Sovaldi and rivibirin gave me CANCER

[Pensativo]

 Hi everybody I was cured last year 2016. And not need a follow up according to my specialist doctor. I live in Canada Ottawa On. And 12 days ago I started having abdominal pain, nausea, insomnia, appetite loss. They did an MRI. And it came with liver cancer. I was shock because my liver was in fibrosis 2 for 30 year how that is posible that after treatment with sovaldi and rivibirin I got cancer. If I did not have it for 30year how come I got it after teartment. It wal the medication because there is not other logic. I am crying badly Now I regret taking sovaldi/rivibirin . Because with my condicion fibrosis 2 I was able todo everything around me and I could live much longer what a tragedy.


Pensativo. God bless U.

[strangerbynight]

Hi everybody I was cured last year 2016. And not need a follow up according to my specialist doctor. I live in Canada Ottawa On. And 12 days ago I started having abdominal pain, nausea, insomnia, appetite loss. They did an MRI. And it came with liver cancer. I was shock because my liver was in fibrosis 2 for 30 year how that is posible that after treatment with sovaldi and rivibirin I got cancer. If I did not have it for 30year how come I got it after teartment. It wal the medication because there is not other logic. I am crying badly Now I regret taking sovaldi/rivibirin . Because with my condicion fibrosis 2 I was able todo everything around me and I could live much longer what a tragedy.


Pensativo. God bless U.

I am very sorry to hear that, have they done any ultrasound every 6 months? I know you are an F2 and i heard they only do annual ultrasound on F3 or F4, i am just wondering if you had it done and if so did they ever find any lesions prior to treatment? These DAA has always been my concern for me because i am an F0-1 and before my treatment they have found 2 lesions on my liver and was told one is just a hemggioma and the other they think its a cyst, i am getting scare from this too, just done my 12 weeks generics harvoni 5 days ago..i wish you all the best and please stay positive..pray for you..

[Mike]

Hi Pensativo,

I'm very sorry to hear this and wish you the best. I would note, however, that cancer is pernicious and there could  well be other factors that led to this dx, including, but not limited to  the diagnosis was missed prior to HCV treatment, the cancer originated outside the liver and so forth.   

This is by no means a minimization of what you are going through; rather it is to point out that unknown factors could be involved and it may be more complicated than HCV treatment.

Best wishes, Mike

[lporterrn]

I am so sorry. There were many studies on this at the recent liver meeting, all supporting the safety of the new treatments. My favorite showed that eradication of HCV by direct-acting antivirals is associated with a 79% reduction in HCC (liver cancer) risk.

However, I just wrote a blog that will appear tomorrow - I am posting a copy of it here barbecue it directly addresses your issue. (And I am quite distressed about this, especially to learn of your recent diagnosis.) It may explain your situation.

Unsettling Hepatitis C Research

Let’s start with a fact about hepatitis C treatment. When it works (which is most of the time), hepatitis C antiviral therapy eliminates the virus. This means that people with the virus don’t have hepatitis C any longer. However, successful treatment does not guarantee anything beyond that. If you have cirrhosis you may continue to have cirrhosis and all of its signs and symptoms. You may develop liver cancer, lose kidney function, need a liver transplant, or die from liver failure. Being cured from hepatitis C doesn’t cure everything.

This is news to many who were not well-prepared about the realities of hepatitis C treatment. However, to the majority of those who were cured of hepatitis C, life changed dramatically. Cirrhosis was averted, liver cancer risk dropped, and all the other nasty potential consequences that hepatitis C may cause quietly slipped away. Personally, I could breathe a sigh of relief.

That relief was shattered while browsing through the latest research from the 2017 Liver Meeting sponsored by the American Association for the Study of Liver Diseases. Titled, Increase In Hepatocellular Carcinoma in Hepatitis C Patients Without Cirrhosis, the study examined the prevalence and trends in HCV-related hepatocellular carcinoma (liver cancer) from 2000 to 2015.

Sanath K.Allampati and colleagues analyzed electronic medical record data obtained from 2,328 subjects diagnosed with HCC; 20% of the subjects did not have cirrhosis at presentation. They found that liver cancer rates were trending consistently higher. Further, this increase was more pronounced in the non-cirrhotic group, increasing from under 10% to nearly 22%.

The researchers were concerned that with the advent of new hepatitis C treatments, there might be a large number of HCV-cured patients who could potentially develop hepatocellular carcinoma even though they do not have cirrhosis.

The Bottom Line: If your hepatitis C was treated and cured, talk to your doctor about follow-up tests. The HCV Guidelines recommend hepatocellular carcinoma surveillance for everyone with fibrosis stage 3 or 4. Personally, I am not sure that is generous enough, and perhaps people with earlier stages need following.

Hepatitis C treatment is an incredible opportunity, but not if you don’t continue to take care of your health.

https://www.hepmag.com/blog/unsettling-hepatitis-c-research

[strangerbynight]

Can you provide a link for the above info? Thanks

[I fightis thetitis]

Pensitivo I am so sorry to hear this. The Good news is there are very encouraging options for you right now. What are your next steps?
 
Hi Lucinda,

Thank you for this.. I browsed the recent DC meetings pages for any info and eager to see any follow up.
I have been posting re this for several mos.
My GI has been concerned as several patients that cleared via DAA tx w/out prev hcc or history of cancer, have showed a marked increase in hcc and colon cancer post tx. Specifically, several F4 patients have developed hcc within 6-9 mos post viral eradication, not @ EOT.
Further, it is a very aggressive form of HCC.

This study seems to validate his concerns that with certain patients (apparently not just F4s) there MAY be a connection that rapid hcv elimination may compromise  T cells, or cells that suppress cancer can become dormant. 

I have seen some on the forums dismiss that narrative.

Post tx my bilirubin doubled and my platlets are now 120 down from 170 pre tx.
Bili went from .08 to 1.6 and he has me on 3 mo US.
So far all clear and I follow up with him.

For those concerned I recommend they show their GI's your findings as DAA/hcc connection remains suspicious.

All that said, based on where the science is right now I would still choose TX and cure hcv.
However, I would NOT be surprised if a definitive report appears that connects the dots
and exposes risks for certain people.
Too many unanswered questions and horrible stories.

Best always,

Greg


 

[I fightis thetitis]

I should also mention for every unfortunate story there seems to be 10x's that in positive stories..
New developments with hcc treatment are encouraging.

[lporterrn]

Here are the requested links - The full presentation is member only, but fingers-crossed, you can see the abstracts for free:

Abstract #142 http://onlinelibrary.wiley.com/doi/10.1002/hep.29500/full

Abstract #997 http://onlinelibrary.wiley.com/doi/10.1002/hep.29501/full#hep29501-sec-2927

[Steve76]

I rarely post here, this is bad news.  Thing is this is not the first time this kind of news about DAA's has made headlines. I have also seen large studies that show the exact opposite.

 I fightis thetitis I understand your angst about your blood work changing. It would be helpful if you had  historical  numbers to compare with. Possibly there has been these kinds of swings in your Bilirubin and Platelets in the past. 

I use a medical portal that has the history of my issues and labs before treatment and after treatment.


My most recent labs showed my AST 22 and ALT 15 and my Platelets at 169 and Bilirubin .9 INR has stayed the same at 1.0

Last year 6 months after treatment AST 26 Alt23 Platelets 184 Bilirubin .7

I checked the portal going back 7 years and my Platelets jumped around from the 160s to the 180s. Same thing with the Bilirubin from .7 to 1.0. Check your portal and see if if this happened in the past.

Possibly nothing to do with the treatment. Have a good day BTW I am f4 fibroscan 16 and was treated for 6 months with Harvoni.

[I fightis thetitis]

Hey Steve,

Yes my portal goes back two years and I have hard copies of my labs since 2002.

My Bili doubled post tx. I just checked and my Platlets were 182 pre tx on 10/25/15 and now 120 @18 mos post tx, and 23 mos viral eradication.
The other marker still out of range is ALPHA 2 MACROGLOBULIN. pre tx 547 now 441.
Range is supposed to be 106 to 279.
All of these numbers indicate advanced liver disease consistent with cirrhosis.

The concern of course is the rapid "out of range" spike in bilirubin and rapid decline of  platlets by 62 points post DAA. Bili and platelets have been in normal range since I have kept copies of labs starting 2002. 

Something sudden triggered those numbers. However I feel fine and have no symptoms. Take better care now with exercise and only cheat on occasion with pizza or a restaurant whose food is prob loaded with salt. Almost all veggie too. Will keep you posted and I hope others chime in with their labs pre and post DAA.

Best to all,

Greg

[I fightis thetitis]

Hi Lucinda,

From the second report I noticed it said some patients in the study who were treated that were not cirrhotic went on to develop hcc. It did not mention they were SVR, rather that they were treated.
I wonder if that is taken into account or they mean SVR and the article onlys uses the word treated.

Greg

[Steve76]

How about this?


Impact of Sustained Virologic Response with Direct-Acting Antiviral Treatment on Mortality and Hepatocellular Carcinoma - significantly lower mortality, HCC 60% to 84%
 
 
    Reported by Jules Levin
AASLD: The Liver Meeting® 2017, October 20-24, 2017, Washington, DC
 
L. Backus, P.S. Belperio, T.A. Shahoumian, L.A. Mole Population Health Services, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
1024171

Successfully treating HCV before the development of advanced liver disease translates into a significant mortality benefit. 
1024172

Hepatitis C virus (HCV) antiviral treatment effectiveness is assessed by the surrogate end point of sustained virologic response (SVR), however, reduced all-cause mortality remains the ideal marker of treatment benefit and the ultimate goal.
 
In light of Cochrance Review, need for evidnece of mortality benefit of DAAs The large number of veterans treated in VA - both with and without ALD make VA  an ideal setting to examine these important outcomes Second, the long-term care integration affords the opportunity to follow up on individual patient outcomes over time thirdly, there is national VA guidance and treatment considerations in place which apply to all VA facilities providing some consistency in the general management and use of DAAs across its population.
 
Fourth, VA has not had restrictions on specific populations of patients that can or cannot receive DAA treatment,  Lastly, the diverse real-world population treated within VA allows for examination of the impact of comorbidities on all-cause mortality after DAA treatment.
1024173

This observational cohort analysis used data from the VA's Clinical Case Registry for HCV, an extract of the VA's electronic medical record for all HCV-infected veterans receiving care at VA medical facilities.
 
Overall mortality rates were calculated as deaths per 100 years of patient follow-up.  In addition, since follow-up is relatively limited given the recent introduction of DAAs and it is possible that the mortality rate changes over time, one-year mortality rates were also determined.  The one-year mortality rates were calculated as the number of deaths within one year of the EOT among those people who stopped treatment by May 31, 2016 so there was at least one year of follow-up on all included patients.
 
Multivariable Cox proportional hazard models were constructed to identify predictors of mortality and the impact of SVR The one-year mortality rates were calculated as the number of deaths within one year of the EOT among those people who stopped treatment by May 31, 2016 so there was at least one year of follow-up on all included patients.
 
Kaplan-Meier curves of survival and of HCC-free survival by SVR were compared with log-rank tests.  Mortality and incident HCC rates per 100 patient years of follow-up were compared with the Exact Poisson test.  One-year mortality and HCC rates were compared with proportion tests.  Cox proportional hazard models were constructed to identify predictors of mortality and the impact of SVR.
1024174

ACLD - Among No SVR patients, 195 died during a mean follow-up period of 1.5 years after EOT.  Among SVR patients, 598 died during a mean follow-up period of 1.6 years after the EOT.
1024175

As seen by KM curves In unadjusted analysis, SVR was associated with statistically significantly reduced all-cause mortality compared to No SVR (p<0.001)(Figure 1).  The cumulative mortality curves for No SVR and SVR diverged early in the follow-up period and the reductions in all-cause mortality among SVR patients appear clinically significant. SVR was strongly associated with delayed time until development of HCC Kaplan-Meier curves of survival and of HCC-free survival by SVR were compared with log-rank tests.
1024176

Deaths ≥12 weeks after EOT; Deaths occurring within 1 year of the EOT among patients with ≥1 year of available follow-up
 
Among 15,059 ACLD patients, 195/1,067 with No SVR and 598/13,992 with SVR died over a mean follow-up period of 1.6 years; When considering deaths per 100 patient years of follow-up, SVR was associated with a 78.9% reduction in mortality.  The percentage reductions across genotypes 1a, 1b, 2 and 3, were similar .
 
A similar pattern of significantly reduced mortality associated with SVR was evident when considering one-year mortality rates.  SVR was associated with a 79.6% reduction
1024177

Incident HCC diagnosis ≥12 weeks after EOT; Incident HCC occurring within 1 year of EOT in patients with ≥1 year of available follow-up. Excludes patients with HCC diagnosis prior to DAA initiation (n=818), and HCC diagnosis while on DAAs or ≤12 weeks after DAA completion (n=217)
 
During follow-up, 140 of 871 No SVR patients and 397 of 13,153 SVR patients had a first diagnosis of HCC. When considering HCC per 100 patient years of follow-up, SVR was associated with an 83.5% reduction in incident HCC.  A similar reduction associated with SVR was evident when considering one-year HCC rates. 
1024178

There were 732 patients who had HCC first diagnosed within five years before the start of DAA; 135 were No SVR of whom 39 died in follow-up and 597 were SVR of whom 72 died in follow-up.  The death rate for those with prior HCC and No SVR was 21.0 deaths/100 patient years (95%CI 14.9-28.7) compared to 7.5 deaths/100 patient years (95%CI 5.9-9.5) for those with prior HCC and SVR - a 64.3% reduction in the death rate .
 
For those without a diagnosis of HCC prior to DAA, 871 were No SVR of whom 133 died in follow-up and 13,153 were SVR of whom 497 died in follow-up.  Deaths rates for those without prior HCC and No SVR were 10.1 deaths/100 patient years (95%CI 8.4-11.9) compared to 2.3 deaths/100 patient years (95%CI 2.1-2.5) for those without prior HCC and SVR - a 77.2% reduction in the death rate (p<0.001).
1024179

In unadjusted analysis displayed in the Kaplan Meier survival curves, SVR was associated with statistically significantly reduced all-cause mortality compared to No SVR (Figure 1A).  When examined separately for patients with FIB-4 <1.45 and 1.45-3.25, SVR was also associated with reduced all-cause mortality compared to No SVR although the statistical significance of the effect was reduced for those with FIB-4<1.45 (Figure 1B and 1C).
10241710

When considering deaths per 100 patient years of follow-up, SVR was associated with a 58.9% reduction in mortality . For patients with FIB-4 <1.45 and 1.45-3.25, SVR was associated with a significant 45.7% and 64.0% reduction in mortality respectively.  The percentage reductions across genotypes ranged from a 48.4% reduction for genotype 1a to a 79.5% reduction for genotype 2.  (Not Shown, When considering one-year mortality rates, the mortality rate was significantly lower for those with SVR than those with No SVR
10241711

presents the hazard ratios (HR) for death from multivariable Cox proportional hazard models for patients with and without advanced liver disease treated with DAAs. a Reduced risk of all-cause mortality occurred with achievement of SVR compared to No SVR in BOTH ACLD and Non-ACLD patients while controlling for numerous baseline demographic and clinical characteristics listed.
 
In ACLD , patients with a history of decompensated liver disease had an increased risk of death.  Each 1 g/dL decrease in albumin was also independently associated with increased risk of death.
 
Non ACLD Models included variables selected a priori of age, sex, race/ethnicity, BMI, other baseline comorbidities, albumin, eGFR, and SVR status.  Additional sensitivity models were constructed: including a variable for genotype for the most common genotypes (1a, 1b, 2 and 3), separately for patients with each of these genotypes, limited to patients with FIB-4 <1.45, limited to patients with FIB-4 1.45-3.25, and as indicators of adherence, limited to patients who had at least a 2 log decrease in HCV RNA while on treatment and limited to patients who achieved an HCV RNA below the limit of quantification while on treatment.
 
ACLD Models included variables selected a priori of age, sex, race/ethnicity, BMI, history of decompensated liver disease, HIV, other baseline comorbidities, albumin, eGFR, and SVR status.  Additional multivariable sensitivity models were constructed: using age, albumin and eGFR as categorical variables, including a variable for genotype for the four most common genotypes, separately for patients with each of the four most common genotypes, separately for patients with and without a history of decompensated liver disease, limited to patients who achieved SVR, and limited to those with No SVR.  A final multivariable Cox model considered a composite outcome of death or liver transplant in follow-up.
 


 

[Steve76]

Eradication of HCV induced by DAAs is associated with a 71% reduction in HCC risk.

Go to Natap.org
 
 
    

[lporterrn]

They were treated and had an SVR.
So this is what the professional community is discussing - now that we have good treatment, we are treating a lot of people. We aren't doing liver biopsies, and some of the non-invasive screening tests aren't being done. We treat people, and then assume those without cirrhosis are going to be fine. BUT, what if some of those stage 2s and 3s are actually 4s. If these patients were stage 4, they should be watched closely, because hep C or no hep C (regardless of what treatment they had), they are at risk for liver cancer. But they are discharged back to primary care with no follow-up. This may explain Pensativo's situation.
Bottom line, we need to talk to our primary care docs about our post-treatment follow-up.

[strangerbynight]

They were treated and had an SVR.
So this is what the professional community is discussing - now that we have good treatment, we are treating a lot of people. We aren't doing liver biopsies, and some of the non-invasive screening tests aren't being done. We treat people, and then assume those without cirrhosis are going to be fine. BUT, what if some of those stage 2s and 3s are actually 4s. If these patients were stage 4, they should be watched closely, because hep C or no hep C (regardless of what treatment they had), they are at risk for liver cancer. But they are discharged back to primary care with no follow-up. This may explain Pensativo's situation.
Bottom line, we need to talk to our primary care docs about our post-treatment follow-up.

So what would you recommend for people who are at F0-1 stage? Should they be monitor annually?  I am at F0-1 and i just done my treatments 6 days ago..thanks

[lporterrn]

Without data or a license to practice medicine, I can't make a recommendation. What I am going to do is talk to my doc about liver enzyme tests every 6 to 12 months and a CBC every 6 mos. Platelets are the key thing here, because as long as they are clearly normal, then no cirrhosis, and with no cirrhosis, I am not going to worry. I am also going to discuss a baseline ultrasound (which is better than AFP).

I was at stage 2+; I'd worry less if I was a 0-1, but I'd do a annual CBC and watch platelets.

[strangerbynight]

Without data or a license to practice medicine, I can't make a recommendation. What I am going to do is talk to my doc about liver enzyme tests every 6 to 12 months and a CBC every 6 mos. Platelets are the key thing here, because as long as they are clearly normal, then no cirrhosis, and with no cirrhosis, I am not going to worry. I am also going to discuss a baseline ultrasound (which is better than AFP).

I was at stage 2+; I'd worry less if I was a 0-1, but I'd do a annual CBC and watch platelets.

Nice and clear, thank you very much for replied, i will ask my doctor to do an annual CBC blood work and watch for platelets..

[andrew j]

(Excuse me, Pensativo) -

Lucinda,

Could you post the abstracts / links in your 'Reply #7' (above) to the homepage - or your blog?

There is a lot of interesting info. there.

Many thanks,
A.