An August 2022 study in the MMWR found that only 1 out of 3 people with hepatitis C are getting treated… and all of the patients in the study had health insurance. What are the barriers to treatment and how can we overcome them?
- Hepatitis C is common: 2 million Americans have chronic active infection.
- Hepatitis C is under-treated: only 1 out of 3 insured Americans diagnosed with hepatitis get treated.
- New therapy regimens have simplified the treatment of hepatitis C
- It is time for primary care physicians and advance practice providers to treat most patients with hepatitis C
Hepatitis C is incredibly common. Worldwide, 100 million people have been infected and 71 million have chronic liver disease from the virus… that’s 1% of the world’s population! Here in the United States, hepatitis C has infected 1.5% of Americans and 2 million Americans have chronic active infection. More than 75% of infected people have no symptoms and do not realize that they are infected. Once initially infected, two-thirds of people go on to have chronic active infection. Of those, about one out of five will develop cirrhosis about 20 – 30 years after the initial infection. It causes 19,000 deaths per year in the U.S. It is the most common cause of chronic liver disease and is the leading reason for liver transplantation.
Because it is so common and because most patients are initially asymptomatic, the Centers for Disease Control and the United States Preventive Services Task Force both recommend that all adults > 18 years of age be tested at least once for hepatitis C. The screening test is a simple and widely available blood antibody test. If the screening test is positive, then the next step is a blood hepatitis C RNA test to determine if the patient has chronic active infection. If the RNA test is negative, then the patient has resolved the infection and does not have chronic hepatitis C. But if the RNA test is positive, then the patient has a chronic infection and and should be considered for treatment.
Prior to 1991, hepatitis C was incurable. For the next 20 years, alpha interferon and ribavirin were the only available treatments. However, these drugs had significant toxicity, required a very long duration of treatment, and only resulted in cure of 6% of treated patients. Over the past 10 years, new anti-viral drugs have been developed that can cure the vast majority of patients and only require 8 to 12 weeks of treatment. So, why aren’t more people being treated and cured?
There are not enough hepatologists
Unlike most infections, the treatment of hepatitis C has been the realm of hepatologists, rather than infectious disease specialists or primary care physicians. However, hepatologists are relatively few in number. Most hepatologists do a 1-year hepatology fellowship following completion of a 3-year gastroenterology fellowship. Hepatology is a relatively new subspecialty. In 2006, the first board examination for hepatology was offered and there are only 59 hepatology fellowship training programs in the United States. Currently, there are 7,296 U.S. healthcare providers whose self-described practice is > 50% hepatology. However, the majority of these are gastroenterologists and advance practice providers with only a minority being board-certified hepatologists. There is little financial incentive for gastroenterology fellows to train for an extra year to become hepatologists. A study published in the January 2021 edition of Hepatology Communications found that the median total compensation for hepatologists in the U.S. is $320,728 which was less than the total compensation for gastroenterology assistant professors at $329,600. In other words, the reward for doing a hepatology fellowship is that you make less money than you would had you not done the extra year of training.
Most hepatologists practice at a relatively few large, referral hospitals. Consequently, most hospitals do not have a hepatologist on their medical staff, thus requiring patients with hepatitis C to travel long distances in order to be evaluated and treated by a hepatologist. This has resulted in a geographic barrier for most patients and is a contribution to the low rate of infected patients getting treated.
What is so complicated about treating hepatitis C?
Treating most infections is relatively simple: you get a culture, you give an inexpensive antibiotic for 5-7 days, and you’re done. But treating hepatitis C is a lot more complicated and requires specialized testing, counseling, expensive medications, and laboratory follow-up. The current recommendations for treatment are published jointly by the American Association for the Study of Liver Disease and the Infectious Disease Society of America. This is a lengthly document that is daunting for most non-hepatologists. A Simplified HCV Treatment Algorithm for Treatment-Naive Adults Without Cirrhosis is available that summarizes the recommendations in just 1 page:
Initial evaluation. Once a patients are diagnosed with hepatitis C, they need to undergo a series of laboratory tests including:
- FIB-4 calculation. This is based on the patient’s age and three blood tests (AST, ALT, and platelet count). An on-line calculator is available to easily determine the FIB-4 score.
- Cirrhosis assessment. Cirrhosis can be identified by a FIB-4 score > 3.25, liver biopsy, transient elastography (“Fibroscan”), imaging (CT or ultrasound), clinical evidence of cirrhosis, or laboratory test (such as the “Fibrosure” blood test).
- Liver function tests
- Glomerular filtration rate
- Hepatitis C viral load (HCV RNA)
- HIV test
- Hepatitis B surface antigen
- Pregnancy test (for women of childbearing potential)
Treatment regimens. There are 12 drugs approved to treat hepatitis C and choosing among them can be formidable for non-hepatologists. Different drug regimens are used for different viral genotypes. In addition, several drugs that were approved in the past 10 years have been recently discontinued as more effective newer medications have been introduced. The result is that physicians who do not keep up with new developments in hepatitis C medications on a regular basis often feel uneasy prescribing treatments. Fortunately, there are two currently recommended medication treatments for hepatitis C in patients without cirrhosis, regardless of which genotype of hepatitis C patients are infected with:
- Mavyret – glecaprevir (300 mg) + pibrentasvir (120 mg) for 8 weeks
- Epclusa – sofosbuvir (400 mg) + velpatasvir (100 mg) for 12 weeks.
Laboratory monitoring. The newer hepatitis C medications do not require routine lab monitoring. This is a significant improvement over previous drugs that required regular blood tests during treatment. Because of the possibility of drug interactions, patients with diabetes taking hypoglycemic drugs should have their glucose levels checked periodically and patients taking warfarin should have their INR levels checked periodically.
Post-treatment testing. 12 weeks after completing treatment, patients should have liver enzymes checked. They should also have a hepatitis C RNA level checked at that time to confirm that they are cured. Those patients who continue to have detectable HCV RNA may require referral to a specialist.
The two drugs used to treat hepatitis C are expensive. Mavyret costs $34,000 for an 8-week course if purchased out of pocket ($13,000 to $16,000 if purchased using GoodRx). Eclusa costs $31,000 for a 12-week course ($11,000 to $19,000 if purchased using GoodRx). Because of their expense, most commercial insurance companies require prior authorization when these medications are prescribed and this poses another barrier for non-hepatologists who are less familiar with the drugs.
The simplified recommended treatment regimen for patients with compensated cirrhosis is very similar to that used for patients without cirrhosis with the main difference being that Mavyret can be used for any genotype of hepatitis C but Eclusa can only be used for genotypes 1, 2, 4, 5, & 6. To make things utterly simple, if prescribing Mavyret, the same management protocol can be used whether or not a patient has compensated cirrhosis.
The simplified treatment regimens are applicable to most patients with chronic hepatitis C infection. Patients not eligible for one of the two simplified regimens will likely require referral to a specialist. This includes patients with:
- Prior hepatitis C treatment
- End-stage renal disease
- Decompensated cirrhosis
- HIV or HBsAg positive
- Current pregnancy
- Known or suspected hepatocellular carcinoma
- Prior liver transplantation
So, who should treat hepatitis C?
It is clear that the shear number of Americans infected with hepatitis C is too great for all patients to be treated by the country’s relatively few hepatologists. But fortunately, the newer regimens are very protocolized, making their use much simpler that previous regimens. Because of this, two groups of providers are now in position to treat most patients with hepatitis C.
- Primary care physicians. In the past, primary care physicians referred patients with hepatitis C to hepatologists or gastroenterologists for treatment. The drugs were toxic, expensive, and required complex regular monitoring. Furthermore, busy primary care physicians did not want to deal with insurance prior authorization for drugs that they were not very familiar with. The simplicity of the new treatment regimens now makes it easier for primary care physicians. All that is required is creation of a hepatitis C order set in the electronic medical record and a fairly straight forward prior authorization that the office nurses can usually do on their own.
- Advance practice providers. Treatment regimens that are based on protocols are ideal for nurse practitioners and physician assistants. This can be a great option for larger primary care groups or for hospitals that designate an advance practice provider to specialize as the go-to hepatitis C treatment provider.
A time for change…
In summary, the number one cause of chronic liver disease and number one indication for liver transplantation can now be cured relatively easily. In communities that lack easy access to a trained hepatologist, the newer hepatitis C treatment regimens lend themselves to implementation by either primary care physicians or advance practice providers. In order to improve the numbers of Americans who are cured of hepatitis C before it results in cirrhosis, we must overcome historical barriers to treatment. Our hospitals can help by sponsoring CME programs to train primary care physicians in hepatitis C management and by financially supporting advance practice providers to specialize in hepatitis C management.
September 22, 2022