Drug-Induced Liver Injury

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Questions and Answers

What percentage of hospital admissions for jaundice are caused by DILI?

3-5% (correct)

20-25%

10-15%

1-2%

What is the estimated incidence of DILI per 100,000 persons?

20 to 25 cases

10 to 15 cases

30 to 40 cases

14 to 19 cases (correct)

What is the percentage of DILI cases accompanied by jaundice?

10%

30% (correct)

40%

20%

What is the most frequent cause of acute liver failure in most Western countries?

DILI Signup and view all the answers

What is a major diagnostic element of DILI?

The timing of the onset of injury after the implicated agent has been started Signup and view all the answers

What is another term for the resolution of symptoms after the agent is stopped?

Dechallenge Signup and view all the answers

What is the primary purpose of special tests like liver biopsy, imaging, and serologic markers in drug-induced liver injury?

To rule out other causes of liver injury Signup and view all the answers

Approximately how many agents are described on the LiverTox website as having potential to cause liver injury?

Over 1200 agents Signup and view all the answers

What percentage of prescription drugs described on LiverTox have been implicated in causing liver injury in at least one published case report?

46% Signup and view all the answers

What is direct hepatotoxicity caused by?

Agents that are intrinsically toxic to the liver Signup and view all the answers

What is the typical latency period for direct liver injury?

Within 1 to 5 days after high therapeutic or supratherapeutic doses Signup and view all the answers

What is the characteristic of direct liver injury in terms of dosage?

Predictable and dose-dependent Signup and view all the answers

What is the classification of drug-induced liver injury based on?

The mechanism of liver injury Signup and view all the answers

What is the term for liver injury caused by agents that are intrinsically toxic to the liver?

Direct liver injury Signup and view all the answers

What is the characteristic of idiosyncratic hepatotoxicity?

Unpredictable, not dose-dependent, and not reproducible in animal models Signup and view all the answers

What is the R ratio used for in idiosyncratic liver injury?

To determine the type of liver injury Signup and view all the answers

What is the definition of hepatocellular injury based on the R ratio?

R value of more than 5 Signup and view all the answers

What is an example of indirect liver injury?

Induction of immune-mediated hepatitis Signup and view all the answers

What is the main difference between idiosyncratic and indirect hepatotoxicity?

Idiosyncratic is caused by the drug's properties, while indirect is caused by the drug's action Signup and view all the answers

What is an example of a preexisting condition that can be exacerbated by indirect hepatotoxicity?

Hepatitis B or C Signup and view all the answers

What is the frequency of idiosyncratic liver injury in patient-exposures?

1 in 2000 to 1 in 100,000 Signup and view all the answers

What is the reference cited in the text for drug-induced liver injury?

N Engl J Med 2019;381:264-73 Signup and view all the answers

Study Notes

Drug-Induced Liver Injury (DILI)

DILI is an uncommon but challenging clinical problem with respect to both diagnosis and management.
Its incidence is estimated to be 14 to 19 cases per 100,000 persons, with jaundice accompanying 30% of cases.
DILI is responsible for 3 to 5% of hospital admissions for jaundice and is the most frequent cause of acute liver failure in most Western countries.

Pathogenesis

The diagnosis of DILI is particularly challenging, since it is based largely on exclusion of other causes.
The major diagnostic elements of DILI are:
- The timing of the onset of injury after the implicated agent has been started (latency).
- Resolution after the agent is stopped (“dechallenge”).
- Recurrence on re-exposure (rechallenge).
- Knowledge of the agent’s potential for hepatotoxicity (likelihood).
- Clinical features (phenotype).

Diagnosis

With few exceptions, there are no specific diagnostic markers for DILI.
Special tests (liver biopsy, imaging, and testing for serologic markers) are helpful mostly in ruling out other causes of liver injury.
Exclusion of other causes of liver injury is essential.

Types of Drug-Induced Liver Injury

DILI is typically classified as:
- Direct
- Idiosyncratic
- Indirect injury

Direct Liver Injury

Caused by agents that are intrinsically toxic to the liver.
The injury is common, predictable, dose-dependent, and reproducible in animal models.
The latency period is typically short, usually with an onset within 1 to 5 days after high therapeutic or supratherapeutic doses.

Idiosyncratic Liver Injury

Caused by agents that have little or no intrinsic toxicity and that cause liver injury only in rare cases.
The injury is unpredictable, not dose-dependent, and not reproducible in animal models.
Idiosyncratic liver injury is categorized as:
- Hepatocellular
- Cholestatic
- Mixed (on the basis of the R ratio)

R Ratio

Calculated by dividing the alanine aminotransferase level by the alkaline phosphatase level from the time of initial presentation.
Hepatocellular injury is defined as an R value of more than 5.
Cholestatic injury as a value of less than 2.
Mixed injury as a value of 2 to 5.

Indirect Liver Injury

Caused by the action of the drug (what it does) rather than by its toxic or idiosyncratic properties (what it is).
Indirect injury can represent induction of a new liver condition or an exacerbation of a preexisting condition, such as:
- Induction of immune-mediated hepatitis.
- Worsening of hepatitis B or C or fatty liver disease.