Which of the following findings support the diagnosis of primary biliary cholangitis?

Diagnostic Findings Supporting Primary Biliary Cholangitis

The correct answers are b (AMA positive) and c (elevated alkaline phosphatase), as these are the two hallmark diagnostic criteria for PBC according to current guidelines.

Core Diagnostic Criteria for PBC

The diagnosis of PBC requires two key findings 1:

• Positive antimitochondrial antibodies (AMA) at a titer ≥1:40 by immunofluorescence, which are detected in more than 90% of PBC patients with specificity greater than 95% 1
• Elevated alkaline phosphatase (ALP) of hepatobiliary origin for at least 6 months, representing the cholestatic pattern characteristic of PBC 1

The combination of abnormal serum ALP and presence of AMA (≥1:40) allows confident diagnosis of PBC 1

Analysis of Each Answer Choice

Option A: AST, ALT elevated >5x ULN - INCORRECT

• Aminotransferases in PBC are typically normal or only mildly elevated, not markedly elevated 2
• In early-stage PBC, 50% have normal ALT and 37.5% have normal AST 2
• When elevated, ALT and AST levels are usually <3 times the upper limit of normal 2
• Marked transaminase elevation (>5x ULN) suggests autoimmune hepatitis or other hepatocellular injury, not PBC 3

Option B: AMA positive - CORRECT

• AMA is the diagnostic hallmark and mandatory test for all adults with chronic intrahepatic cholestasis 1
• Positive at titer ≥1:40, with specificity >95% for PBC 1
• Anti-AMA-M2 (anti-PDC-E2) can be used as alternative with even higher sensitivity and specificity 1

Option C: Elevated alkaline phosphatase - CORRECT

• ALP elevation is a sensitive marker for PBC diagnosis, though not specific 4
• Represents the cholestatic biochemical pattern essential for diagnosis 1
• Must confirm hepatobiliary origin using GGT or ALP fractionation, as bone-derived ALP can confound interpretation in post-menopausal women 1

Option D: Magnetic cholangiography showing strictures & dilations - INCORRECT

• This describes primary sclerosing cholangitis (PSC), not PBC 4
• PSC shows multifocal strictures and beading on MRCP/ERCP 4
• PBC does not have characteristic cholangiographic abnormalities 1
• The guidelines explicitly state that AMA positivity should raise suspicion of alternative diagnoses when typical cholangiographic features are present 4

Option E: ANA positive, SMA positive - INCORRECT for PBC alone

• These antibodies suggest autoimmune hepatitis, not PBC 3
• ANA is positive in 80% and SMA in 63% of autoimmune hepatitis patients 3
• When present with PBC features, this suggests PBC-autoimmune hepatitis overlap syndrome, which requires liver biopsy for confirmation 1, 3
• In AMA-negative patients, specific ANA patterns (anti-Sp100, anti-gp210) can support PBC diagnosis, but general ANA/SMA positivity points toward autoimmune hepatitis 1

Important Clinical Caveats

AMA-positive patients with normal ALP deserve special attention:

• 80-82% of AMA-positive patients with normal ALP have histological PBC on liver biopsy 5, 6
• These patients should be monitored with annual biochemical reassessment 1
• GGT may be more robustly elevated than ALP in early PBC, with 29.2% having normal ALP but significantly elevated GGT 2
• Current guidelines may not capture the full spectrum of PBC presentation 5

In AMA-negative cases:

• Specific ANA patterns (anti-Sp100, anti-gp210) have >95% specificity for PBC and can serve as diagnostic markers 1
• Liver biopsy should be considered in patients with unexplained cholestasis and negative AMA 1, 3