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• W4239697798 abstract "We thank Drs. Desmet and Roskams for their comments on this optimistic subject, and we recognize their important publications in this field. This subject was also well discussed recently by Bonis et al.1Bonis P.A. Friedman S.L. Kaplan M.M. Is liver fibrosis reversible?.N Engl J Med. 2001; 344: 452-454Crossref PubMed Scopus (145) Google Scholar commenting on a nice description of improvement of cirrhosis (disappearance?) in secondary biliary cirrhosis.2Hammel P. Couvelard A. O’Toole D. et al.Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct.N Engl J Med. 2001; 344: 418-423Crossref PubMed Scopus (362) Google Scholar We agree that there is no single perfect term to define the improvement of cirrhosis. As a matter of fact we were very prudent and never emphatically stated that treatment can result in a “complete cirrhosis regression.” The proposal of Desmet and Roskams remains ambiguous: “cirrhosis can regress to variable extent, ... but true cirrhosis remains irreversible to variable extent.”The pathologist of the study, Zach Goodman, applied the METAVIR criteria. From this methodology and as we discussed in the article we used a simple histological end point with its limitations as discussed. It has its limits like another scoring system but was validated for interobserver variation. Of course skilled pathologists as Dr Desmet or Dr Goodman are used to presuming or suspecting cirrhosis in a fragmented small biopsy with many septa.Because of the limitations of intercostal liver biopsy, sampling error and discordance between pathologists, the recent development of biochemical markers may also be useful for the observation of cirrhosis improvement.3Imbert-Bismut F. Ratziu V. Laurence Pieroni L. Charlotte F. Benhamou Y. Poynard T. MULTIVIRC groupBiochemical markers of liver fibrosis in patients with hepatitis C virus infection a prospective study.Lancet. 2001; 357: 1069-1075Abstract Full Text Full Text PDF PubMed Scopus (1267) Google Scholar Among one multicenter study of patients treated 48 weeks with PEG-Interferon and Ribavirin versus Interferon and Ribavirin4Manns M.P. McHutchison J.G. Gordon S.C. et al.PEG-Interferon alfa-2b in combination with ribavirin compared to interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C.Lancet. 2001; 358: 958-965Abstract Full Text Full Text PDF PubMed Scopus (5869) Google Scholar we measured the FibroTest and ActiTest in 352 patients, before treatment at baseline and 24 weeks after the end of the treatment.5Poynard T. McHutchison J. Manns M. Myers R.P. Albreht J. Biochemical markers as surrogate markers of liver fibrosis and activity in patients infected by hepatitis C virus an example in a randomized trial of pegylated-interferon alfa-2b and ribavirin combination.Hepatology. 2002; 36 (abstr): 351AGoogle Scholar Among these patients 32 had cirrhosis at baseline. For 15 patients stage remains F4 and the Fibrotest did not significantly changed (0.67 ± 0.05 vs. 0.64 ± 0.05). For 17 patients there was at least one fibrosis stage improvement. These patients had a very significant Fibrotest improvement (Wilcoxon signed-rank test Z value = 3.58; P < 0.0001) from 0.68 to 0.44 for 3 stages improvement, 0.60 to 0.47 for 2 stages improvement and from 0.61 to 0.56 for one stage improvement.One clinical proof of cirrhosis improvement, unexpected years ago, is the reversal (disappearance) of cirrhosis and its clinical complications by medical treatment. In hepatitis B nucleoside treatment are associated both with cirrhosis improvement6Dienstag J.L. Goldin R.D. Healthcote E.J. Hann H.W.L. Woessner M. Stephenson S.L. Gardner S. Gray D.F. Schiff E. Histological outcome during long-term lamivudine therapy.Gastroenterology. 2003; 124: 105-117Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar and with disappearance of encephalopathy, jaundice, and ascites.7Yao F.Y. Terrault N.A. Freise C. Maslow L. Bass N.M. Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation a comparative study using a matched, untreated cohort.Hepatology. 2001; 34: 411-416Crossref PubMed Scopus (248) Google Scholar As such, whilst there are discrepancies and disagreements over nomenclature and terminology as pointed out by Dr. Desmet and colleagues, we believe that our findings are important, real and require further confirmation in subsequent treatment studies in hepatitis C infection and other liver diseases. We thank Drs. Desmet and Roskams for their comments on this optimistic subject, and we recognize their important publications in this field. This subject was also well discussed recently by Bonis et al.1Bonis P.A. Friedman S.L. Kaplan M.M. Is liver fibrosis reversible?.N Engl J Med. 2001; 344: 452-454Crossref PubMed Scopus (145) Google Scholar commenting on a nice description of improvement of cirrhosis (disappearance?) in secondary biliary cirrhosis.2Hammel P. Couvelard A. O’Toole D. et al.Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct.N Engl J Med. 2001; 344: 418-423Crossref PubMed Scopus (362) Google Scholar We agree that there is no single perfect term to define the improvement of cirrhosis. As a matter of fact we were very prudent and never emphatically stated that treatment can result in a “complete cirrhosis regression.” The proposal of Desmet and Roskams remains ambiguous: “cirrhosis can regress to variable extent, ... but true cirrhosis remains irreversible to variable extent.” The pathologist of the study, Zach Goodman, applied the METAVIR criteria. From this methodology and as we discussed in the article we used a simple histological end point with its limitations as discussed. It has its limits like another scoring system but was validated for interobserver variation. Of course skilled pathologists as Dr Desmet or Dr Goodman are used to presuming or suspecting cirrhosis in a fragmented small biopsy with many septa. Because of the limitations of intercostal liver biopsy, sampling error and discordance between pathologists, the recent development of biochemical markers may also be useful for the observation of cirrhosis improvement.3Imbert-Bismut F. Ratziu V. Laurence Pieroni L. Charlotte F. Benhamou Y. Poynard T. MULTIVIRC groupBiochemical markers of liver fibrosis in patients with hepatitis C virus infection a prospective study.Lancet. 2001; 357: 1069-1075Abstract Full Text Full Text PDF PubMed Scopus (1267) Google Scholar Among one multicenter study of patients treated 48 weeks with PEG-Interferon and Ribavirin versus Interferon and Ribavirin4Manns M.P. McHutchison J.G. Gordon S.C. et al.PEG-Interferon alfa-2b in combination with ribavirin compared to interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C.Lancet. 2001; 358: 958-965Abstract Full Text Full Text PDF PubMed Scopus (5869) Google Scholar we measured the FibroTest and ActiTest in 352 patients, before treatment at baseline and 24 weeks after the end of the treatment.5Poynard T. McHutchison J. Manns M. Myers R.P. Albreht J. Biochemical markers as surrogate markers of liver fibrosis and activity in patients infected by hepatitis C virus an example in a randomized trial of pegylated-interferon alfa-2b and ribavirin combination.Hepatology. 2002; 36 (abstr): 351AGoogle Scholar Among these patients 32 had cirrhosis at baseline. For 15 patients stage remains F4 and the Fibrotest did not significantly changed (0.67 ± 0.05 vs. 0.64 ± 0.05). For 17 patients there was at least one fibrosis stage improvement. These patients had a very significant Fibrotest improvement (Wilcoxon signed-rank test Z value = 3.58; P < 0.0001) from 0.68 to 0.44 for 3 stages improvement, 0.60 to 0.47 for 2 stages improvement and from 0.61 to 0.56 for one stage improvement. One clinical proof of cirrhosis improvement, unexpected years ago, is the reversal (disappearance) of cirrhosis and its clinical complications by medical treatment. In hepatitis B nucleoside treatment are associated both with cirrhosis improvement6Dienstag J.L. Goldin R.D. Healthcote E.J. Hann H.W.L. Woessner M. Stephenson S.L. Gardner S. Gray D.F. Schiff E. Histological outcome during long-term lamivudine therapy.Gastroenterology. 2003; 124: 105-117Abstract Full Text Full Text PDF PubMed Scopus (668) Google Scholar and with disappearance of encephalopathy, jaundice, and ascites.7Yao F.Y. Terrault N.A. Freise C. Maslow L. Bass N.M. Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation a comparative study using a matched, untreated cohort.Hepatology. 2001; 34: 411-416Crossref PubMed Scopus (248) Google Scholar As such, whilst there are discrepancies and disagreements over nomenclature and terminology as pointed out by Dr. Desmet and colleagues, we believe that our findings are important, real and require further confirmation in subsequent treatment studies in hepatitis C infection and other liver diseases." @default.
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