A 52-year-old man develops jaundice, hepatomegaly, and elevated transaminases 6 weeks after starting an antituberculous regimen. Liver biopsy shows cholestasis with bile duct proliferation and minimal inflammation. Which feature best distinguishes this Type C (continuing) reaction from a Type A hepatotoxic reaction?
A. Presence of fever and rash indicating immune-mediated hypersensitivity
B. Delayed onset after weeks to months of continuous drug exposure, with dose-independent progression
C. Immediate onset within hours of drug administration with dose-dependent severity
D. Reversibility within 24 hours of drug discontinuation
Explanation
Type C (Continuing/Cumulative) Reactions vs Type A Hepatotoxicity
Type C (Continuing) Reactions
Key Point
Type C reactions develop insidiously after prolonged drug exposure and continue to progress even after the drug is stopped. They represent cumulative organ damage.
Onset: Delayed, after weeks to months of continuous exposure
Dose-dependence: Dose-independent (occurs at therapeutic doses)
Progression: Continues or worsens after drug withdrawal
Mechanism: Cumulative toxicity, often from reactive metabolites or chronic inflammation
Reversibility: Rapid and complete upon discontinuation
Clinical Scenario Analysis
The patient in the vignette presents with:
6-week delay (not immediate) → suggests Type C
Cholestasis with bile duct proliferation (chronic pattern) → suggests Type C
Continuing on antituberculous drugs (cumulative exposure) → Type C signature
Minimal inflammation (not acute hepatitis) → Type C pattern
This is antituberculous drug-induced cholestasis, a classic Type C reaction (most commonly from isoniazid or rifampicin).
Comparison Table
Table
Feature
Type A (Augmented)
Type C (Continuing)
Onset
Dose-related, variable
Delayed (weeks–months)
Dose-dependence
Yes, predictable
No, occurs at therapeutic doses
Progression after withdrawal
Stops immediately
Continues or worsens
Reversibility
Rapid and complete
Slow, often incomplete
Mechanism
Direct toxicity or exaggerated action
Cumulative metabolite injury
Histology
Acute hepatocellular necrosis
Cholestasis, fibrosis, cirrhosis
Examples
Acetaminophen OD, statin toxicity
Antituberculous drugs, methotrexate
High-YieldNEET PG
The delayed onset after prolonged exposure and dose-independent nature are the hallmarks of Type C reactions. They differ from Type A by continuing to progress after drug withdrawal.
Mnemonic
C = Continuing, Cumulative, Chronic — Type C reactions develop slowly, accumulate over time, and persist after drug withdrawal.
Clinical Pearl
Type C reactions are particularly important in antituberculous therapy monitoring. Baseline and periodic liver function tests are essential to detect early cholestasis before irreversible cirrhosis develops.
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