Challenges of recurrent hepatitis C in the liver transplant patient

Cirrhosis secondary to hepatitis C virus (HCV) is a very common indication for liver transplant. Unfortunately recurrence of HCV is almost universal in patients who are viremic at the time of transplant. The progression of fibrosis has been shown to be more rapid in the post-transplant patients than in the transplant naïve, hence treatment of recurrent HCV needs to be considered for all patients with documented recurrent HCV. Management of recurrent HCV is a challenging situation both for patients and physicians due to multiple reasons as discussed in this review. The standard HCV treatment with pegylated interferon and Ribavarin can be considered in these patients but it leads to a lower rate of sustained virologic clearance than in the non-transplanted population. Some of the main challenges associated with treating recurrent HCV in post-transplant patients include the presence of cytopenias; need to monitor drug-drug interactions and the increased incidence of renal compromise. In spite of these obstacles all patients with recurrent HCV should be considered for treatment since it is associated with improvement in survival and a delay in fibrosis progression. With the arrival of direct acting antiviral drugs there is renewed hope for better outcomes in the treatment of post-transplant HCV recurrence. This review evaluates current literature on this topic and identifies challenges associated with the management of post-transplant HCV recurrence.

Chemoembolization Combined with RFA for HCC:Survival Benefits and Tumor Treatment Response

Purpose: To investigate survival benefits and tumor treatment response among patients who received treatment with transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) and TACE alone. Materials and Methods: A total of 108 HCC patients were treated with TACE between the period of 1998 and 2008. 51 (47.2%) received TACE followed by planned RFA and 57 (52.8%) received TACE alone. 57 patients received Precision TACE with Doxorubicin drug eluting beads and 51 received conventional TACE. Survival analysis was performed using Kaplan Meier Estimator with a log rank test, Fischer exact test was performed for categorical variables and the t test for continuous variables. Results: Mean MELD (Model for End Stage Liver Disease) score among the TACE-RFA and TACE-only groups were 12.87 and 12.33 respectively (p = 0.64). The number of patients in Child’s Class A, B, C in the two groups were 28/15/8 and 23/23/11 (p = 0.30);in Okuda Class I, II and III in the two groups were 22/23/6 and 14/30/9 (p = 0.2). Median survival among patients who received TACE-RFA and TACE alone were 566 days and 209 days (p = 0.01). Median survival of patients treated with Precision-TACE + RFA was 566 days and that of patients treated with conventional TACE + RFA was 336 days (p = 0.510). Mean progression-free duration by RECIST criteria among the TACE + RFA group was 210 days vs. TACE only group 97 days (p = 0.04). Conclusion: Combination therapies of TACE and RFA were associated with improved overall survival than TACE alone. Patients with single tumors cm appeared to have a survival advantage with combination therapy when compared to larger tumors. TACE-RFA was associated with improved tumor response and progression-free duration than TACE alone.

Incidentally Discovered HCC (iHCC) in Explant Liver-Histopathologic Features and Clinical Outcome

Incidentally discovered hepatocellular carcinomas (iHCC) are tumors which are discovered on the explanted liver which were not present on imaging prior to transplant. The natural history, histopathologic characteristics and prognosis of iHCC are not clearly defined. Methods: A retrospective analysis was performed to compare the characteristics of iHCC and established HCC within Milan criteria (eHCC) in patients who underwent liver transplantation at our center between 2000 and 2010. Results: During the study period a total of 975 adult patients were transplanted in our center;124 (12.7%) patients had eHCC and 26 (2.6%) patients had iHCC. A larger number of patients with iHCC (73.1%) had ascites when compared to eHCC (41.3%) (p = 0.035). Patients with iHCC had a higher mean bilirubin (p 0.001) and mean INR (p = 0.05) than patients with eHCC. Around 70% of patients with iHCC had a Model for End Stage Liver Disease (MELD) score greater than 15 at the time of listing while only 25% of patients with eHCC had a MELD greater than 15 at listing (p 0.001).The mean alphafetoprotein (AFP) in patients with iHCC was significantly lower (11.6 ± 16.5) than the patients with eHCC (564.9 ± 2180;p = 0.024). In patients with iHCC, 30.8% had a multiple tumors and 23% had bilobar involvement. The average number of tumors was 1.6 and the cumulative tumor size was 2.1 cm (SD 1.4). The cumulative tumor size in iHCC was significantly smaller than in eHCC (mean 3.9 cm) (p = 0.035). American Joint Committee on Cancer (AJCC) T1 tumor stage was found in 58% of patients with iHCC and 48.4% of patients with eHCC (p = 0.829).The median survival was 9.47 years for iHCC (95% CI 7.0 - 11.9) and 8.7 years (95% CI 6.1 - 11.4) for eHCC (p = 0.328). While none of the patients with iHCC had recurrence of HCC, the incidence of recurrence in patients with eHCC was 6.4%. Conclusion: iHCC occurred in patients with more advanced liver disease than eHCC. AFP was usually not elevated in patients with iHCC. The cumulative tumor size of iHCC was smaller than eHCC but around a third of iHCC were multifocal, supporting the theory of multicentric hepatic carcinogenesis. Survival of patients with iHCC was similar to patients with eHCC and recurrence was not noted in patients with iHCC.