What are the other Names for this Condition? (Also known as/Synonyms)

• DIAH (Drug-Induced Autoimmune Hepatitis)
• DIAIH (Drug-Induced Autoimmune Hepatitis)
• Medication-Induced Autoimmune Hepatitis

What is Drug-Induced Autoimmune Hepatitis? (Definition/Background Information)

• Autoimmune hepatitis (AIH) is an autoimmune disease of unknown cause that results in the body’s own immune system attacking the liver. When this happens, abnormal inflammation characteristic of hepatitis occurs, causing damage to the liver. The condition is mostly seen in females
• Drug-Induced Autoimmune Hepatitis (DIAH or DIAIH) occurs secondary to the use of certain medication, as an adverse reaction of the body. DIAH is most often caused by medications, such as minocycline, nitrofurantoin, and propylthiouracil, among others; a majority of the cases are noted in women
• Drug-Induced Autoimmune Hepatitis and autoimmune hepatitis have many overlapping features; but, experts believe that these two conditions are distinct clinical entities. Also, it is difficult to differentiate between DIAH and autoimmune hepatitis caused by other factors such as diabetes mellitus, celiac disease, Hashimoto's thyroiditis, and inflammatory bowel disease
• A definitive diagnosis of Drug-Induced Autoimmune Hepatitis may be arrived at only on the analysis of clinical findings, thorough medical history, lab tests, and recent medication use history. The signs and symptoms are similar to autoimmune hepatitis and may include yellowing of the skin, nausea, vomiting, loss of appetite, and abdominal pain
• Stopping or discontinuing the use of such medications may decrease progression of Drug-Induced Autoimmune Hepatitis and/or may result in resolution of the condition. Unlike autoimmune hepatitis, the prognosis of DIAH is reported to be excellent in a vast majority of cases with adequate treatment

Who gets Drug-Induced Autoimmune Hepatitis? (Age and Sex Distribution)

• Individuals of all ages may be affected by Drug-Induced Autoimmune Hepatitis
• Both males and females are affected, although many cases are noted in women
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Drug-Induced Autoimmune Hepatitis? (Predisposing Factors)

The key risk factor for Drug-Induced Autoimmune Hepatitis (DIAH) is the use of certain medications that cause the condition as a side effect.

• A strong association is noted between DIAH and the following medications:
  • Halothane
  • Lipitor
  • Minocycline
  • Nitrofurantoin
• Some association is noted between DIAH and the following medications:
  • Atorvastatin
  • Diclofenac
  • Infliximab
  • Isoniazide
  • Propylthiouracil
• Some of the medications suspected of causing DIAH include:
  • Adalimumab
  • Cephalexin
  • Fenofibrate
  • Imatinib
  • Indomethacin
  • Meloxicam
  • Methylphenidate
  • Rosuvastatin

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Drug-Induced Autoimmune Hepatitis? (Etiology)

The exact cause of autoimmune hepatitis (AIH) is currently unknown. It is reportedly caused by a combination of environmental, genetic, and immunological factors.

• Drug-Induced Autoimmune Hepatitis develops from the use of certain medications/drugs that are administered for various health conditions. It is believed that the offending drug potentially causes an abnormal cell-mediated immune response in the body 
• Sometimes, the appearance of signs and symptoms due to the drug may not be observed immediately after starting the medication. The condition may arise after a period of time

What are the Signs and Symptoms of Drug-Induced Autoimmune Hepatitis?

The signs and symptoms of Drug-Induced Autoimmune Hepatitis may vary from one individual to another. It may also be mild or severe and may be related to the type and usage of the drug. In some, it may be mild, resulting in a delayed diagnosis of the condition. Some individuals are diagnosed incidentally during wellness checkups. The condition is known to get better after stoppage of the offending medication.

In general, the signs and symptoms of autoimmune hepatitis may include:

• Jaundice (yellowing of the skin)
• Icterus (yellowing of the eyes)
• Loss of appetite
• Nausea and vomiting
• Fatigue
• Abdominal pain and swelling 
• Skin rashes/itching
• Dark-colored urine
• Light-colored stools 
• Joint pain
• Enlarged or swollen liver (hepatomegaly)
• Amenorrhea in women (absence of menstruation)

The onset of Drug-Induced Autoimmune Hepatitis may be slow or rapid. In some cases, it may not be immediately observed, but may take a long period of time to manifest following intake of the medication.

How is Drug-Induced Autoimmune Hepatitis Diagnosed?

The diagnosis of Drug-Induced Autoimmune Hepatitis (DIAH) is based upon a combination of clinical findings and lab test abnormalities. There is no single diagnostic test specifically available for autoimmune hepatitis (AIH). It is important to rule out other causes of chronic hepatitis before arriving at a diagnosis of AIH, including alcohol-induced hepatitis, viral hepatitis, and drug-induced hepatitis, before arriving at a diagnosis of AIH.

The following tests and exams may be used in the diagnosis of Drug-Induced Autoimmune Hepatitis:

• A complete medical history and a thorough physical examination. The physician may request for a list of all medications that are currently being taken
• Often times, the physician may recommend blood tests to assess the functioning of liver, in order to confirm a diagnosis. The liver contains a large number of enzymes. When the liver is injured, these enzymes are released into blood and they may be analyzed through various blood tests:
  • Testing for common enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) - elevated enzyme levels may be noted
  • A blood test in an individual with DIAH may also show elevated levels of bilirubin and autoantibodies such as ANA and ASMA
• Liver biopsy: If blood tests are not adequate in diagnosing AIH, a liver biopsy may be performed. During this procedure, a small sample of the liver is removed from the body and sent to the laboratory for analysis. Liver biopsies show characteristic features which helps make a diagnosis of DIAH (interface hepatitis, as described by a pathologist, is observed)
• Radiological studies, such as USG of abdomen and CT abdomen, are usually not helpful in diagnosing autoimmune hepatitis. However, they are often performed to rule-out other conditions causing similar signs and symptoms

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Drug-Induced Autoimmune Hepatitis?

If Drug-Induced Autoimmune Hepatitis is left untreated, it can result in certain complications. Some of the complications include:

• Accumulation of fluid within the abdomen, known as ascites
• Formation of esophageal varices resulting in vomiting of blood
• Chronic liver injury leading to cirrhosis (scarring) of the liver
• Total liver failure if the condition is left untreated
• Recurrence/relapse of the condition

How is Drug-Induced Autoimmune Hepatitis Treated?

The most important component of treatment for Drug-Induced Autoimmune Hepatitis is a prompt and accurate diagnosis of the condition. Following a diagnosis, the treatment provided may include:

• Discontinuing the medication responsible for the side effect, which may result in a cure, or in improvement of the condition
• Steroid therapy is known to be an effective treatment measure
• In general, autoimmune hepatitis is most commonly treated using immunosuppressive medications

Follow-up care with screening and check-ups are important at regular intervals.

How can Drug-Induced Autoimmune Hepatitis be Prevented?

Current medical research has not established a method of preventing Drug-Induced Autoimmune Hepatitis. However, the following measures may be considered to help lower one’s risk for the condition:

• Drugs that cause the condition may be discontinued or alternative medication prescribed; nevertheless, this has to be decided by the healthcare expert
• If the use of certain medications places an individual at an elevated risk for this liver condition, it is advisable to check with the physician on the same
• Avoid self-medication or bringing about any changes to one’s medication dosage without consulting the healthcare provider
• Inform your physician if you are allergic to any medication
• Undertaking early and appropriate treatment of an underlying autoimmune disease may help in lowering one’s risk for autoimmune hepatitis

Periodic monitoring or follow-up of the condition with the healthcare provider is recommended.

What is the Prognosis of Drug-Induced Autoimmune Hepatitis? (Outcomes/Resolutions)

The prognosis for Drug-Induced Autoimmune Hepatitis is usually good in many cases, upon discontinuation of the medication and adequate treatment of the condition.

• It is reported that in almost all cases, the response to treatment is excellent (including drug discontinuation); also, no drug-related relapses have been noted
• However, the prognosis may also depend upon the type of medication involved, the period of exposure to the offending medication, and severity of the symptoms. In many individuals, relapses may be observed

Additional and Relevant Useful Information for Drug-Induced Autoimmune Hepatitis:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/immune-related-disorders/