Monday, May 20, 2013

Hepatitis C: A Summary of Recent Research

Hepatitis is an infection of the liver that causes liver inflammation. There are several forms of hepatitis. Hepatitis C is one type that is caused by the hepatitis C virus, which infects 170 million people across the world.  Most patients with this condition suffer from a chronic form of the infection, but 40-80% of these patients can clear with standard treatment.

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While some patients with hepatitis C will not have symptoms, some will develop scarring of the liver (known as fibrosis) and/or fatty deposits in the liver (known as steatosis). As fibrosis worsens, so does liver stiffness.  As a painless alternative to liver biopsy (invasive tissue sample) for monitoring of liver stiffness, this can now be done with an FDA-approved, painless, and non-invasive imaging procedure known as Fibroscan. Research shows that liver stiffness measured by Fibroscan is linked to the degree of liver fibrosis, liver activity, and fatty liver (Boursier et al., 2013). Hepatitis C can also cause hepatocellular carcinoma (HCC), which is the most common type of liver cancer (Takagi et al., 2013). In worst cases, it can cause death.

In addition to causing liver damage, hepatitis C can also result in brain damage. Advanced neuroimaging technology has shown poor integrity and impairment of the white matter (nerve fibers that conduct information very fast),  underactivity of the cerebral cortex (the outermost layer of brain tissue),  and abnormalities in the basal ganglia (an area of gray tissue deep inside the brain that controls movement), the latter of which may be an indicator of brain inflammation (Bladowska et al., 2013).

Current standard treatment for hepatitis C includes antiviral medications and interferons (proteins that “interfere” with viral reproduction). Research shows that combining interferons with the antiviral drug, ribavirin, results in an absence of detectable hepatitis C virus in RNA (a type of genetic material) for 6 months after stopping treatment (Dogan, Akin, & Yalaki, 2013). When this happens, a patient is said to have achieved a sustained virological response (SVR).

Unfortunately, interferon treatment can have toxic effects and newer oral treatments regimens are being developed to avoid the use of interferons. These newer medications are known as direct acting antivirals (DAA).  The DAAs for hepatitis C are types of protease inhibitors known as telaprevir, simeprevir, and boceprevir,  which all prevent viral reproduction. Recent evidence indicates that cure rates are exceeding more than 90% with 12 weeks of oral DAA treatment that does not use interferons, including hard to treat patients (Luetkemeyer, Havlier, & Currier, 2013).

Because transmission of hepatitis C can occur via intravenous drug use and intercourse, many patients with hepatitis also have HIV.  In Brazil, most of these patients are male and in their mid-20s, with the average con-infection rate among HIV patients  being 20.3% (Kuehlkamp & Schuelter-Trevisol F, 2013).

For patients co-infected with hepatitis C and HIV, cure rates are presently at 75% with combined treatment of simeprivir, interferon, and ribavirin (Luetkemeyer, Havlier, & Currier, 2013). Incidentally, cardiovascular problems in HIV are worsened with hepatitis C co-infection (Syed & Sani, 2013). HIV patients with hepatitis C are also known to be at increased risk of bone fractures due to osteoporosis (an abnormal loss of bone thickness and a wearing away of bone tissue), which is partly explained by liver disease severity (Maalouf et al, 2013). One of the markers of liver disease in hepatitis C is the level of bilirubin, a yellow-orange substance excreted by the liver. If the bilirubin levels are high for long periods, this usually indicates severe liver damage. In patients with hepatitis C and HIV, the antiviral (protease inhibitor) medication, atazanavir, only resulted in small changes in bilirubin level, which is good (Cotter et al., 2013).

Many patients with hepatitis C do not receive treatment due to lack of insurance, poor financial resources, and serious psychiatric illness, and/or substance abuse.  However, in one study, when treatment for hepatitis C was initiated in nine individuals with serious mental illness and substance abuse, adherence to antiviral treatment was high and the SVR was comparable with published studies (Sockalingham et al, 2013). 

References:

Bladowska J, Zimny A, Knysz B, Małyszczak K, Kołtowska A, Szewczyk P, Gąsiorowski J, Furdal M, Sąsiadek MJ. (2013). Evaluation of early cerebral metabolic, perfusion and microstructural changes in HCV-positive patients: a pilot study. J Hepatol. (Epub). 

Boursier J, de Ledinghen V, Sturm N, Amrani L, Bacq Y, Sandrini J, Le Bail B, Chaigneau J, Zarski JP, Gallois Y, Leroy V, Al Hamany Z, Oberti F, Fouchard-Hubert I, Dib N, Bertrais S, Rousselet MC, Calès P; Multicentre group. (2013). Precise evaluation of liver histology by computerized morphometry shows that steatosis influences liver stiffness measured by transient elastography in chronic hepatitis C. J Gastroenterol. (Epub).

Cotter AG, Brown A, Sheehan G, Lambert J, Sabin CA, Mallon PW. Predictors of the change in bilirubin levels over twelve weeks of treatment with atazanavir. (2013). AIDS Res Ther. 10(1):13.

Dogan UB, Akin MS, Yalaki S. (2013). Sustained virological response based on the week 4 response in hepatitis C virus genotype 1 patients treated with peginterferons α-2a and α-2b, plus ribavirin. Eur J Gastroenterol Hepatol. (Epub).

Kuehlkamp VM, Schuelter-Trevisol F. (2013). Prevalence of human immunodeficiency virus/hepatitis C virus co-infection in Brazil and associated factors: a review. Braz J Infect Dis. (Epub).

Luetkemeyer AF, Havlir DV, Currier JS. (2013): CROI 2013: Complications of HIV disease, viral hepatitis, and antiretroviral therapy. Top Antivir Med. 21(2):62-74.

Maalouf N, Zhang S, Drechsler H, Brown G, Tebas P, Bedimo R.(2013). Hepatitis C co-infection and severity of liver disease as risk factors for osteoporotic fractures among HIV-infected patients. J Bone Miner Res. (Epub).

Sockalingam S, Blank D, Banga CA, Mason K, Dodd Z, Powis J. (2013). A novel program for treating patients with trimorbidity: hepatitis C, serious mental illness, and active substance use. Eur J Gastroenterol Hepatol. (Epub).

Syed FF, Sani MU. (2013). Recent advances in HIV-associated cardiovascular diseases in Africa. Heart. (Epub).

Takagi K, Fujiwara K, Takayama T, Mamiya T, Soma M, Nagase H. (2013). DNA hypermethylation of zygote arrest 1 (ZAR1) in hepatitis C virus positive related hepatocellular carcinoma. Springerplus.10;2(1):150.

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