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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
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.:)
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?
"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?
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?
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
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
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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.