Hepatitis C and its virus:
Hepatitis C is an inflammation of the liver caused by the hepatitis C virus. The disease can be either acute or chronic. Chronic hepatitis C is considered one of the most common causes of cirrhosis (i.e. shrinking liver) and liver carcinoma (i.e. liver cancer). The virus is an RNA virus (i.e. ribonucleic acid, usually only one strand, unlike DNA) and belongs to the flavivirus family. After its discovery in 1989, the virus previously known as hepatitis non-A non-B was given its current name, hepatitis C. Currently, any suspicion of the virus, as well as any proven infection (and deaths from hepatitis C), must be reported by physicians to the appropriate health department with the patient's name.
Difference in disease progression:
The causative agent of the virus, which is spread worldwide, is transmitted primarily through human blood. Geographically, the eastern Mediterranean region and Europe are most affected. In about 75% of cases, infections with hepatitis C cause no symptoms or only non-specific symptoms. These include: Fatigue Loss of appetite, nausea, muscle and joint pain or mild fever. The remaining 25% of infected individuals may develop acute liver inflammation with a possible mild course. The resulting symptoms would be moderately elevated liver enzymes and icterus (i.e. jaundice), yellowing of the skin mucous membranes and the white sclera in the human eye.
Although direct-acting virustatics (i.e., antiviral agents) are used more widely to treat chronic hepatitis C infection, few reports of clinical efficacy in patients are found. A study published in 2019, in the journal The Lancet, compared the incidence of death, cirrhosis, and hepatocellular carcinoma in a French cohort between patients treated with direct-acting virustatics and those not administered such treatment.
The observational study was conducted on adult patients with chronic hepatitis C infection who were hospitalized in 32 different hepatology expert centers in France. Patients with chronic hepatitis B, a history of liver cirrhosis or hepatocellular carcinoma were excluded - as well as patients with liver transplantation or those treated with interferon-ribavirin (antiviral agent). Primary outcomes of the study were incidence of all-cause mortality, hepatocellular carcinoma, and liver cirrhosis. The association between direct-acting viral drugs and these outcomes was measured using time-dependent Cox models. These models are among the most popular statistical analysis techniques for studying survival data.
Between August 2012 and December 2015, 10 166 patients participated in this study. 97% of them, or 9895 patients, provided so-called follow-up information, which was included in this analysis. Follow-up refers to the subsequent verification of the efficacy and sustainability of research - or a follow-up investigation. Treatment with direct-acting antiviral drugs, for example with sofosbuvir combinations such as sofosbuvir and ledipasvir or sofosbuvir and daclatasvir, was started in 7344 patients during the follow-up. Approximately one quarter, or 2551 patients, remained untreated until the last follow-up. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had cirrhosis (74 treated, 32 untreated). Use of direct-acting antiviral drugs was associated with an increased risk of hepatocellular carcinoma and cirrhosis.
Adjustment for variables:
Because the two treatment groups differed greatly, preliminary results suggested that virustatic treatment may be more likely to be harmful. Due to ethical reasons, a controlled intervention study could not be conducted, resulting in such a finding. According to the study, the patients differed in significant ways that could influence the risk factor. Thus, study participants in the treatment group were older or more likely to have a history of severe liver cirrhosis or excessive alcohol consumption.
After adjusting for variables such as age, sex, BMI level, geographic origin, route of infection, hepatitis C treatment or type, and alcohol consumption, the use of direct-acting viral drugs was associated with a 52% decrease in all-cause mortality and a 33% reduction in the risk of developing hepatocellular carcinoma. However, this adjustment could not be associated with liver cirrhosis, because even after this, a non-significant risk increase of 14% was recorded.
Treatment with direct-acting antiviral agents is associated with a reduced risk of all-cause mortality and hepatocellular carcinoma, according to the study. Due to the high cost of such a 12-week treatment cycle (for example with the drug Sovaldi )- about 40,000€ - it is not easy to make this therapy available to a larger group of patients. Thus, NGOs such as Médecins Sans Frontières or Doctors of the World are trying to challenge these patent rights in order to enable the production of cheaper drugs.