Hepatitis C virus (HCV), one of the most significant causes of liver inflammation, has a high annual mortality rate. Injection drug use among people of reproductive age is the leading cause of new HCV infections. Prior treatment required the combination of oral medications and weekly injections. Pregnancy is a crucial period of health-care engagement, and HCV treatment during pregnancy would not only cure maternal HCV infection, but might also prevent perinatal HCV transmission and future community HCV transmission. Unfortunately, in general pregnant women with HCV do not receive treatment during pregnancy because there is an absence of data regarding the safety and efficacy of highly effective direct-acting antivirals in pregnancy. Pregnant women are usually excluded from participating in clinical trials of new drugs. Prospective evaluations of medications for use in pregnancy often lag by years after approval or are not done at all.
Luckily, HCV treatment by direct-acting antiviral interventions has made possible expansion of treatment programs. Also, HCV screening has been extended to cover all adults, and in many countries, pregnant individuals in concerted efforts to fully eradicate HCV. Since pregnant women are severely underrepresented in clinical research, many take the position that the exclusion of pregnant women from research must be justified unless there are compelling “scientific reasons” for their exclusion. Unfortunately, almost universally, pregnant individuals have been systematically excluded from hepatitis C virus treatment programs and research. Including pregnant individuals in HCV treatment and research may play an important role in eliminating perinatal HCV transmission and improve transmission care after delivery. The unjustified exclusion of this population from HCV treatment and research denies them and the future generation of the potential health benefits. It also raises justice concerns going by the ever-rising data on direct-acting antivirals safety and efforts being made to ensure equitable and extensive hepatitis C virus eradication.
In light of these concerns, Northwestern University Feinberg School of Medicine researchers, Lynn M. Yee, Swati Antala, Margaret Murphy, William A. Grobman, Seema K. Shah and Ravi Jhaveri sought to systematically analyze data on HCV treatment in pregnancy and assess ethical consideration for fair and responsible inclusion of pregnant individuals in HCV treatment and research programs. They advocate that pregnancy could be an ideal time to provide HCV treatment because of increased engagement in the health-care system. Eventually the authors proposed a potential pathway for research and treatment during pregnancy to further the efforts of HCV eradication. The original research article is now published in journal, Hepatology.
The authors conducted a systematic review of literature in a bid to investigate the evidence on HCV and direct-acting antivirals treatment in pregnancy. They included any comparative studies such as quasi-experimental designs, randomized control studies, and observational studies in the review to evaluate the efficacy of therapy. Of the 1783 unique references identified as potentially relevant, only 31 study addressed HCV treatment during pregnancy. Far worse, only one was an interventional treatment study of sofosbuvir/ledipasvir started during pregnancy in a small study of eight individuals. In all, the scarcity of studies on this subject demonstrates clearly the unjustified exclusion of pregnant individuals from HCV clinical research.
The authors uncovered from the review a historical pattern of excluding pregnant individuals from clinical research. The desire to protect the fetuses and pregnant individuals often classified as ‘vulnerable’ was highlighted as the main reasoning behind this. This was stemming from unethical studies where researchers often exploited vulnerable species.
A fundamental first step towards the development of a clinical pathway for treating HCV during pregnancy is to establish safe and therapeutic drug exposures during pregnancy. Regulators, bioethicists and researchers seemed to have reached consensus that the inclusion of pregnant women in research should be promoted. Recently, the US federal regulations on research removed pregnant individuals from the list of groups vulnerable to coercion. Despite the increased awareness of the benefits of including more pregnant individuals in research, progress is still slow paced. For example, the authors noted that there were no safety data reported in pregnancy for the 73% of drugs approved by the FDA in 2011. Also, pregnant individuals were largely excluded from Ebola and COVID 19 pandemic clinical trials.
The authors propose a clear benefit of including pregnant individuals in HCV treatment rather than delaying until after pregnancy. Treatment during pregnancy could reduce and possibly eliminate perinatal HCV transmission altogether. Viremia is an absolute perinatal HCV transmission requirement, and existing direct-acting antivirals swiftly reduce HCV RNA levels to undetectable within a fortnight of initiation.
Teratogenic effects and toxicity are potential HCV treatment risks during pregnancy. However, a review of product label information and pan-genotypic regimens didn’t show any notable toxicities in pregnant populations. Also, potential teratogenic effects could be avoided considering that direct-acting antivirals could be started and concluded before delivery. The new study concluded that HCV screening and treatment during pregnancy are possible and provides a fundamental step towards the development of a safe and effective clinical pathway for treating HCV during pregnancy.
Ravi Jhaveri, Lynn M. Yee, Swati Antala, Margaret Murphy, William A. Grobman, and Seema K. Shah. Responsible Inclusion of Pregnant Individuals in Eradicating HCV. Hepatology, Vol. 74, No. 3, 2021.