Case report: 8 years after liver transplantation: de novo hepatocellular carcinoma 8 months after HCV clearance through IFN-free antiviral therapy

Giuliano Ramadori, Patrizia Bosio, Federico Moriconi, Ihtzaz A. Malik

After orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC), recurrent HCC mostly develops within 2 years. All cases of de novo HCC described so far occurred later than 2 years after OLT. Prevention of post-transplantation HCC has usually been tried to achieve by curing or controlling recurrent liver disease. This has been rationale for treatment with interferon (IFN)/ribavirin of HCV-recurrence in patients after OLT, transplanted for advanced HCV-induced liver disease and/or HCC. The availability of new and more efficient drugs has improved chances also for previously difficult-to-treat HCV-positive patients. A 75 year-old male patient who had undergone OLT for decompensated HCV-cirrhosis in 2009, and bilio-digestive surgery in 2011 under tracrolimus (0.5 mg/day) and prednisone (5 mg/day) immunosuppressive therapy, started to receive antiviral treatment for recurrent HCV-infection of graft with 200 mg/day ribavirin in combination with ledipasvir and sofosbuvir by the end of October 2015. Because of multiple side effects (anemia, asthenia, infections, and reduction of kidney functions - palliated by treatment with erythropoietin), treatment was stopped after 16 weeks. At the third control, a minimal increase in alpha-fetoprotein (AFP) serum level to 10 μg/L was measured 8 months after therapy, whereas both liver sonography and serum transaminases were normal. The patient's general condition; however, remained poor, and a magnetic resonance imaging (MRI) of abdomen was performed 2 months later. A nodule of 3 cm in diameter with a pseudocapsule was found centrally in the liver. The patient had to be hospitalized for recurrent infections of the lung, overt ascites and peritonitis. Rapid tumor growth (10 cm) was detected during last stay in hospital (April 2017), concomitant with a rise of AFP-serum levels to 91 μg/L. The family decided to take the patient home, and best supportive care was provided by a general practitioner, local nurses and the patient's dedicated wife until his death. Before treating OLT patients with HCV graft reinfection one should not only consider possible advantages of newly effective antiviral-therapies, but also life expectancy and possible side effects (difficult to manage at an outpatient service basis), including severe disadvantages such as the development of HCC.