Update from the Liver Meeting

I'm at the American Association for the Study of Liver Diseases' annual Liver Meeting, the major U.S. conference on hepatitis C and other liver diseases. Here's some quick notes from the research presented so far:

- Daily marijuana (cannabis) smoking appears to accelerate and worsen fibrosis progression, according to French researchers. They found that long-term daily marijuana smokers were more likely to experience rapid fibrosis progression, and more likely to have serious fibrosis, than non-smokers or occasional smokers. Other research to be presented today will suggest a biological mechanism to explain these findings. While this data should be confirmed through other studies, it suggests that people with chronic hepatitis C should avoid daily marijuana smoking.

- A growing body of data implicates insulin resistance (associated with obesity and diabetes) in poorer responses to hepatitis C treatment. Poorer response to treatment has been seen in people with greater weights and body mass indices, and insulin resistance may explain why this group is less likely to experience sustained virologic responses. In test tube studies, high insulin levels appear to mitigate the antiviral effects of interferon.

- New research suggests that in people who achieve sustained virologic responses, very low levels of hepatitis C can persist for several years, despite undetectable viral loads using conventional tests. The implications of these findings is unclear -- rates of relapse to detectable viral loads remain low in long-term follow-up studies, and growing evidence shows that people who achieve sustained virologic responses have good long-term outcomes overall, low rates of liver cancer, and improvements in fibrosis and liver inflammation. But this research suggests that it would be premature to classify a sustained virologic response as having "cured" hepatitis C infection.

- New (acute) hepatitis C infection can be successfully treated with only 3 months of pegylated interferon monotherapy (e.g., no ribavirin), according to two new studies from Europe. One of these studies, conducted in Italy, included a large proportion of acutely infected injection drug users. Sustained virologic response rates were very high (in the range of 70-90%), and tolerability and adherence were very good. These results suggest the value of very early diagnosis and treatment, particularly in groups with high rates of new infections -- injection drug users. Currently, very few hepatitis C infections are diagnosed during the acute phase.

More later -- several presentations today will provide results on clinical trials of new drugs to treat hepatitis C.

Comments

[Mark Howard]

"New research suggests that in people who achieve sustained virologic responses, very low levels of hepatitis C can persist for several years, despite undetectable viral loads using conventional tests."

So what non-conventional test do they have to detect these low levels of HCV? " New research suggest". What research? That’s a hell of a thing to throw out there without a more detailed explanation of how they came to this conclusion. A dozen of these guys introduced to the bloodstream by a needle prick or a razor nick can turn into a lifelong chronic infection. Interferon doesn’t permanently alter the immune system how could it now suppress a virus that eluded it before interferon?

[Daniel Raymond]

Let me quote from one paper published earlier this year by a group that presented additional data at the Liver Meeting -- here's the abstract:

J Virol. 2004 Jun;78(11):5867-74.

Hepatitis C virus persistence after spontaneous or treatment-induced resolution of hepatitis C.

Pham TN (1), MacParland SA (1), Mulrooney PM (1), Cooksley H (2), Naoumov NV (2), Michalak TI (1,3).

Molecular Virology and Hepatology Research, Division of Basic Medical Science (1), Division of Pathology, Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada (3), Institute of Hepatology, University College London, London, England (2)

It is presumed that resolution of hepatitis C, as evidenced by normalization of liver function tests and disappearance of hepatitis C virus (HCV) RNA from serum, as determined by conventional laboratory assays, reflects virus eradication. In this study, we examined the expression of the HCV genome in the sera, peripheral blood mononuclear cells (PBMC), and, on some occasions, monocyte-derived dendritic cells (DC) long after resolution of hepatitis C by using a highly sensitive reverse transcription (RT)-PCR-nucleic acid hybridization (RT-PCR-NAH) assay. The samples obtained from 16 randomly selected patients (5 with spontaneous and 11 with treatment-induced resolution), monitored for up to 5 years, were studied by qualitative and semiquantitative RT-PCR-NAH and by real-time RT-PCR to detect the HCV RNA positive strand. The replicative HCV RNA negative strand was examined in PBMC after culture with a T-cell proliferation stimulating mitogen. The findings show that HCV RNA was carried in the convalescent-phase sera and/or PBMC in all 16 individuals investigated. Also, DC from six of seven patients were reactive for the HCV genome. Importantly, traces of the HCV RNA negative strand, suggesting progressing virus replication, were detected in the majority of mitogen-stimulated PBMC, including four samples collected 5 years after recovery. Sequencing of the HCV 5' untranslated region fragment revealed genotype 1b in four of nine individuals examined and genotypes 1a and 2a in three and two patients, respectively. These results imply that HCV RNA can persist at very low levels in the serum and peripheral lymphoid cells and that an intermediate replicative form of the HCV genome can persist in PBMC for many years after apparently complete spontaneous or antiviral therapy-induced resolution of chronic hepatitis C.

So what does this really mean? They looked at people who cleared hepatitis C, either during acute infection (their immune systems controlled it) or through treatment. They didn't look in liver tissue, but found signs of hepatitis C in certain types of blood cells. In some cases, they found signs that hepatitis C was still replicating.

Conventional tests to detect and measure levels of hepatitis C in the blood -- the ones a doctor would order, specifically the Roche Amplicor HCV v2.0 test in this case -- could not detect any circulating virus. These researchers used more refined techniques (ones not available outside of research labs):

"...the samples were analyzed using reverse transcription (RT) and nested PCRs followed by Southern blot hybridization of the amplified products to virus-specific probes (RT-PCR-NAH assay; sensitivity, 10 vge/ml)."

So what does this all mean? As I wrote earlier, it's not clear. Here's a couple of possibilities:

1. There's a lot of viruses out there that people apparently clear (think measles) even though the virus may actually persist in the body at very low, completely harmless levels. In the people described in the study above, it's possible that virtually all of the virus was eradicated (either by the immune system or by treatment), except for a very small amount of hepatitis C that will ultimately fade away. And in the meantime, these people will remain perfectly healthy.

2. Long-term studies of people who achieve an undetectable hepatitis C viral load after treatment (sustained virologic responders) show that after several years, at least 90-95% of them remain undetectable. That's good news -- if you achieve a sustained virologic response, you can be pretty confident that for all intents and purposes, you've gotten rid of the virus. Even if small amounts of hepatitis C remain, as in the studies I've mentioned, you wouldn't expect it to come back in full force.

So those are a couple of ways of looking at this -- I posted the news not to be alarmist, or suggest that the virus will never go away and always be a threat to anyone who was ever infected, but rather to highlight new data which we're likely to hear more about in the future.

I'll try to write about this in more detail in the next couple of months, along with some other related research. One leading virologist I talked to about the above study said he didn't think it would be anything but a hypothetical concern for people who've cleared the virus. But these studies are one reason why a lot of doctors and researchers are still wary about using the word 'cure' in the context of hepatitis C treatment.

[Mark Howard]

Thank you very much for posting that Daniel. SVR cure or not has been a frequent topic on many HCV support forms for obvious reasons. I look forward to any more info you can find on this.
Thanks again,
Mark

[theresa]

i know someone who is having problems with their liver and he is the hospital a liver doctor came in to talk to him i would like to know more if it is his hiv meds or hepatitius

[Donna Geiger FNP]

ANything new on the RT-PCR NAH assay showing virus capable of replicating - I liked your thoughtful analysis - I guess I will stop using the C word (for Cure) OR it could be much like HBV where we KNOW that anyone with a core total antibody positive test (HBcAb Total) but who is HBsAg negative still have some of those virions that are being suppressed by the immune system. They will only rear their ugly heads should immunosuppressive drugs - ie. in the post-transplant seeting for example - be needed. These are very subterranean infections at very low level and should not cost long term or even minimal disease.

[Thomas Walton]

In treating African Americans with genotype 1b there seems to a poor response to treatment. What time schedules in treatment of AA patients with genotype 1b do you use and what is your success rate?

[Thomas Walton]

In treating African Americans with genotype 1b there seems to a poor response to treatment. What time schedules in treatment of AA patients with genotype 1b do you use and what is your success rate?

[heidi]

Hello,
Your article was great. It answered my question. I would still like to hear it again. If I clear the hepatitis c, will all my blood tests come back negative for the virus? I want to possibly work in the health field and if I ever get tested for any employment, I just want to make sure it is gone. I would like to have your opinion.

Sincerely,
Heidi

[Daniel Raymond]

Hi Heidi --

If you clear hepatitis C, you'll still have antibodies to hepatitis C produced by your immune system. Antibodies persist even after people have cleared the virus. Therefore, a hepatitis C antibody test will continue to be positive -- but does not indicate current infection. However, a standard blood test to detect the presence of the virus (sometimes called a qualitative PCR) will be negative. It's this second test which determines whether or not someone still has the virus. If there are any questions from employers about your hepatitis C status, make sure they know to look at the results of the qualitative PCR.

To the best of my knowledge, hepatitis C status (including chronic infection) should not disqualify anyone from a profession in health care. Universal precautions are designed to protect both health care workers and patients. However, I don't know whether their are any legal protections for health care workers against discrimination based on hepatitis C status.

Hope that helps --

Daniel

[MARY]

my son was told he has hepatitis C of the liver,we would like to know more about hep.c and would like to know the sits to go to.
thank you
mary

[Dr . Mrs Gursaran Sidhu]

I got a needle prick injury while performing a Liver biopsy on a HCV +ve young patient while capping up the needle which I had used for injecting local anesthesia. I was wearing double gloves but the prick was deep and lot of blood came out. I pressed it hard and let it bleed. I washed it with soap and water. This happened today only ( 27-10-07 ) just 6 hours back.I am a 46 years old non smoker/ non alcholic/vegetarian female physician. Kindly advise the protocaol to be followed.
Thanks