“Yellow jaundice”, a redundant phrase that literally means “yellow yellow,” is a sign of a very sick liver. I recall a patient of mine, a quiet woman with chronic hepatitis C infection who visited me looking like a lemon. As I examined her fluid-filled belly, she sheepishly admitted that she’d fallen off the bandwagon and, unbeknownst to her family, had started drinking alcohol again. Her husband was in the waiting room, and she begged me not to tell him. I got her admitted to the hospital and she died a week later from fulminate liver failure.
A year later in 2014, headlines trumpeted new drugs that cured 95% of hepatitis C cases. It was then, as I rode the wave of optimism following the first cure for a chronic viral infection, that I drafted this article. I thought I was looking toward a future where hepatitis C would become an easily treatable but annoying infection, like syphilis. Almost a decade later, I see that I was wrong for a lot of reasons.
Syphilis is an interesting comparison because it was a chronic disease for most of human history. It is a sexually-transmitted bacterial infection that when left untreated, can cause many problems and affect almost any organ. In the 1940s, syphilis cases plummeted owing to improved diagnostics, effective antibiotics and prevention initiatives. Today, it is taken for granted that a short course of antibiotics cures people who then avoid decades of debility. While syphilis cases are still diagnosed at a low hum, punctuated by the occasional outbreak, I’ve only seen one case of advanced syphilis (neurosyphilis) in my 22 years of studying and practicing internal medicine in the U.S.
Hepatitis C is a different story. The only commonalities it shares with syphilis are that it’s an infectious disease that can cause complications and debility. Otherwise, it is a virus, not a bacteria. It attacks the liver, spreads largely by blood-to-blood contact and is less frequently sexually transmitted. Some people who contract the hepatitis C virus spontaneously clear it and are no longer infected. Scientists thought that spontaneous clearance happened in 15 to 20% of people, but we now see it’s closer to 50%1. Is that because the virus or environment has changed or because of better data collection? Who knows. Either way, we don’t know in whom the infection will resolve or persist. Of those who do not clear the infection, 20% go on to develop liver scarring and cirrhosis, and 20% of those cirrhosis patients develop liver cancer within a few decades2. A cure, ideally, prevents these outcomes.
By the early 2000s, hepatitis C treatments were brutal. The hope of cure lay at the end of a yearlong journey through interferon-based therapy that caused debilitating side effects like depression, nausea, headaches, and the other flu-like symptoms. If patients could complete treatment, they faced a high risk of relapse. When well-tolerated and highly effective cures came to market in 2014, it was a welcome reprieve. Known hepatitis C cases were rising in the U.S. and presumably so were unknown cases3. The headlines celebrated the eradication of hepatitis C in the not-so-distant future. So why didn’t the hepatitis C cure cause cases to plummet?
Instead, a decade later, hepatitis C infection rates in the U.S. continue to rise, while administration of curative therapy has steadily declined4. Cures should reduce viral infection rates and transmission since theoretically, fewer people would have the disease to pass to another, right?
A common practice today is to look for obvious scapegoats to blame for these unexpected and dissatisfying trends. In this case, there are three scapegoats: intravenous drug abusers, cost of treatment, and unidentified cases of hepatitis C.
First, since intravenous drug abusers (IVDA) are the source of 60% of acute hepatitis C cases and up to 50% of abusers have hepatitis C, they win the attention of prevention and treatment initiatives5,6. Given that IVDA patients may struggle with unemployment, poverty, incarceration, lack of health insurance, have difficulty adhering to prolonged medical regimens, and 85% of the time relapse into drug abuse within a year of rehabilitation, they represent a challenging population to heal. This makes IVDA the logical and usual scapegoat in explaining most hepatitis C cases. Public agencies use “obvious” behavioral observations and storytelling skills to connect contaminated needles to people’s arms. For example, bored youth shuddered in their homes and increased opioid availability due to illegal trafficking create a tempting string of “risk factors” for hepatitis C that fit today’s paradigm.
Second, the cost of curative therapy is prohibitively expensive. At $1000 or more a day, completing a 12- to 24-week treatment regimen is outrageous for anyone, including insurance companies. People literally cannot afford to be cured which contributes to rising hepatitis C numbers. Also, the cure due not produce lasting immunity which means people can get reinfected. A second round of treatment is effective, but it is just as expensive as the first. Here’s the brutal truth: Why buy expensive cures for people when up to half will spontaneously clear the infection and many are likely to contract it again because of their lifestyle choices? It’s the fodder of heated debates that blame “the system” or the patients until treatments become cheaper and faster.
The third scapegoat for rising incidence is a nebulous stew called “people who don’t know they have it.” Arrival of curative treatment coincided with screening recommendations to find hepatitis C in the general population. This campaign targeted Baby Boomers with the idea that that many didn’t get through the Hippie years without injecting drugs. Today, the Boomers represent a wealthy and stable population who can afford expensive cures. That is the stuff of political and equity debates, but it’s not the issue.
When we stay focused on disease, we see a different problem. In 2018, there were 3621 newly reported cases of acute hepatitis C and 137,713 newly diagnosed chronic cases3. Given that half of the acute cases could theoretically resolve, that doesn’t leave enough acute cases to feed the number of chronic cases observed. To make the numbers work, the CDC estimated that there were 50,300 acute cases of hepatitis C, 93% of which went undiagnosed4. These statistical shell games create more problems than they solve. Obsessing over obtaining “accurate data” and forcing observations into “balanced equations” is not our problem. Accurate interpretation of the data is. We’re so lost in generating data and calculating statistics that we’ve lost sight of the relevant context needed to understand what is really going on with hepatitis C.
The situation gets messier. There are two age brackets where chronic hepatitis C is most commonly diagnosed: age 25 to 35 and age 55 to 653. Using today’s thinking, the two groups have different explanations. The older group was alive before the virus was recognized in 1989, and plausibly could have been exposed via transfusion, needle sticks or sexual contact. As for the surge in the younger group, there’s the default explanation: an assumed resurgence in IV drug abuse. However, since IVDA only accounts for 20 to 50% of chronic cases6, it does not adequately explain the majority of chronic cases in younger people. Where are the rest coming from? Is it possible that a rise in IVDA contributes to rising hepatitis C? Sure, but don’t be fooled to thinking that’s a complete explanation. Despite the common stigma, the link between IVDA and hepatitis C is just not as strong as we want it to be. Something else is going on outside our awareness.
Finally, the undiagnosed stew includes a huge variety of people, the majority of whom have never abused IV drugs. They experience hepatitis C infection differently or not at all. While we traditionally treat this population as an unmitigated disease reservoir, what it really represents is near total ignorance about hepatitis C. Why do so many people have no symptoms until decades later, if at all? We think this is because of a mysterious interplay between virus and host. Why is the history of blood exposure needed to transmit hepatitis C often missing? Clinicians typically assume patients don’t recall or are hiding information. What if that is not the reason?
The mess surrounding hepatitis C including how to pay for it, overcoming the socioeconomic challenges needed to eradicate it, and the logistics of identifying and treating everyone are only perceived challenges. The real problem is we still don’t understand hepatitis C, a quandary that not even a vaccine would solve.
It’s time to start with an honest question.
Did we really cure hepatitis C?
Works Cited
- Seo S, Silverberg MJ, Hurley LB, et al. “Prevalence of spontaneous clearance of hepatitis C virus infection doubled from 1998 to 2017.” Clin Gastroenterol Hepatol 2020;18:511–3. PubMed https://doi.org/10.1016/j.cgh.2019.04.035
- Ahar B, Miller R, and Sisson, S. The Johns Hopkins Internal Medicine Board Review, 5th ed. Elsevier Inc 2016, 254-5.
- Centers for Disease Control and Prevention. “Viral Hepatitis Surveillance Report 2018 – Hepatitis C.” Statistics & Surveillance. 28 Aug 2020. Retrieved on 3 March 2023 from https://www.cdc.gov/hepatitis/statistics/2018surveillance/HepC.htm
- Centers for Disease Control and Prevention. “New estimates reveal declines in hepatitis C treatment in the U.S. between 2015 and 2020.” NCHHSTP Newsroom. 8 Nov 2021. Retrieved on 3 March 2023 from https://www.cdc.gov/nchhstp/newsroom/2021/2014-2020-hepatitis-c-treatment-estimates.html
- Ahar, p 255.
- Ferri, F. “Hepatitis C” in Ferri’s Clinical Advisor 2017 . Philadelphia: Elsevier, 2017. 573-5
- Ibid.