Study: Occult Hep B and Hep C non-response

[TnHepGuy_]

"The aim of this study was to evaluate the prevalence of occult HBV among HCV chronic carriers in France and to assess its impact on liver histology and response to antiviral therapy....In conclusion, HBV-DNA is found in 1/4 of French chronic hepatitis C patients regardless of the presence of anti-HBc. Such an occult HBV co-infection is associated with more severe liver disease, higher HCV viral load and decreased response to antiviral therapy irrespective of HCV genotypes."


http://tinyurl.com/yrfa9c


TnHepGuy

[TnHepGuy_]

Liver enzyme flares and occult hepatitis B in persons with chronic hepatitis C infection.

"We screened hepatitis B surface antigen negative injection drug users with untreated chronic hepatitis C viral (HCV) infection for unexplained ALT/AST flares....CONCLUSIONS: In this population at high risk for occult HBV, AST/ALT flares can be associated with detection of HBV DNA. These findings may link occult hepatitis B to liver injury."


http://tinyurl.com/3brzb4


TnHepGuy

[jmjm530]

Thanks for the study.

For those unfamiliar with occult HBV (like me) here is a little primer I googled up that may fill in some of the blanks. http://tinyurl.com/2owsnt

David, the reference above states in part:

"...In general, the prevalence of occult HBV infection is highest in those who are anti–HBc-positive but anti–HBs-negative, intermediate in patients positive for both anti-HBc and anti-HBs, and quite rare in the seronegative group..."

Is this consistent with the article posted,  and does it mean that most of us can be at ease regarding having occult HBV as long as we are "seronegative" with what I assume is measured with commonly available tests.  I'm a bit confused here.

All the best,

-- Jim

[TnHepGuy_]

Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: a prospective study.

"Previous exposure to hepatitis B virus (HBV) and occult HBV infection may have an important role in the development of hepatocellular carcinoma (HCC) in patients with chronic liver disease related to hepatitis C virus (HCV). OBJECTIVE: To prospectively study the association between antibody to hepatitis B core antigen (anti-HBc) and clinical outcomes in patients with HCV-related chronic liver disease....CONCLUSIONS: Anti-HBc-positive results on serologic testing are a marker of high risk for HCC among patients with HCV-related cirrhosis. Interferon therapy might be less effective in preventing HCC among patients with chronic hepatitis C who are anti-HBc-positive than in those with chronic hepatitis C who are anti-HBc-negative."


http://tinyurl.com/2kkqgm


TnHepGuy

[TnHepGuy_]

Thanks for the link on occult Hep B.

From that page, they define occult Hep B as those who are "negative for HBsAg but harbor low levels of HBV DNA in serum or liver tissue."

Then, they divide the occult B group into 2 further sub-categories: those who are “seropositive” - (i.e. - blood test positive for anti-HBc with either anti-HBs positive or negative results) and, those who are "seronegative" - (blood test negative for both anti-HBc and anti-HBs).

Then, from looking at previous studies, they suggest that patients from the seropositive group have the greatest prevalance of occult Hep B - with those who test positive for anti-HBc but negative anti HBs being the highest %, then followed by those test positve for both anti-HBc and anti HBs with a smaller %. Finally, they suggest that the group who tests seronegative has the smallest (i.e. - rare) % chance.


The first study posted determined occult Hep B seropositivity via use of PCR that looks at the S and the X genes. They go on to conclude that "HBV-DNA is found in 1/4 of French chronic hepatitis C patients regardless of the presence of anti-HBc.", meaning that as defined from the article you linked, both groups - seropostive and seronegative - are equally affected.


Also - Jim, the article you linked was published in 2003. PCR sensitivity and occult testing/detection have both come a long way in just the past few years. No telling what might be determined more conclusively today as opposed to the testing that was available for this paper. Hopefully, someone will publish an updated look in the not-too-distant future.


David

[TnHepGuy_]

I just had the chance to sit down and take a good look at what you had posted below re: occult Hep C (http://tinyurl.com/24u4r7). Fascinating and frightening stuff - (frightening mainly in the sense of immunocompromised rebound scenarios but also in the possibility of potential negative outcomes caused by immune response to the occult virons). In layman's terms, it appears as if "stealth duds" are flying under-the-radar. But how is it that in this setting, the replicating wild-type get to fly under, too???


Thanks again for posting that - and would it be possible for you to e-mail the pdf to me? I'd enjoy taking a good look at it.


TnHepGuy

[willing]

I'll try not to be too alarmed here but...I'm going to make an appt. with my hepatologist and check on low-level HBV-DNA detection ( I don't usually think there's much call, at least in my uncomplicated case, for bringing in the heavy-caliber firepower but this may be an exception).

Needless to say, I've had a lot of time to puzzle over why I was the only one in my "graduating class" to relapse and this may not be the answer but it bears investigating. I don't have access to my HBV results at the moment but as I recall they showed surface antigen neg. and antibody for surface and core antigen positive. This is the trademark signature of a "resolved" infection - which is supposed to account for around 80% of infections.

(jim btw neg for both s and c ab's would also exclude anyone vaccinated for hbv)

I don't know whether available commercial tests can detect the presence of low-level HBV DNA even when HBVsAg is not found, but suspect the answer is no since the Mrani'07 paper you posted used lab-brew PCRs to detect and quantify the occult HBV DNA even though they used stock tests for everything else (antibody, antigen and HCV RNA tests).

The implications are not nice.  Per Mrani : only 33% of the HBV negs had severe (3-4) fibrosis and 45% got to SVR vs. 60% cirrhosis and 28% SVR among the HBV pos. (and I don't think I even want to read that HCC article yet).

The Mrani tx protocol was a bit strange 3x3Mill. units a week ifn (not peg) for 6 months, regardless of geno, yet they found no difference in SVR rates among 1s and others..

As for the Bernandin article, I'm not sure there's anything ominous there. My read was that it (1) underscored that what you measure floating around in serum is not necessarily indicative of what's buried in tissue cells (2) confirmed, for the first-time, that non-viable, HCV virions exist and, with help, can replicate (in abundance!)  and (3) confirmed that low-level replication of HCV can happen in cells without leaving any clues in your blood sample. This last point  needs a closer reading : I'm not sure whether their serum tests showed no full-length genomes or just a much lower level than truncated genomes.

[TnHepGuy_]

Thanks for sending those along.

One thing I find interesting that they mentioned in Bernandin is: "Immune responses may prevent the outgrowth of defective variants by continually selecting for novel immune response escape variants resulting in serial
population bottlenecks as immune escape variants are repeatedly selected."

The theory being that there is enough of an immune response to keep the 'duds' in a constant state of change/flux, with the implication therefore being that they continue to stay at the 'occult' level.

Also interesting: "The presence of in frame E1-NS2 truncated HCV genomes
resembling those reported here has been recently reported in liver biopsies of 4/24 hepatitis patients and 2/2 hepatocarcinoma (HCC) patients (Yagi et al., 2005). Interestingly the ratio of truncated to full-length genomes appeared to be 100-fold greater in the liver than serum." ..... which they go on to call the liver .... "this recombination hot spot."

And what implications, if any, might you see from this?: "The long-term stable detection of HCV subgenomes in plasma reported here may therefore reflect the occasional generation of intracellular replicons whose deleted structural
functions, including envelope glycoproteins, can be provided by trans-complementation in cells co-infected with wild-type helper HCV. Resulting subgenome RNA containing particles released into the bloodstream from co-infected cells would be competent for cell entry and further RNA replication into new target cells thereby amplifying truncated genomes and sustaining
the high and chronic plasma levels seen here."


As to Mrani, if you and your hepatologist think that HBV DNA testing may be of use to you, perhaps you could contact HR and discuss the possibilities. His lab may have the capabilities - or he may know where to point you to. To rule in or out occult HBV before re-treatment would certainly be helpful info, as well as knowing in relation to potential implications of having HBV while continuing to wait.


TnHepGuy

[friole]

Interesting connections here.  I know on my initial testing - I must look for the results to check exactly -  the doctor told me I had been exposed to hepB but not enough for me to develop the immunity.  He wanted my to take the vaciine which I have not yet done.  I will need to read all of these articles since I, like Willing,  relapsed.

[mikesimon]

I posted this earlier and I am not sure it's even relevant but that hasn't stopped me before.
From:http://www.medscape.com/viewarticle/556992_1

Profound Suppression of Chronic Hepatitis C Following Superinfection With Hepatitis B Virus
Posted 06/05/2007

To our knowledge, there is only one case of apparent clearance of chronic HCV following acute HBV superinfection. Sergi et al.[8] described a 36-year-old male who underwent orthopic liver transplantation for HCV-related liver cirrhosis. The patient required retransplantation for chronic rejection. After retransplantation, HCV RNA was undetectable but de novo HBV infection was diagnosed in the retransplanted liver. Sequencing analysis of the 5'-UTR region of the HCV genome in the explanted livers revealed a mutation that disrupted the virus internal ribosome entry site. The authors hypothesized that the mutant HCV is more susceptible than HBV to antiviral cytokines released by activated cytotoxic T lymphocytes.

The use of more sensitive assays for detection of HBV and HCV genomes in our study allowed for identification of HBV replication in lymphoid cells, as well as low levels of circulating HCV. This is not surprising, considering the similar results demonstrated in recent studies.[9-13] The single PBMC sample examined showed replicating HBV, although the cells were negative for HCV RNA. It is acknowledged that both HBV and HCV are lymphotropic viruses.[9,12] In this regard, HCV RNA was found in PBMC in up to 40% of individuals with occult HCV infection. However, this number increased to 80% after PBMC ex vivo stimulation with mitogens.[11] Limitations in the patient samples available made analysis of HCV expression in mitogen-treated cells unfeasible. Nevertheless, persistence of HCV in lymphoid cells appears to be a common characteristic of either spontaneous or therapeutically induced resolution of hepatitis C. This study indicates that a careful longitudinal evaluation is necessary to determine accurately the profiles and the outcomes of HBV/HCV coinfection from clinical and virological viewpoints.

Mike

[TnHepGuy_]

Prevalence of Low-Level Hepatitis B Viremia in Patients with HBV Surface Antigen-Negative Hepatocellular Carcinoma with and without Hepatitis C Virus Infection in Japan: Analysis by COBAS TaqMan Real-Time PCR

"The effect of circulating low-level hepatitis B virus (HBV), defined as one of the states of 'occult HBV infection', on the development of hepatocellular carcinoma (HCC) in HBV surface antigen (HBsAg)-negative patients is controversial. In addition, the prevalence of occult HBV infection strongly depends on the sensitivity of the HBV detection method. We investigated the prevalence of low-level HBV in the serum of HBsAg-negative patients with HCC using a newly developed, sensitive method based on real-time polymerase chain reaction.....Conclusion: The prevalence of the detection of circulating low-level HBV was low in both HBsAg-negative HCC patients with HCV infection and those without detectable hepatitis virus, even with the use of the most sensitive method for the detection of HBV. Circulating low-level HBV does not appear to play an important role in hepatocarcinogenesis in HBsAg-negative HCC."

http://tinyurl.com/3ybd4a


TnHepGuy

[TnHepGuy_]

COBAS AmpliPrep-COBAS TaqMan hepatitis B virus (HBV) test: a novel automated real-time PCR assay for quantification of HBV DNA in plasma

"Success in antiviral therapy for chronic hepatitis B is supported by highly sensitive PCR-based assays for hepatitis B virus (HBV) DNA. Nucleic acid extraction from biologic specimens is technically demanding, and reliable PCR results depend on it. The performances of the fully automatic system COBAS AmpliPrep-COBAS TaqMan 48 (CAP-CTM; Roche, Branchburg, NJ) for HBV DNA extraction and real-time PCR quantification were assessed and compared to the endpoint PCR COBAS AMPLICOR HBV monitor (CAHBM; Roche)......CAP-CTM detected HBV DNA in liver biopsy samples from 15% of HBsAg-negative, anti-HBcAg-positive graft donors with no HBV DNA in plasma. The amount of intrahepatic HBV DNA was significantly lower in occult HBV infection than in overt disease. CAP-CTM can improve the management of HBV infection and the assessment of antiviral therapy and drug resistance, supporting further insights in the emerging area of occult HBV infection."

http://tinyurl.com/22jg6t


TnHepGuy

[TnHepGuy_]

Natural history of patients with recurrent chronic hepatitis C virus and occult hepatitis B co-infection after liver transplantation.

"It is uncertain whether occult hepatitis B virus co-infection will hasten progressive liver disease in chronic hepatitis C patients after liver transplantation. This study evaluated fibrosis progression and severe fibrosis in 118 consecutive hepatitis B surface antigen-negative patients with virological and histological evidence of recurrent chronic hepatitis C infection co-infected with occult hepatitis B virus after liver transplantation......In conclusion, occult hepatitis B virus co-infection in patients with recurrent chronic hepatitis C infection was not associated with accelerated fibrosis progression or severe fibrosis after liver transplantation."

http://tinyurl.com/2639ly


TnHepGuy

[TnHepGuy_]

HBV vaccination of HCV-infected patients with occult HBV infection and anti-HBc-positive blood donors.

"Anti-HBc positivity is a frequent cause of donation rejection at blood banks. Hepatitis B virus (HBV) infection may also occur in HBsAg-negative patients, a situation denoted occult infection. Similarly, very low levels of HBV-DNA have also been found in the sera of patients with chronic hepatitis C virus (HCV) infection, even in the absence of serum HBsAg......The disappearance of HBV-DNA in the majority of vaccinated patients suggests that residual HBV can be eliminated in patients with occult infection."

http://tinyurl.com/yvl3b7


TnHepGuy

[TnHepGuy_]

Comparative study on the clinical and virological characteristics among patients with single occult hepatitis B virus (HBV), single occult hepatitis C virus (HCV) and occult HBV and HCV dual infection.

"Occult hepatitis B virus (HBV) and occult hepatitis C virus (HCV) infection are two recently described different forms of HBV and HCV infections. This work compares the clinical, virologic, and histologic characteristics of patients with occult dual infection to those of patients with single occult HBV or HCV infection......In conclusion, liver disease in patients with occult dual infection was not more severe than in patients with single occult HBV or occult HCV infection. Moreover, in occult dual infection there is no a reciprocal inhibition of the viral genomes."

http://tinyurl.com/2vox3e


TnHepGuy

[Tater_ToT]

Boy... This is a REFRESHING Thread... Feels like old times!
Thanks Ya'll
;)

[mikesimon]

Those were different days, were they not? Be well, Mike