Alimentary Pharmacology and Therapeutics Letter to the Editors
Letter: reversibility of hepatic fibrosis and immunosuppression withdrawal in patients with autoimmune hepatitis/ primary biliary cirrhosis overlap syndrome B. Yilmaz* & R. Dayanan† *Department of Gastroenterology, Bolu Izzet Baysal Education and Research Hospital, Bolu, Turkey. † Deparment of Internal Medicine, Batman State Hospital, Batman, Turkey. E-mail: [email protected] doi:10.1111/apt.13123
SIRS, In his recent articles,1, 2 Dr Czaja has evaluated the prevention of hepatic fibrosis and permanent immunosuppression withdrawal, which are very important issues in the management of autoimmune hepatitis (AIH). Patients with AIH may also present with features of primary biliary cirrhosis (PBC) or vice versa. The term of overlap or variant syndromes have been used to describe this clinical condition.3, 4 AIH/PBC is rare, but a real clinical entity that should be better diagnosed and treated. We would like to discuss these issues in patients with AIH/PBC overlap. In a recent large population-based study,5 the authors evaluated data from 88 AIH/PBC patients. Among them, control liver biopsy was performed in 23 biochemical responders. The fibrosis scores decreased or remained unchanged in 90% (21/23) of patients. Furthermore, immunosuppression was successfully withdrawn in 75% (15/20) of patients with AIH/PBC. In another study,6 fibrosis progression was prevented in 100% (6/6) of patients treated by immunosuppression, and relapses
Letter: reversibility of hepatic fibrosis and immunosuppression withdrawal in patients with autoimmune hepatitis/ primary biliary cirrhosis overlap syndrome – author’s reply A. J. Czaja Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA. E-mail: [email protected] doi:10.1111/apt.13126
794
were not observed in 100% (4/4) of patients after immunosuppression withdrawal. Despite small cohort sizes, these results suggest that prevention of fibrosis progression and immunosuppression-free management is a realistic expectation for patients with AIH/PBC overlap. These studies also raise an old question as to whether AIH/PBC is a coexistence of two different autoimmune liver diseases, or a variant of AIH or PBC, with some overlapping features. Relapse-free rates after immunosuppression withdrawal are higher in AIH/PBC overlap than patients with pure AIH. Furthermore, prevention of fibrosis progression seems to be more common in overlap patients than those with pure AIH or PBC.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Czaja AJ. Review article: permanent drug withdrawal is desirable and achievable for autoimmune hepatitis. Aliment Pharmacol Ther 2014; 39: 1043–58. 2. Czaja AJ. Review article: the prevention and reversal of hepatic fibrosis in autoimmune hepatitis. Aliment Pharmacol Ther 2014; 39: 385–406. 3. Efe C, Wahlin S, Ozaslan E, et al. Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome and associated extrahepatic autoimmune diseases. Eur J Gastroenterol Hepatol 2012; 24: 531–4. 4. Czaja AJ. Cholestatic phenotypes of autoimmune hepatitis. Clin Gastroenterol Hepatol 2014; 12: 1430–8. 5. Ozaslan E, Efe C, Heurgue-Berlot A, et al. Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis. Clin Gastroenterol Hepatol 2014; 12: 863–9. 6. Chazouilleres O, Wendum D, Serfaty L, et al. Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. J Hepatol 2006; 44: 400–6.
SIRS, The experience of Drs Yilmaz and Dayanan1 in patients with features of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) is similar to that in patients with classical AIH.2, 3 Liver inflammation is probably the principal driver of fibrosis in each of these clinical syndromes.4 As Drs Yilmaz and Dayanan suggest, the suppression of inflammation can be an effective anti-fibrotic strategy even when the inflammation is accompanied by features of PBC. Other studies of PBC support these observations.5, 6 The inflammatory features associated with AIH lack disease-specificity, and their occurrence in PBC has idenAliment Pharmacol Ther 2015; 41: 789–796 ª 2015 John Wiley & Sons Ltd
Letter: reversibility of hepatic fibrosis and immunosuppression withdrawal in patients with autoimmune hepatitis/ primary biliary cirrhosis overlap syndrome B. Yilmaz* & R. Dayanan† *Department of Gastroenterology, Bolu Izzet Baysal Education and Research Hospital, Bolu, Turkey. † Deparment of Internal Medicine, Batman State Hospital, Batman, Turkey. E-mail: [email protected] doi:10.1111/apt.13123
SIRS, In his recent articles,1, 2 Dr Czaja has evaluated the prevention of hepatic fibrosis and permanent immunosuppression withdrawal, which are very important issues in the management of autoimmune hepatitis (AIH). Patients with AIH may also present with features of primary biliary cirrhosis (PBC) or vice versa. The term of overlap or variant syndromes have been used to describe this clinical condition.3, 4 AIH/PBC is rare, but a real clinical entity that should be better diagnosed and treated. We would like to discuss these issues in patients with AIH/PBC overlap. In a recent large population-based study,5 the authors evaluated data from 88 AIH/PBC patients. Among them, control liver biopsy was performed in 23 biochemical responders. The fibrosis scores decreased or remained unchanged in 90% (21/23) of patients. Furthermore, immunosuppression was successfully withdrawn in 75% (15/20) of patients with AIH/PBC. In another study,6 fibrosis progression was prevented in 100% (6/6) of patients treated by immunosuppression, and relapses
Letter: reversibility of hepatic fibrosis and immunosuppression withdrawal in patients with autoimmune hepatitis/ primary biliary cirrhosis overlap syndrome – author’s reply A. J. Czaja Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA. E-mail: [email protected] doi:10.1111/apt.13126
794
were not observed in 100% (4/4) of patients after immunosuppression withdrawal. Despite small cohort sizes, these results suggest that prevention of fibrosis progression and immunosuppression-free management is a realistic expectation for patients with AIH/PBC overlap. These studies also raise an old question as to whether AIH/PBC is a coexistence of two different autoimmune liver diseases, or a variant of AIH or PBC, with some overlapping features. Relapse-free rates after immunosuppression withdrawal are higher in AIH/PBC overlap than patients with pure AIH. Furthermore, prevention of fibrosis progression seems to be more common in overlap patients than those with pure AIH or PBC.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Czaja AJ. Review article: permanent drug withdrawal is desirable and achievable for autoimmune hepatitis. Aliment Pharmacol Ther 2014; 39: 1043–58. 2. Czaja AJ. Review article: the prevention and reversal of hepatic fibrosis in autoimmune hepatitis. Aliment Pharmacol Ther 2014; 39: 385–406. 3. Efe C, Wahlin S, Ozaslan E, et al. Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome and associated extrahepatic autoimmune diseases. Eur J Gastroenterol Hepatol 2012; 24: 531–4. 4. Czaja AJ. Cholestatic phenotypes of autoimmune hepatitis. Clin Gastroenterol Hepatol 2014; 12: 1430–8. 5. Ozaslan E, Efe C, Heurgue-Berlot A, et al. Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis. Clin Gastroenterol Hepatol 2014; 12: 863–9. 6. Chazouilleres O, Wendum D, Serfaty L, et al. Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. J Hepatol 2006; 44: 400–6.
SIRS, The experience of Drs Yilmaz and Dayanan1 in patients with features of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) is similar to that in patients with classical AIH.2, 3 Liver inflammation is probably the principal driver of fibrosis in each of these clinical syndromes.4 As Drs Yilmaz and Dayanan suggest, the suppression of inflammation can be an effective anti-fibrotic strategy even when the inflammation is accompanied by features of PBC. Other studies of PBC support these observations.5, 6 The inflammatory features associated with AIH lack disease-specificity, and their occurrence in PBC has idenAliment Pharmacol Ther 2015; 41: 789–796 ª 2015 John Wiley & Sons Ltd
