Myths and Facts: Hepatitis C

Last August, the Centers for Disease Control and Prevention (CDC) issued a public recommendation that U.S. resident baby boomers born between 1945 and 1965 be tested for the hepatitis C virus (HCV).¹ HCV is a contagious disease that is caused by a virus that infects the liver. It is only one of five types of hepatitis that is spread when a person is exposed to the blood of another person who has the virus.

The CDC recommendation was in response to a recent study published in the Annals of Internal Medicine that found HCV causes 15,000 deaths annually, and that number is rising.² Baby boomers make up more than two million of the 3.9 million U.S. residents who have HCV. Since most individuals with HCV have no symptoms, and the infection often leads to cirrhosis and liver cancer, the CDC’s strategy for baby boomers to receive a one-time, voluntary test for the virus is to identify a potential 800,000 new cases and to prevent potentially 120,000 deaths.

HCV was only identified in 1989, but the medical profession has come a long way in understanding the disease. Unfortunately, the increasing health burden and mortality from HCV in the U.S. are significant. By 2007, HCV had superseded HIV as a cause of death in the U.S.1 And, while deaths from HCV have disproportionately occurred in middle-aged persons, all ages are at risk. Therefore, understanding the facts about this disease is becoming increasingly more important.

Separating Myth from Fact

MYTH: HCV is not a prevalent disease.

FACT: The prevalence of HCV is increasing worldwide. According to the World Health Organization, approximately 130 million to 170 million people are chronically infected with HCV, and more than 350,000 people die from HCV-related liver disease each year. In the U.S., the CDC estimates that 1.8 percent, or 3.9 million, Americans have been infected with HCV, 2.7 million of whom are chronically infected.³

MYTH: HCV is not a serious disease.

FACT: HCV is a potentially lethal disease. In 15 percent of cases, people experience acute HCV, which means it lasts less than six months, and symptoms are generally mild and vague, including a decreased appetite, fatigue, nausea, muscle or joint pain, and weight loss. In the other 85 percent of cases, HCV infection is chronic. Most people with chronic HCV experience minimal or no symptoms during the initial few decades of the infection. If left undiagnosed and untreated for many years, chronic HCV becomes the primary cause of cirrhosis and liver cancer. In fact, about 10 percent to 30 percent of people develop cirrhosis over 30 years. Those who develop cirrhosis have a 20-fold greater risk of hepatocellular carcinoma, and for those who drink alcohol in excess, the risk becomes 100-fold greater. Chronic HCV is the cause of 27 percent of cirrhosis cases and 25 percent of hepatocellular carcinoma worldwide. It also is the most common reason for liver transplantation in the U.S.⁴

MYTH: People with HCV would know if they have the disease.

FACT: In the U.S., 80 percent of people who have chronic HCV don’t know it. The reason is that they don’t look or feel sick even though the virus may be causing damage to their liver. Indeed, most people with chronic HCV don’t have symptoms until serious liver damage develops. In addition, 70 percent of people with chronic HCV don’t know how they got it. Therefore, if someone has any reason to believe HCV has been contracted, he or she should be tested for it.5

The CDC recommends screening for HCV infections in the following persons: those having ever injected illegal drugs; those having received a blood transfusion or organ transplant before July 1992 (when the blood supply began being monitored in the U.S.); those having received clotting factor concentrates produced before 1987; those ever on long-term dialysis; children born to HCV-positive women; healthcare, emergency medicine and public safety workers after needle-sticks, sharps or mucosal exposure to HCV-positive blood; and those with evidence of chronic liver disease.⁶

MYTH: Hepatitis A can lead to hepatitis B, which can then lead to HCV.

FACT: There are five types of hepatitis viruses — A, B, C, D and E — each of which differs in structure, exposure and disease. If a person had hepatitis A and now has HCV, that person was infected with two different viruses; one virus can’t change into another. The only thing the viruses have in common is that they all affect the liver.⁷

MYTH: Most people have been vaccinated against HCV.

FACT: A vaccine to prevent HCV is often confused with one for hepatitis A or B. While there is an approved vaccine for use in the U.S. for hepatitis A and B, there is not one for HCV. Researchers are experiencing breakthroughs in HCV vaccine development; however, creating an effective vaccine is proving difficult since the virus constantly mutates.⁸

MYTH: All people infected with HCV have the same virus.

FACT: Not all types of HCV are the same. There are at least six major distinct strains, or genotypes, numbered one to six in order of discovery, and 50 variants or subtypes within genotypes designated by letters as 1a, 1b, 1c, 2a, 2b, 2c, 3a, 3b, 4a, 5a and 6a, etc. These different genotypes are a result of mutations when the virus replicates.

In the U.S., genotype 1 (subtypes a and b) is the most common, accounting for 83 percent of HCV cases. People infected with genotype 1a or 1b have a more severe type of HCV, are less likely to respond to treatment than genotypes 2 or 3 and usually require longer therapy. Those with genotype 1b are significantly older than patients with other genotypes because they were infected in the 1960s when drug experimentation was predominant. Genotype 2, a milder form of HCV, accounts for 12 percent of U.S. cases. And, genotype 3 accounts for 5 percent of U.S. HCV cases. This genotype has been linked to fatty liver due to an enzyme known to play a crucial role in lipid production that has been found at high levels in human liver cells exposed to HCV.⁹

The possibility of becoming infected with more than one genotype, known as superinfection, is possible if risk factors for HCV infection continue. Superinfection happens when a cell previously infected by one virus becomes co-infected with a different strain of the virus. Studies have shown that HCV reinfection and superinfection are common among actively injecting drug users. And, in rare cases, a sexually transmitted HCV superinfection in HIV/HCV co-infected patients with high-risk sexual behavior have been reported.10

MYTH: HCV is a sexually transmitted disease (STD).

FACT: While there is some truth to this, HCV is a disease of the liver that is spread through blood-to-blood exposure. HCV can be transmitted sexually, but the risk is very low in most populations. The majority of studies have shown a 0 percent to 3 percent prevalence in HCV in people in stable, monogamous heterosexual relationships. For those in high-risk groups, however, usually defined as people with multiple sexual partners, men who have sex with men, women who have sex with women, prostitutes and people seen at STD clinics, the risk of contracting HCV through unsafe sex is believed to be higher, although more studies are needed.⁸

MYTH: People with HCV are alcoholics and/or drug users.

FACT:While many people with HCV are alcoholics, and half of all new cases of HCV are drug users, it is untrue to say that all people with HCV are alcoholics and/or drug users. That would be the same as saying all diabetics are overweight. There is a different type of hepatitis called alcoholic hepatitis that is linked with alcohol, but someone who drinks alcohol in moderation might develop alcoholic hepatitis, while very few people who drink excessive amounts of alcohol develop alcoholic hepatitis. The only similarity between HCV and alcoholic hepatitis is that they both often lead to cirrhosis, which could lead to liver failure.⁷

MYTH: HCV viral load correlates to symptoms and disease progression.

FACT: The HCV viral load is the number of viral particles, or copies of the genetic material of the virus, floating in the blood (circulating through the body). Viral load is based on technology that measures extremely small quantities of HCV RNA, the building block of the virus.11 Viral load is measured to confirm active infection, to predict treatment response, to make sure HCV medications are working during treatment, and to make sure the virus is still undetectable after treatment is completed.⁸

No studies have shown that someone with a higher viral load has more symptoms compared with someone with a lower viral load. And, while it’s logical to assume that if a person has more virus (a higher viral load), they would experience a faster disease progression, but studies have not shown a correlation between the amount of the virus and the degree of liver damage.⁸

MYTH: Liver enzyme levels are a predictor of HCV disease progression.

FACT: Many experts don’t believe that measurement of liver enzymes is a good predictor of HCV progression. Instead, they submit that the only way to really tell whether HCV has progressed to the point of liver damage is by doing a liver biopsy. Liver enzyme levels are measured through alanine aminotransferase (ALT), an enzyme that is produced in liver cells and released into the bloodstream when there is damage taking place in the liver. While most people with HCV and normal ALT levels have minimal liver disease progression, about 20 percent with normal ALT levels have moderate to severe HCV disease progression.⁸

MYTH: People with chronic HCV shouldn’t take Tylenol.

FACT: Doctors often recommend acetaminophen (Tylenol) to relieve symptoms associated with HCV and treatmentrelated side effects. In fact, clinical data demonstrate that acetaminophen is an appropriate pain-relief choice for patients with chronic liver disease. According to a literature review, which was published in the March 2005 issue of the American Journal of Therapeutics, there is no evidence that acetaminophen at therapeutic doses aggravates liver disease. Instead, studies have shown that patients with liver disease are able to metabolize acetaminophen appropriately.¹²

MYTH: There are no effective medical treatments for HCV.

FACT: There are effective treatments for both acute and chronic HCV. Patients with acute HCV have an excellent chance of responding to six months of standard therapy with interferon (IFN). And, while IFN should result in spontaneous resolution, there is not a definitive time for when therapy should be started. However, waiting two to four months after the onset of illness is common.

Treatment for chronic HCV has evolved over the years. Initially, studies used IFN monotherapy. Today, treatment is a combination therapy consisting of Ribavirin and IFN or IFN to which polyethylene glycol (PEG) molecules have been added (PEG-IFN). A third feature of combination therapy that is emerging is protease inhibitors. The first protease inhibitor indicated for use in HCV infection, boceprevir (Victrelis), was approved by the U.S. Food and Drug Administration in May 2011.

There are two goals of chronic HCV treatment. The first is to achieve sustained eradication of HCV, which is defined as the persistent absence of HCV RNA in serum for six months or more after antiviral treatment. The second is to prevent progression to cirrhosis, hepatocellular carcinoma (HCC) and decompensated liver disease requiring liver transplantation.

Patients with HCV-related decompensated cirrhosis should be referred for consideration of liver transplantation.¹³

For physicians, knowing the genotype of HCV can be helpful in making a therapeutic recommendation. Individuals with HCV genotypes 2 and 3 are almost three times more likely than individuals with genotype 1 to respond to IFN monotherapy and combination therapy.¹⁴ Unfortunately, viral superinfections are common causes of treatment resistance.10

MYTH: Everyone with chronic HCV should be treated for the disease.

FACT: Not every person with chronic HCV will benefit from treatment, and antiviral therapy should be determined on a case-by-case basis. Those most widely recommended for treatment are patients with elevated serum ALT levels who are older than 18, have positive HCV antibody and serum HCV RNA test results, have compensated liver disease, have acceptable hematologic and biochemical indices (hemoglobin at least 13 g/dL for men and 12 g/dL for women; neutrophil count greater than 1,500/mm3 and serum creatinine less than 1.5 mg/dL), a willingness to be treated and to adhere to treatment requirements, and no contraindications for treatment. A further criterion is liver biopsy findings consistent with a diagnosis of HCV; however, a pretreatment liver biopsy is not mandatory.¹³

Individuals not suitable for combination therapy are those who cannot tolerate side effects or who have contraindications to IFN or Ribavirin therapy. For instance, individuals who have low values of red and white blood cells and platelets may not be able to tolerate IFN therapy safely. In addition, IFN therapy may affect the brain, so it is not given to individuals who have a seizure disorder that cannot be controlled with anti-epileptic therapy, and it is thought unwise to use IFN therapy in individuals who have some immune disorders, particularly those with autoimmune diseases, for fear of it causing a flare-up of the disease. Because of Ribavirin’s side effects, it should never be given to individuals who would become rapidly unwell with a sudden fall in hemoglobin, such as those who have poor oxygen supply to their heart or brain from hardening of arteries. Ribavirin also should not be given to individuals with renal failure. And, because Ribavirin is damaging to the unborn child (teratogenic), neither a male nor female may impregnate or conceive during treatment and for six months after stopping treatment.¹⁵

MYTH: Most people can’t be treated for HCV because they can’t tolerate the side effects.

FACT: Some patients can’t tolerate HCV therapy for a variety of reasons, including side effects, but these people are the exception rather than the rule. However, the inability to tolerate side effects can be a cause of failure to complete therapy. Fortunately, there have been dramatic improvements in the way that side effects are managed.

Many of the side effects of therapy superimpose upon the pre-existing fatigue, depression, nausea and myalgias (muscle aches) that already plague the HCV patient. The most serious side effects are changes in the hematologic system. Other side effects include depression, anxiety, insomnia, headaches, muscle aches and skin rashes. Depression and anxiety often become the most troublesome problems for patients, particularly in those with pre-existing problems. For all of these side effects, there are other medications available to counteract them.¹⁶

Dispelling the Myths Now

The medical profession has had little more than a quarter of a century to understand HCV, but diagnosis and treatment have come a long way. Unfortunately, for patients and others, many myths about the disease exist that lead to fear and make living with HCV even more difficult. Fortunately, HCV is not a death sentence for most. Only 10 percent to 25 percent of people chronically infected with HCV will experience serious liver disease progression that may result in death. The remaining 75 percent to 90 percent will live long and productive lives⁸ — as long as the facts about HCV are understood.