The renowned liver expert parses results of 3 studies presented at The Liver Meeting 2018 that could expand the role for DAA therapy in unexpected ways.
In this interview, Jordan Feld, MD, MPH, discusses key highlights from studies presented at The Liver Meeting 2018, held recently in San Francisco by the American Association for the Study of Liver Diseases (AASLD). Dr. Feld is the R. Phelan Chair in Translational Liver Research, Toronto Centre for Liver Disease, Toronto General Hospital, and is on the HCV guidance panel for the AASLD and the Infectious Diseases Society of America (IDSA).
Read on as Dr. Feld discusses whether it’s worth considering universal screening of pregnant women at risk for HCV infection, treatment of HCV-infected people who inject drugs, and transplanting HCV-infected hearts-all based on the latest evidence presented at this important clinical conference.
Q1. At the Liver Meeting this year, Dr. Rose and colleagues reported that universal screening of pregnant women at risk for HCV infection was an efficient and cost-effective diagnostic approach, compared to risk-based screening, in a region of the United States that’s heavily affected by the opioid epidemic.
How does this study advance the discussion of risk-based versus universal screening in this population?
Dr Feld. To me, the most striking finding of this study was the incredibly high prevalence of hepatitis C among these young pregnant women, which was 4.3% with risk-based screening, and even more striking, the prevalence was the same if not higher, at 4.7%, after this institution transitioned to universal screening. If you compare that to universal screening of baby boomers, which has been advocated since 2012, the prevalence is much higher in the pregnant women-and most remarkably the same whether risk-based or universal-something we almost never see.
I think this speaks to the fact that we, as health care professionals, are actually really bad at identifying HCV risk factors. Presumably most of the women in the universal screening cohort had a risk factor, given the similar prevalence rate compared to the risk-based screening cohort. What makes this scenario really challenging is the fact that pregnant women are not always forthcoming-they have a significant disincentive to acknowledge the risk factor, particularly if it’s injection drug use. As you can imagine, they are probably quite concerned about having their child taken away from them, or other consequences of being open about drug use.
All of this confirms that there’s a real purpose to doing universal HCV screening of pregnant women, as is advocated in treatment guidelines from the AASLD and IDSA due to the uptick in HCV prevalence among young women that’s largely due to the opioid crisis.
Really the goal here is to identify women with hepatitis C-even if we can't prevent transmission to the baby with this pregnancy, we can get those women linked to care, and prevent transmission in a subsequent pregnancy by ensuring that they get direct-acting antiviral therapy.
The study authors stressed that universal screening was a cost-effective strategy, but of course it had to be cost-effective, since the prevalence was similar between the risk-based and universal strategies. The reason that universal screening is usually more costly than risk-based screening is that the yield goes way down-the percentage of positives usually goes down because the general population is at lower risk than those identified by their risk factors. In this study, that was not the case. The rate of HCV was the same or higher with universal screening, which is remarkable but means that expanding to universal screening will certainly be cost-effective.
I actually think that with a slightly more thorough cost-effectiveness analysis that accounts for ancillary benefits of identifying these individuals, such as getting them into treatment related to the drug use, it would be almost certain that universal screening is cost-saving. It is important to remember that this study was carried out in an area that has been hit hard by the opioid crisis. Whether the results would be as generalizable to other regions of the country is not known but it is likely that prenatal screening is cost-effective in most setting in the US, which is why it is recommended by the AASLD/IDSA guidance panel.
Q2. That leads us to the study by Dr. Kattakuzhy and colleagues which showed that, despite concern to the contrary, people who inject drugs who are infected with HCV actually have high rates of treatment adherence, and relatively high rates of sustained virologic response.
What are the implications for clinical practice?
Dr Feld. I think unfortunately some of us in the hepatology and infectious disease community are still a bit stuck in the interferon era. When we were using interferon-based therapy, there was good reason to exercise caution in treating people who were actively using injection drugs, or who had mental health or substance abuse issues. Interferon therapy can exacerbate those issues, and there was a high risk of complications without proper oversight of their treatment.
That changes entirely with these new direct-acting antiviral treatments. They are easy to take, extremely well tolerated, and perhaps more importantly, very safe. And what this study showed was, first of all, that people who inject drugs are more adherent to antiviral therapy than they might have been expected to be, particularly given significant social comorbidities such as a high unemployment rate and unstable housing. But even in people who had imperfect adherence, as long as they got through their treatment, even if treatment took a lot longer than the prescribed 12 weeks, they still had a very high rate of sustained virologic response (SVR).
When we think about controlling the HCV epidemic at the population level, every cost-effectiveness analysis shows that the most cost-effective group to treat are people with advanced liver disease. But the second most important group is people who are actively injecting drugs, because by curing them, you have the added benefit of preventing transmission to other individuals.
What needs to change is we need to get rid of all restrictions to antiviral therapy based on drug use. There should be none. The restrictions on sobriety from drug use or alcohol are frankly not evidence-based. There are now multiple studies, including this one, showing equal or very close to equal SVR rates among people who are actively injecting drugs, compared to people who have no history of drug use.
Q3. The final study of interest is from Dr. Bethea and co-investigators, which demonstrated that, in cardiac transplant patients who are HCV-negative, pre-emptive treatment with direct-acting antiviral therapy prevents chronic HCV infection when they receive donor hearts infected with the virus.
How does this fit in with other recent studies of HCV-infected donor organs?
Dr Feld. It’s an emerging concept, not just in heart transplant but across all organ transplants, that because the current antiviral therapies are so safe and so effective, we could actually start doing what before we would have never thought possible-which is to actually intentionally infect people, but then treat them in order to give them access to these HCV-infected but otherwise life-saving organs.
Unfortunately, we're seeing people who have otherwise very healthy, good organs being discarded that could be lifesaving for someone else. The opioid crisis is an absolute tragedy, but if someone is going to die a totally devastating premature death because of the opioid crisis, at least if we can have some good outcome out of that, that their otherwise healthy organs can save someone else's life, then that's just a massive benefit.
This was first pioneered with kidney transplants, and it's now been extended to cardiac transplants, such as we have seen in this study from Boston, and the outcomes have been outstanding. I would just caution that these procedures should be done carefully, because this isn't the same as treating your treatment-naÃ¯ve, non-cirrhotic person who has no other comorbidities. These patients, particularly post-heart and lung transplant, are quite sick.
My colleagues and I presented our findings on HCV-infected lung transplants at the Liver Meeting, and we did see some relapses, including a few that were severe. That means these procedures have to be done carefully in experienced centers, and ideally, the treatments need to be started as early as possible after transplant to reduce the risk of relapse.
Please click here for short summaries of the three studies discussed by Dr Feld.