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
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.”
Samer El-Kamary, MBChB, MS, MPH
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
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
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.
Adeel A. Butt, MD
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.
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
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’
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
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