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Liver Fibrosis Develops Early, Progresses Quickly After HCV Seroconversion
From Medscape:
Liver Fibrosis Develops Early, Progresses Quickly After Hepatitis C Virus Seroconversion
By Will Boggs MD, December 14, 2014
Liver fibrosis develops early after hepatitis C virus (HCV) seroconversion and progresses quickly to cirrhosis in many patients, according to new findings.
"Within 10 years of HCV infection, about 18% have developed cirrhosis, and this is 3 times higher than controls," Dr. Adeel A. Butt from University of Pittsburgh School of Medicine in Pennsylvania told Reuters Health by email. "Most of this occurs within the first 5 years after infection."
Dr. Butt and colleagues used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) to identify 1,840 patients who seroconverted to HCV antibody and then to determine their rate of liver fibrosis progression, compared with 1,840 matched controls who remained HCV antibody-negative.
They plotted the FIB-4 score, which provides an estimation of the degree of liver fibrosis based on routinely obtained blood tests, over time. A FIB-4 score greater than 3.5 indicates cirrhosis.
FIB-4 score progression started early after seroconversion, was most pronounced within the first five years, and continued over a period of 11 years. Progression was consistently higher among HCV-positive patients than among HCV-negative patients, the researchers report in JAMA Internal Medicine, online December 8.
In the HCV-positive group, 18.4% of patients went on to develop cirrhosis, compared with only 6.1% in the HCV-negative group, and the HCV-positive patients had a significantly shorter time to development of liver cirrhosis.
By five years, more than 15% of HCV-positive patients had a diagnosis of cirrhosis, compared with less than 5% of HCV-negative controls.
Only 3.1% of patients in the HCV-positive group developed hepatic decompensation (compared with 1.4% of HCV-negative patients), but their time to first hepatic decompensation was significantly shorter than it was for HCV-negative patients. More than half of the hepatic decompensation events occurred within the first two years of diagnosis of cirrhosis.
Factors associated with a higher risk of cirrhosis among HCV-positive patients included increasing age, white race, hypertension, history of alcohol abuse or dependence, and anemia. Diabetes, hypertension, and anemia were associated with a higher risk of developing hepatic decompensation.
"Future studies should look at a risk prediction model to determine which characteristics most accurately predict future cirrhosis in a given individual," Dr. Butt said. "Contrary to popular thought, a significant proportion of hepatic decompensation occurs without prior diagnosis of cirrhosis. Hence careful follow-up and evaluation for hepatic decompensation should be carried out in all HCV-infected persons regardless of duration of infection and prior diagnosis of cirrhosis."
"If newer treatments demonstrate slowing or reversal of fibrosis progression and delaying development of cirrhosis, our data would suggest treating early in the course of infection," the authors conclude. "On the other hand, if the cirrhosis has already set in, treatment may be helpful in preventing hepatic decompensation in only a small number of those with cirrhosis, since the number who go on to develop this complication is small."
Dr. Marc G. Ghany from the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, addressed the ongoing debate of whom to treat for chronic HCV in a related editorial.
"All patients with chronic HCV infection should be considered candidates for therapy, and mild liver disease is not a reason to deny a patient therapy who otherwise qualifies for treatment," he told Reuters Health by email.
But treatment is expensive, with costs ranging from $66,000 for 12 weeks of treatment with simeprevir to $84,000 for 12 weeks of treatment with sofosbuvir.
"The hope is that with the approval of other regimens, competition will drive down costs," Dr. Ghany said. "It remains to be seen how much cheaper the drugs will become, but it is unlikely in the near future that costs will decrease to the point where we will be able to treat everyone who is infected with hepatitis C virus."
"We still have to identify the large number of people who are unaware of their diagnosis and get them into care, including counseling on measures to prevent transmission, disease progression, and treatment," he concluded.
"This kind of study should remind physicians about the importance of non-viral, modifiable factors of accelerated liver fibrosis progression," Dr. Francesco Negro from Geneva University Hospital in Switzerland, who has published extensively on HCV infection, told Reuters Health. "One may think that treating HCV with antivirals may be the end of the story, thus forgetting about the formidable impact of alcohol drinking, cannabis smoking, and the metabolic syndrome. The VA population is particularly vulnerable in this respect."
"That their progression seemed to slow down once the diagnosis of cirrhosis was made suggests (although other explanations may be possible) that these persons became aware of the severity of their liver disease and tried to adopt a healthier lifestyle," said Dr. Negro, who was not involved in the research. "If this is true, our job should be to avoid reaching the cirrhotic stage, a stage when the risk of developing liver cancer may be hard to eliminate completely."
"We still have a lot of things to learn regarding the pathophysiology of hepatitis C," he said.
Liver Fibrosis Develops Early, Progresses Quickly After Hepatitis C Virus Seroconversion
By Will Boggs MD, December 14, 2014
Liver fibrosis develops early after hepatitis C virus (HCV) seroconversion and progresses quickly to cirrhosis in many patients, according to new findings.
"Within 10 years of HCV infection, about 18% have developed cirrhosis, and this is 3 times higher than controls," Dr. Adeel A. Butt from University of Pittsburgh School of Medicine in Pennsylvania told Reuters Health by email. "Most of this occurs within the first 5 years after infection."
Dr. Butt and colleagues used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) to identify 1,840 patients who seroconverted to HCV antibody and then to determine their rate of liver fibrosis progression, compared with 1,840 matched controls who remained HCV antibody-negative.
They plotted the FIB-4 score, which provides an estimation of the degree of liver fibrosis based on routinely obtained blood tests, over time. A FIB-4 score greater than 3.5 indicates cirrhosis.
FIB-4 score progression started early after seroconversion, was most pronounced within the first five years, and continued over a period of 11 years. Progression was consistently higher among HCV-positive patients than among HCV-negative patients, the researchers report in JAMA Internal Medicine, online December 8.
In the HCV-positive group, 18.4% of patients went on to develop cirrhosis, compared with only 6.1% in the HCV-negative group, and the HCV-positive patients had a significantly shorter time to development of liver cirrhosis.
By five years, more than 15% of HCV-positive patients had a diagnosis of cirrhosis, compared with less than 5% of HCV-negative controls.
Only 3.1% of patients in the HCV-positive group developed hepatic decompensation (compared with 1.4% of HCV-negative patients), but their time to first hepatic decompensation was significantly shorter than it was for HCV-negative patients. More than half of the hepatic decompensation events occurred within the first two years of diagnosis of cirrhosis.
Factors associated with a higher risk of cirrhosis among HCV-positive patients included increasing age, white race, hypertension, history of alcohol abuse or dependence, and anemia. Diabetes, hypertension, and anemia were associated with a higher risk of developing hepatic decompensation.
"Future studies should look at a risk prediction model to determine which characteristics most accurately predict future cirrhosis in a given individual," Dr. Butt said. "Contrary to popular thought, a significant proportion of hepatic decompensation occurs without prior diagnosis of cirrhosis. Hence careful follow-up and evaluation for hepatic decompensation should be carried out in all HCV-infected persons regardless of duration of infection and prior diagnosis of cirrhosis."
"If newer treatments demonstrate slowing or reversal of fibrosis progression and delaying development of cirrhosis, our data would suggest treating early in the course of infection," the authors conclude. "On the other hand, if the cirrhosis has already set in, treatment may be helpful in preventing hepatic decompensation in only a small number of those with cirrhosis, since the number who go on to develop this complication is small."
Dr. Marc G. Ghany from the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, addressed the ongoing debate of whom to treat for chronic HCV in a related editorial.
"All patients with chronic HCV infection should be considered candidates for therapy, and mild liver disease is not a reason to deny a patient therapy who otherwise qualifies for treatment," he told Reuters Health by email.
But treatment is expensive, with costs ranging from $66,000 for 12 weeks of treatment with simeprevir to $84,000 for 12 weeks of treatment with sofosbuvir.
"The hope is that with the approval of other regimens, competition will drive down costs," Dr. Ghany said. "It remains to be seen how much cheaper the drugs will become, but it is unlikely in the near future that costs will decrease to the point where we will be able to treat everyone who is infected with hepatitis C virus."
"We still have to identify the large number of people who are unaware of their diagnosis and get them into care, including counseling on measures to prevent transmission, disease progression, and treatment," he concluded.
"This kind of study should remind physicians about the importance of non-viral, modifiable factors of accelerated liver fibrosis progression," Dr. Francesco Negro from Geneva University Hospital in Switzerland, who has published extensively on HCV infection, told Reuters Health. "One may think that treating HCV with antivirals may be the end of the story, thus forgetting about the formidable impact of alcohol drinking, cannabis smoking, and the metabolic syndrome. The VA population is particularly vulnerable in this respect."
"That their progression seemed to slow down once the diagnosis of cirrhosis was made suggests (although other explanations may be possible) that these persons became aware of the severity of their liver disease and tried to adopt a healthier lifestyle," said Dr. Negro, who was not involved in the research. "If this is true, our job should be to avoid reaching the cirrhotic stage, a stage when the risk of developing liver cancer may be hard to eliminate completely."
"We still have a lot of things to learn regarding the pathophysiology of hepatitis C," he said.
Best Answer
Hey, I'm just a country boy.
But here is what the FDA wrote in the Abbvie 3 D HCV approval today;
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427530.htm
"Hepatitis C is a viral disease that causes inflammation of the liver that can lead to reduced liver function, liver failure or liver cancer. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take decades. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV, and without proper treatment, 15-30 percent of these people will go on to develop cirrhosis."
===============
It could be however that certain groups of HCV infected may have differing rates of fibrosis progression for a variety of reasons.
I just don't think a small study of a sub-group can be used to infer larger truths about entire populations.
And yes.....
It would seem that the FDA has not gotten the news yet as well.
Good news is that there are now two interferon free treatments available, and both have very very high cure rates.
Many of us will be cured in the next 5 years, and almost all of us are curable.
In spite of some disagreements I know that we all are on the same side; of getting people through their infection with the least amount of damage.
We may not agree on just how....
....but that makes for interesting discussion.
best,
willy
But here is what the FDA wrote in the Abbvie 3 D HCV approval today;
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427530.htm
"Hepatitis C is a viral disease that causes inflammation of the liver that can lead to reduced liver function, liver failure or liver cancer. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take decades. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV, and without proper treatment, 15-30 percent of these people will go on to develop cirrhosis."
===============
It could be however that certain groups of HCV infected may have differing rates of fibrosis progression for a variety of reasons.
I just don't think a small study of a sub-group can be used to infer larger truths about entire populations.
And yes.....
It would seem that the FDA has not gotten the news yet as well.
Good news is that there are now two interferon free treatments available, and both have very very high cure rates.
Many of us will be cured in the next 5 years, and almost all of us are curable.
In spite of some disagreements I know that we all are on the same side; of getting people through their infection with the least amount of damage.
We may not agree on just how....
....but that makes for interesting discussion.
best,
willy
Willy, I agree the controls are supposed to be normal and that might imply healthy. But these normal people are turning cirrhotic for some reason, and the only thing we know is that they are not infected with HCV.
Well, the article in Medscape was from Reuters Health, based on this paper: http://www.ncbi.nlm.nih.gov/pubmed/25485735 Liver Fibrosis Progression in Hepatitis C Virus Infection After Seroconversion
______________
Abstract
IMPORTANCE:
Knowing the rate of liver fibrosis progression in hepatitis C virus (HCV)-infected persons can help inform patients and providers (clinicians, medical institutions or organizations, and third-party payers) in making treatment decisions.
OBJECTIVE:
To determine the rate and factors associated with liver fibrosis progression and hepatic decompensation in persons after acquiring HCV infection.
DESIGN, SETTING, AND PARTICIPANTS:
Secondary data analysis of persons in the (ERCHIVES), a national Veterans Affairs (VA) database, between 2002 and 2012. Among 610 514 persons in ERCHIVES (half were HCV positive), we identified those with an initial negative and subsequent positive test result for HCV antibody and positive HCV RNA test result (HCV+). Controls had 2 negative HCV antibody test results (HCV-) in a comparable time frame and were matched 1:1 on age (in 5-year blocks), race, and sex. We excluded persons with human immunodeficiency virus, hepatitis B, less than 24 months of follow-up, hepatocellular carcinoma, and cirrhosis at baseline.
MAIN OUTCOMES AND MEASURES:
Progression of liver fibrosis as estimated by the Fibrosis-4 (FIB-4) index; development of cirrhosis, defined by a FIB-4 score greater than 3.5; and development of hepatic decompensation.
RESULTS:
The evaluable data set consisted of 1840 persons who were HCV+ and 1840 HCV- controls. The HCV+ persons were younger and had a lower mean (SD) body mass index (27.39 [5.51] vs 29.49 [6.16]; P < .001), a higher prevalence of alcohol and drug abuse and dependence diagnoses, and higher serum aminotransferase levels, but had a lower prevalence of diabetes and hypertension. Fibrosis progression started early after infection among HCV+ persons and tapered off after 5 years. A total of 452 cirrhosis and 85 hepatic decompensation events were recorded. After 10 years of follow-up, HCV+ persons were more likely to have a diagnosis of cirrhosis compared with HCV- controls (18.4% vs 6.1%). Nine years after diagnosis of cirrhosis, hepatic decompensation events were uncommon but had a higher rate in the HCV+ group (1.79% vs 0.33%).
CONCLUSIONS AND RELEVANCE:
Persons who seroconverted for HCV have a more rapid progression of liver fibrosis and accelerated time to development of cirrhosis after seroconversion compared with HCV- controls. Fibrosis progression occurs early after infection; however, hepatic decompensation is uncommon after diagnosis of cirrhosis.
___________________
So, here is what they did: They scanned the VA database that lists HCV-positive veterans and among 610, 514 people there, found 1,840 who seroconverted during 2002-2012 (in other words, who got infected in that time frame). They took their control group from the same database, from people who were still HCV-negative in the same time frame (presumably they became HCV-positive after 2012). From that second group they picked 1,840 people and matched them to the HCV-positive group by age, race and sex. They excluded people with HIV, hepatitis B, HCC, cirrhosis at baseline or less than 2 years of follow-up.
It does not say why liver fibrosis was progressing in HCV-negative group other than they were older, heavier and had a higher prevalence of diabetes and hypertension.
______________
Abstract
IMPORTANCE:
Knowing the rate of liver fibrosis progression in hepatitis C virus (HCV)-infected persons can help inform patients and providers (clinicians, medical institutions or organizations, and third-party payers) in making treatment decisions.
OBJECTIVE:
To determine the rate and factors associated with liver fibrosis progression and hepatic decompensation in persons after acquiring HCV infection.
DESIGN, SETTING, AND PARTICIPANTS:
Secondary data analysis of persons in the (ERCHIVES), a national Veterans Affairs (VA) database, between 2002 and 2012. Among 610 514 persons in ERCHIVES (half were HCV positive), we identified those with an initial negative and subsequent positive test result for HCV antibody and positive HCV RNA test result (HCV+). Controls had 2 negative HCV antibody test results (HCV-) in a comparable time frame and were matched 1:1 on age (in 5-year blocks), race, and sex. We excluded persons with human immunodeficiency virus, hepatitis B, less than 24 months of follow-up, hepatocellular carcinoma, and cirrhosis at baseline.
MAIN OUTCOMES AND MEASURES:
Progression of liver fibrosis as estimated by the Fibrosis-4 (FIB-4) index; development of cirrhosis, defined by a FIB-4 score greater than 3.5; and development of hepatic decompensation.
RESULTS:
The evaluable data set consisted of 1840 persons who were HCV+ and 1840 HCV- controls. The HCV+ persons were younger and had a lower mean (SD) body mass index (27.39 [5.51] vs 29.49 [6.16]; P < .001), a higher prevalence of alcohol and drug abuse and dependence diagnoses, and higher serum aminotransferase levels, but had a lower prevalence of diabetes and hypertension. Fibrosis progression started early after infection among HCV+ persons and tapered off after 5 years. A total of 452 cirrhosis and 85 hepatic decompensation events were recorded. After 10 years of follow-up, HCV+ persons were more likely to have a diagnosis of cirrhosis compared with HCV- controls (18.4% vs 6.1%). Nine years after diagnosis of cirrhosis, hepatic decompensation events were uncommon but had a higher rate in the HCV+ group (1.79% vs 0.33%).
CONCLUSIONS AND RELEVANCE:
Persons who seroconverted for HCV have a more rapid progression of liver fibrosis and accelerated time to development of cirrhosis after seroconversion compared with HCV- controls. Fibrosis progression occurs early after infection; however, hepatic decompensation is uncommon after diagnosis of cirrhosis.
___________________
So, here is what they did: They scanned the VA database that lists HCV-positive veterans and among 610, 514 people there, found 1,840 who seroconverted during 2002-2012 (in other words, who got infected in that time frame). They took their control group from the same database, from people who were still HCV-negative in the same time frame (presumably they became HCV-positive after 2012). From that second group they picked 1,840 people and matched them to the HCV-positive group by age, race and sex. They excluded people with HIV, hepatitis B, HCC, cirrhosis at baseline or less than 2 years of follow-up.
It does not say why liver fibrosis was progressing in HCV-negative group other than they were older, heavier and had a higher prevalence of diabetes and hypertension.
When you're right, you're right, but just maybe, they werre looking for support to treat earlier that heppers @ F3/4. If so, they got justification.
Oh, well. : -)
Oh, well. : -)
I honestly don't know how anything like this can even be published! It's as full of holes as Swiss cheese and as smelly as Roquefort.
Goes back to what I said about who did the study, what theyhought they were measuring, what their control group and test group patients and their histories were, etc! etc., etc., There are studies and then studies. Not all all done accurately or taking into account and allowing for all variables.
Example, Many many years ago when I was taking a statistics class, we read a study that flatly stated that Entry level Women wore much higher heels than upper management women. Well, duh!, No ajdustments for age, education, job requirements, etc. Any woman , and most men could have told them that and saved the cost of the study.
Example, Many many years ago when I was taking a statistics class, we read a study that flatly stated that Entry level Women wore much higher heels than upper management women. Well, duh!, No ajdustments for age, education, job requirements, etc. Any woman , and most men could have told them that and saved the cost of the study.
There's something here I'm not getting at all. The control group does not have the virus right? Or did they have it and achieve SVR? But then they would still have the antibodies and it says the control group is HCV antibody negative.
Why would any of the control group develop fibrosis/cirrhosis at all? Are there drinkers in the group? If so how come this is not mentioned? They talk about alcohol abuse in the HCV positive group, but not the control group. Also how do they know the exact time of seroconversion of the study group? Did they inoculate them or something? (I of course realize this is not the case)
It doesn't take a rocket scientist to figure that everyone with the virus should be treated and the sooner is better than later when irreversible damage has set in. This whole thing about only treating the sickest patients is just plain wrong, both scientifically and morally.
Why would any of the control group develop fibrosis/cirrhosis at all? Are there drinkers in the group? If so how come this is not mentioned? They talk about alcohol abuse in the HCV positive group, but not the control group. Also how do they know the exact time of seroconversion of the study group? Did they inoculate them or something? (I of course realize this is not the case)
It doesn't take a rocket scientist to figure that everyone with the virus should be treated and the sooner is better than later when irreversible damage has set in. This whole thing about only treating the sickest patients is just plain wrong, both scientifically and morally.
I don't buy it at all. First, how do they know when seroconversion occurs for each person in the group. Second, they are using a lesser accurate (blood test) to determine cirrhosis progress. Third, it seems like the VA is involved for God's sake.
"Fibrosis
"If left untreated, the inflamed liver will start to scar. As excess scar tissue grows, it replaces healthy liver tissue. This process is called fibrosis. (Scar tissue is a kind of fibrous tissue.)
Scar tissue cannot do the work that healthy liver tissue can. Moreover, scar tissue can keep blood from flowing through your liver. As more scar tissue builds up, your liver may not work as well as it once did. Or, the healthy part of your liver has to work harder to make up for the scarred part.
If your liver disease is diagnosed and treated successfully at this stage, there’s still a chance that your liver can heal itself over time."
There is a difference.
----------------------------------------
Worriedmom
" She went from late stage 3 to stage 0-1 in 5 years of successful treatment."
Late stage 3 would be what's called borderline or "early" so no surprise there was healing.
"If left untreated, the inflamed liver will start to scar. As excess scar tissue grows, it replaces healthy liver tissue. This process is called fibrosis. (Scar tissue is a kind of fibrous tissue.)
Scar tissue cannot do the work that healthy liver tissue can. Moreover, scar tissue can keep blood from flowing through your liver. As more scar tissue builds up, your liver may not work as well as it once did. Or, the healthy part of your liver has to work harder to make up for the scarred part.
If your liver disease is diagnosed and treated successfully at this stage, there’s still a chance that your liver can heal itself over time."
There is a difference.
----------------------------------------
Worriedmom
" She went from late stage 3 to stage 0-1 in 5 years of successful treatment."
Late stage 3 would be what's called borderline or "early" so no surprise there was healing.
I agree I think one should treat as soon as possible, with the new drugs. The only reason I think I had it for 30 years was because I was given an injection of a blood product back in 77, gama globulin. I was exposed to Hepatitis and the doctor thought it would help my immune system :)
Is there anyway to tell exactly how long someone has had hepatitis C? Because it my understanding is for the most part people don't know. Except maybe if from a documented blood transfusion where infection was proven.
Or a documented accident where the hepatitis C factor was known.
This watchful waiting after you find out you have hepatitis C seems like a gamble. There are so many variables in how fast hepatitis C can advance once your infected. Lifestyle, general health, your own chemistry could change how fast hepatitis C advances over the years. So a study of any kind is going to be difficult to show accurate results.
Do I think you should treat your hepatitis C as soon as you find out at any stage. Yes! The sooner the better.
Or a documented accident where the hepatitis C factor was known.
This watchful waiting after you find out you have hepatitis C seems like a gamble. There are so many variables in how fast hepatitis C can advance once your infected. Lifestyle, general health, your own chemistry could change how fast hepatitis C advances over the years. So a study of any kind is going to be difficult to show accurate results.
Do I think you should treat your hepatitis C as soon as you find out at any stage. Yes! The sooner the better.
Now the study Lynn just quoted, cited the limitations of comparasion/generalizibility, i.e., such as country, type of tx used (we ALL know how that affects outcomes) and, ithought this was special, named study sponsors. Good practice. The reader has more tools to evaluate the article.
Do sponsors affect results? Could be, as they would be looking for specific things as opposed to finding what you find on a wide net cast, fishing expedition. Could the results be the same in either case? Could be.
Do I think all heppers should be treated early, or late? YES, and the sooner, the quicker! There are many facets of health which could be affected by that. - a big one is that it calls the conditions/issues to the patient's attention in such a way that beneficial lifestyle changes are made, potentially affecting. the patient's whole health picture for the better.
It amazes me. at how many medical conditions could possibly be improved by consistently healthy lifestyle choices,HOWEVER, no matter how heathful one is, there are still many many things that ARE NOT the result of choice.
Sorry, off my soapbox, now.
Do sponsors affect results? Could be, as they would be looking for specific things as opposed to finding what you find on a wide net cast, fishing expedition. Could the results be the same in either case? Could be.
Do I think all heppers should be treated early, or late? YES, and the sooner, the quicker! There are many facets of health which could be affected by that. - a big one is that it calls the conditions/issues to the patient's attention in such a way that beneficial lifestyle changes are made, potentially affecting. the patient's whole health picture for the better.
It amazes me. at how many medical conditions could possibly be improved by consistently healthy lifestyle choices,HOWEVER, no matter how heathful one is, there are still many many things that ARE NOT the result of choice.
Sorry, off my soapbox, now.
The first article you reference is by one of the principle investigators in the HALT C study, Dr, Mitch Shiffman. At the time he was at MCV in Richmond, Va. I had a friend in that study and he let me hold her hand through her 5 year post treatment biopsy. She went from late stage 3 to stage 0-1 in 5 years of successful treatment. Dr. Shiffman had written a paper on HALT C that broke down his patients in to before treatment stage and 5 year SVR stage. 20% had complete reversal, 20% had no reversal and everyone else had improvement. This was a well run trial with 3000 patients. It would be interesting to know what those with no reversal or limited reversal, look like today, many years after SVR.
Also
http://hepatitiscnewdrugs.blogspot.com/2014/11/well-controlled-hepatitis-c-no-dent-on.html?m=1
Laurie Barclay, MD
November 12, 2014
Survival in patients with chronic hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis who achieved sustained virological response (SVR) is similar to that of the general population, according to a retrospective study published in the November 12 issue of JAMA. However, patients who did not achieve SVR had lower life expectancy than their peers.
"Among patients with chronic HCV infection and bridging fibrosis or cirrhosis, attaining SVR was associated with survival comparable with that of the general population, whereas not attaining SVR was associated with reduced survival," write Adriaan J. van der Meer, MD, PhD, from the Erasmus MC University Medical Center Rotterdam, the Netherlands, and colleagues.
Previous studies have shown that patients with chronic HCV infection have a reduced lifespan compared with the general population. However, patients with chronic HCV infection and advanced hepatic fibrosis and SVR have a lower all-cause mortality than patients without SVR. What has not been clear until now is whether those patients with SVR have a shorter life expectancy than the general population.
Therefore, the investigators used data from a previous study to compare overall survival in patients with chronic HCV infection with and without SVR with that in the general population in the Netherlands, matched for age-, sex-, and calendar time-specific death rates. The sample consisted of 530 consecutive patients with chronic HCV monoinfection and biopsy-proven advanced hepatic fibrosis (Ishak fibrosis scores of 4, 5, or 6) who began interferon-based antiviral treatment between 1990 and 2003 at one of five large hepatology units in Europe and Canada.
At 24 weeks after patients stopped antiviral therapy, they underwent testing for SVR, defined as blood sample being negative for HCV RNA. Median duration of follow-up was 8.4 years, median age was 48 years, and 70% were male.
Of 454 patients (86%) with complete follow-up, 192 achieved SVR, 13 of whom died. Cumulative 10-year overall survival in patients who achieved SVR was 91.1%, which did not differ significantly from that in the age- and sex-matched general population.
Among patients who did not achieve SVR, there were 100 deaths, yielding a cumulative 10-year survival of 74.0%, which was significantly lower than that in the age- and sex-matched general population (P < .001).
Limitations of this study include its retrospective design, restriction to general population data available only for the Netherlands, and receipt of interferon-based therapy by all patients, limiting generalizability to those with other treatment regimens.
"The excellent survival among patients with advanced liver disease and SVR might be explained by the associations between SVR and regression of hepatic inflammation and fibrosis, reduced hepatic venous pressure gradient, reduced occurrence of hepatocellular carcinoma and liver failure, as well as reduced occurrence of diabetes mellitus, end-stage renal disease, and cardiovascular events," the study authors write. "Even though patients with cirrhosis and SVR remain at risk for hepatocellular carcinoma, the annual hepatocellular carcinoma incidence is low and survival is substantially better compared with those without SVR. Competing risks could also contribute."
The Foundation for Liver and Gastrointestinal Research in Rotterdam, the Netherlands, funded this study. Some of the study authors reported various financial disclosures involving Merck Sharp & Dohme, Gilead, Roche, Abbott, Novartis, Bristol-Myers Squibb, Hoffmann-LaRoche, Tibotec, Vertex, Clinical Care Options, Bayer, Novartis, Transgene, Achillion, AstraZeneca, Boehringer Ingelheim, Santaris, Janssen, Idenix, Presidio, Anadys, and/or Medtronic.
JAMA. 2014;32:1927-1928. Abstract
http://hepatitiscnewdrugs.blogspot.com/2014/11/well-controlled-hepatitis-c-no-dent-on.html?m=1
Laurie Barclay, MD
November 12, 2014
Survival in patients with chronic hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis who achieved sustained virological response (SVR) is similar to that of the general population, according to a retrospective study published in the November 12 issue of JAMA. However, patients who did not achieve SVR had lower life expectancy than their peers.
"Among patients with chronic HCV infection and bridging fibrosis or cirrhosis, attaining SVR was associated with survival comparable with that of the general population, whereas not attaining SVR was associated with reduced survival," write Adriaan J. van der Meer, MD, PhD, from the Erasmus MC University Medical Center Rotterdam, the Netherlands, and colleagues.
Previous studies have shown that patients with chronic HCV infection have a reduced lifespan compared with the general population. However, patients with chronic HCV infection and advanced hepatic fibrosis and SVR have a lower all-cause mortality than patients without SVR. What has not been clear until now is whether those patients with SVR have a shorter life expectancy than the general population.
Therefore, the investigators used data from a previous study to compare overall survival in patients with chronic HCV infection with and without SVR with that in the general population in the Netherlands, matched for age-, sex-, and calendar time-specific death rates. The sample consisted of 530 consecutive patients with chronic HCV monoinfection and biopsy-proven advanced hepatic fibrosis (Ishak fibrosis scores of 4, 5, or 6) who began interferon-based antiviral treatment between 1990 and 2003 at one of five large hepatology units in Europe and Canada.
At 24 weeks after patients stopped antiviral therapy, they underwent testing for SVR, defined as blood sample being negative for HCV RNA. Median duration of follow-up was 8.4 years, median age was 48 years, and 70% were male.
Of 454 patients (86%) with complete follow-up, 192 achieved SVR, 13 of whom died. Cumulative 10-year overall survival in patients who achieved SVR was 91.1%, which did not differ significantly from that in the age- and sex-matched general population.
Among patients who did not achieve SVR, there were 100 deaths, yielding a cumulative 10-year survival of 74.0%, which was significantly lower than that in the age- and sex-matched general population (P < .001).
Limitations of this study include its retrospective design, restriction to general population data available only for the Netherlands, and receipt of interferon-based therapy by all patients, limiting generalizability to those with other treatment regimens.
"The excellent survival among patients with advanced liver disease and SVR might be explained by the associations between SVR and regression of hepatic inflammation and fibrosis, reduced hepatic venous pressure gradient, reduced occurrence of hepatocellular carcinoma and liver failure, as well as reduced occurrence of diabetes mellitus, end-stage renal disease, and cardiovascular events," the study authors write. "Even though patients with cirrhosis and SVR remain at risk for hepatocellular carcinoma, the annual hepatocellular carcinoma incidence is low and survival is substantially better compared with those without SVR. Competing risks could also contribute."
The Foundation for Liver and Gastrointestinal Research in Rotterdam, the Netherlands, funded this study. Some of the study authors reported various financial disclosures involving Merck Sharp & Dohme, Gilead, Roche, Abbott, Novartis, Bristol-Myers Squibb, Hoffmann-LaRoche, Tibotec, Vertex, Clinical Care Options, Bayer, Novartis, Transgene, Achillion, AstraZeneca, Boehringer Ingelheim, Santaris, Janssen, Idenix, Presidio, Anadys, and/or Medtronic.
JAMA. 2014;32:1927-1928. Abstract
And for another take on SVR and cirrhosis
http://www.healio.com/hepatology/hepatitis-c/news/print/hcv-next/%7B5d67c14e-d5f3-4e2b-9cc0-c2e235920ca3%7D/svr-after-therapy-reduced-inflammation-fibrosis-in-hcv-patients
SVR After Therapy Reduced Inflammation, Fibrosis in HCV Patients
Shiffman ML. Ann Hepatol. 2014;13:340-349.
HCV Next, November 2014
In a new study, patients with chronic hepatitis C virus infection who achieved a sustained virologic response with interferon-based therapy experienced decreases in inflammation and fibrosis scores vs. patients who did not undergo therapy or those who underwent therapy but did not achieve a sustained virologic response.
And further on in the article
“The future of HCV treatment is to suppress HCV with multiple oral antiviral agents without interferon and/or ribavirin,” the researchers wrote. “The observations of the present study strongly suggest that fibrosis regression, including resolution of cirrhosis, will occur in the vast majority of patients who will achieve SVR with these future therapies.”
I prefer my cup half full and anyway we will find out when we get there.
Or as they say "individual results may vary"
Best to all
http://www.healio.com/hepatology/hepatitis-c/news/print/hcv-next/%7B5d67c14e-d5f3-4e2b-9cc0-c2e235920ca3%7D/svr-after-therapy-reduced-inflammation-fibrosis-in-hcv-patients
SVR After Therapy Reduced Inflammation, Fibrosis in HCV Patients
Shiffman ML. Ann Hepatol. 2014;13:340-349.
HCV Next, November 2014
In a new study, patients with chronic hepatitis C virus infection who achieved a sustained virologic response with interferon-based therapy experienced decreases in inflammation and fibrosis scores vs. patients who did not undergo therapy or those who underwent therapy but did not achieve a sustained virologic response.
And further on in the article
“The future of HCV treatment is to suppress HCV with multiple oral antiviral agents without interferon and/or ribavirin,” the researchers wrote. “The observations of the present study strongly suggest that fibrosis regression, including resolution of cirrhosis, will occur in the vast majority of patients who will achieve SVR with these future therapies.”
I prefer my cup half full and anyway we will find out when we get there.
Or as they say "individual results may vary"
Best to all
This will sound like a very naive comment but I have always wondered why, since the liver is capable of regeneration, there are not attempts to remove parts of the liver that are not functioning well and somehow encourage the good bits to regenerate?
Perhaps I've been reading too many sic-fi novels?
Perhaps I've been reading too many sic-fi novels?
"I've read people describe their condition with ascites and HE and hospitalizations who live and move on to lead a normal life."
Don't disagree there. Many years ago even before Hep C was known I visited a friend in the hospital that was only 35. The person had have several bleed outs, was so bloated and yellow I didn't even recognize him. His parents told me the doctor said he wouldn't live 6 months. Well when he got out he went on using drugs and drinking and continued in and out of the hospital until he died at age 59. It was known then he had Hep C all those years. So your right , who knows?
Don't disagree there. Many years ago even before Hep C was known I visited a friend in the hospital that was only 35. The person had have several bleed outs, was so bloated and yellow I didn't even recognize him. His parents told me the doctor said he wouldn't live 6 months. Well when he got out he went on using drugs and drinking and continued in and out of the hospital until he died at age 59. It was known then he had Hep C all those years. So your right , who knows?
SVR is the first step.
Who knows CanDo?
I've read people describe their condition with ascites and HE and hospitalizations who live and move on to lead a normal life. The damage is done but take away that alcohol and amazing things happen. Take away that virus and why shouldn't amazing things be able to happen?
I agree the odds are terribly slim with decompensation but again, who knows?
Who knows CanDo?
I've read people describe their condition with ascites and HE and hospitalizations who live and move on to lead a normal life. The damage is done but take away that alcohol and amazing things happen. Take away that virus and why shouldn't amazing things be able to happen?
I agree the odds are terribly slim with decompensation but again, who knows?
American liver foundation.
Cirrhosis
But if left untreated, your liver may become so seriously scarred that it can no longer heal itself. This stage – when the damage cannot be reversed – is called cirrhosis.
Cirrhosis can lead to a number of complications, including liver cancer. In some people, the symptoms of cirrhosis may be the first signs of liver disease.
http://www.liverfoundation.org/abouttheliver/info/progression/
------------------------------------------------------------
Now there's a whole lot of difference between being borderline cirrhotic or very early cirrhotic where there is very little scar tissue compared to someone that cirrhosis has "set in". I have been SVR now for 5 years and my last fibroscan showed no improvement. Was my Hepatologist surprised? Not at all. When I asked him when will the scans for HCC stop or the upper GI's he said never.
Do I think one's liver can heal itself that has little scar tissue? Sure up to a point. The problem I have is when I read that someone who is decompensated thinking ones liver can heal to and almost brand new liver.
I'm sorry but I just cringe at the thought that even if you wait till you become cirrhotic treatment will solve all your problems once your SVR. All one needs to do is just look at the pictures of a healthy liver and one that is cirrhosis. I fully believe that those of us with cirrhosis that take care of the healthy part that is left can live a fairly normal life. Wishing you the very best. Maybe I'm wrong, sure wouldn't be the first time.:)
Cirrhosis
But if left untreated, your liver may become so seriously scarred that it can no longer heal itself. This stage – when the damage cannot be reversed – is called cirrhosis.
Cirrhosis can lead to a number of complications, including liver cancer. In some people, the symptoms of cirrhosis may be the first signs of liver disease.
http://www.liverfoundation.org/abouttheliver/info/progression/
------------------------------------------------------------
Now there's a whole lot of difference between being borderline cirrhotic or very early cirrhotic where there is very little scar tissue compared to someone that cirrhosis has "set in". I have been SVR now for 5 years and my last fibroscan showed no improvement. Was my Hepatologist surprised? Not at all. When I asked him when will the scans for HCC stop or the upper GI's he said never.
Do I think one's liver can heal itself that has little scar tissue? Sure up to a point. The problem I have is when I read that someone who is decompensated thinking ones liver can heal to and almost brand new liver.
I'm sorry but I just cringe at the thought that even if you wait till you become cirrhotic treatment will solve all your problems once your SVR. All one needs to do is just look at the pictures of a healthy liver and one that is cirrhosis. I fully believe that those of us with cirrhosis that take care of the healthy part that is left can live a fairly normal life. Wishing you the very best. Maybe I'm wrong, sure wouldn't be the first time.:)
When I said "small number", I meant in comparison to those without cirrhosis when it comes to deciding who should be given priority for treatment. I agree that the article is saying everyone should be treated, and think that was the main point of what they were trying to get across.
In order to drive the idea home that everyone should be treated they addressed why not only cirrhotics should be treated (they may decompensate regardless of getting rid of the hcv and die) but also why those more healthy should be treated (before they get cirrhosis, which can happen in only a few years). Since the guidelines give priority to cirrhotics and insurance goes by AASLD guidelines for those with Medicaid they needed to make the point that it might not be the best decision to give this group priority. And so they did.
Anyway the numbers are interesting. I had HCV for around 40 years before getting cirrhosis and I didn't exactly lead a pristine lifestyle during those years.
AWorriedMom
my understanding is the same as your's on the reversal of cirrhosis after getting rid of hcv. This is based on what my hepatologist has shared with me and on articles I've read in journals. And even if my doctor had not told me this and I had read no such articles, I would still insist on believing that cirrhosis can be reversed just because it gives me hope.
In order to drive the idea home that everyone should be treated they addressed why not only cirrhotics should be treated (they may decompensate regardless of getting rid of the hcv and die) but also why those more healthy should be treated (before they get cirrhosis, which can happen in only a few years). Since the guidelines give priority to cirrhotics and insurance goes by AASLD guidelines for those with Medicaid they needed to make the point that it might not be the best decision to give this group priority. And so they did.
Anyway the numbers are interesting. I had HCV for around 40 years before getting cirrhosis and I didn't exactly lead a pristine lifestyle during those years.
AWorriedMom
my understanding is the same as your's on the reversal of cirrhosis after getting rid of hcv. This is based on what my hepatologist has shared with me and on articles I've read in journals. And even if my doctor had not told me this and I had read no such articles, I would still insist on believing that cirrhosis can be reversed just because it gives me hope.
Let me know if you think this describes normal walk of life people;
(from the quoted study)
"By five years, more than 15% of HCV-positive patients had a diagnosis of cirrhosis, compared with less than 5% of HCV-negative controls. "
================================================
Good God, the people in the controls group (5%) without HCV are progressing to cirrhosis in 5 years!!! Does this strike you as normal, typical? Is it *possible* that veteran sub-groups of HCV infected have different fibrosis advancement outcomes? Hmmm?
I read that 30% of gulf war vets have contemplated suicide, and more have died from suicide (22 each day die) than were killed in combat. There is a very high rate of PTSD, but you assert they progress at the same rate as the aggregate of HCV infected. I question if this is factual.
I scored cirrhotic in two fibrotests, done roughly 8 months apart, then an APRI test (AST to Platelet Ratio Index) also indicated cirrhosis.
My biopsy, done at a large facility by a top liver guy showed stage 2
That is 3 out of 3 misses, and since you have read in forums you know better than to trust a blood test to diagnose cirrhosis. I've seen them be off more than mine was.....right here in this forum.
Show me that they achieved their data using liver biopsy, then I may believe you and the weak study.
Where is the proof of your assertion that veterans groups have the same rate progression to cirrhosis as the HCV infected aggregate?
The study that didn't confirm cirrhosis with biopsy? : )
The majority of the world is still using interferon to treat HCV.
Hepatologists have been warehousing HCV patients, waiting for better treatments *as they get approved* , each time treatment TX improvements occur. That's what is happening in the real world with real doctors.
=================
Regarding cirrhosis reversing itself
I believe Andiamo was cirrhotic and has improved, and I have two former cirrhotic other friends whose fibrosis has improved.
http://journals.lww.com/jpgn/Fulltext/2007/04000/Reversal_of_Liver_Cirrhosis__A_Desirable_Clinical.1.aspx
(from the quoted study)
"By five years, more than 15% of HCV-positive patients had a diagnosis of cirrhosis, compared with less than 5% of HCV-negative controls. "
================================================
Good God, the people in the controls group (5%) without HCV are progressing to cirrhosis in 5 years!!! Does this strike you as normal, typical? Is it *possible* that veteran sub-groups of HCV infected have different fibrosis advancement outcomes? Hmmm?
I read that 30% of gulf war vets have contemplated suicide, and more have died from suicide (22 each day die) than were killed in combat. There is a very high rate of PTSD, but you assert they progress at the same rate as the aggregate of HCV infected. I question if this is factual.
I scored cirrhotic in two fibrotests, done roughly 8 months apart, then an APRI test (AST to Platelet Ratio Index) also indicated cirrhosis.
My biopsy, done at a large facility by a top liver guy showed stage 2
That is 3 out of 3 misses, and since you have read in forums you know better than to trust a blood test to diagnose cirrhosis. I've seen them be off more than mine was.....right here in this forum.
Show me that they achieved their data using liver biopsy, then I may believe you and the weak study.
Where is the proof of your assertion that veterans groups have the same rate progression to cirrhosis as the HCV infected aggregate?
The study that didn't confirm cirrhosis with biopsy? : )
The majority of the world is still using interferon to treat HCV.
Hepatologists have been warehousing HCV patients, waiting for better treatments *as they get approved* , each time treatment TX improvements occur. That's what is happening in the real world with real doctors.
=================
Regarding cirrhosis reversing itself
I believe Andiamo was cirrhotic and has improved, and I have two former cirrhotic other friends whose fibrosis has improved.
http://journals.lww.com/jpgn/Fulltext/2007/04000/Reversal_of_Liver_Cirrhosis__A_Desirable_Clinical.1.aspx
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Being cirrhotic this really jumped out at me.
"On the other hand, if the cirrhosis has already set in, treatment may be helpful in preventing hepatic decompensation in only a small number of those with cirrhosis, since the number who go on to develop this complication is small."
Not only is he saying its still possible to go on to decompensation but not a damn word on reversing cirrhosis. Which I already knew.