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Current Opinions and Controversies in Research & Treatment of Hepatitis C Virus (HCV)

July 9-14, 2000

Over 40 hepatitis and infectious disease researchers, clinicians, primary care physicians, government heath administrators, industry representatives, and patients with viral hepatitis were interviewed by telephone or in person. They were all asked about their work and their thoughts on the current state of hepatitis C virus (HCV) research. Many were asked about their recent or upcoming articles which provide a basis for our current understanding of the epidemiology, pathogenesis, natural history and treatments used on patients with HCV or hepatitis and HIV coinfection. They were asked questions in three broad areas: 1) epidemiology; 2) natural history and prognostic factors; and 3) treatments.

Specific comments from those interviewed are unattributed. The assurance of anonymity allowed individuals to relate sensitive issues that they may not have otherwise.

I. Epidemiology & Risk Factors for Transmission of HCV

A. Do you think that we know the exact prevalence of HCV in the United States?

Some expressed their concern about the estimated prevalence of HCV in the U.S. They believe the CDC's NHANES III epidemiology study may have underestimated the number of people infected because they did not use intravenous drug use (IVDU) as a surrogate for HCV infection.

Infectious disease doctors who treat people with HIV/AIDS said that they only began widespread screening of their patients for HCV two to three years ago, after the advent of highly active antiretroviral therapy (HAART). The recent epidemiology data documenting that 35% to 90% of HIV-positive patients are coinfected with HCV motivated them to use HCV testing as a routine part of clinical practice.

There was concern that we will see a dramatic rise in the HCV epidemic over the next ten years. Many individuals underwent blood transfusions before 1989 or engaged in IVDU but have not been tested for HCV antibodies. A large percentage of these unidentified asymptomatic individuals with HCV will soon become symptomatic.

B. Do you believe that HCV is sexually transmissible?

A majority admitted this is a controversial subject, yet only a few felt certain that sexual transmission of HCV exists. Most of the old-guard hepatologists said that sexual transmission was not a risk factor and cited studies which documented no sexual transmission in monogamous heterosexual couples. However, some infectious disease doctors or gastroenterologists who treat HIV/HCV-coinfected patients have a strong conviction that sexual transmission of HCV exists. They explained that after hours of discussion with patients (mainly homosexual men) on HCV transmission and possible IVDU, they felt comfortable in believing that approximately 10% had no other risk factors except high-risk sexual behavior with multiple partners.

Individuals with HCV and HCV/HIV coinfection eagerly want an answer to this question because they are unsure about the risk of HCV transmission during anal intercourse. A few admit to no condom use with consenting partners and question whether they are putting others at risk.

C. Why did it take so long to recognize the seriousness of HCV/HIV coinfection?

Many AIDS clinical researchers said they were fully aware that many of their HIV-positive patients were coinfected with HCV, yet for those who were HCV-asymptomatic, the first priority was to control the HIV viral replication, immunosuppression and life-threatening opportunistic infections. In the 1980s and mid-1990s, most believed that their patients would die from HIV-related complications years before HCV would cause symptomatic liver disease.

Now that their HIV-positive patients are living longer on HAART, AIDS clinicians and researchers said that they felt the need to explore treatment options and initiate coinfection studies.

II. Natural History of HCV Infection

A. Can individuals with HCV drink alcohol?

There was great concern about alcohol usage in HCV-positive patients. Some were quick to remind me that heavy use of alcohol was one of most significant risk factors for disease progression yet felt uncomfortable defining what "heavy alcohol use" was. Most felt the need to tell their HCV-positive patients to abstain from alcohol. All agreed that this needs further study.

Many of the European hepatologists discussed their concern about heavy alcohol use in their HCV-positive patients with a past history of IVDU. They said that many patients had conquered their drug addiction but were using excessive amounts of alcohol (possibly as a coping mechanism) and ruining their liver. I was told that patient advocates like myself should openly discuss the deleterious effects of alcohol with HCV-positive patients.

B. Do you think that HCV RNA levels affect the natural history of HCV infection?

No one felt that HCV RNA was a predictor of liver disease progression and many cited seminal natural history studies. I was reminded that in the absence of treatment, host factors (i.e., gender, age at infection) are the strongest determinant of liver disease progression. Many were quick to note that a lower level of HCV RNA is preferable if one is considering treatment.

With regard to HIV/HCV coinfection, many pointed out that HAART has the tendency to raise HCV RNA levels, but it should only be a concern if the coinfected patients goes on to initiate HCV therapy.

C. Do you believe that HCV patients with genotype 1 are at increased risk for liver disease progression and/or death?

Most all who were interviewed felt that in the absence of HCV therapy, genotype 1 had no bearing on the natural history of HCV infection.

D. Is the natural history of HCV infection worse in HIV/HCV coinfected patients compared to HCV patients without HIV?

Answers to this question were mixed. Those unfamiliar with treating coinfected patients cited data documenting that coinfected patients had faster liver disease progression. HIV clinicians also believed the data, but admitted that most of the studies were conducted before the advent of HAART. There were those who said that control of HIV viral replication and halting immune suppression may put both types of patients on a level playing field. Nonetheless, most agreed that large natural history studies are needed to answer this question.

III. Treatment of HCV Infection

A. Do you insist on a liver biopsy before treating a patient with HCV?

There were some who insisted on having the findings of a liver biopsy, and said that they would not treat a patient unless one was performed. However, many would treat in the absence of a liver biopsy and felt comfortable with simply knowing the patient's lab values (i.e., ALT, HCV RNA, albumin). A few claimed that they could roughly predict their patient's liver histology grade and stage with the right lab values.

B. Why are so many hepatologists unwilling to treat HIV/HCV coinfected patients?

One researcher said that a majority of hepatologists believe that HIV infection is something outside their expertise and because the field is changing so rapidly, it is difficult to keep up-to-date. He also said that hepatologists have difficulty with HIV patients being on so many medications and felt that most would want to take patients off all drugs to see exactly how the liver was functioning on its own. A number of researchers did tell me that they were encouraging fellows to explore HIV/HCV coinfection research. Many believe that a combined ID/GI approach will offer the patient the best care.

C. Should all patients with HCV be treated with combination therapy?

The answers were surprisingly mixed on this question. Many did not see the harm in treating all of their patients with a 6-month course of IFN/RBV and seeing what happens. They believed that HCV is a progressive disease and if left untreated, it would eventually get worse. Other clinicians were much more conservative in their approach to treating HCV and would not recommend therapy unless the patient had at least stage 1 fibrosis. I was reminded that less than half of HCV-infected patients progress to cirrhosis and therapy is only effective in one out of three patients. Many felt comfortable monitoring their patients over time to decide when treatment might be warranted. More effective and less toxic therapies might become available when the patient finally needs therapy.

D. Do you believe the retrospective Japanese studies which document a decrease in hepatocellular carcinoma (HCC) and death in HCV patients with IFN?

An overwhelming majority of U.S. and European researchers did not believe the data, especially that which demonstrated a benefit in IFN non-responders. Their reasons were that all the data are retrospective and riddled with methodological flaws.

Many are excited about the NIDDK's HALT-C study and hope that it will tell us whether or not long-term IFN therapy decreases the risk of HCC.

E. Is there a benefit to maintaining an IFN non-responder or relapser on IFN?

Some felt strongly that IFN has antifibrotic properties and that those HCV patients with cirrhosis or transition to cirrhosis might need something to halt liver disease progression. If the patient could reasonably tolerate therapy, they saw no problem with recommending continuation of IFN.

Many researchers said that more work needs to be done to find anti-fibrotic drugs which would be active in patients with HCV.

F. Do you feel comfortable treating HIV/HCV coinfected patients?

Most of those interviewed said that they feel comfortable treating coinfected patients and have done so for many years. They believe that IFN or IFN/RBV response rates are similar in both patient populations. Nonetheless, many believe that heavily immunosuppressed HIV-positive patients (i.e., those with <200 CD4 cell/m3) fare worse.

Just about all clinicians who treat coinfected patients said that they preferred to have them initiate HAART first, get the HIV viral load undetectable and CD4 cells up before beginning HCV therapy. Most of the European clinicians felt comfortable working as a team with infectious disease doctors at their institutions.

G. Should HCV patients on a treatment study have access to their HCV viral load?

Compared to patients, researchers and clinicians did not have strong feelings one way or the other. Patients believed that they have a right to timely access of their HCV viral load so that they can discontinue therapy at 3 or 6 months if HCV RNA is detectable.

H. How serious is the depression and emotional unrest in IFN-treated patients?

Quite a few clinicians believe that IFN takes a serious psychological toll on their patients. Some advise patients to initiate antidepressants or even consider a short-term leave of absence from work.

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This article was provided by Treatment Action Group. It is a part of the publication The Hepatitis Report.