A 49-year-old male underwent orthotopic liver transplantation (LT) for hepatitis C (HCV) cirrhosis in October 2006. Pretransplant alpha fetoprotein (AFP) was 39.7 ng/mL (reference range: 1.0-10.0 ng/mL) and computed tomography (CT) scan demonstrated changes consistent with cirrhosis without mass lesions. Explant pathology was consistent with HCV cirrhosis and showed no evidence of hepatocellular carcinoma (HCC). Posttransplant immunosuppression for this patient consisted of tacrolimus and mycofenolate mofetil, after initially starting prednisone and OKT3.
Six months posttransplant, a liver biopsy showed recurrent HCV and the patient started pegylated interferon and ribavirin. Unable to tolerate the side effects, therapy was discontinued after 1 week. A 12-month posttransplant liver biopsy showed HCV progression with bridging fibrosis. He developed hepatic hydrothorax requiring transjugular intrahepatic portosystemic stent (TIPS) placement in March of 2008. In subsequent years the patient was admitted several times for hepatic encephalopathy. In June 2011 a routine ultrasound showed a new 1-cm hypoechoic mass in the dome of the liver which was indeterminate on contrast CT scan. The alphafetoprotein level was 117.5 ng/mL. The lesion grew to 1.9 × 1.4 × 1.7 cm in March 2012 on ultrasonography. On contrast CT the lesion was hypervascular but indeterminate, as it measured less than 1 cm (Fig. 1A,B). The AFP was 107.6 ng/mL in October 2011 but was 4.3 ng/mL in May 2012 (Fig. 1C). Due to the increasing size of the lesion an ultrasound-guided biopsy of the liver mass was performed in April 2012 and reviewed by three pathologists who concurred that there was evidence of well-differentiated HCC on a background of HCV cirrhosis (Fig. 2). The patient was scheduled for radiofrequency ablation (RFA) therapy and relisted for LT, but died from complications of liver failure while waiting.
HCV accounts for nearly half of all LT done in the U.S. and Europe. Unfortunately, viremia persists in over 95% of patients posttransplant and cirrhosis can occur within 5 years of HCV recurrence in transplant patients,[2, 3] resulting in liver failure and death. HCV is a well-established risk factor for HCC in patients with cirrhosis, but to our knowledge no case has been reported of a patient with recurrent HCV developing HCC posttransplant. The rapid development of HCC in our patient was likely multifactorial and related to the development of recurrent HCV. Immunosuppression affects the natural history of recurrent HCV and accelerates the development of cirrhosis. Mechanistically, CD8 T cells are responsible for lysis of tumor and virus-infected cells by way of antigen presentation with up-regulation of cytokines by CD4 T cells. Thus, the T-cell response to HCV is critical in achieving long-term control of the virus and prolonging the time between viremia and the presence of tumor. Immunosuppressive medications decrease immune-mediated viral elimination and suppress the immune tumor surveillance system. Consequently, transplant recipients have a 2-4 times greater risk of de novo malignancy compared to transplant-naïve patients. Specifically, posttransplant immunosuppression may also promote tumorigenesis. Tacrolimus has been shown to accelerate the doubling time for recurrent HCC from 273 to 37 days and may have accelerated the doubling time of this patient's cancer. The role of surveillance for HCC is still unclear. AFP levels may be elevated in patients with HCV and this may account for the discordance seen in our patient (Fig. 1D).
In conclusion, cirrhosis from recurrent HCV after OLT can be associated with de novo HCC. The incidence and role of surveillance have yet to be defined and need further study.