The first question most of us ask before starting treatment is :
Will treatment reverse my liver damage ?
,
This study isn't new but it answers a lot of questions for anyone who is treating with cirrhosis. If you take the time to look it over make sure you read the comment following the study.
News > 2009 > April /
Cirrhosis Regression in Chronic Hepatitis C: An Old Tale With a New Ending
Journal of Gastroenterology
Regression of liver fibrosis and cirrhosis has been a main topic of research and discussion in the community of liver experts for decades. Scar formation in the liver has long been considered a unidirectional pathway and regression or reversibility of fibrosis has been perceived to be not much more than a myth. However, recent data have convincingly demonstrated the occurrence of fibrosis regression in a wide spectrum of chronic liver diseases, including viral, metabolic, autoimmune, and cholestatic diseases. Still, whether this holds true also for the extreme degree of fibrosis, namely, cirrhosis, is somewhat less clear, especially in patients with chronic hepatitis C, where the long-term histologic benefit of interferon (IFN)-based therapies is still debated.
To address this issue, Mallet et al studied 96 patients with chronic hepatitis C virus (HCV) infection and biopsy-proven cirrhosis (Child-Pugh class A) followed at a single hepatology unit, who underwent antiviral treatment with an IFN-based regimen and had at least 1 posttreatment liver biopsy. The primary aim of the study was to evaluate the effect of regression of cirrhosis on a composite end point of liver-related complications (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma [HCC], livertransplantation), and death from liver-related causes. Regression of cirrhosis was defined as a decrease in the Metavir fibrosis staging system of at least 2 points, that is, from 4 Metavir fibrosis units (evidence of cirrhosis) to 2 units (evidence of few septa), on a posttreatment liver biopsy performed a median of 17 months after the end of antiviral treatment. This cutoff was chosen to avoid a sampling error bias, which accounts for differences in staging score of at least 1 point in up to 20% of cases when liver biopsies are performed in both liver lobes (Am J Gastroenterol 2002;97:2614–2618). . for a median of 118 months, 39 (41%) patients achieved a sustained virologic response (SVR) to IFN-based therapies and remained persistently HCV RNA negative.
.
When analyzing the histologic outcome, 18 patients (19%) were classified as having cirrhosis regression since the Metavir staging score was F2 or less at the second liver biopsy, whereas 69 (72%) still had F4 Metavir stage and 9 (9%) had F3. Of the 18 patients with cirrhosis regression, 17 (94%) had had a SVR, and 1 patient had a biochemical response, defined as normal liver function tests and no detectable activity on liver biopsy, but persistence of HCV viremia. When comparing the baseline characteristics of patients with or without regression of cirrhosis, lower AST values and higher platelet count were associated with regression of cirrhosis. When analyzing response to therapy, SVR also emerged as being correlated with cirrhosis regression. Interestingly, though, not all patients with a SVR achieved cirrhosis regression; 18 (51%) still had F4 (evidence of cirrhosis) or F3 (evidence of many septa) Metavir scores at the posttreatment liver biopsy. , Moreover, although patients with cirrhosis regression did not experience any liver-related complications during follow-up, the same was not true for SVR patients. In fact, although a significantly lower incidence of liver -related death or transplantation, ascites, and encephalopathy was observed in SVR patients compared with patients who did not achieve viral eradication, no benefit was shown in terms of development of HCC or variceal bleeding. Overall, 4 ,patients with a SVR (11%), developed a liver-related event, including variceal bleeding (1 patient) and HCC (3 patients). Interestingly, all 4 of these patients had serum anti-hepatitis B core antigen antibodies. The incidence of cirrhosis-related complications per 100 patients was 1.14 in patients with a SVR versus 4.63 in those without (P = .009); respective values in patients with and without regression of cirrhosis were 0 and 4 (P = .002).
The authors conclude that in hepatitis C-related cirrhosis, sustained suppression of necroinflammation, more frequent in SVR patients than in non-SVR patients may result in regression of cirrhosis and a reduced risk of cirrhosis-related complications.
Comment
Chronic hepatitis C is a major health problem with an estimated prevalence of 1.6%–2% worldwide (Ann Intern Med 2006;144:705–714; J Hepatol 2008;48:148–162). In Europe, more than 9 million chronic carriers and approximately 86,000 deaths per year owing to the late complications of HCV are estimated (J Hepatol 2007;46:827–839). In Southern and Eastern Europe, hepatitis C was spread in the general population mainly through iatrogenic transmission of the virus, which peaked in the 1960s. In Northern Europe, where the virus has been predominantly spread by parenteral risk factors, the infection clusters primarily among injection drug users, HIV patients, prisoners, and immigrants from endemic regions (Semin Liver Dis 2000;20:1–16). Hepatitis C has also an important socioeconomic impact, because the most affected age groups are 25- to 45-year-olds followed by 15- to 24-year-olds (J Hepatol 2007;47:608–617). The prognosis of chronic hepatitis C depends on the rate of fibrosis progression that, over a 20- to 30-year time span, may determine the risk of developing cirrhosis and its complications, namely HCC, liver decompensation, hepatic encephalopathy, and esophageal variceal bleeding (NIH Consens State Sci Statements 2002;19:1–46; Hepatology 2002;36[suppl 1]:S35–S46). Despite the identification of several cofactors, such as viral coinfections and comorbidities, that accelerate the course of chronic hepatitis C (Gastroenterology 2008;134:1699–1714), the only therapeutic measure able to halt this progressive process is HCV reradication by IFN-based therapies. HCV clearance benefits both patients with chronic hepatitis C, by preventing the progression to cirrhosis (Gastroenterology 2002;122:1303–1313), as well as those with established cirrhosis, by effectively reducing the risk of liver-related complications (Hepatology 2007;45:579–587). Still, this risk is not completely negated, and liver-related complications will eventually occur in cirrhotic patients with a SVR, although at a lower rate compared with non-SVR patients. The paper by Mallet et al adds nicely to these findings; it demonstrates that cirrhosis regression, more than SVR, is the main determinant of outcome in patients with chronic hepatitis C. In fact, patients with cirrhosis regression (94% of them had a SVR) did not develop any liver-related complication during a median follow-up of 123 months, in contrast with 4 SVR patients who did not have cirrhosis regression and did develop liver complications. Interestingly, as noted by the authors, all 4 of these patients had hepatitis B core antigen antibodies (anti-HBc), thus refreshing an old dispute about the potential negative role of occult HBV infection on the outcome of anti-HCVtherapy (Lancet 1998;351:1535–1539; Ann Intern Med 2007;146:649–656). However, whether occult HBV infection plays such a clinically important role in HCV patients is still unclear, whereas more convincing data exist that past exposure to hepatitis B virus can actually modify the natural history of chronic hepatitis C patients independently on anti HCV therapy (J Hepatol 2008;49:652–657).
The paper by Mallet et al effectively questions us clinicians as to whether cirrhosis regression, rather than SVR, should be the goal of antiviral therapy in hepatitis C–infected patients with established cirrhosis. The evidence that cirrhosis actually does regress when SVR is achieved is mounting; since the pivotal study by Shiratori et al (Ann Intern Med 2000;132:517–524), at least 2 other studies have convincingly demonstrated cirrhosis regression after HCV eradication (Hepatology 2004;39:333–342; Gastroenterology 2008;135:821–829). These findings are easier to digest now that we have established the essential mechanisms behind this phenomenon. Hepatic stellate cells activity and tissue inhibitors of matrix metalloproteinases have emerged as the key players in fibrosis production and degradation (Hepatology 2006;43[suppl 1]:S82–S88). Unfortunately, we still lack the ability to understand which patients with chronic hepatitis C will eventually revert to earlier stages of fibrosis. In fact, only a minority (<40%)> Mallet V, Gilgenkrantz H, Serpaggi J, et al. (Université Paris Descartes; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, INSERM U 567, Paris, France). Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med 2008;149:399–403 .
http://www.hepctrust.org.uk/news/2009/April/Cirrhosis+Regression+in+Chronic+Hepatitis+C+An+Old+Tale+With+a+New+Ending
Will treatment reverse my liver damage ?
,
This study isn't new but it answers a lot of questions for anyone who is treating with cirrhosis. If you take the time to look it over make sure you read the comment following the study.
News > 2009 > April /
Cirrhosis Regression in Chronic Hepatitis C: An Old Tale With a New Ending
Journal of Gastroenterology
Regression of liver fibrosis and cirrhosis has been a main topic of research and discussion in the community of liver experts for decades. Scar formation in the liver has long been considered a unidirectional pathway and regression or reversibility of fibrosis has been perceived to be not much more than a myth. However, recent data have convincingly demonstrated the occurrence of fibrosis regression in a wide spectrum of chronic liver diseases, including viral, metabolic, autoimmune, and cholestatic diseases. Still, whether this holds true also for the extreme degree of fibrosis, namely, cirrhosis, is somewhat less clear, especially in patients with chronic hepatitis C, where the long-term histologic benefit of interferon (IFN)-based therapies is still debated.
To address this issue, Mallet et al studied 96 patients with chronic hepatitis C virus (HCV) infection and biopsy-proven cirrhosis (Child-Pugh class A) followed at a single hepatology unit, who underwent antiviral treatment with an IFN-based regimen and had at least 1 posttreatment liver biopsy. The primary aim of the study was to evaluate the effect of regression of cirrhosis on a composite end point of liver-related complications (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma [HCC], livertransplantation), and death from liver-related causes. Regression of cirrhosis was defined as a decrease in the Metavir fibrosis staging system of at least 2 points, that is, from 4 Metavir fibrosis units (evidence of cirrhosis) to 2 units (evidence of few septa), on a posttreatment liver biopsy performed a median of 17 months after the end of antiviral treatment. This cutoff was chosen to avoid a sampling error bias, which accounts for differences in staging score of at least 1 point in up to 20% of cases when liver biopsies are performed in both liver lobes (Am J Gastroenterol 2002;97:2614–2618). . for a median of 118 months, 39 (41%) patients achieved a sustained virologic response (SVR) to IFN-based therapies and remained persistently HCV RNA negative.
.
When analyzing the histologic outcome, 18 patients (19%) were classified as having cirrhosis regression since the Metavir staging score was F2 or less at the second liver biopsy, whereas 69 (72%) still had F4 Metavir stage and 9 (9%) had F3. Of the 18 patients with cirrhosis regression, 17 (94%) had had a SVR, and 1 patient had a biochemical response, defined as normal liver function tests and no detectable activity on liver biopsy, but persistence of HCV viremia. When comparing the baseline characteristics of patients with or without regression of cirrhosis, lower AST values and higher platelet count were associated with regression of cirrhosis. When analyzing response to therapy, SVR also emerged as being correlated with cirrhosis regression. Interestingly, though, not all patients with a SVR achieved cirrhosis regression; 18 (51%) still had F4 (evidence of cirrhosis) or F3 (evidence of many septa) Metavir scores at the posttreatment liver biopsy. , Moreover, although patients with cirrhosis regression did not experience any liver-related complications during follow-up, the same was not true for SVR patients. In fact, although a significantly lower incidence of liver -related death or transplantation, ascites, and encephalopathy was observed in SVR patients compared with patients who did not achieve viral eradication, no benefit was shown in terms of development of HCC or variceal bleeding. Overall, 4 ,patients with a SVR (11%), developed a liver-related event, including variceal bleeding (1 patient) and HCC (3 patients). Interestingly, all 4 of these patients had serum anti-hepatitis B core antigen antibodies. The incidence of cirrhosis-related complications per 100 patients was 1.14 in patients with a SVR versus 4.63 in those without (P = .009); respective values in patients with and without regression of cirrhosis were 0 and 4 (P = .002).
The authors conclude that in hepatitis C-related cirrhosis, sustained suppression of necroinflammation, more frequent in SVR patients than in non-SVR patients may result in regression of cirrhosis and a reduced risk of cirrhosis-related complications.
Comment
Chronic hepatitis C is a major health problem with an estimated prevalence of 1.6%–2% worldwide (Ann Intern Med 2006;144:705–714; J Hepatol 2008;48:148–162). In Europe, more than 9 million chronic carriers and approximately 86,000 deaths per year owing to the late complications of HCV are estimated (J Hepatol 2007;46:827–839). In Southern and Eastern Europe, hepatitis C was spread in the general population mainly through iatrogenic transmission of the virus, which peaked in the 1960s. In Northern Europe, where the virus has been predominantly spread by parenteral risk factors, the infection clusters primarily among injection drug users, HIV patients, prisoners, and immigrants from endemic regions (Semin Liver Dis 2000;20:1–16). Hepatitis C has also an important socioeconomic impact, because the most affected age groups are 25- to 45-year-olds followed by 15- to 24-year-olds (J Hepatol 2007;47:608–617). The prognosis of chronic hepatitis C depends on the rate of fibrosis progression that, over a 20- to 30-year time span, may determine the risk of developing cirrhosis and its complications, namely HCC, liver decompensation, hepatic encephalopathy, and esophageal variceal bleeding (NIH Consens State Sci Statements 2002;19:1–46; Hepatology 2002;36[suppl 1]:S35–S46). Despite the identification of several cofactors, such as viral coinfections and comorbidities, that accelerate the course of chronic hepatitis C (Gastroenterology 2008;134:1699–1714), the only therapeutic measure able to halt this progressive process is HCV reradication by IFN-based therapies. HCV clearance benefits both patients with chronic hepatitis C, by preventing the progression to cirrhosis (Gastroenterology 2002;122:1303–1313), as well as those with established cirrhosis, by effectively reducing the risk of liver-related complications (Hepatology 2007;45:579–587). Still, this risk is not completely negated, and liver-related complications will eventually occur in cirrhotic patients with a SVR, although at a lower rate compared with non-SVR patients. The paper by Mallet et al adds nicely to these findings; it demonstrates that cirrhosis regression, more than SVR, is the main determinant of outcome in patients with chronic hepatitis C. In fact, patients with cirrhosis regression (94% of them had a SVR) did not develop any liver-related complication during a median follow-up of 123 months, in contrast with 4 SVR patients who did not have cirrhosis regression and did develop liver complications. Interestingly, as noted by the authors, all 4 of these patients had hepatitis B core antigen antibodies (anti-HBc), thus refreshing an old dispute about the potential negative role of occult HBV infection on the outcome of anti-HCVtherapy (Lancet 1998;351:1535–1539; Ann Intern Med 2007;146:649–656). However, whether occult HBV infection plays such a clinically important role in HCV patients is still unclear, whereas more convincing data exist that past exposure to hepatitis B virus can actually modify the natural history of chronic hepatitis C patients independently on anti HCV therapy (J Hepatol 2008;49:652–657).
The paper by Mallet et al effectively questions us clinicians as to whether cirrhosis regression, rather than SVR, should be the goal of antiviral therapy in hepatitis C–infected patients with established cirrhosis. The evidence that cirrhosis actually does regress when SVR is achieved is mounting; since the pivotal study by Shiratori et al (Ann Intern Med 2000;132:517–524), at least 2 other studies have convincingly demonstrated cirrhosis regression after HCV eradication (Hepatology 2004;39:333–342; Gastroenterology 2008;135:821–829). These findings are easier to digest now that we have established the essential mechanisms behind this phenomenon. Hepatic stellate cells activity and tissue inhibitors of matrix metalloproteinases have emerged as the key players in fibrosis production and degradation (Hepatology 2006;43[suppl 1]:S82–S88). Unfortunately, we still lack the ability to understand which patients with chronic hepatitis C will eventually revert to earlier stages of fibrosis. In fact, only a minority (<40%)> Mallet V, Gilgenkrantz H, Serpaggi J, et al. (Université Paris Descartes; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, INSERM U 567, Paris, France). Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med 2008;149:399–403 .
http://www.hepctrust.org.uk/news/2009/April/Cirrhosis+Regression+in+Chronic+Hepatitis+C+An+Old+Tale+With+a+New+Ending