What disease in medicine was thought to be well understood but had its management completely changed by a discovery?

From the Guidelines

Chronic hepatitis C is a disease in medicine that was thought to be well understood but had its management completely changed by the discovery of direct acting antivirals (DAA). The development of DAA against hepatitis C virus (HCV) has changed the paradigm for the pharmacological management of chronic hepatitis C, as stated in the 2018 update of the Korean Association for the Study of the Liver (KASL) treatment guidelines 1. Before the introduction of DAA, treatment for chronic hepatitis C focused on interferon-based therapies, which had limited efficacy and significant side effects. However, with the advent of DAA, the ease of administration and high sustained virologic response rate (SVR) have made treatment more effective and tolerable. Some key points to consider in the management of chronic hepatitis C include:

• The use of DAA has improved treatment outcomes and reduced the risk of complications such as liver cirrhosis and hepatocellular carcinoma.
• The 2018 KASL guidelines recommend the use of DAA for the treatment of chronic hepatitis C, based on the patient's genotype and other factors 1.
• Other guidelines, such as those from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), also recommend the use of DAA for the treatment of chronic hepatitis C.
• The discovery of DAA has transformed the management of chronic hepatitis C from a focus on symptom management to a focus on cure, as noted in the 2001 clinical guidelines on the management of hepatitis C 1.
• The management of chronic hepatitis C must be individualized, taking into account the patient's clinical data and other factors, as stated in the 1998 recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Disease Management Revolution

• The disease in question is Hepatitis C, which was thought to be well understood but had its management completely changed by a discovery.
• Prior to the discovery, the standard treatment for chronic Hepatitis C (CHC) patients comprised a combination of pegylated interferon (IFN) and ribavirin, which was associated with suboptimal efficacy and severe adverse reactions 2.
• The introduction of direct-acting antivirals (DAAs) such as sofosbuvir, ledipasvir, and daclatasvir revolutionized the treatment of CHC, offering higher efficacy and better tolerability 3, 4.

Impact of Discovery

• The discovery of DAAs has led to the development of interferon-free therapies, which have achieved high rates of sustained virological response (SVR) in clinical trials and real-world practice 3, 5.
• Studies have shown that DAAs such as sofosbuvir/ledipasvir and sofosbuvir/daclatasvir are effective and well-tolerated in patients with HCV genotype 4 infection, with SVR rates of 96-98% 4.
• The use of DAAs has also been shown to be effective in special populations, such as patients with cirrhosis, liver transplant, and HIV co-infection 3.

Future Directions

• Despite the success of DAAs, challenges remain, including the high cost of these therapies and the ability of HCV to mutate, limiting the potential for vaccine development 6.
• Ongoing research is focused on developing more cost-effective strategies to control the spread of HCV and creating novel, highly effective, and affordable DAAs 6.
• The World Health Organization (WHO) has developed a global health sector strategy for the elimination of viral hepatitis by 2030, which includes evidence-based guidelines for national hepatitis program managers 5.