Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Infrarenal versus supraceliac aorto-hepatic arterial revascularisation in adult liver transplantation: multicentre retrospective study.

When the standard arterial reconstruction is not feasible during liver transplantation (LT), aorto-hepatic arterial reconstruction (AHAR) can be the only solution to save the graft. AHAR can be performed on the infrarenal (IR) or supraceliac (SC) tract of the aorta, but the possible effect on outcome of selecting SC versus IR reconstruction is still unclear. One hundred and twenty consecutive patients who underwent liver transplantation with AHAR in six European centres between January 2003 and December 2018 were retrospectively analysed to ascertain whether the incidence of hepatic artery thrombosis (HAT) was influenced by the type of AHAR (IR-AHAR vs. SC-AHAR). In 56/120 (46.6%) cases, an IR anastomosis was performed, always using an interposition arterial conduit. In the other 64/120 (53.4%) cases, an SC anastomosis was performed; an arterial conduit was used in 45/64 (70.3%) cases. Incidence of early (≤ 30 days) HAT was in 6.2% (4/64) in the SC-AHAR and 10.7% (6/56) IR-AHAR group (p = 0.512) whilst incidence of late HAT was significantly lower in the SC-AHAR group (4.7% (3/64) vs 19.6% (11/56) - p = 0.024). IR-AHAR was the only independent risk factor for HAT (exp[B] = 3.915; 95% CI 1.400-10.951; p = 0.009). When AHAR is necessary at liver transplantation, the use of the supraceliac aorta significantly reduces the incidence of hepatic artery thrombosis and should therefore be recommended whenever possible.

Multicentre analysis of the learning curve for laparoscopic liver resection of the posterosuperior segments.

BACKGROUND: Laparoscopic liver resection demands expertise and a long learning curve. Resection of the posterosuperior segments is challenging, and there are no data on the learning curve. The aim of this study was to evaluate the learning curve for laparoscopic resection of the posterosuperior segments. METHODS: A cumulative sum (CUSUM) analysis of the difficulty score for resection was undertaken using patient data from four specialized centres. Risk-adjusted CUSUM analysis of duration of operation, blood loss and conversions was performed, adjusting for the difficulty score of the procedures. A receiver operating characteristic (ROC) curve was used to identify the completion of the learning curve. RESULTS: According to the CUSUM analysis of 464 patients, the learning curve showed an initial decrease in the difficulty score followed by an increase and, finally, stabilization. More patients with cirrhosis or previous surgery were operated in the latest phase of the learning curve. A smaller number of wedge resections and a larger number of anatomical resections were performed progressively. Dissection using a Cavitron ultrasonic surgical aspirator and the Pringle manoeuvre were used more frequently with time. Risk-adjusted CUSUM analysis showed a progressive decrease in operating time. Blood loss initially increased slightly, then stabilized and finally decreased over time. A similar trend was found for conversions. The learning curve was estimated to be 40 procedures for wedge and 65 for anatomical resections. CONCLUSION: The learning curve for laparoscopic liver resection of the posterosuperior segments consists of a stepwise process, during which accurate patient selection is key.

ANTECEDENTES: La resección hepática laparoscópica exige experiencia y una larga curva de aprendizaje. La resección de los segmentos posterosuperiores (PS) es un reto, y no hay datos acerca de la curva de aprendizaje (learning curve, LC). El objetivo de este estudio fue evaluar la LC de la resección laparoscópica de los segmentos PS. MÉTODOS: Se realizó un análisis CUSUM de la puntuación de dificultad (difficulty score, DS) de la resección en pacientes de 4 centros especializados. La técnica CUSUM se ajustó al riesgo (risk-adjusted CUSUM, RA-CUSUM) para el tiempo operatorio, la pérdida de sangre y las conversiones a cirugía abierta ajustando según la DS de los procedimientos. Se utilizó una curva ROC para identificar el momento en el que se consideró que la LC había sido completada. RESULTADOS: De acuerdo con el análisis CUSUM de los 464 pacientes incluidos, se observó una DS baja al inicio, que posteriormente se fue incrementando hasta llegar a una estabilización. En la última fase de la LC se operaron más pacientes con cirrosis o cirugía previa. De forma progresiva se fueron reduciendo el número de resecciones hepáticas en cuña y aumentando el de resecciones anatómicas. A lo largo del tiempo se introdujo el CUSA y la maniobra de Pringle con mayor frecuencia. El RA-CUSUM mostró una reducción progresiva del tiempo operatorio. La pérdida de sangre inicialmente aumentó ligeramente, luego se estabilizó y finalmente disminuyó con el tiempo. Una tendencia similar se observó para las conversiones. La LC se estimó en 40 casos para las resecciones en cuña y en 65 casos para las resecciones anatómicas. CONCLUSIÓN: La LC de la resección hepática laparoscópica de los segmentos PS es un proceso paso a paso durante el cual la selección del paciente es clave.

Multicentre propensity score-matched study of laparoscopic versus open repeat liver resection for colorectal liver metastases.

BACKGROUND: Repeat liver resection is often the best treatment option for patients with recurrent colorectal liver metastases (CRLM). Repeat resections can be complex, however, owing to adhesions and altered liver anatomy. It remains uncertain whether the advantages of a laparoscopic approach are upheld in this setting. The aim of this retrospective, propensity score-matched study was to compare the short-term outcome of laparoscopic (LRLR) and open (ORLR) repeat liver resection. METHODS: A multicentre retrospective propensity score-matched study was performed including all patients who underwent LRLRs and ORLRs for CRLM performed in nine high-volume centres from seven European countries between 2000 and 2016. Patients were matched based on propensity scores in a 1 : 1 ratio. Propensity scores were calculated based on 12 preoperative variables, including the approach to, and extent of, the previous liver resection. Operative outcomes were compared using paired tests. RESULTS: Overall, 425 repeat liver resections were included. Of 271 LRLRs, 105 were matched with an ORLR. Baseline characteristics were comparable after matching. LRLR was associated with a shorter duration of operation (median 200 (i.q.r. 123-273) versus 256 (199-320) min; P < 0·001), less intraoperative blood loss (200 (50-450) versus 300 (100-600) ml; P = 0·077) and a shorter postoperative hospital stay (5 (3-8) versus 6 (5-8) days; P = 0·028). Postoperative morbidity and mortality rates were similar after LRLR and ORLR. CONCLUSION: LRLR for CRLM is feasible in selected patients and may offer advantages over an open approach.

Development and validation of a difficulty score to predict intraoperative complications during laparoscopic liver resection.

BACKGROUND: Previous studies have demonstrated that patient, surgical, tumour and operative variables affect the complexity of laparoscopic liver resections. However, current difficulty scoring systems address only tumour factors. The aim of this study was to develop and validate a predictive model for the risk of intraoperative complications during laparoscopic liver resections. METHODS: The prospectively maintained databases of seven European tertiary referral liver centres were compiled. Data from two-thirds of the patients were used for development and one-third for validation of the model. Intraoperative complications were based on a modified Satava classification. Using the methodology of the Framingham Heart Study, developed to identify risk factors that contribute to the development of cardiovascular disease, factors found to predict intraoperative complications independently were assigned points, and grouped into low-, moderate-, high- and extremely high-risk groups based on the likelihood of intraoperative complications. RESULTS: A total of 2856 patients were included. Neoadjuvant chemotherapy, lesion type and size, classification of resection and previous open liver resection were found to be independent predictors of intraoperative complications. Patients with intraoperative complications had a longer duration of hospital stay (5 versus 4 days; P < 0·001), higher complication rates (32·5 versus 15·5 per cent; P < 0·001), and higher 30-day (3·0 versus 0·3 per cent; P < 0·001) and 90-day (3·8 versus 0·8 per cent; P < 0·001) mortality rates than those who did not. The model was able to predict intraoperative complications (area under the receiver operating characteristic (ROC) curve (AUC) 0·677, 95 per cent c.i. 0·647 to 0·706) as well as postoperative 90-day mortality (AUC 0·769, 0·681 to 0·858). CONCLUSION: This comprehensive scoring system, based on patient, surgical and tumour factors, and developed and validated using a large multicentre European database, helped estimate the risk of intraoperative complications.

Outcome after laparoscopic and open resections of posterosuperior segments of the liver.

BACKGROUND: Laparoscopic resection of posterosuperior (PS) segments of the liver is hindered by limited visualization and curvilinear resection planes. The aim of this study was to compare outcomes after open and laparoscopic liver resections of PS segments. METHODS: Patients who underwent minor open liver resection (OLR) and laparoscopic liver resection (LLR) between 2006 and 2014 were identified from the institutional databases of seven tertiary referral European hepatobiliary surgical units. Propensity score-matched analysis was used to match groups for known confounders. Perioperative outcomes including complications were assessed using the Dindo-Clavien classification, and the comprehensive complication index was calculated. Survival was analysed with the Kaplan-Meier method. RESULTS: Some 170 patients underwent OLR and 148 had LLR. After propensity score-matched analysis, 86 patients remained in both groups. Overall postoperative complication rates were significantly higher after OLR compared with LLR: 28 versus 14 per cent respectively (P = 0·039). The mean(s.d.) comprehensive complication index was higher in the OLR group, although the difference was not statistically significant (26·7(16·6) versus 18·3(8·0) in the LLR group; P = 0·108). The mean(s.d.) duration of required analgesia and the median (range) duration of postoperative hospital stay were significantly shorter in the LLR group: 3·0(1·1) days versus 1·6(0·8) days in the OLR group (P < 0·001), and 6 (3-44) versus 4 (1-11) days (P < 0·001), respectively. The 3-year recurrence-free survival rates for patients with hepatocellular carcinoma (37 per cent for OLR versus 30 per cent for LLR; P = 0·534) and those with colorectal liver metastases (36 versus 36 per cent respectively; P = 0·440) were not significantly different between the groups. CONCLUSION: LLR of tumours in PS segments is feasible in selected patients. LLR is associated with fewer complications and does not compromise survival compared with OLR.

Indocyanine green near-infrared fluorescence in pure laparoscopic living donor hepatectomy: a reliable road map for intra-hepatic ducts?

Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet ; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts.

Indocyanine Green Near-Infrared Fluorescence in Pure Laparoscopic Living Donor Hepatectomy: a Reliable Road Map for Intra-Hepatic Ducts ?

Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts.

Laparoscopic cholecystectomy in acute cholecystitis: support for an early interval surgery.

BACKGROUND AND STUDY AIMS: Although laparoscopic cholecystectomy is advocated for acute cholecystitis, debate still exists about its optimal timing. This retrospective study compares the outcome of laparoscopic cholecystectomy within versus later than 5 days of onset of symptoms in patients with acute cholecystitis. PATIENTS AND METHODS: One hundred thirty six patients with acute cholecystitis grade I or II were included in the study and divided in two groups. Group 1 received surgery within 5 days of symptoms and group 2 received conservative therapy and delayed surgery after 6 weeks. RESULTS: Group 1 and 2 consisted of 100 and 36 patients respec- tively. Because of failure of conservative therapy 5 patients of group 2 had surgery before 6 weeks. The remaining 31 patients underwent surgery after 6 weeks. Preoperative ERCP was indicated in 2 and 11 patients in groups 1 and 2 respectively (p < 0.001). The median total hospital stay was 3.0 days for group 1 and 11.0 days for group 2 (p < 0.001). In terms of operation time, conversion rates, intraoperative cholangiography, postoperative ERCP, morbidity or mortality both groups were comparable (p > 0.05). CONCLUSION: Laparoscopic cholecystectomy can be performed safely within 5 days after the onset of symptoms in patients with acute cholecystitis. Because of shortened total hospital stay and risk of failure of conservative therapy, early laparoscopic cholecystectomy should be favored.

Cutaneous infection by Alternaria infectoria in a liver transplant recipient: a case report.

We report the case of a 65-year-old man who developed multiple crusty ulcerative skin lesions on both lower extremities six months after liver transplantation. The causative pathogen was identified as Alternaria Infectoria, an opportunistic fungal agent. The patient was successfully treated with fluconazole for 27 weeks, with complete regression of the lesions. Due to the lack of well-designed clinical studies it is difficult to determine the best treatment course regarding solid organ transplant recipients presenting with invasive fungal infections. And for now, the clinician must lean upon case-reports or retrospective analyses to compose the most suited therapy for his patient. Based upon literature, it seems that the combination of a broad spectrum azole and reducing the dose of immunosuppressive drugs is the cornerstone of treating invasive fungal infections in solid organ transplant patients.

Laparoscopic liver resection compared to open approach in patients with colorectal liver metastases improves further resectability: Oncological outcomes of a case-control matched-pairs analysis.

AIMS: Liver resection is considered the standard treatment of colorectal metastases (CRLM). However, to date, no long term oncological results and data regarding repeat hepatectomy after laparoscopic approach are known. The aim of this study is to analyze single center long-term surgical and oncological outcomes after liver resection for CRLM. METHODS: A total of 57 open resections (OR) were matched with 57 laparoscopic resections (LR) for CRLM. Matching was based mainly on number of metastases, tumor size, segmental position of lesions, type of hepatectomy and type of resection. RESULTS: Morbidity rate was significantly less in the LR group (p = 0.002); the length of hospital stay was 6.5 ± 5 days for the LR group and 9.2 ± 4 days for the OR group (p = 0.005). After a median follow up of 53.7 months for the OR group and 40.9 months for the LR group, the 5-y overall survival rate was 65% and 60% respectively (p = 0.36) and the 5-y disease free survival rate was 38% and 29% respectively (p = 0.24). More patients in the LR group received a third hepatectomy for CRLM relapse than in the OR group (80% vs. 14.3% respectively; p = 0.015). CONCLUSIONS: Laparoscopic resection for CRLM offers advantages in terms of reduced blood loss, morbidity rate and hospital stay. It provides comparable long-term oncological outcomes but can improve further resectability in patients with recurrent disease.

Meso-Rex shunt using deep femoral vein conduit: first report.

The Meso-Rex shunt (MRS) procedure was first described in 1992 by de VILLE et al. for the treatment of extrahepatic portal vein obstruction (EHPVO) in paediatric liver transplant patients. This technique provides more physiological relief of portal hypertension compared to the porto-systemic shunts, which can lead to long-term complications such as hyperammonaemia and hepato-pulmonary syndrome. Different conduits as autologous and cryopreserved veins or prosthetic grafts have been previously reported. We present herein the first case of a MRS using the autologous deep femoral vein in a 17-year-old female patient affected by EHPVO from unknown reasons.

Pure laparoscopic full-left living donor hepatectomy for calculated small-for-size LDLT in adults: proof of concept.

Adult-to-adult living donor liver transplantation (A2ALDLT) is an accepted mode of treatment for end-stage liver disease. Right-lobe grafts have usually been preferred in view of the higher graft volume, which lowers the risk of a small-for-size syndrome. However, donor left hepatectomy is associated with less morbidity than when it is compared to right hepatectomy. Laparoscopic donor hepatectomy (LDH) has been considered almost exclusively in pediatric transplantation. The results of laparoscopic left-liver graft procurement for calculated small-for-size A2ALDLT in four donors are presented. The graft-to-recipient body weight ratio was <0.8 in all recipients. The mean portal vein flow and the pressure and hepatic artery flows were measured at 190 ± 56 mL/min/100 g, 13 ± 1.4 mm/Hg and 109 ± 19 mL/min, respectively. No early postoperative donor complications were recorded. One graft was lost due to intrahepatic abscesses. Asymptomatic stenosis of a right posterior duct was treated with a Roux-en-Y loop 4 months later in one donor. We show that LDH of the full-left lobe is feasible. LDH is a very demanding operation, potentially decreasing donor morbidity. Standardization of this procedure, making it accessible to the growing number of experienced laparoscopic liver surgeons, could help renewing the interest for A2ALDLT in the Western world.

Open preperitoneal mesh repair of inguinal hernias using a mesh with nitinol memory frame.

PURPOSE: To prospectively evaluate the use of a continuous Nitinol containing memory frame patch during a TIPP-technique in the open repair of inguinal and femoral hernias. METHODS: Over a 3-year period all consecutive adult patients that needed treatment for an inguinal or femoral hernia were treated by the TIPP repair using the Rebound Shield mesh. Intra-operatively the type and size of the hernia were evaluated according to the EHS classification, as well as the size of the mesh used. Baseline characteristics for all patients were evaluated considering age, gender, BMI and American society of Anesthesiologists score. Standard X-ray was performed to evaluate mesh position. All patients were evaluated for post-operative pain using the visual analogue scale (VAS 0-10 scale). RESULTS: In total 289 groin hernias were operated using a nitinol containing patch in 235 patients. The mean operating time was 38 min for unilateral hernias and 59 min for bilateral hernias. The median follow-up is 21.2 months (14-33 months) during which three patients died, unrelated to the groin hernia repair. At the time of re-evaluation 12 patients (5.0 %) complained of chronic pain, with a VAS score higher than 3 after 3 months (range 3-10). Two of these patients already had severe pain pre-operatively. A total of 3 recurrences (2.9 %) were noted with strong correlation with X-ray findings. CONCLUSION: A nitinol memory frame containing mesh is a valuable tool to achieve complete deployment of a large pore mesh in a TIPP repair for inguinal hernias with acceptable morbidity and a low recurrence rate.

Long-term outcomes and quality of life in critically ill patients with hematological or solid malignancies: a single center study.

PURPOSE: Data concerning long-term outcomes and quality of life (QOL) in critically ill cancer patients are scarce. The aims of this study were to assess long-term outcomes and QOL in critically ill patients with hematological (HM) or solid malignancies (SM) 3 months and 1 year after intensive care unit (ICU) discharge, to compare these with QOL before ICU admission, and to identify prognostic indicators of long-term QOL. METHODS: During a 1 year prospective observational cohort analysis, consecutive patients with HM or SM admitted to the medical or surgical ICU of a university hospital were screened for inclusion. Cancer data, demographics, co-morbidity, severity of illness, organ failures, and outcomes were collected. The QOL before ICU admission, 3 months, and 1 year after ICU discharge was assessed using standardized questionnaires (EuroQoL-5D, Medical Outcomes Study 36-item Short Form Health Survey). Statistical significance was attained at P < 0.05. RESULTS: There were 483 patients (85 HM, 398 SM) (64% men) with a median age of 62 years included. Mortality rates of HM compared to SM were, respectively: hospital (34 vs. 13%), 3 months (42 vs. 17%), and 1 year (66 vs. 36%) (P < 0.001). QOL declined at 3 months, but improved at 1 year although it remained under baseline QOL, particularly in HM. Older age (P = 0.007), severe comorbidity (P = 0.035), and HM (P = 0.041) were independently associated with poorer QOL at 1 year. CONCLUSIONS: Long-term outcomes and QOL were poor, particularly in HM. Long-term expectations should play a larger role during multidisciplinary triage decisions upon referral to the ICU.

Pathophysiology and management of post resection liver failure.

Post resection liver failure (PRLF) is defined by the occurrence of jaundice, coagulopathy and encephalopathy after liver resection. When PRLF is present, it has a high morbidity and mortality. The incidence of PRLF ranges between 0-30%. For having a healthy regeneration of the liver remnant an adequate number of hepatocytes and nonparenchymal cells, a normal functional and regenerative capacity and also a good accommodation of haemodynamic changes without congestion are needed. To avoid the presence of PRLF ongoing parenchymal damage after the liver resection should be avoided. So, ischemia reperfusion injury should be minimalized, infection and sepsis should be treated immediately and small for size syndrome should be avoided.

Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial.

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.

Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation.

The efficacy and safety of dual-therapy regimens of twice-daily tacrolimus (BID; Prograf) and once-daily tacrolimus (QD; Advagraf) administered with steroids, without antibody induction, were compared in a multicenter, 1:1-randomized, two-arm, parallel-group study in 475 primary liver transplant recipients. A double-blind, double-dummy 24-week period was followed by an open extension to 12 months posttransplant. The primary endpoint, event rate of biopsy-proven acute rejection (BPAR) at 24 weeks, was 33.7% for tacrolimus BID versus 36.3% for tacrolimus QD (Per-protocol set; p = 0.512; treatment difference 2.6%, 95% confidence interval -7.3%, 12.4%), falling within the predefined 15% noninferiority margin. At 12 months, BPAR episodes requiring treatment were similar for tacrolimus BID and QD (28.1% and 24.7%). Twelve-month patient and graft survival was 90.8% and 85.6% for tacrolimus BID and 89.2% and 85.3% for tacrolimus QD. Adverse event (AE) profiles were similar for both tacrolimus BID and QD with comparable incidences of AEs and serious AEs. Tacrolimus QD was well tolerated with similar efficacy and safety profiles to tacrolimus BID.