CASE REPORT Fibrosing cholestatic hepatitis with hepatitis C virus treated by double filtration plasmapheresis and interferon plus ribavirin after liver transplantation Teruki Miyake Æ Kojiro Michitaka Æ Yoshio Tokumoto Æ Shinya Furukawa Æ Teruhisa Ueda Æ Yoshiko Soga Æ Masanori Abe Æ Bunzo Matsuura Æ Taro Nakamura Æ Taiji Tohyama Æ Nobuaki Kobayashi Æ Yoichi Hiasa Æ Morikazu Onji Received: 19 August 2008 / Accepted: 24 November 2008 / Published online: 10 January 2009 Ó Springer 2009 Abstract Fibrosing cholestatic hepatitis (FCH) is a seri- ous disease in patients with recurrent hepatitis C after liver transplantation (LTx). Antiviral therapy is indicated in these patients; however, it is not always effective, and the prognosis of FCH is generally poor. Double filtration plasmapheresis (DFPP) has been shown to be effective at eliminating hepatitis C virus (HCV) in patients with chronic hepatitis C. We report a case of FCH with severe cholestasis (total bilirubin 34.2 mg/dl) after LTx. Combi- nation therapy with interferon (IFN) and ribavirin (RBV) was unsuccessful for improving cholestasis; however, the addition of DFPP to IFN and RBV alleviated cholestasis and improved renal function. Although IFN and RBV with DFPP could not eliminate HCV, results of liver function tests improved and remained stable for several months. This treatment with DFPP combined with IFN and RBV would be useful for resolving cholestasis due to FCH. Moreover, treatment of DFPP could improve liver and renal function test results and could stop the worsening condition of patients with FCH. Keywords Liver failure Á Hyperviremia Á Hyperbilirubinemia Á Cholestasis Introduction Re-infection with hepatitis C virus (HCV) occurs in most patients who undergo liver transplantation (LTx) [1–3]. Approximately 10–25% LTx patients re-infected with HCV progress to liver cirrhosis within 5–10 years after LTx [1–3]. About 40% of recipients who progress to cirrhosis are at risk for hepatic decompensation [2, 3]. Interferon (IFN) monotherapy is not effective against recurrent hepatitis C after LTx because the sustained virological response (SVR), that is, elimination of HCV- RNA, has been reported to be low [4, 5]. Recently, pegylated IFN (peg-IFN) plus ribavirin (RBV) therapy has become the standard therapy for patients with chronic hepatitis C, with a SVR rate of approximately 50% in non-LTx patients. However, the SVR rate for HCV re-infected patients after LTx is lower (17–45%) [6–8]. Fibrosing cholestatic hepatitis (FCH) is rare and serious for recipients with recurrent HCV. It is known to progress rapidly and result in graft failure [9–12]. Results of liver function tests for FCH are characterized by cholestasis [i.e., hyperbilirubinemia, high levels of alkaline phosphatase (ALP), c-glutamyl transpeptidase (c-GTP), and leucine aminopeptidase] and mild-to-moderate elevations in serum aspartate aminotransferase (AST) and alanine aminotrans- ferase (ALT) levels. Pathological findings of FCH are characterized by sinusoidal fibrosis, portal infiltration of mononuclear cells without interface hepatitis, signs of histological cholestasis, and ballooning of hepatocytes without findings of acute or chronic rejection [9–13]. If antiviral therapy is not effective or liver re-transplantation is not done, most patients with FCH follow a progressive course leading to death. Antiviral therapy with IFN, with or without RBV, has been used in these patients. A few cases T. Miyake Á K. Michitaka Á Y. Tokumoto Á S. Furukawa Á T. Ueda Á Y. Soga Á M. Abe Á B. Matsuura Á Y. Hiasa (&) Á M. Onji Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan e-mail: hiasa@m.ehime-u.ac.jp T. Nakamura Á T. Tohyama Á N. Kobayashi Department of Organ Regulatory Surgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan 123 Clin J Gastroenterol (2009) 2:125–130 DOI 10.1007/s12328-008-0057-5