Hepatitis C Treatment

The hepatitis C virus induces chronic infection in 50%-80% of infected persons. Approximately 20-50% of these do not respond to therapy, depending on the genotype they are infected with. There is a very small chance of clearing the virus spontaneously in chronic HCV carriers (0.5% to 0.74% per year). However, the majority of patients with chronic hepatitis C will not clear it without treatment.

In May 2011, the Food and Drug Administration approved 2 drugs for hepatitis C. The first one is boceprevir and the other is telaprevir (Incivek). Both drugs block an enzyme that helps the virus reproduce. The drugs are intended to improve on standard treatments using the injected drug pegylated interferon alpha and the pill ribavirin.

Medications
Treatment is generally recommended for patients with proven hepatitis C virus infection and persistently abnormal liver function tests. Current treatment is a combination of pegylated interferon-alpha-2a or pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) and the antiviral drug ribavirin for a period of 24 or 48 weeks, depending on hepatitis C virus genotype. In a large multicenter randomized control study among genotype 2 or 3 infected patients (NORDymanIC), patients achieving HCV RNA below 1000 IU/mL by day 7 who were treated for 12 weeks demonstrated similar cure rates as those treated for 24 weeks.

Pegylated interferon-alpha-2a plus ribavirin may increase sustained virological response among patients with chronic hepatitis C as compared to pegylated interferon-alpha-2b plus ribavirin according to a systematic review of randomized controlled trials. The relative benefit increase was 14.6%. For patients at similar risk to those in this study (41.0% had sustained virological response when not treated with pegylated interferon alpha 2a plus ribavirin), this leads to an absolute benefit increase of 6%. About 16.7 people need to be treated for one to benefit.

Treatment during the acute infection phase has much higher success rates (greater than 90%) with a shorter duration of treatment; however, this must be balanced against the 15-40% chance of spontaneous clearance without treatment (see Acute Hepatitis C section above). Those with low initial viral loads respond much better to treatment than those with higher viral loads (greater than 400,000 IU/mL). Current combination therapy is usually supervised by physicians in the fields of gastroenterology, hepatology or infectious disease.

The treatment may be physically demanding, particularly for those with a prior history of drug or alcohol abuse. It can qualify for temporary disability in some cases. A substantial proportion of people will experience a panoply of side effects ranging from a 'flu-like' syndrome (the most common, experienced for a few days after the weekly injection of interferon) to severe adverse events including anemia, cardiovascular events and psychiatric problems such as suicide or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the patient.

Boceprevir
Boceprevir is a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site on hepatitis C genotype 1. There have been several recent randomized double-blinded clinical trials studying boceprevir in conjunction with peginterferon-ribavirin as therapy for untreated chronic HCV genotype 1 infection and previously treated chronic HCV genotype 1 infection. These studies have shown improved sustained virologic response at 44 weeks compared to therapy with peginterferon-ribavirin therapy alone. Anemia was a common side effect in these two studies.

Boceprevir was approved by the FDA on May 13, 2011 for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin. The indication is for adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

Host factors
For genotype 1 hepatitis C treated with pegylated interferon-alpha-2a or pegylated interferon-alpha-2b combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in response to the treatment. This finding, originally reported in Nature, showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more likely to achieve sustained virological response after the treatment than others. A later report from Nature demonstrated the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus. It has subsequently been reported that polymorphisms in IL28B are strongly associated with the elimination of HCV RNA during the first days of peginterferon-α/ribavirin therapy (“first phase decline”), irrespective of HCV genotype.

Similarly, baseline pretreatment plasma levels of IP-10 (also known as CXCL10) are elevated in patients chronically infected with hepatitis C virus (HCV) of genotypes 1 or 4 who do not achieve a sustained viral response (SVR) after completion of antiviral therapy. IP-10 in plasma is mirrored by intrahepatic IP-10 mRNA, and both strikingly predict the first first phase decline during interferon/ribavirin therapy for all HCV genotypes. And combining both pre-treatment levels of IP-10 and IL28B polymorphism further improves prognostication of therapeutic outcome.

Increased levels of ferritin pre treatment seem to be associated with a poor response to treatment.

Pregnancy and breastfeeding
If a woman who is pregnant has risk factors for hepatitis C, she should be tested for antibodies against HCV. About 4% infants born to HCV-infected women become infected. While there is no preventative treatment, there is a high probability of the baby clearing the infection in the first 12 months.

In a mother who also has HIV, the rate of transmission can be as high as 19%. There are currently no data to determine whether antiviral therapy reduces perinatal transmission. Ribavirin and interferons are contraindicated during pregnancy. However, avoiding fetal scalp monitoring and prolonged labor after rupture of membranes may reduce the risk of transmission to the infant.

HCV antibodies from the mother may persist in infants until 15 months of age. If an early diagnosis is desired, testing for HCV RNA can be performed between the ages of 2 and 6 months, with a repeat test done independent of the first test result. If a later diagnosis is preferred, an anti-HCV test can be performed after 15 months of age. Most infants infected with HCV at the time of birth have no symptoms and do well during childhood. There is no evidence that breast-feeding spreads HCV. To be cautious, an infected mother should avoid breastfeeding if her nipples are cracked and bleeding.

Alternative medicine
Several alternative therapies are claimed by their proponents to be helpful for hepatitis C, or are being researched to see if they can be effective treatments. Among them are milk thistle, ginseng, colloidal silver, licorice root (or its extract glycyrrhizin), lactoferrin, TJ-108 (a mixture of herbs used in Japanese Kampo medicine), schisandra, and oxymatrine (an extract from the sophora root).

In March 2011, the United States National Center for Complementary and Alternative Medicine (NCCAM) wrote:

    A review of the scientific evidence on complementary and alternative medicine (CAM) and hepatitis C found the following:

        No CAM treatment has been scientifically proven to successfully treat hepatitis C.
        A 2003 analysis of results from 13 clinical trials testing the effects of various medicinal herbs on hepatitis C concluded that there is not enough evidence to support using herbs to treat the disease.
        Two other reviews that covered a variety of CAM modalities for hepatitis C concluded that conventional therapies are the only scientifically proven treatments for the disease.
        In a 2002 NIH consensus statement on the management of hepatitis C, a panel of medical and scientific experts concluded that "alternative and nontraditional medicines" should be studied. Participants in a 2001 NIH research workshop on the benefits and risks of CAM therapies for chronic liver disease recommended research support for related laboratory and clinical studies.

Additional recommendations
Current guidelines strongly recommend that hepatitis C patients be vaccinated for hepatitis A and B if they have not yet been exposed to these viruses, as infection with a second virus could worsen their liver disease.

Alcoholic beverage consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more likely; insulin resistance and metabolic syndrome may similarly worsen the hepatic prognosis. There is also evidence that smoking increases the fibrosis (scarring) rate.

Special groups
Hemophilia and thalassemia are special group in HCV infected patients. Using the ribavirin in thalassemia group is not approved by FDA yet and hemophilia is at higher risk of complication in therapy with standard drugs.