Primary biliary cirrhosis, AMA negative Chapter 4 Diseases of the Biliary Tract 1 Primary biliary cirrhosis, AMA negative Case 4.5

Clinical Presentation 4 Diseases of the Biliary Tract 2 Clinical Presentation A 59-year-old woman with a history of diabetes and hypertension presented with right upper quadrant pain. Workup noted abnormal liver tests with a markedly elevated alkaline phosphatase value. An ultrasound and CT scan of the liver showed no abnormalities.

Laboratory Values Course in Hospital Total Protein: 8.2 Albumin: 4.9 Diseases of the Biliary Tract 3 Laboratory Values Total Protein: 8.2 Albumin: 4.9 GGTP: 416 (elevated) Serum IgG and IgM: Normal Serologies: HBsAg, anti-HCV, HIV, SMA, AMA: Negative AST: 59 ALT: 87 Alk Phos: 549 Total Bilirubin: 0.4 Course in Hospital The diagnosis was uncertain and a liver biopsy was performed.

4 Diseases of the Biliary Tract 4 Pathology Portal fibrosis was present without bridging, some of the portal tracts showing interlobular bile ducts surrounded and focally infiltrated by lymphocytes (a) while other portal tracts were devoid of interlobular ducts (b). Little periportal or intralobular inflammation was seen. Figure 4.5(a) Figure 4.5(b)

4 Diseases of the Biliary Tract 5 Diagnosis Non-suppurative duct injury with focal duct loss, consistent with AMA negative primary biliary cirrhosis (PBC)

4 Diseases of the Biliary Tract 6 Comment About 5% of patients who have all of the clinical signs and symptoms of PBC are AMA M2 negative; in this case example the patient was asymptomatic but had typical liver tests and pathology on biopsy of PBC. Although autoimmune hepatitis with duct injury (autoimmune cholangitis) is then considered as a possible diagnosis, the negative SMA, normal serum IgG value, and virtual absence of periportal and intralobular necroinflammatory activity are all against a diagnosis of autoimmune hepatitis. Note that a subset of these patients may have antibodies that are PBC specific such as anti-gp210 and anti-sp100. The prognosis and response to treatment for these patients overall is the same as in the AMA-positive cases.