Hepatitis C FAQ’s
What is Hepatitis C (HCV)?
Hepatitis C is a virus that was discovered and named in 1990. Its existence was suspected long before the virus could be individually tested for and studied. Therefore, early researchers could only be certain that the virus differed from the previously known Hepatitis A and Hepatitis B (HBV). Therefore, prior to 1991 HCV was simply referred to as Non A/Non B hepatitis virus. Prior to a test to identify HCV, the virus was widely present in the US blood supply and many patients were infected via blood transfusion in American hospitals prior to 1992. Canada began universally testing its blood supply in 1990.
Are there different types of HCV?
Yes. There are generally accepted to be 6 genotypes of HCV (1, 2, 3, 4, 5, and 6). Some genotypes have subtypes (e.g. 1a, 1b, 2a, 2b). The different genotypes differ slightly in medicines are used to treat them and how easy they are to cure. Genotype 1 is the most common genotype in the US (70%). Genotype 2 and 3 are the next most common. Genotype 3 is slightly harder to cure with new medications and appears to cause a higher risk of cirrhosis and fatty liver disease.
Who is at risk for HCV? Who should be tested?
Patients with a history of blood transfusion before 1992 or the use of intravenous drugs or an unregulated tattoo should all be tested. To simplify things for patients and doctors the Center for Disease Control and the US Preventative Health Task Force recommend testing everyone born between 1945 and 1965. Patients with HIV should also be tested. (www.cdc.gov, US Preventative Task Force) . The current opiate abuse epidemic is leading to a rise in new infections,
What about sexual transmission?
Sexual transmission between a man and a woman with monogamous, vaginal intercourse is exceedingly rare with only 1 infection per 125,000 encounters. Other than not sharing a tooth brush or razor, we recommend no special precautions when living with an HCV infected patient. Any other precautions are unreasonable and do nothing more than make the patient feel socially isolated. (Terrault, N. Hepatology. 2013 Mar;57(3):881-9)
Unfortunately, sexual transmission between 2 men, especially when one or both have HIV is not rare. Barrier protection (e.g. condoms) is recommended in this case
What if I am pregnant or planning to get pregnant?
Fortunately HCV virus is only spread to the unborn child 4% of the time. Unfortunately there is currently no way to reduce that number to 0%. Experts do not discourage breast feeding. Treatment for HCV is not recommended for pregnant women or infants currently. Future medications may ensure that no children born with HCV develop or die from advanced liver disease.
How does the virus behave? How do you know if you have it?
3.6 million Americans are infected with HCV. Unfortunately 50% of patients with HCV don’t know they are infected (Holmberg S, N Engl J Med 2013; 368: 1859). Most patients who come into contact with the virus via needle (tattoo, hypodermic) or blood transfusion will become chronically infected, meaning their blood will have detectable virus (HCV RNA) at all times. Interestingly, 25% of patients will clear the virus from their blood without the aid of medications. These patients will then carry the HCV antibody (Ab) for life, but not suffer any liver disease. Often the so called “liver function tests” (LFT’s) will be abnormally elevated, including AST, ALT, and GGT. Bilirubin and Alkaline phosphatase do not elevate until late in the course of disease.
25% to 40% of patients with chronic HCV will suffer daily damage and repair of their liver which after 20 to 40 years will lead to severe scarring and eventual dysfunction of the liver call cirrhosis. Patients can have no symptoms at all while the cirrhosis is forming and only become aware of infection once they are very ill. Signs of decompensated cirrhosis are jaundice, ascites, hepatic encephalopathy, and muscle wasting. Even small amounts of alcohol make cirrhosis much more common in HCV and should be avoided. Liver cancer, which is very rare in general, is quite common in patients with cirrhosis and they should be checked frequently via ultrasound or other imaging to detect small tumors.
Is HCV curable?
HCV is curable. The definition of cure is to have no detectable virus in the blood 12 weeks (3 months) after medication for HCV has been stopped. We also recommend checking at 24 weeks, 48 weeks and 72 weeks after therapy is stopped. In cured patients, the HCV antibody will always be positive but the HCV RNA will no longer be detectable, liver inflammation disappears, liver scarring can partially or completely reverse, cirrhosis risk decreases, need for liver transplant declines, liver cancer risk can be reduced 70%, and the patient cannot pass the infection to anyone else---A cure! In the past, 1 out a 100 patients would have virus in their blood long after they had previously been thought to be cured, leading some to say the virus could not necessarily be cured. In hindsight these cases may represent reinfection with new HCV after additional risky behavior, not re-emergence of the previous HCV infection from a hidden place in the body.
How is HCV cured?
Currently, most HCV patients can be cured with medications taken by mouth for 90 days to 180 days. The side effects of these medications are minimal and require only occasional blood lab monitoring. The most common side effects are mild headache, mild nausea, and loose stools. All of these side effects are managed rather easily with over the counter or prescription medications. The rate of cure is approximately 90% (9 out 10) in scientific trials. Regimens and cure rates may vary somewhat based on type of HCV (1, 2, 3, 4, 5, and 6), presence of cirrhosis, or previously failed attempts at treatment with interferon.
Genotype 1
In early October 2014, Harvoni (Gilead), the first all oral medication for Hepatitis C genotype 1 disease was approved in the united states. The medication is highly effective with minimal side effects. Treatment course can last 8, 12, or 24 weeks depending on whether of not a patient has previously undergone treatment with older medications or has cirrhosis. Currently this is the state of the art for HCV genotype 1 treatment.
8 weeks of Harvoni may be reasonable for patients who have never been treated for HCV (naïve) and who do not have cirrhosis and who have a viral load less than 6 million IU/ml
12 weeks is recommended for patients who have been treated in the past but were not cured and who do not have cirrhosis ("Non-responders" or "relapsers") and patients who have never been treated before but have cirrhosis of the liver.
24 weeks of Harvoni is recommended for patients with cirrhosis who were not cured by previous therapies. However, data presented in November 2014 indicate that 12 weeks of Harvoni with Ribavirin may be equally as effective and considerably cheaper
In 2016 the FDA expanded Harvoni's indication to no include Genotypes 4,5, and 6, patients infected with HIV, and patients with deompensated cirrhosis.
In December 2014 the Viekira Pakby Abbvie was approved by the FDA for the treatment of Chronic Genotype 1 Hepatitis C in patients with compensated liver disease, including patients coinfected with HIV. Like Harvoni, Viekira Pak us highly effective with cure rates raniging as high as 100% in certain patient types. Dose duration and the possible inclusion of Ribavirin is determined by the the presence or absence of cirrhosis as well as the Genotype 1 subtype (1A or 1B). Viekira Pak is approved for patients with severe renal impairment and dialysis.
12 Weeks without Ribavirn is approved for patients with genotype 1B disease with or without cirrhosis.
24 weeks if Viekira Pak with weight based Ribavirin is approved for Genotype 1a patients with cirrhosis.
In July 2015 Daklinza TM (daclatasvir) by Bristol Myers Squib was approved for use in genotype 3 HCV. However there is Genotype 1 experienced with Daklinza combined with Sovaldi from Gilead. The combined AASLD-IDSA guidelines list Daklinza + Sovaldi for 12 weeks a s viable treatment option for Genotype 1.
Zepatier, a combination of the protease inhibitor Grazeprevir and the NS5A inhibitor Elbasvir. Combined into a singe pill these direct acting antivirals cure over 95% of genotype 1 patients in 12 to 16 weeks with or without ribavirin depending of genotype 1 subtype (a or b), treatment experience, and the presence or abcense of NS5A resistant variants before treatment.
Epclusa (sofosbuvir/velpatasvir) is a comibation NS5B and NS5A regimen formulated in to a single pill taken once daily. Made by Gilead, Epclusa is the first single table anti-HCV regimen that treats all genotypes 1,2,3,4,5& 6. The recommended treatment duration is 12 weeks in all cases and ribavirin may be added in cirrhosis, particularly in genotype 3 patients.
Genotype 2
In 2016 Epclusa was approved and now is the most appropriate treatment for genotype 2 patients. Cure rates ar 96-99% with 12 weeks of treatment once a day.
In July 2015 Daklinza TM (daclatasvir) by Bristol Myers Squib was approved for use in genotype 3 HCV. However there is Genotype 2 experience with Daklinza combined with Sovaldi from Gilead.
Genotype 3
Recently the Genotype 3 cure rates have lagged behind the other genotypes. Patients without cirrhosis who had never been treated before could expect cure rates of 80 to 90% with 24 weeks of Sovaldi and Ribavirin. However, patients with a lot of liver scarring or who failed previous treatment experienced lower chances of success.
Eplusa is now the preferred treatment in these patients. When used for 12 weeks cure rates can be expected in the 90 to 95% range with no ribavirin.
In July 2015 Daklinza TM (daclatasvir) by Bristol Myers Squib was approved as the fist all oral direct acting antiviral medication for use without ribavirin for use in genotype 3 HCV in the US. Daklinza used with Sovaldi for 12 weeks cures 89% of non-cirrhotic Genotype 3 patients. The results are lower for cirrhotic patients (59%). Some small studies suggest longer durations of this combination can increase cure rates in patients with cirrhosis. As of July 2015 the joint AASLD/IDSA guidelines recommend 24 weeks of Daklinza/Sovaldi with or without Ribavirin in cirrhotic Genotype 3 patients.
Research reported in November 2014 at the Liver Meeting indicated that Harvoni and Ribavirin for 12 weeks can yield reasonable results in genotype 3 patients. The main advantage would be lower cost to society of a shorter treatment than the original Sovaldi and Ribavirin regimen.
Genotype 4
Genotype 4 disease is uncommon in the US but not unheard of. Most busy gastroenterologists will encounter a case. Technivie, the first all oral DAA combination specific for Genotype 4 was FDA approved July 2015. Technivie when combined with ribavirin has excellent results.
Harvoni and Epclusa by Gilead and Zepatier by Merck are all now approved to be used in genotype 4 patients. The Harvoni treatment duration is 12 weeks without ribavirin while Zepatier treatment lasts 16 weeks. Both have excellent cure rates and side effect profiles.
Genotype 5 and 6
Harvoni and Epclusa by Gilead is are approved for the more rare genotypes 5 and 6. The treatment is 12 weeks without ribavirin. Cure rates are very high here as with genotype 1.
How is this different from previous treatments for HCV?
Previously the cure of HCV required 3, 6 or 12 months of injectable interferon. Interferon is associated with fatigue anemia, low white blood cells and fever in almost all patients. Some patients cannot tolerate the drug at all physically. Other patients must quit due to severe psychological complications, like depression or anxiety. The newly available oral medications have none of these problems. Almost no patients voluntarily quit the newer oral medications in scientific studies.
Is curing HCV worth the trouble?
Yes. For patients with scarred livers, the benefit is obvious: Less death from liver failure and liver cancer (Annals of Internal Medicine 2013; 158(1): 329-337). However, curing HCV has been proven to be associated with decreased risk of dying from any cause! This suggests that cured patients die less often than uncured patients regardless of severity of liver disease (van der Meer AJ, et al. JAMA. 2012;308:2584-2593) This may be because active HCV disease has been linked to heart disease, non-liver cancers, kidney failure, diabetes and fatigue. What kinds of doctors treat HCV? Hepatologists (liver specialists),
Gastroenterologists, and Infectious Disease specialists treat HCV. Primary care doctors may treat HCV in the future, but that depends on the individual physician and the insurance company (i.g. some insurance companies will require a specialist to prescribe the medications).
What should I expect if I see a physician to treat my HCV?
You can expect a thorough history of risk factors like blood transfusion and needle stick to determine how long you have had the disease. Blood labs, and ultrasound and physical exam will be ordered to determine what genotype of HCV you have and if you have advanced scarring of the liver. Occasionally a liver biopsy is need to determine how scarred the liver is; however, liver biopsies are becoming increasing less useful in decision making. Biopsies are not definitely required to begin newer HCV medications. A second clinic visit is usually needed to discuss all of the results gathered and recommend a treatment plan. All alcohol must be stopped during treatment because it can prevent the medications from curing the HCV.
Will I be able to afford HCV treatment?
Yes. This is a common question resulting from the publicity over the price of newer HCV treatment regimens. Almost never does a patient take their HCV prescription to a pharmacy, pay on the spot and walk away with HCV medication. Due to the expense and complexity of the medications, most insurance companies require a prior authorization request and the use of a specialty pharmacy. Your physician will write your prescription and forward the order to a specialty pharmacy along with some basic clinical information.
The pharmacy will then contact the pharmacy benefits office of your insurance company and obtain permission to fill the prescription. With most plans the Co-pay for the meds is affordable once approved. Often the drug companies that make the medicines will cover all or part of the monthly co-pay. This helps a lot. Especially since most patients will only be on the medication 3 to 6 months, not for life as with other diseases!
Completely uninsured patients can often get the medications free of charge directly from the manufacturer.
Can I use Harvoni or Epclusa if I previously failed cure with Sovaldi?
From a scientific point of view Harvoni has a high chance of curing patients who previously were not cured with Sovaldi.
A recent presentation at the 2014 Liver Meeting sponsored by the AASLD showed results of 51 genotype 1 patients who previously failed SOF/PegIFN/RBV, SOF/RBV or a SOF placebo/PegIFN/RBV treatment regimen and received Harvoni plus RBV for 12 weeks. Twenty-nine percent of study patients (n=15/51) had cirrhosis. Ninety-eight percent (n=50/51) achieved SVR12 following 12 weeks of treatment with Harvoni plus RBV.”
An additional Study in the Annals of Internal Medicine (Ann Intern Med. 2014;161:634-638. doi:10.7326/M14-1211) found that all 14 patients who previously failed sovaldi based regimens were cured with Harvoni (100% SVR). The uniquely high barrier to resistance seen with Sovaldi is the most likely reason Harvoni is successful in salvaging previous treatment failures that used Sovladi without the potent Ledipasvir. This data was not presented to the FDA at Harvoni's initial approval and it is unclear whether insurance companies will pay for patients who failed Sovaldi to use Harvoni any time soon.