Control comorbid conditions as well as focusing on hepatitis C

Ameliorating comorbidities before initiating hepatitis C antiviral therapy should be the goal. Although the recently approved therapies are opening new doors for hepatitis C treatment, a recently published study found that mortality from all causes is higher in those infected with hepatitis C, even after accounting for deaths from liver disease, emphasizing that controlling those other causes is as important as targeting the hepatitis C virus itself.

An estimated 4 million adults in the United States tested positive for hepatitis C, according to the Third National Health and Nutritional Examination Survey, a large, nationally representative survey conducted from 1988 to 1994. It is estimated that in the United States, approximately one-quarter of those with HCV also have HIV. These percentages of patients who are coinfected are even higher in urban areas and among those who acquire the infection via IV drug use, between 50% and 90%.

In the recently published study, Samer El-Kamary, MBChB, MS, MPH, and colleagues from the University of Maryland School of Medicine in Baltimore, assessed data from a survey and concluded that during a follow-up period of almost 15 years, 614 deaths occurred among 9,378 adults. Of those, 203 had chronic HCV, and of those, 44 died. Thirty-five of those deaths were related to HIV infection, cancer, heart disease, diabetes and other comorbidities such as other infectious diseases. Compared with those who tested negative for hepatitis C, patients with chronic hepatitis C infection had more than a twofold risk of dying from liver- and non-liver related causes.

In an interview with Infectious Disease News, El-Kamary said the study emphasizes that “while a hepatitis C infection itself may not be the cause of death, patients with the disease may be at a higher risk of dying due to other high-risk behaviors that may have also caused the infection. Furthermore, it is possible that other comorbidities, like diabetes and cardiovascular disease, could get worse if there is an underlying hepatitis C infection.”

In their paper, the Maryland researchers advocate liberal early screening for other types of comorbidities as a strategy to prevent morbidity and mortality.

Eric A. Engels, MD, MPH, a senior investigator at the National Cancer Institute, said in an interview that even in this new era of expanded treatment options for hepatitis C, it will be several years before randomized trials can advise on the best treatments for HIV coinfected patients, so early detection and treatment of other conditions should be a paramount priority.

HIV/HCV coinfection

HCV infection is more serious in those living with HIV because it can lead to liver damage more quickly, according to data from the CDC. Coinfection with HCV may also affect the treatment of HIV infection. Therefore, it is important for those with HIV to know whether they are also infected with HCV and, if they are not, to take steps to prevent infection.

This is particularly true for certain at-risk populations, such as those living in prisons. According to the US Bureau of Justice Statistics, 20,449 state prisoners and 1,538 federal prisoners were HIV-positive during 2008 — five times the rate of the general population infected with HIV. Moreover, most recent data from the CDC indicates an almost 10-fold increased rate for hepatitis C virus among inmates compared with the general population. So screening in this population, as well as other at-risk populations, is encouraged.

Cancer and HCV

Hepatitis C is a major cause of liver cancer, as well as non Hodgkin’s lymphoma, according to Engels. Recent data show that the frequency of liver cancer in the United States overall is rising. This increase is due primarily to rising rates of diabetes and chronic hepatitis C.

The relationship of HCV to non-Hodgkin lymphoma is well established, although the mechanisms are not well understood, Engels said. It is likely that lymphoma occurs because the immune system is overactive for longer periods of time, causing genetic damage. In patients with HCV, the risk factors for developing liver cancer can include male sex, cirrhosis, alcohol use and, in some studies, genotype.

Typically, Engels said, patients who present with NHL are treated for their cancer first, with the goal of obtaining a remission so they can be treated for the HCV. There are some preliminary data that suggest that treating HCV is linked with remission of certain lymphomas, but this is “probably true for less aggressive cases.”

Cardiovascular complications and HCV

According to published data from Adeel A. Butt, MD, of the University of Pittsburgh School of Medicine and VA Pittsburgh Healthcare System, HCV RNAs have been found in the hearts of patients with cardiomyopathies.

In an interview, Butt said patients with HCV may be at an elevated risk for coronary artery disease. In a paper that looked at data from VA facilities, Butt and colleagues found that the average total plasma cholesterol was 175 ± 40.8 mg/dL in patients with HCV compared with 198 ± 41 mg/dL in those who were not infected (P<.001). Their data showed that patients with HCV were less likely to have hypertension, hyperlipidemia and diabetes, but still had a higher risk for coronary artery disease, which may suggest that these patients are predisposed to lipid abnormalities in the myocardium.

Butt said his data suggest that patients with HCV who have cardiovascular issues must be carefully considered, adding that studies are needed using the recently approved hepatitis C medications in this population of patients because early data are suggesting that patients on boceprevir (Victrelis, Schering) and lipid-lowering agents fared well.

Endocrinology issues

Other metabolic issues such as being overweight, insulin resistance and liver steatosis are typically associated with more severe and progressive liver fibrosis in patients with chronic hepatitis C, Butt said, adding that this suggests that all efforts “should be made to improve the metabolic steatosis of the patient.”

“If a physician diagnoses HCV in a diabetic or cardiovascular patient, it is always considered clinically prudent to closely follow these patients to manage both diseases appropriately,” El-Kamary said.

Other potential comorbidities

There are several other conditions that have been found in patients with chronic hepatitis C, including other forms of hepatitis, such as B and A, renal disease, and psychological diseases such as depression and addiction to drugs and alcohol.

According to published data, coexistent HCV infection has been estimated to be present in 10% to 15% of patients with chronic hepatitis B and, as seen in the HIV coinfected population, is more common among injecting drug users.

“Combined chronic hepatitis B and C leads to more severe liver disease, an increased risk of hepatocellular carcinoma and lower response to interferon-gamma,” El-Zayhadi and colleagues wrote in a 2009 paper. “Furthermore, coinfected patients represent a treatment challenge. No standard recommendations exist for treatment of viral hepatitis due to dual HBV/HCV infection, and therefore treatment must be individualized. Treatment decisions should be based upon the determination of the ‘dominant’ hepatitis virus.”

Communicating risk to patients

Although the recently approved hepatitis C medications are offering new choices for patients, it will be a while before data are certain on the best courses of treatment, and even longer before trials compare the best choices for these patients. So in the interim, emphasizing screening and prevention are pivotal, experts who spoke to Infectious Disease News said.

“The recently approved medications are add-ons to existing therapy — interferon and ribavirin — and hence, their side effects are even more due to their additive effect,” El-Kamary said. “Physicians need to be vigilant about how these additive side effects can impact existing comorbidities — over and beyond how the side effects of interferon and ribavirin alone impacted them. There is a lot of experience with interferon and ribavirin, but the new drugs will still need time for physicians to identify their effect on existing comorbidities.”

Engels said it is important to counsel patients about good health practices.

The prevalence of coinfections of hepatitis C and B viruses in those with HIV puts them at greater risk for longer-term health problems, such as liver cancer and cardiovascular disease, so continued vigilance is important, he said.

“The key message to people with HCV should be avoiding drinking alcohol, which can exacerbate any liver disease, and seek treatment,” Engels said.

For patients already diagnosed with HCV, El-Kamary recommended screening for HIV and hepatitis B, and vaccination against hepatitis A and B and, in some countries, hepatitis E.

“Patients should also avoid sharing needles for any purpose — IV drug use, medication use, home-tattooing or home-piercing — since those activities can infect others,” he said. “Also, they should avoid high-risk sexual activities such as unprotected sex with many partners, or sexual activities that may lead to blood exposure. All these activities can transfer HCV to an uninfected person.” – by Colleen Zacharyczuk

For more information:

• Butt AA. Clin Infect Dis. 2009;49:225-232.
• El-Kamary SS. Clin Infect Dis. 2011;53:150-157.
• El-Zayhadi A. World J Gastroenterol. 2009;15:4993-4999.
• Strader DB. Clin Infect Dis. 2005;41(Suppl 1):S7-13.

Disclosures: Drs. El-Kamary, Engels and Butt reported no relevant financial disclosures.

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