The current study was undertaken to assess whether fibrosis could regress under venesection therapy in patients with C282Y homozygous genetic hemochromatosis. The 36 patients studied were recruited from a subfile of our database consisting of 125 C282Y homozygotes with either severe fibrosis or cirrhosis (F3 or F4 fibrosis stage, respectively, according to the METAVIR grading system). The second liver biopsy was performed for management of liver cancer, extrahepatic surgery, or assessment of liver fibrosis. All paired biopsies were reviewed by two pathologists without knowledge of clinical data. Among the 13 patients who had F3 fibrosis on their initial liver biopsy, 3 had F0, 6 had F1, and 2 had F2 on their second liver biopsy. Among the 23 patients with cirrhosis on their initial liver biopsy, 1 had F0, 4 had F1, 3 had F2, and 2 had F3 on their second liver biopsy. When defining regression of fibrosis as a decrease of at least 2 METAVIR units, fibrosis regressed in 9 of 13 (69%) F3 and in 8 of 23 (35%) F4. When the ratio of gammaglobulins (g/L) to (platelets [n/mm 3 ] ؋ prothrombin activity [%]) was greater than 7.5, fibrosis never regressed. In conclusion, these data extend the concept of regression of fibrosis to patients with treated genetic hemochromatosis and suggest that some simple biochemical tests would be predictive of further regression of fibrosis as a result of venesection therapy. If confirmed on larger series, this could modify the ultrasound screening policy of hepatocellular carcinoma in genetic hemochromatosis.
(HEPATOLOGY 2006;44:472-477.) R ecent evidence indicates that fibrosis could be reversible even when at an advanced stage. In experimentally induced fibrosis, secondary biliary cirrhosis was shown to be reversible with no functional consequences. 1 In humans, spontaneous resolution of liver fibrosis may occur after successful treatment of the underlying disease. This was described in a small series of patients with chronic hepatitis B 2-5 and D, 6 hemochromatosis, 7-9 primary or secondary biliary cirrhosis, 10-12 nonalcoholic steatohepatitis, 13 Indian childhood cirrhosis, 14 and autoimmune hepatitis. [15][16][17] Chronic hepatitis C virus infection has been the most extensively studied, and therapy with interferon alone or in association with riba-virin has been shown to induce regression of fibrosis irrespective of its virological effects. [18][19][20][21][22][23] Genetic hemochromatosis (GH) benefits from an efficient treatment based on regular phlebotomies. However, data on regression of fibrosis in this disease are scarce, and no study of well-defined patients using a reproducible grading method has been published. The aim of the current study was to assess whether fibrosis could regress under venesection therapy in patients with C282Y homozygous GH.