Federico Aucejo

The Significance of Metabolic Syndrome in the Setting of Recurrent Hepatitis C After Liver Transplantation

Although hyperinsulinemia and its associated metabolic syndrome (MS) have been implicated in the progression of hepatic fibrosis in hepatitis C virus (HCV) patients, little is known about the consequences of MS after orthotopic liver transplantation (OLT). The aim of this study was to assess the association between MS and fibrosis progression in patients with recurrent HCV after OLT. We identified all OLT/HCV patients (1998‐2005) with at least 2 post‐OLT liver biopsies. MS was defined with Adult Treatment Panel III criteria at 1 year post‐OLT. The Ludwig‐Batts scoring system was used to stage all biopsies (408 biopsies from 95 patients). The first biopsy that showed progression post‐OLT was used for the time‐to‐progression analysis. Univariable and multivariable logistic regression analysis was performed to identify factors associated with fibrosis progression. MS was present in 50% of patients. Average follow‐up to last available biopsy was 24 ± 17 months, during which 72% of subjects had fibrosis progression. The overall median rate of fibrosis progression was 0.08 units per month (Q25, Q75: 0.0, 0.17). By univariable analysis, high HCV RNA at 4 months post‐OLT (P < 0.001), diabetes (P = 0.046), cytomegalovirus infection (P = 0.006), and MS (P = 0.049) were associated with progression of fibrosis. In multivariable analysis, MS was independently associated with progression of fibrosis beyond 1 year after OLT (odds ratio = 6.3, P = 0.017). A high viral load at 4 months post‐OLT (odds ratio = 1.1, P = 0.004) and steroid therapy for acute rejection (odds ratio = 1.9, P = 0.05) were independently associated with fibrosis progression. In conclusion, MS, a potentially modifiable disease, is common and is strongly associated with long‐term fibrosis progression in the setting of recurrent HCV after OLT. Liver Transpl 14:1287–1293, 2008.

Robotic versus laparoscopic resection of liver tumours

BACKGROUND There are scant data in the literature regarding the role of robotic liver surgery. The aim of the present study was to develop techniques for robotic liver tumour resection and to draw a comparison with laparoscopic resection. METHODS Over a 1-year period, nine patients underwent robotic resection of peripherally located malignant lesions measuring <5 cm. These patients were compared prospectively with 23 patients who underwent laparoscopic resection of similar tumours at the same institution. Statistical analyses were performed using Students t-test, χ(2) -test and Kaplan-Meier survival. All data are expressed as mean ± SEM. RESULTS The groups were similar with regards to age, gender and tumour type (P= NS). Tumour size was similar in both groups (robotic -3.2 ± 1.3 cm vs. laparoscopic -2.9 ± 1.3 cm, P= 0.6). Skin-to-skin operative time was 259 ± 28 min in the robotic vs. 234 ± 17 min in the laparoscopic group (P= 0.4). There was no difference between the two groups regarding estimated blood loss (EBL) and resection margin status. Conversion to an open operation was only necessary in one patient in the robotic group. Complications were observed in one patient in the robotic and four patients in the laparoscopic groups. The patients were followed up for a mean of 14 months and disease-free survival (DFS) was equivalent in both groups (P= 0.6). CONCLUSION The results of this initial study suggest that, for selected liver lesions, a robotic approach provides similar peri-operative outcomes compared with laparoscopic liver resection (LLR).

Use of tissue plasminogen activator in liver transplantation from donation after cardiac death donors.

Ischemic‐type biliary stricture (ITBS) occurs in up to 50% after liver transplantation (LT) from donation after cardiac death (DCD) donors. Thrombus formation in the peribiliary microcirculation is a postulated mechanism. The aim was to describe our experience of tissue plasminogen activator (TPA) administration in DCD‐LT. TPA was injected into the donor hepatic artery on the backtable (n = 22). Two recipients developed ITBS including one graft failure. Although excessive postreperfusion bleeding was seen in 14 recipients, the amount of TPA was comparable between those with and without excessive bleeding (6.4 ± 2.8 vs. 6.6 ± 2.8 mg, p = 0.78). However, donor age (41 ± 12 vs. 29 ± 9 years, p = 0.02), donor BMI (26.3 ± 5.5 vs. 21.7 ± 3.6 kg/m2, p = 0.03), previous laparotomy (50% vs. 0%, p = 0.02) and lactate after portal reperfusion (6.3 ± 4.6 vs. 2.8 ± 0.9 mmol/L, p = 0.005) were significantly greater in recipients with excessive bleeding. In conclusion, the use of TPA may lower the risk of ITBS‐related graft failure in DCD‐LT. Excessive bleeding may be related to poor graft quality and previous laparotomy rather than the amount of TPA. Further studies are needed in larger population.

Comparative Analysis of the Safety and Efficacy of Transcatheter Arterial Chemoembolization and Yttrium-90 Radioembolization in Patients with Unresectable Hepatocellular Carcinoma

PURPOSE To compare retrospectively the safety and efficacy of yttrium-90 ((90)Y) radioembolization with the safety and efficacy of chemoembolization in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Survival and complication rates were evaluated for patients with HCC who underwent chemoembolization or radioembolization at a single institution between August 2007 and April 2010. Complications were graded according to a standardized grading system for embolization procedures. Survival was determined via the Kaplan-Meier method, and multivariable analysis for factors affecting survival was performed. RESULTS This study included 73 patients with HCC who underwent index embolization with radioembolization (n = 38; 52.1%) or chemoembolization (n = 35; 47.9%). The two patient populations were similar in terms of demographics, etiology of cirrhosis, functional status, tumor characteristics, Child-Pugh class, previous liver-directed therapy, and number of patients with bilirubin > 2.0 mg/dL. There was no significant difference in survival between the radioembolization (median 8.0 months) and chemoembolization (median 10.3 months) cohorts (P = .33). Postembolization syndrome was significantly more severe in patients who underwent chemoembolization, which led to increased total hospitalization rates in these patients. The rates of other complications and rehospitalization were similar between groups. Increased age, Child-Pugh class B, hepatitis seropositivity, bilobar tumor distribution, tumor vascular invasion, and presence of extrahepatic metastases were associated with reduced patient survival. CONCLUSIONS Patients treated with radioembolization did not show a survival advantage over patients treated with chemoembolization. However, patients who underwent chemoembolization had significantly higher rates of hospitalization as a result of postembolization syndrome.

Recurrent Hepatitis C After Liver Transplantation : On-Treatment Prediction of Response to Peginterferon/Ribavirin Therapy

Sustained virologic response (SVR) in the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) remains suboptimal. We evaluated efficacy of pegylated interferon alfa (PEG) and ribavirin (RBV) (PEG/RBV) combination therapy in LT recipients with recurrent HCV and predictive values of rapid virological response (RVR) and early virologic response (EVR). Between January 2001 and October 2005, LT recipients with recurrent HCV were intended to be treated for 48 weeks with PEG/RBV combination therapy independent of genotype or virologic response [53 patients (79% genotype 1)]. On‐treatment predictor of response at week 4 (RVR) was defined as undetectable HCV RNA, and at week 12 (EVR) as undetectable HCV RNA or a >2 log10 drop from pretreatment viral load. SVR was seen in 19 (35%) patients. Patients with genotype 2/3 were more likely to achieve SVR than those with genotype 1 (87% versus 23%; P = 0.001). The highest rate of SVR was seen in patients with RVR [specificity and positive predictive value (PPV) = 100%] while the highest rate of treatment failure was seen in those who did not have EVR [sensitivity and negative predictive value (NPV) = 100%]. The NPV of RVR to identify those who will not achieve SVR was also very high (88%). EVR had low PPV (63%) to identify those with SVR. In conclusion, PEG/RBV combination therapy is effective in the treatment of post‐LT recurrent HCV. On‐treatment virologic monitoring is highly predictive of SVR and may optimize the virologic response and minimize toxicity. Given its high PPV and NPV, RVR appears to be the most appropriate decision time point for continuation of therapy. Liver Transpl 14:53–58, 2008.

“Splenic artery steal syndrome” is a misnomer: The cause is portal hyperperfusion, not arterial siphon

Splenic artery embolization (SAE) improves hepatic artery (HA) flow in liver transplant (OLT) recipients with so‐called splenic artery steal syndrome. We propose that SAE actually improves HA flow by reducing the HA buffer response (HABR). Patient 1: On postoperative day (POD) 1, Doppler ultrasonography (US) showed patent vasculature with HA resistive index (RI) of 0.8. On POD 4, aminotransferases rose dramatically; his RI was 1.0 with no diastolic flow. Octreotide was begun, but on POD 5 US showed reverse diastolic HA flow with no signal in distal HA branches. After SAE, US showed markedly improved flow, RI was 0.6, diastolic flow in the main artery, and complete visualization of all distal branches. By POD 6, liver function had normalized. RI in the main HA is 0.76 at 2 months postsurgery. Patient 2: On POD 1, RI was 1.0. US showed worsening intrahepatic signal, with no signal in the intrahepatic branches and reversed diastolic flow despite good graft function. On POD 7, SAE improved the intrahepatic waveform and RI (from 1.0 to 0.72). Patient 3: Intraoperative reverse diastolic arterial flow persisted on PODs 1, 2, and 3, with progressive loss of US signal in peripheral HA branches. SAE on POD 4 improved the RI (0.86) and peripheral arterial branch signals. Patient 4: US on POD 1 showed good HA flow with a normal RI (0.7). A sudden waveform change on POD 2 with increasing RI (0.83) prompted SAE, after which the wave form normalized, with reconstitution of a normal diastolic flow (RI 0.68). In conclusion, these reports confirm the usefulness of SAE for poor HA flow but suggest that inflow steal was not the problem. Rather than producing an increase in arterial inflow, SAE worked by reducing portal flow and HABR, thereby reducing end‐organ outflow resistance. Evidence of this effect is the marked reduction of the RI after the SAE to 0.6, 0.72, 0.86, and 0.68, in patients 1‐4, respectively. SAE reduces excessive portal vein flow and thereby ameliorates an overactive HABR that can cause graft dysfunction and ultimately HA thrombosis. Liver Transpl 14:374–379, 2008.

Safety and Feasibility of Using Sorafenib in Recurrent Hepatocellular Carcinoma after Orthotopic Liver Transplantation

Background and Aim: The majority of patients who undergo orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have a very good prognosis if the tumor is within the Milan criteria. However, 10–15% of patients will have reoccurrence after OLT. Currently, sorafenib is available for advanced HCC. The safety and efficacy of sorafenib in this population has not been reported. Methods: We retrospectively looked at 54 patients who received sorafenib for advanced HCC. Out of 54 patients, we analyzed 9 who received sorafenib after OLT for HCC reoccurrence at Cleveland Clinic. Result: The median age at the time treatment with sorafenib was initiated was 59 years (range 46–77). Two patients received prior local therapy. Most of the toxicity was expected side effects from sorafenib except in 1 patient who developed hematological toxicity. Six patients required dose reduction secondary to toxicity. There were no unexpected complications from interaction with immunosuppressive medication. One patient achieved complete radiographic remission. Median survival from the start of sorafenib had not been reached at the time of writing; however, the 4-month survival rate is currently estimated to be 84 ± 15%, and 1 patient with lung reoccurrence has been treated for almost 18 months thus far. Conclusion: Sorafenib can be used in patients with recurrent HCC after liver transplantation with tolerable toxicity; however, dose adjustment may be required. A larger prospective study is necessary to determine the efficacy of sorafenib in this group of patients.

Measurement of CD4+ T-cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation.

Hashimoto K, Miller C, Hirose K, Diago T, Aucejo F, Quintini C, Eghtesad B, Corey R, Yerian L, Lopez R, Zein N, Fung J. Measurement of CD4+ T‐cell function in predicting allograft rejection and recurrent hepatitis C after liver transplantation.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01169.x
© 2009 John Wiley & Sons A/S.

Safety and efficacy of sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation.

Recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) carries a poor prognosis. The aim of our study was to assess the safety and efficacy of sorafenib in patients with recurrent HCC following LT.

Rate of Tumor Growth Predicts Recurrence of Hepatocellular Carcinoma After Liver Transplantation in Patients Beyond Milan or UCSF Criteria

BACKGROUND It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC). METHODS We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr3, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed. RESULTS Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7-30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P=.001), poorly differentiated tumors (HR 13; P=.039), the presence of microvascular invasion (HR 7.9; P=.001), higher TTV (HR 1.03; P<.001), and faster tumor growth (HR 1.09; P<.001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm3/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth<1.61 cm3/mo experienced less recurrence (11% vs 58%; P=.023) than those beyond the Milan criteria with tumor growth>1.61 cm3/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria. CONCLUSIONS Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.