Natural Course of Treated and Untreated Chronic HCV Infection

Here are two excerpts from a recent study. It is located at:  http://www.medscape.com/viewarticle/703614

I posted the excerpts just to give you an idea of the article. I do recommend reading the entire article and assess any limitations in the methodology. The author(s) did mention one limitation. I found it surprising and interesting.

"....Results: During follow-up, 48 patients developed liver decompensation and 24 HCC. Older age was significantly related to disease progression (HR = 2.6 per 10 years of increasing age). Stratified by baseline cirrhosis, Cox analysis showed that patients with SVR, but not without SVR, had significantly lower hazard for events compared with nontreated patients (HR = 0.16; P < 0.001), whereas the detrimental effect of older age remained highly significant. Separate group analysis demonstrated that in cirrhosis, the beneficial effect of treatment was evident even without SVR. Treatment effect interacted significantly with age, indicating that older patients, mainly noncirrhotic, gained the most benefit.
Conclusions: IFNα-based treatment does alter the natural course of CHC. A protective effect is mostly present in patients with SVR, but older patients, at higher risk of events, gain the greatest benefit. In established cirrhosis, treatment carries a protective effect even among those without SVR....."

"...Discussion

In this large, multicentre, national Greek study involving 993 treated and 734 untreated patients with chronic hepatitis C, it was demonstrated that the most important factor affecting the progression of liver disease was older age at diagnosis and that IFNα-based treatment significantly improved the outcome of the disease. Patients with SVR had the best clinical outcome compared to untreated patients and the beneficial effect of SVR was present in all patients, irrespective of cirrhosis. Moreover, in patients with cirrhosis, a protective effect of treatment was found even among those without SVR. For patients without cirrhosis, the beneficial effect of IFNα treatment was particularly evident in older patients, that is, in patients with the worst prognosis if left untreated...."

[JennyPenny]

Thanks Mike. It's good to know that in this study, even though maintenance does not work, a first treatment in cirrhotic patients, even those without SVR, have a benefit. Very interesting article.

[nygirl7]

Thanks Mike.  This is what both the doctors told me when I first considered treatment. Both of them said that it was good because at least it would help my chances of not getting HCC greatly. To me, that was a key factor and I had decided to treat because of it even before I found out I was stage 3 and really didn't have any time to do a watch and wait type thing (which I wouldn't have considered probably anyway unless I was stage 0 but was a moot point).  It's very good for people who don't get SVR the first time to hold onto this information - and realize that they've significantly helped themselves regardless.

[mikesimon]

HCC? Clinical Care Options:

Defining the Incidence and Risk Factors for Hepatocellular Carcinoma in the Setting of HCV Infection
Nancy Reau, MD
Lok and colleagues unearthed several very important findings in this analysis:

1. Patients with a previous nonresponse to peginterferon/ribavirin who received low-dose maintenance peginterferon developed HCC at a rate equal to that of untreated controls. This finding strongly discourages the use of maintenance therapy to decrease malignancy risk.

2. Hepatocellular carcinoma developed in 4.8% of the HALT-C cohort, with an estimated annual incidence of 1.1% and a 5-year incidence of 5.9%. Based on these data, the investigators were able to stratify the cohort into low-, intermediate-, and high-risk groups for the development of HCC using a mathematical model requiring only routine laboratory results and clinical data. Older age, black or black plus Hispanic race, high alkaline phosphates levels, low platelet counts, presence of esophageal varices, and having ever smoked were significant in predicting HCC risk. This suggests that it may be possible to identify patients in need of intensive HCC screening and monitoring.

3. Patients without cirrhosis developed malignancy. Unlike with hepatitis B, the development of HCC in HCV-infected patients without cirrhosis has been viewed as an exception to the rule. Yet in this study, HCC was identified in 23 patients without cirrhosis at enrollment (48% of all patients with HCC). This suggests that significant fibrosis is also a risk factor for HCC and that our current screening recommendations[13] should be expanded to include this subset of patients. Some of these patients had progressed to cirrhosis at the time of HCC diagnosis, reminding us that HCV liver disease is a dynamic condition and that patients should be reassessed at regular intervals for disease progression. Screening should be initiated as soon as a patient is considered to be at increased risk for malignancy.

4. Only 75% of malignancies were diagnosed at an early stage (T1/T2), and only 54.2% were eligible for potentially curable therapy. This suggests that our current screening recommendations fail to identify nearly one half of tumors at a time when therapy can be of maximal benefit.

This important study has several implications. The findings indicate that no patient should be receiving maintenance peginterferon solely for liver cancer prevention. In addition, this study suggests that our current HCC screening recommendations[13] are not adequate. Screening is likely necessary for a subset of patients with advanced fibrosis (without cirrhosis) and should ideally be performed every 6 months. Our current practice guidelines do not recommend using alpha-fetoprotein (AFP) levels as a screening tool; however, this study found that AFP and des-gamma-carboxyprothrombin (DCP) levels on univariate analysis were both significantly associated with HCC. Until the appropriate population for screening can be identified, all patients with advanced fibrosis should be screened every 6 months for HCC using a combination of imaging and tumor markers (ie, AFP and DCP).

Mike

[newleaf09]

Thanks Mike.  Reversal of cirrhosis to back away from HCC is, and maybe always was, my greatest interest in pursuing SVR.  The idea of having to stay hooked to medical screening for another 10 years of my life, looking for liver cancer, is pretty repellant to me.  I just want to get on with a normal life and put HCV forever behind me.

[nygirl7]

Amen I do not want to have to be thoroughly tested for another 8 years but honestly it seems like we probably should. Heck I was nervous enough about getting another PCR last week and my liver enzymes were at like 10. That was enough testing for me.

[Marc1955]

I spoke with a hepatologist at Johns Hopkins in the spring. He recommended an annual screening for HCC for folks who had achieved SVR. He said that was the current state of the research. More importantly, he said that you needed to stay in touch with a hepatologist even if you cleared the virus because the research picture is changing so rapidly. He said one year the hepatologist might recommend a HCC screening and the next year there might be a new study that would say it was unnecessary. But in any event, you do need to stay in touch with a hepatologist. That was this guy's recommendation. I know there are different points of view since I've heard of people on this board who's doctors said they should go away and come back in a decade after they achieve SVR.

[nygirl7]

I just found out a few minutes ago I'm still SVR - it never gets ANY easier even two and a half years later. The idea of having to check in for what seems like ever really isn't a happy one cause I do wanna check back in in a decade. But I guess after going through tx to make sure we are cured it's just what we gotta do.

I do have a friend who died of HCC just a few years ago (when I was just starting tx she was already very ill) so I dn't want to get there!

[newleaf09]

NYgirl, did you ever re-biopsy?  I plan to rebiopsy after one year and, yes I will still keep getting the cat scans to look for HCC until my doc tells me not to.  I have to say I disagree with docs who say SVR means it's all over, go away.

I just spent an hour searching for the press release of the 5-7 yr. rebiopsy study to find this sentence:
"For patients with cirrhosis on first biopsy (19 percent of the cohort with SVR), 50 percent had improved on second biopsy — 10 percent had no scarring, 10 percent had portal scarring and 30 percent had improved to bridging fibrosis. "

I'd really like to be one of the 10% who get back to zero but would also be thrilled with stage 2.  HCC can still occur in stage 3's but wouldn't it be great to move away from 3 and finally stop the darn doctor dance?

[eureka254]

mikesimon: Thanks for the post, I always appreciate new info on hcc.  Really good to see research encouraging AFPs on a wider scope.  It's a low-cost test to detect a high-risk disease, and the benefits are enormous, even if the test falls far short of what one would call a good diagnosis tool.  I'm hoping that adding DCP or other analytes in the future will increase the specificity and the sensitivity of hcc serum screening.

The early detection and cure rates for HCC are appalling -- and the 'dynamics' of hepatitis and it's relationship to HCC is anything but linear.  When my husband got his hcc diagnosis back in 2007 and I plunged into research, I was fluxomed by the lack of information on hcc and appropriate or effective medical management.

What I came away with after months of research was frustrating:  it's usually found with cirrhosis (but not always), it is usually detectable by AFP and/or imaging (but not always), it's usually fatal (but not always), could be cured by transplant or resection (but not always), it can be treated palliatively (but not always by the same method), it usually recurs (but not always), -- I was almost a madwoman, learning to cope with seemingly infinite variables.  (Boy, did disease diagnosis teach me a lot about rolling with the punches...)

Anyway, I sympathize with those who dread the surveillance-- believe me, my husband does too -- but the irony is when the doc suggested perhaps spacing out his AFPs and CT-Scans to 6 months, whereas his surgical oncologist had him doing them done every 3 months -- he decided to stick with every 3 months.  (It's not unusual for hcc under 2cm to go undiagnosed, and hcc's "doubling" time is 2-12 months...if you do the math, it's pretty staggering.)  The quarterly roller-coaster ride is less scary than the thought of not finding it early.  It's more frequent testing than what US protocol dictates, and perhaps what some docs call "unnecessary", but the his hepatologist docs from the tp center call it "aggressive" surveillance. (Btw, I'm not suggesting everyone with cirrhosis needs such frequent surveillance, but I think some regular surveillance is wise.)

The odd thing is, when posed the question, none of the docs my husband sees: not oncologists, surgeons, nor hepatologists,  would speculate about whether SVR would decrease the odds of developing hcc.  (Our hope is that no virus=no further hepatocyte damage/mutation/inflammation=lower risk of cancer, but no one will confirm it... seems to make sense, though, if only theory... )

[merryBe]

cool Mike,
I can't know how long it will last but I can attest that my spleen and liver have both recovered from their enlarged enflammed and painful state. That reduction has been a welcome relief.

Eureka,

here's my concern with all those CAT scans. Every Cat scan radiates the whole liver, and radiation is know to cause free radical and ergo cancer formation.
Ergo, the very device they are being "aggressive" with, is known to be contributory towards cancer.
My doc used the word "aggressive" also in regards to screenings, but he added that doing only CAt scans could be counter productive due to the radiation.
I didn't ask him for this info, he beat me to the punch and volunteered the information, so my guess is he is not as sold on it as some docs may be on all the aggression.
(Since he heads the clinic, it follows the more expensive scans done more often would make him more money, yet he did not suggest more of these, so the fact that he did not holds a good weight with me.)
What he recommended was a 6 month schedule, with rotation of methods split between the 3 methods (CAt/MRI/UltraSound) as long as there was no change or elevation in the AFP he thought this was a more reasonable approach.

I'm not sure xrays (which is what Cat scans are) every 3 months would be a wise thing to do.
I agree your hubby should have frequent scans, but maybe mixing up the methods might help rather than hurt? Just an idea. What I did, since we decided to do this mix, was I told the Ultra Sound technician about our stategy, and since telling her she has been spending about 45 minutes doing my scans. She goes quite deep, a lot of pressure and it's very uncomfortable, but done this way ultrasounds are now pretty reliable. My urologist said they are incredibly improved over the machines of a few years ago so I'm pretty comfortable mixing it up.

mb