Preoperative Prognostic Nutritional Index May Be a Strong Predictor of Hepatocellular Carcinoma Recurrence Following Liver Transplantation.

Purpose: Malnutrition is a major risk factor of immune dysfunction and poor outcome in cancer patients. The prognostic nutritional index (PNI), which is established by serum albumin level and peripheral lymphocyte count, was shown to correlate with prognosis of hepatocellular carcinoma (HCC) patients following liver resection and non-surgical interventions. The aim of this study was to analyze the predictive value of preoperative PNI in liver transplantation (LT) patients with HCC. Patients and Methods: A total of 123 HCC patients that underwent LT were included in the analysis. The prognostic impact of preoperatively assessed clinical factors including the PNI on post-LT outcome was analyzed by uni- and multivariate analysis. Results: Post-transplant tumor recurrence rates were 5.1% in high-PNI (> 42) and 55.6% in low-PNI (≤ 42) patients (p < 0.001). Preoperative high-PNI could be identified as a significant and independent promoter of both recurrence-free survival (hazard ratio [HR] = 10.12, 95% CI: 3.40-30.10; p < 0.001) and overall survival (HR = 1.69, 95% CI: 1.02-2.79; p = 0.004) following LT. Apart from that low-PNI proved to be a significant and independent predictor of microvascular tumor invasion (OR = 7.71, 95% CI: 3.17-18.76; p < 0.001). In contrast, no tumor morphology features including the Milan criteria revealed an independent prognostic value. Conclusion: Our data indicate that preoperative PNI correlates with biological tumor aggressiveness and outcome following LT in HCC patients and may therefore be useful for refining oncologic risk stratification.

Prophylactic Anti-Cytomegalovirus Hyperimmunoglobulin in Critically Ill Liver Transplant Patients: Impact on Early Immunology and Survival.

BACKGROUND: Anti-cytomegalovirus hyperimmunoglobulin (CMVIg) was shown to provide beneficial immunodulatory properties beyond antiviral efficacies. The aim of this retrospective study was to assess the impact of prophylactic CMVIg treatment on early outcome following liver transplantation (LT) in critically ill patients. METHODS: Forty-three cirrhotic patients requiring pre-LT intensive care due to multiorgan failure were analyzed. Twenty-eight patients with enhanced CMV risk (D+/R+; D+/R-; D-/R+) received prophylactic CMVIg for a minimum of 7 days, while 15 patients (D-/R-) did not. RESULTS: Post-transplantation rates of intra-abdominal infections (28% vs. 61.1%; p = 0.03), Epstein-Barr virus infections (0% vs. 33.3%; p = 0.034), allograft rejections (0% vs. 22.2%; p = 0.013) and sepsis-related mortality (4% vs. 27.8%; p = 0.026) were significantly lower, whereas incidence of CMV infections (4% vs. 22.2%; p = 0.066) tended to be lower in the CMVIg subset. In multivariate analysis, only pretransplant elevated serum lactate level (hazard ratio = 34.63; p = 0.009) and absence of CMVIg therapy (hazard ratio = 21.76; p = 0.023) were identified as independent promoters of 3-month mortality. CONCLUSION: Prophylactic treatment with CMVIg reduces predisposition for severe immunological and septic events and, thereby, early mortality in critically ill liver recipients.

The role of preoperative albumin-bilirubin grade for oncological risk stratification in liver transplant patients with hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Albumin-bilirubin (ALBI) score was shown to correlate with liver function and tumor recurrence after hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to assess the prognostic value of ALBI grade in liver transplantation (LT) patients with HCC. METHODS: Pre-LT available independent predictors of recurrence-free survival (RFS) and microvascular tumor invasion (MVI) were determined in 123 patients with HCC. RESULTS: Posttransplant HCC recurrence rates were 10.5%, 15.9%, and 68.2% in ALBI grade 1, 2, and 3, respectively (P < .001). Along with serum α-fetoprotein (AFP) and C-reactive protein (CRP) levels, ALBI grades 1 or 2 was identified as an independent predictor of RFS (hazard ratio, 3.52; 95% confidence interval [CI], 1.577-7.842; P = .002). Furthermore, ALBI grade 3 proved to be the strongest indicator of MVI (odds ratio, 11.59; 95% CI, 3.412-39.381; P < .001). A novel oncological risk score-based on AFP, CRP, and ALBI grade provided the best discriminative capacity (c-statistic 0.806) in selecting liver recipients with low oncological risk profile. CONCLUSION: Preoperative ALBI grade seems to be valuable for refinement of oncological risk stratification at LT for HCC.

18F-fludeoxyglucose positron emission tomography for diagnosis of HCC: implications for therapeutic strategy in curative and non-curative approaches.

Hepatocellular carcinoma (HCC) is a global health issue with increasing incidence and high mortality rate. Depending on the tumor load and extent of underlying liver cirrhosis, aggressive surgical treatment by hepatectomy or liver transplantation (LT) may lead to cure, whereas different modalities of liver-directed locoregional or systemic tumor treatments are currently available for a noncurative approach. Apart from tumor burden and grade of liver dysfunction, assessment of prognostic relevant biological tumor aggressiveness is vitally important for establishing a promising multimodal therapeutic strategy and improving the individual treatment-related risk/benefit ratio. In recent years, an increasing body of clinical evidence has been presented that 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), which is a standard nuclear imaging device in oncology, may serve as a powerful surrogate for tumor invasiveness and prognosis in HCC patients and, thereby, impact individual decision making on most appropriate therapy concept. This review describes the currently available data on the prognostic value of 18F-FDG PET in patients with early and advanced HCC stages and the resulting implications for treatment strategy.

Serological Risk Index Based on Alpha-Fetoprotein and C-Reactive Protein to Indicate Futile Liver Transplantation Among Patients with Advanced Hepatocellular Carcinoma.

BACKGROUND: The aim of this study was to establish a preoperatively available serological risk index using alpha-fetoprotein (AFP) and C-reactive protein (CRP) for predicting oncologically futile liver transplantation (LT) in hepatocellular carcinoma (HCC) patients. METHODS: A total of 119 liver transplant patients with HCC were retrospectively analyzed. The prognostic impact of clinical and histopathologic factors including pre-LT serum AFP and CRP values was determined. RESULTS: Apart from microvascular tumor invasion (MVI; odds ratio [OR] 15.77), pretransplant serum levels of AFP > 100 ng/ml (OR 13.31) and CRP > 0.8 mg/dl (OR 13.97) were identified as independent predictors of HCC recurrence. The cumulative risk of HCC relapse at 5 years post-LT was 2.3% in low serological tumor activity (STA) index (AFP ≤ 100 ng/ml + CRP ≤ 0.8 mg/dl), 17.1% in intermediate STA (AFP ≤ 100 ng/ml or CRP ≤ 0.8 mg/dl), and 91.6% in high STA index (AFP > 100 ng/ml + CRP > 0.8 mg/dl; p < 0.001), respectively. High STA index was identified as most powerful pre-LT available predictor of MVI (OR 15.31) and posttransplant HCC recurrence (OR 54.44). Five-year recurrence-free survival rate in Milan Out patients with high STA was 0%, compared to 91.7% and 83.6% in those with low or intermediate STA index (p < 0.001), respectively. CONCLUSION: Our proposed serological risk index based on pretransplant serum AFP and CRP values is able to predict oncologically futile LT among advanced HCC patients.

Combining 18F-FDG positron emission tomography with Up-to-seven criteria for selecting suitable liver transplant patients with advanced hepatocellular carcinoma.

The Up-to-seven (UTS) criteria (sum of tumor size and number not exceeding 7) for indicating liver transplantation (LT) in hepatocellular carcinoma (HCC) were originally based on explant pathology features and absence of microvascular invasion (MVI). 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) was shown to indicate the risk of MVI and tumor recurrence. The aim of this study was to analyze the prognostic significance of the clinical UTS criteria when being combined with PET-status of the tumor. Data of 116 liver transplant patients were subject to retrospective analysis. Five-year recurrence-free survival (RFS) rates in patients meeting (n = 85) and exceeding (n = 21) the radiographic UTS criteria were 81% and 55.1%, respectively (p = 0.014). In the UTS In subset, RFS was significantly better in PET-negative (94.9%) than in PET-positive patients (48.3%; p < 0.001). In the UTS Out subset, 5-year RFS rates were 87.1% and 19% in patients with non- 18F-FDG-avid and 18F-FDG-avid tumors (p < 0.001), respectively. Positive PET-status was identified as the only independent clinical predictor of tumor recurrence in beyond UTS patients (Hazard ratio [HR] 19.25; p < 0.001). Combining radiographic UTS criteria with FDG-PET may safely expand the HCC selection criteria for LT.

18F-FDG-PET for Assessing Biological Viability and Prognosis in Liver Transplant Patients with Hepatocellular Carcinoma.

Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis. Currently, patient selection for LT is strictly based on tumor size and number, provided by the Milan criteria. This may, however, exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option. It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome. In particular, microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse. Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), an established nuclear imaging device in oncology, was demonstrated to non-invasively correlate with unfavorable histopathologic features. Currently, there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties. In order to safely expand the HCC selection criteria and the pool of eligible liver recipients, tumor evaluation with 18F-FDG-PET should be implemented in pretransplant decision process.

Prognostic Impact of Intraoperative Blood Loss in Liver Transplant Patients with Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: The aim of this retrospective study was to analyze the impact of intraoperative blood loss (IOBL) on outcome in liver transplant (LT) patients with advanced hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 108 LT patients with HCC were retrospectively analyzed. They were all clinically staged according to the Milan criteria and to 18F-fluoro-D-glucose (18F-FDG) uptake on positron-emission tomography (PET). RESULTS: Recurrence-free survival rates at 3 and 5 years post-LT were 91.9% and 91.9% among patients with low (≤1,500 ml) IOBL, and 43.9% and 37.1% in those with high (>1,500 ml) IOBL (log-rank p<0.001). Multivariate analysis demonstrated low IOBL to be an independent predictor of better recurrence-free survival in patients with HCC exceeding the Milan criteria (hazard ratio=3.66; p=0.029) and in those with PET-positive tumors (hazard ratio=4.13; p=0.007). CONCLUSION: Intraoperative bleeding is associated with increased likelihood of tumor recurrence following LT for HCC. Limiting IOBL should be considered for improving post-LT outcome, particularly in patients with HCC beyond standard criteria.

Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma.

CONTEXT: C-reactive protein (CRP), a biomarker of inflammation, may correlate with prognosis in several malignancies. OBJECTIVE: To investigate the prognostic impact of early postoperative peak serum levels of CRP on tumor-specific outcome in 106 liver transplant patients with hepatocellular carcinoma (HCC). METHODS AND RESULTS: In multivariate Cox regression analysis, a posttransplant elevated peak CRP level (>versus ≤ 3.5 mg/dl) was identified as an independent predictor of poor recurrence-free survival (p = 0.01; HR = 4.04; CI = 1.399-11.640). CONCLUSION: Early postoperative serum CRP may serve as a useful inflammation-based biomarker of outcome in liver transplant patients with HCC.

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation.

Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liver disease (MELD) score helped to reduce waiting list mortality in liver transplantation (LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins (IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.

Extended Ischemia Times Promote Risk of HCC Recurrence in Liver Transplant Patients.

BACKGROUND: There is increasing evidence that ischemia-reperfusion injury (IRI) promotes vasculogenesis and tumor outgrowth in the liver. Hepatic IRI is exaggerated by prolongation of ischemia times. AIMS: The aim of this retrospective analysis was to assess the impact of ischemia times on risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Subgroup analysis focused on patients with (18)F-fluoro-deoxy-glucose ((18)F-FDG)-avid HCC on pretransplant positron emission tomography (PET). METHODS: A total of 103 liver transplant patients with HCC were included in this study. The impact of cold (CIT), warm (WIT), and total ischemia times (TIT) along with other prognostic variables on posttransplant outcome was analyzed in uni- and multivariate analysis. RESULTS: Twenty-four patients (23.3 %) developed tumor relapse after LT. Mean durations of CIT (468.0 vs. 375.5 min; P = 0.001), WIT (58.4 vs. 45.7 min; P = 0.001), and TIT (525.8 vs. 422.0 min; P < 0.001) were significantly longer in patients with compared to those without HCC recurrence. In multivariate regression analysis, (18)F-FDG-avid HCC (odds ratio [OR] 73.4), WIT >50 min (OR 52.5), alpha-fetoprotein level >400 IU/ml (OR 11.1), and Milan Out status (OR 7.4) were identified as independent predictors of HCC recurrence. In the subgroup of patients with PET-positive HCC, WIT remained the only independent variable to predict HCC recurrence (OR 15.5). CONCLUSION: Prolongation of ischemia times promotes the risk of HCC recurrence after LT, especially in patients with unfavorable tumor biology on PET imaging.

Dissection of the hepatic artery and the celiac trunk after a liver transplant: description of a complication and endovascular management.

Dissection of the common hepatic artery is a rare complication after orthotopic liver transplant. Subsequent thrombosis and occlusion of the transplant artery can result in graft failure requiring retransplant. We describe a case of hepatic artery dissection, occurring on the basis of primary vasculopathy, extending into the celiac trunk, with subtotal occlusion of the vessel through accompanying thrombosis. An attempt of endovascular rescue led to successful recanalization of the vessel and graft survival.

Extended postinterventional tumor necrosis-implication for outcome in liver transplant patients with advanced HCC.

BACKGROUND: Locoregional interventional bridging therapy (IBT) is an accepted neoadjuvant approach in liver transplant candidates with hepatocellular carcinoma (HCC). However, the prognostic value of IBT in patients with advanced HCC is still undefined. AIM: The aim of this trial was to evaluate the impact of postinterventional tumor necrosis on recurrence-free long-term survival after liver transplantation (LT) in patients with HCC, especially focusing on those exceeding the Milan criteria on pretransplant radiographic imaging. PATIENTS AND METHODS: A total of 93 consecutive liver transplant candidates with HCC were included in this trial. In 36 patients, tumors were clinically staged beyond Milan criteria prior LT. Fifty-nine patients underwent IBT by transarterial chemoembolization or radiofrequency ablation pretransplantation. Postinterventional tumor necrosis rate as assessed at liver explant pathology was correlated with outcome post-LT. RESULTS: There was no significant difference in 5-year tumor-free survival rate between the IBT- and the non-IBT subpopulation (78% versus 68%, P=0.25). However, tumor response following IBT (≥ 50% tumor necrosis rate at explant pathology) resulted in a significantly better outcome 5 years post-LT (96%) than tumor non-response to IBT (<50% tumor necrosis rate at explant pathology; 21%; P<0.001). Five-year recurrence-free survival rate was 80% in Milan Out patients with extended post-IBT tumor necrosis versus 0% in Milan Out patients without tumor response to IBT (P<0.001). None of macromorphological HCC features, but only the absence of increased (18)F-fluoro-deoxy-glucose ((18)FDG) uptake on pretransplant positron emission tomography (PET) was identified as independent predictor of postinterventional tumor response (P<0.001). CONCLUSION: Our results implicate that extended postinterventional tumor necrosis promotes recurrence-free long-term survival in patients with HCC beyond standard criteria. Pretransplant PET assessment may identify those patients with advanced HCC that will benefit from post-IBT tumor response and may, thereby, achieve excellent posttransplant outcome.

Heparin-induced thrombocytopenia (HIT II) in liver transplant recipients: a retrospective multivariate analysis of prognostic factors.

We investigated the prevalence of HIT II in liver transplant recipients and analysed associated factors. In recipients with clinically suspected HIT II in the 4Ts pretest clinical scoring system HIPA-assay was performed. Next, 37 clinical variables were analysed retrospectively for their association with HIT II. Factors significantly correlated to our findings in univariate analysis were included in a multivariate model and binary logistic regression analysis. Among 46 recipients 21 patients were suspicious in the 4Ts pretest and 14 of them (30.4%) were diagnosed HIT-antibody positive. Patient's age (P = 0.001), postoperative dialysis (P = 0.028), and postoperative hospital stay (P = 0.035) were significantly associated with development of HIT-antibodies in univariate analysis. Postoperative dialysis and postoperative hospital stay turned out as epiphenomena of patient's age, the only independent predictor (P = 0.021). Using multiple χ(2) -testing, a cut-off could be calculated, assigning patients younger than 59 years to a low risk group and patients of 59 years and older to a high risk group. High incidence of peri-operative HIT II seroconversion in liver transplant recipients is not associated with factors known to induce thrombocyte activation, like blood products or cell-saver. Only patients' age was identified as independent predictor.

Patients with non-[18 F]fludeoxyglucose-avid advanced hepatocellular carcinoma on clinical staging may achieve long-term recurrence-free survival after liver transplantation.

There is increasing evidence that a relevant number of patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria may benefit from liver transplantation (LT). We retrospectively analyzed the prognostic significance of [(18) F]fludeoxyglucose ([(18) F]FDG) positron emission tomography (PET) for identifying appropriate LT candidates with advanced HCC on clinical staging. Between 1995 and 2008, 111 patients with HCC were listed for LT. All underwent a pretransplant PET evaluation. LT was performed for 91 of these patients. The tumor recurrence rate after LT was 3.6% for patients with non-[(18) F]FDG-avid (PET(-) ) tumors, but it was 54.3% for patients with [(18) F]FDG-avid (PET(+) ) tumors (P < 0.001). The 5-year recurrence-free survival rates were comparable for patients with tumors meeting the Milan criteria (86.2%) and patients with PET(-) HCC exceeding the Milan criteria (81%) at LT, but these rates were significantly higher than the rate for liver recipients with [(18) F]FDG-avid advanced HCC (21%, P = 0.002). In a multivariate analysis, negative PET findings (odds ratio = 21.6, P < 0.001), an alpha-fetoprotein level <400 IU/mL (odds ratio = 3.3, P = 0.013), and a total tumor diameter <10 cm (odds ratio = 3.0, P = 0.022) were identified as pretransplant prognostic variables for recurrence-free survival. A PET(+) status was assessed as the only independent clinical predictor of tumor-related patient dropout from the waiting list (hazard ratio = 5.7, P = 0.01). Patients with non-[(18) F]FDG-avid HCC beyond the Milan criteria according to clinical staging may achieve excellent long-term recurrence-free survival after LT.

Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in pancreatic cancer.

BACKGROUND: Pancreatic cancer is 1 of the most common and poorly treated tumors. In search of new therapeutic approaches, the oxygen sensors prolyl hydroxylases (PHD) are potential targets. PHD2 is considered the key oxygen sensor-regulating hypoxia-inducible factor (HIF). Currently, there is conflicting evidence regarding the exact role of PHD2 in tumorigenesis. The objective of this study was to investigate the role of PHD2 in pancreatic cancer growth and progression. METHODS: PHD2 expression was analyzed by quantitative real-time polymerase chain reaction analysis and immunohistochemistry in human tissue specimens and cell lines. Knockdown of PHD2 was done by using short-interfering RNAs (siRNAs) specific against PHD2, and PHD2 overexpression was achieved by stable combinational DNA transfection. In vivo, an orthotopic murine model was used. Angiogenic cytokines were assessed with enzyme-linked immunosorbent assays, and invasion was studied with Matrigel assays. RESULTS: PHD2 expression was not altered substantially in cancer tissues and their metastases. Lymph node-negative tissues had higher levels of PHD2 than lymph node-positive tissues. PHD2 was hypoxia-inducible in pancreatic cancer cell lines and regulated cell growth through cyclin D1 down-regulation samples with PHD2 suppression and through p21 up-regulation in samples with of PHD2 overexpression. In vivo, PHD2 caused tumor growth retardation and reduced tumor invasion by inhibiting angiogenesis. This observation was caused by the suppression of angiogenic cytokines and tumor invasion. CONCLUSIONS: The current results indicated that PHD2 plays an important role in pancreatic tumorigenesis. In summary, the authors concluded that PHD2 may function as a tumor suppressor gene in pancreatic cancer and, thus, may define a potential target for the treatment of pancreatic cancer.

Combined en-bloc liver-pancreas transplantation in patients with liver cirrhosis and insulin-dependent type 2 diabetes mellitus.

We report about our experience with combined en-bloc liver-pancreas transplantation in 14 patients with liver cirrhosis and insulin dependent type 2 diabetes mellitus. Exocrine drainage was achieved by duodeno-duodenostomy. Median posttransplant follow-up is currently 92.5 months. All patients were rendered independent from insulin therapy shortly after transplantation. Levels of glycosylated hemoglobin normalized in all recipients. Mean fasting C-peptide values increased from pretransplant 7.0+/-1.7 ng/mL to 10.5+/-2.9 ng/mL 3 months posttransplantation (P<0.001). One recipient (7.1%) developed recurrent exogenous insulin dependence 7 years after transplantation. Pancreas allograft rejection was confirmed by endoscopic biopsy of donor duodenum mucosa in two patients (14.3%). Calculated 5- and 7-year survival is currently at 64.3% and 64.3%, respectively. Our results indicate that combined en-bloc liver-pancreas transplantation using duodeno-duodenostomy is technically feasible and leads to excellent long-term control of glucose metabolism in patients with liver cirrhosis and insulin-dependent type 2 diabetes.

Sustained clearance of serum hepatitis C virus-RNA independently predicts long-term survival in liver transplant patients with recurrent hepatitis C.

The aim of this study was to analyze the impact of virological response to long-term antiviral therapy using interferon plus ribavirin on survival of 30 liver transplant patients with recurrent hepatitis C. Mean treatment duration is currently 46 months (range: 3-144 months). Sustained clearance of serum hepatitis C virus RNA was achieved in 18 patients (60%). Allograft biopsies demonstrated fibrosis progression in seven virological nonresponders (66.6%), and none of the recipients with viral elimination (0%; P<0.001). Univariately, low pretransplant viral loads, the absence of cytomegalovirus infection, as well as biochemical and virological response to antiviral therapy indicated a positive impact on outcome (P<0.05). Only antiviral treatment induced clearance of viremia, however, was identified as independent predictor of long-term survival (P=0.02). Our data indicate that an antiviral combination should aim at viral eradication in liver transplant patients with recurrent hepatitis C, because it improves survival.