Maddrey's Discriminant Function — Alcoholic Hepatitis
Bilirubin unit
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The Maddrey Discriminant Function (DF) is a clinical scoring tool used to stratify the severity of alcoholic hepatitis (AH) and identify patients who are likely to benefit from corticosteroid therapy. First described by Maddrey and colleagues in 1978, the function was developed from a randomised controlled trial of prednisolone in severe alcoholic hepatitis, and it uses prothrombin time prolongation and serum bilirubin to produce a single composite score. A discriminant function score of 32 or above defines severe alcoholic hepatitis, a threshold associated with a 30-day spontaneous mortality of approximately 30–50% without treatment. Patients meeting this threshold are candidates for prednisolone 40 mg daily for 28 days, assuming there are no contraindications such as active infection, gastrointestinal bleeding, or hepatitis B infection. The biological rationale for the DF rests on two key pathophysiological features of severe alcoholic hepatitis: impaired hepatic synthesis of coagulation factors (reflected by prothrombin time prolongation) and severe hepatocellular dysfunction and cholestasis (reflected by markedly elevated bilirubin). The original formula used a control prothrombin time from a reference laboratory, but this is often simplified by using a fixed control of 12 seconds in clinical practice. The Maddrey DF remains one of the most widely studied and applied scores in alcoholic liver disease, typically used alongside the MELD score and, following initiation of corticosteroids, the Lille score to assess early treatment response at day 7.
DF = 4.6 × (patient PT in seconds − control PT in seconds) + serum bilirubin in mg/dL; DF ≥ 32 = severe alcoholic hepatitis
- 1Measure the patient's prothrombin time (PT) in seconds and obtain the laboratory's control PT (typically 12–13 seconds in most labs). Calculate the PT prolongation: patient PT minus control PT.
- 2Multiply the PT prolongation by 4.6 to obtain the coagulation component. This weighting reflects the importance of synthetic liver failure in prognosis.
- 3Measure the serum total bilirubin in mg/dL. If the bilirubin is reported in µmol/L, convert by dividing by 17.1 (1 mg/dL = 17.1 µmol/L).
- 4Add the bilirubin (mg/dL) directly to the weighted PT prolongation to obtain the DF score.
- 5Interpret the result: DF ≥ 32 defines severe alcoholic hepatitis with approximately 30–50% 30-day spontaneous mortality. DF < 32 indicates non-severe alcoholic hepatitis with better short-term prognosis.
- 6If DF ≥ 32 and no contraindications exist, initiate prednisolone 40 mg orally daily. Evaluate Lille score at day 7 to assess steroid response.
- 7If the Lille score at day 7 is ≥0.45 (non-responder), discontinue prednisolone — continued steroid therapy does not improve survival and may increase infection risk.
Conservative management; steroids not indicated
A DF of 17.8 falls well below the threshold of 32. This patient should receive supportive care (nutritional support, alcohol abstinence counselling, vitamin supplementation) without steroids.
DF exactly 32 — meets criterion for severe AH; steroid trial appropriate if no contraindications
This patient sits precisely at the threshold. Clinical context — including encephalopathy, nutritional status, and comorbidities — should inform the decision to initiate prednisolone.
DF >> 32; initiate prednisolone 40 mg daily; check Lille score at day 7
A DF of 64 indicates severe disease with high 30-day mortality risk. Corticosteroids should be started after excluding active infection, GI bleeding, and hepatitis B.
INR-based DF estimation is imprecise; use actual PT when possible
When control PT is unavailable, some clinicians estimate PT prolongation from INR, but this introduces error. The MELD score (which uses INR directly) is more reliable in this scenario.
Professionals in health and medical use Maddrey Discriminant as part of their standard analytical workflow to verify calculations, reduce arithmetic errors, and produce consistent results that can be documented, audited, and shared with colleagues, clients, or regulatory bodies for compliance purposes.
University professors and instructors incorporate Maddrey Discriminant into course materials, homework assignments, and exam preparation resources, allowing students to check manual calculations, build intuition about input-output relationships, and focus on conceptual understanding rather than arithmetic.
Consultants and advisors use Maddrey Discriminant to quickly model different scenarios during client meetings, enabling real-time exploration of what-if questions that would otherwise require returning to the office for detailed spreadsheet-based analysis and reporting.
Individual users rely on Maddrey Discriminant for personal planning decisions — comparing options, verifying quotes received from service providers, checking third-party calculations, and building confidence that the numbers behind an important decision have been computed correctly and consistently.
Extreme input values
In practice, this edge case requires careful consideration because standard assumptions may not hold. When encountering this scenario in maddrey discriminant calculations, practitioners should verify boundary conditions, check for division-by-zero risks, and consider whether the model's assumptions remain valid under these extreme conditions.
Assumption violations
In practice, this edge case requires careful consideration because standard assumptions may not hold. When encountering this scenario in maddrey discriminant calculations, practitioners should verify boundary conditions, check for division-by-zero risks, and consider whether the model's assumptions remain valid under these extreme conditions.
Rounding and precision effects
In practice, this edge case requires careful consideration because standard assumptions may not hold. When encountering this scenario in maddrey discriminant calculations, practitioners should verify boundary conditions, check for division-by-zero risks, and consider whether the model's assumptions remain valid under these extreme conditions.
| DF Score | Severity | 30-Day Mortality (untreated) | Recommended Action |
|---|---|---|---|
| < 32 | Non-severe alcoholic hepatitis | < 15% | Supportive care: nutrition, abstinence, vitamins |
| ≥ 32 | Severe alcoholic hepatitis | 30–50% | Prednisolone 40 mg/day for 28 days (if no contraindications) |
| ≥ 32 + Lille ≥ 0.45 at Day 7 | Steroid non-responder | High | Stop prednisolone; consider transplant evaluation |
| ≥ 32 + Lille < 0.45 at Day 7 | Steroid responder | Improved | Complete 28-day course; taper prednisolone |
What does a Maddrey DF of 32 mean?
In the context of Maddrey Discriminant, this depends on the specific inputs, assumptions, and goals of the user. The underlying formula provides a deterministic relationship between inputs and output, but real-world application requires interpreting the result within the broader context of health and medical practice. Professionals typically cross-reference calculator output with industry benchmarks, historical data, and regulatory requirements. For the most reliable results, ensure inputs are sourced from verified data, understand which assumptions the formula makes, and consider running multiple scenarios to bracket the range of likely outcomes.
What is the control PT and what if I don't have it?
The control PT is the normal prothrombin time used by the testing laboratory as its reference standard, typically 10–13 seconds. If unavailable, some centres use a fixed control of 12 seconds. Alternatively, the MELD score (which uses INR rather than PT) can be used alongside the DF as a supplementary severity measure.
What are the contraindications to steroids in severe alcoholic hepatitis?
In the context of Maddrey Discriminant, this depends on the specific inputs, assumptions, and goals of the user. The underlying formula provides a deterministic relationship between inputs and output, but real-world application requires interpreting the result within the broader context of health and medical practice. Professionals typically cross-reference calculator output with industry benchmarks, historical data, and regulatory requirements. For the most reliable results, ensure inputs are sourced from verified data, understand which assumptions the formula makes, and consider running multiple scenarios to bracket the range of likely outcomes.
Why is the Lille score checked at day 7?
In the context of Maddrey Discriminant, this depends on the specific inputs, assumptions, and goals of the user. The underlying formula provides a deterministic relationship between inputs and output, but real-world application requires interpreting the result within the broader context of health and medical practice. Professionals typically cross-reference calculator output with industry benchmarks, historical data, and regulatory requirements. For the most reliable results, ensure inputs are sourced from verified data, understand which assumptions the formula makes, and consider running multiple scenarios to bracket the range of likely outcomes.
Is pentoxifylline still used in severe alcoholic hepatitis?
In the context of Maddrey Discriminant, this depends on the specific inputs, assumptions, and goals of the user. The underlying formula provides a deterministic relationship between inputs and output, but real-world application requires interpreting the result within the broader context of health and medical practice. Professionals typically cross-reference calculator output with industry benchmarks, historical data, and regulatory requirements. For the most reliable results, ensure inputs are sourced from verified data, understand which assumptions the formula makes, and consider running multiple scenarios to bracket the range of likely outcomes.
Should bilirubin be in mg/dL or µmol/L?
In the context of Maddrey Discriminant, this depends on the specific inputs, assumptions, and goals of the user. The underlying formula provides a deterministic relationship between inputs and output, but real-world application requires interpreting the result within the broader context of health and medical practice. Professionals typically cross-reference calculator output with industry benchmarks, historical data, and regulatory requirements. For the most reliable results, ensure inputs are sourced from verified data, understand which assumptions the formula makes, and consider running multiple scenarios to bracket the range of likely outcomes.
What is the MELD score's role alongside the Maddrey DF?
The MELD score is increasingly used alongside or instead of the Maddrey DF in alcoholic hepatitis. MELD >20 or >25 is associated with poor prognosis and is a commonly used alternative threshold for steroid therapy. Some centres use MELD rather than DF because it uses INR (readily available) rather than requiring the control PT.
Does the Maddrey DF predict long-term outcomes?
In the context of Maddrey Discriminant, this depends on the specific inputs, assumptions, and goals of the user. The underlying formula provides a deterministic relationship between inputs and output, but real-world application requires interpreting the result within the broader context of health and medical practice. Professionals typically cross-reference calculator output with industry benchmarks, historical data, and regulatory requirements. For the most reliable results, ensure inputs are sourced from verified data, understand which assumptions the formula makes, and consider running multiple scenarios to bracket the range of likely outcomes.
Dica Pro
Always convert bilirubin to mg/dL before entering into the Maddrey formula. If your laboratory reports in µmol/L (common in the UK and Australia), divide by 17.1. A missed unit conversion is the most consequential error in DF calculation.
Você sabia?
The Maddrey Discriminant Function was derived from a clinical trial that enrolled only 57 patients — remarkably small by modern standards. Despite this, the threshold of 32 has remained essentially unchanged for over 45 years and continues to guide clinical decision-making in severe alcoholic hepatitis worldwide, a testament to its biological validity.
Referências
- ›Maddrey WC et al. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology 1978.
- ›Thursz MR et al. (STOPAH Trial) Prednisolone or Pentoxifylline for Alcoholic Hepatitis. NEJM 2015.
- ›EASL Clinical Practice Guidelines: Liver Diseases Related to Alcohol. J Hepatol 2018.
- ›AASLD Practice Guidance: Alcoholic Liver Disease
- ›MDCalc — Maddrey's Discriminant Function for Alcoholic Hepatitis