absence of other problems. If +ve histol, negative ab’s send off pANCA and SLA/LP. Anti SLA/LP (IgG1 subtype) - 10% Useful to dx when ANA or ASMA. Anti-dsDNA +vity assoc with HLA DR4- identifies steroid non-responders PANCA common Asialoglycoprotein in 85% of pre-tx active disease AIH-PBC Overlap
