Drug-induced hepatitis

1. outbreak of infection but no action taken

In 1964, blood safety became a social issue when U.S. Ambassador to Japan Reischauer was attacked and injured by thugs and received a blood transfusion, which resulted in his contracting viral hepatitis. In 1974, all blood products for transfusion came from blood donations in Japan. However, since plasma fractionated products, which are manufactured by extracting the necessary components from blood, require a large amount of human blood, blood from overseas sources was used.

Fibrinogen preparations, the cause of drug-induced hepatitis, were approved in 1964. Fibrinogen was also used overseas, but its approval was withdrawn by the U.S. Food and Drug Administration (FDA) in 1977 due to the high risk of viral infection, questionable clinical efficacy, and the existence of alternative therapies. This information was known within Japanese pharmaceutical companies, but not to the former Ministry of Health and Welfare at the time.

In 1987, a report to the former Ministry of Health and Welfare from an obstetrician/gynecologist that a group of pregnant women had been infected with hepatitis by a fibrinogen preparation prompted the pharmaceutical company to recall the unheated fibrinogen preparation. However, due to this recall and disposal, it was not possible to investigate the route of contamination of the drug or the amount of virus after the fact. In addition, although a list of infected persons was submitted to the former Ministry of Health and Welfare, this list was left without notification to the victims.

The pharmaceutical company applied for approval of the heated fibrinogen formulation on the same day as the recall of the fibrinogen formulation. While the former Ministry of Health and Welfare approved the application, it also proposed to the pharmaceutical companies that the indication for the unheated fibrinogen formulation be limited to congenital diseases, but obstetrics and gynecology organizations opposed the limitation of the range of indications. It was not until 1998 that the former Ministry of Health and Welfare limited the indication for fibrinogen products to congenital hypofibrinogenemia.

In 2000, the former Ministry of Health and Welfare established a “Hepatitis Countermeasures Project Team” within the Ministry, and in 2001 launched a survey on the actual situation regarding hepatitis virus infection through the use of blood products. The results of this investigation were published in 2002 in the “Report on the Investigation of Hepatitis C Virus Infection by Fibrinogen Products,” which recommended measures for the safety of medicines and other products.

2. victims stand up

In 2002, victims and their families filed lawsuits for damages in Tokyo and Osaka, and gradually lawsuits were filed in various regions. At the center of the lawsuits were women who had been infected with hepatitis C after being given fibrinogen drugs during childbirth more than a decade earlier. Many of the women suffered discrimination and prejudice due to their hepatitis infection, as well as the strong side effects of interferon treatment. In response to the women’s lawsuit, young people, their children, also supported the lawsuit and held publicity campaigns on the streets.

The issues at trial included whether the risk of contracting hepatitis was foreseeable and whether the efficacy of the drug really outweighed the side effects. It was also revealed that despite the fact that the government and pharmaceutical companies had multiple opportunities to stop the damage from occurring, such as when the reevaluation slipped through due to changes in manufacturing approval and marketing names, and when the approval was revoked in the US, fibrinogen products continued to be sold due to descent from the pharmaceutical companies and collusion with the medical community.

Following the 2007 court decisions in various parts of the country that found the government and pharmaceutical companies liable, then Prime Minister Yasuo Fukuda announced a policy of uniform relief for all victims through legislation enacted by lawmakers. In 2008, the “Act on Special Measures concerning Payment of Benefits for Victims of Hepatitis C Infection Caused by Specified Fibrinogen Products and Specified Blood Coagulation Factor IX Drugs” (Hepatitis C Relief Act) was unanimously passed by the Diet and a basic agreement was signed between the government and plaintiffs. This was the first relief for drug-induced hepatitis C victims to be provided by a legislator.

In the same year, the Ministry of Health, Labor and Welfare established the “Committee for Review of the Hepatitis Drug Injury Case and Prevention of Recurrence of Drug Injury in the Pharmaceutical Administration” to discuss the prevention of recurrence of drug injury, and made a final recommendation in 2010. In response to the proposal in the final recommendations to establish a “third-party monitoring and evaluation organization” for pharmaceutical administration, the “Committee for Evaluation and Monitoring of Pharmaceutical Administration” was established in the MHLW in 2020, and is expected to serve as a monitoring organization to ensure the safety of pharmaceuticals and prevent the recurrence of drug-related injuries.

references

1. Foundation for Regulatory Science of Pharmaceuticals and Medical Devices, 2012, “Lessons Learned from Drug Injury: Voices from Victims Hoping for the Prevention of Recurrence,” Pharmaceutical Affairs Daily, Inc.
2. Japan Association for Public Publications, 2011, “Knowledge of Drug Hazards You Should Know–To Prevent Health Damage Caused by Drugs,” Jiho.