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Autoimmune hepatitis and immunosuppressive hepatotoxicity drugs - drug-induced liver toxicity

Updated on August 27, 2015
acute liver injury with jaundice have been associated with streptomycin therapy and always in combination with other antituberculosis medications which are hepatotoxic, such as isoniazid, pyrazinamide and rifampin.
acute liver injury with jaundice have been associated with streptomycin therapy and always in combination with other antituberculosis medications which are hepatotoxic, such as isoniazid, pyrazinamide and rifampin. | Source

Liver histology in autoimmune forms of drug induced liver injury resembles the pattern seen in spontaneous or idiopathic autoimmune hepatitis. The medications most frequently linked to drug induced autoimmune hepatitis include nitrofurantoin, minocycline, hydralazine and methyldopa.

There are many reports of drugs associated with autoimmune phenomena: autoimmune hepatitis (dihydralazine, halothane, tienilic acid), drug-induced lupus (dihydralazine, procainamide, propylthiouracil), glomerulonephritis (gold thiomalate), and occulomucocutaneous syndrome (practolol) this are pharmaceutical antiarrhythmic agents used for the medical treatment. The side effects can be quite frequent, e.g., 10-20% of patients receiving procainamide and 5-20% receiving hydralazine develop systemic lupus erythematosus.


 with many patients using steroids and azathioprine in the medium‐term, but many patients with autoimmune hepatitis will ultimately need a liver transplant to survive. These treatments have side effects, and treatments fail in approximately 10%.
with many patients using steroids and azathioprine in the medium‐term, but many patients with autoimmune hepatitis will ultimately need a liver transplant to survive. These treatments have side effects, and treatments fail in approximately 10%. | Source

Approximately 50,000 people (mainly women) in the U.S. suffer from autoimmune hepatitis, an unresolving inflammation of the liver which may lead to end‐stage liver disease and organ failure.

In Scotland, UK, the most common means of transmission of hepatitis is sharing equipment used for injecting drug use.

Autoimmune hepatitis is marked by the presence of autoantibodies (most typically antinuclear antibody) and hyperglobulinemia accompanying the liver injury. Autoimmune hepatitis induced by medications usually has a long latency (sometimes years), insidious onset and a hepatocellular pattern of serum enzyme elevations.

Oxford Journals of Clinical Infectious Disease, Gastrointestinal Unit. reported the first case of autoimmune hepatitis caused by immune reconstitution inflammatory syndrome.
immune reconstitution inflammatory syndrome (IRIS) is an inflammatory response to pathogens ( e.g. a bacterium complex) present in the host, most commonly Mycobacterium tuberculosis, Mycobacterium avium complex, Cryptococcus species, Histoplasma capsulatum, Toxoplasma gondii, Pneumocystis jiroveci, cytomegalovirus, herpes viruses, and JC virus.

IFX drugs ( Infliximab )has been reported to induce acute liver failure by at least three mechanisms: induction of autoimmune hepatitis, cholestatic liver injury and direct toxicity.

Treatment with intermediate and high doses of paracetamol showed typical signs of hepatotoxicity, both in clinical chemistry and in histopathology from Day 1. all hepatotoxicity drugs induce liver damage.

The liver is a multifunctional organ and drugs cause liver injury by many different mechanisms.
The liver is a multifunctional organ and drugs cause liver injury by many different mechanisms. | Source

Autoimmune liver disorders and CD share common HLA class II haplotypes. In caucasian population, two haplotypes have been identified as susceptibility markers of autoimmune hepatitis: the complex HLA A1 B8 DR3 and the haplotype HLA DR4. Similarly, specific HLA class II antigens such as HLA-DR3, particularly the HLA-DQ2 molecule and HLA DR4, confer susceptibility to CD.

Mycobacterial Heat Shock Protein (HSP) has been found in several additional autoimmune diseases: the mycobacterial HSP65 has been implicated in the pathogenesis of rheumatoid arthritis, autoimmune hepatitis, primary biliary cirrhosis, and scleroderma. HSP65 is also implicated in multiple vasculitis-associated systemic autoimmune diseases such as Kawasaki disease, Behcet’s disease and Takayasu’s arteritis.

Drug-induced immunosuppression is associated with an increase incidence of liver infections.
Drug-induced immunosuppression is associated with an increase incidence of liver infections. | Source

Patients with celiac disease have an increased intestinal permeability which may facilitate the absorption of antigens from the gut. Increased permeability to intraluminal antigens could induce, in genetically predisposed individuals, an immune response both against antigens sharing common epitopes to self-liverproteins and/or against cryptic antigens unmasked by the reaction with gliadin. It is known that mucosal damage in CD leads to exposure of tissue transglutaminase enzyme, the target antigen recognised by antiendomysial antibody.

Celiac disease may present as a cryptogenic liver disorder being found in 5-10 % of patients with a persistent and cryptogenetic elevation of serum aminotransferase activity. In fact, a wide spectrum of liver injuries in children and adults may be related to CD and in particular. a mild parenchymal damage characterised by absence of any clinical sign or symptom suggesting a chronic liver disease and by non-specific histological changes reversible on a gluten-free diet. a chronic inflammatory liver injury of autoimmune mechanism, including autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis, that may lead to fibrosis, cirrhosis and a severe liver failure potentially treatable by a gluten-free diet and detox diet.

Drugs Medications that typically cause autoimmune hepatitis include minocycline, nitrofurantoin, hydralazine, methyldopa, statins, fenofibrate, alpha and beta interferon, infliximab, atorvastatin, Methotrexate and etanercept.


List of Autoimmune liver disorders:
Reactive hepatitis ( coeliac hepatitis)
Autoimmune hepatitis
Autoimmune overlap syndrome
Autoimmune (sclerosing) cholangitis
Primary biliary cirrhosis
Non alcoholic fatty liver disease
Acute liver failure
Cryptogenic cirrhosis
Regenerative nodular hyperplasia
Hepatocellular carcinoma
Chronic hepatitis

Hsp65 is the immunodominant antigen during mycobacterial infection and vaccination, and has been linked to the development of autoimmune hepatitis and adjuvant arthritis.
Hsp65 is the immunodominant antigen during mycobacterial infection and vaccination, and has been linked to the development of autoimmune hepatitis and adjuvant arthritis. | Source

Drug induced liver injury is often accompanied by immunological features indicating either hypersensitivity or an autoimmune reaction or both.

Previous studies had shown that exposure to trichloroethylene, a solvent and degreasing compound, induced autoimmune hepatitis in autoimmune-prone patients.

The combination of anakinra and the TNF-blocking agent etanercept resulted in an increase in the number of serious mycobacterium tuberculosis complex infections.

Organic beetroot, ginger and carrot made into juice can be very effective in the detoxification of the liver.
Organic beetroot, ginger and carrot made into juice can be very effective in the detoxification of the liver. | Source

The immune system is constantly protecting the body from invading organisms at a level of complexity most of us cannot comprehend. Modern medicine focuses mainly on the invading organisms as the source of disease without an appreciation for the beauty of the immune system’s ability to protect the body from harm.

Natural and nutritional food is vital in maintaining a healthy immune system and preventing autoimmune hepatitis disorder.

Drug-induced immunosuppression is associated with an increase incidence of infections.

Autoimmune hepatitis is more common in females; 70% of Autoimmune hepatitis patients are women between the ages of 15 and 25.
Autoimmune hepatitis is more common in females; 70% of Autoimmune hepatitis patients are women between the ages of 15 and 25.

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    • autoimmune profile imageAUTHOR

      autoimmune 

      3 years ago from United Kingdom

      Adalimumab (Humira NR) is known as a hepatotoxicity drug.

      long term use of hepatotoxicity drugs induce liver failure.

      the most serious adverse drug reaction of adalimumab (ADR) is tuberculosis reactivation.

      More than 50% of all acute liver failures and near 10% of all acute hepatitis cases are due to drugs nowadays.

      You can read more at; http://livertox.nih.gov/Adalimumab.htm

    • Barbara Kay profile image

      Barbara Badder 

      3 years ago from USA

      Does Humara cause liver problems? I know I"m already on a drug you listed.

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