Acknowledgments Imatinib Mesylate Many thanks are addressed to Dr. Lukas G. Adiossan, Mr. Yao N��Guessan, Ms. Sarah E. Mara, and all the technicians and drivers for their skillful work in the field and the laboratory. Furthermore, we are indebted to the entire Taabo health demographic surveillance system team for their excellent cooperation. Finally, we are deeply grateful for the inhabitants of the selected villages and hamlets for their enthusiastic participation. Funding Statement This study received financial support from the UBS Optimus Foundation. J��rg Utzinger and Giovanna Raso acknowledge financial support from the Swiss National Science Foundation (project no. IZ70Z0_123900 and project no. 32003B_132949/1). Thomas Schmidlin acknowledges financial support from the Swiss Tropical and Public Health Institute (Teaching & Training).
The funders had no role in study design, data collection and analysis, decision to publ
liver fibrosis has long been considered static and irreversible. However, case reports and small cohort studies suggest potential reversibility of liver fibrosis once the pathological trigger is eliminated. Moreover, larger therapeutic studies in patients with chronic hepatitis B or C that were successfully treated with antivirals such as lamivudine and interferon-��, respectively, suggest reversal even in patients with cirrhosis (17, 43). However, these studies have limitations because of biopsy sampling error or small numbers of patients, and the statement that advanced fibrosis (cirrhosis) may reverse has been criticized as premature (11).
Despite the controversies, remarkable progress has been made in the last decade in our understanding of the dynamic nature of liver fibrosis (16, 21, 43), which results from an imbalance of extracellular matrix (ECM) production (fibrogenesis) and its degradation (fibrolysis). Reversibility of liver fibrosis in small rodents is well established (21) although it appears to depend significantly on the degree of preestablished fibrosis and on the particular model. Thus we and others (35) have shown that, despite normalization of profibrogenic gene expression and significant improvement of hepatic architecture and function, collagen content remains unchanged up to 8 wk after toxin withdrawal in thioacetamide (TAA)-induced fibrosis. This contrasts with significant reversal reported in the CCl4 model (22) though reversibility is limited in advanced fibrosis/cirrhosis, possibly attributable to matrix crosslinking (24). In earlier studies, reversibility of secondary biliary fibrosis Batimastat after restoration of bile flow ranged from complete reversal (1) to improvement in liver architecture and function without significant reduction in collagen content (2).