Development and validation of a comprehensive model to predict complications after hepatectomy.

OBJECTIVE: Despite advances in perioperative care, hepatectomy remains associated with morbidity rates of up to 40%. Currently, available nomograms for predicting severe post-hepatectomy complications do not include early postoperative data. This retrospective observational study aimed to determine whether the parameters routinely measured in patients admitted to the Intensive Care Unit (ICU) after hepatectomy could represent risk factors for severe morbidity and to propose a nomogram scoring system to predict severe postoperative complications. PATIENTS AND METHODS: 411 adult patients who underwent elective hepatectomy at a high-volume tertiary care center for hepatic surgery from December 2016 to June 2022 were enrolled. The primary outcome was the assessment of predictors of 30-day severe postoperative complications following hepatectomy, defined as Clavien-Dindo grade 3a or higher. As a secondary outcome, we aimed to develop an easy-to-use scoring system to estimate the risk of severe postoperative complications. RESULTS: Severe complications occurred in 78 patients (19%). The final model included body mass index, preoperative bilirubin level, and ICU data (i.e., pH, lactate clearance, arterial lactate concentration 12 hours after ICU admission, need for packed red blood cell transfusions, and length of stay). Notably, the latter three variables were proven to be independent predictors of the outcomes. The model showed an overall good fit (C-index=0.754, corrected Dxy=0.692). A calibration plot using bootstrap internal validity resampling confirmed the stability of the model (mean absolute error=0.017, root mean square error of approximation=0.00051). CONCLUSIONS: We developed an accurate and practical scoring system based on preoperative and early postoperative data to predict poor outcomes after hepatectomy. Further external validation on larger series could lead to the integration of such a tool in the routine clinical practice to support patients' management and early warning during ICU stay. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-Abstract-NEW-2.pdf.

Serum Trimethylamine-N-oxide Concentrations in People Living with HIV and the Effect of Probiotic Supplementation.

BACKGROUND: The incidence of cardiovascular disorders in people living with HIV (PLWH) is higher than that in non-infected individuals. Traditional and specific risk factors have been described but the role of the gut microbiota-dependent choline metabolite, trimethylamine-N-oxide (TMAO) is still unclear. METHODS: A cross-sectional analysis and a longitudinal analysis (with high-dose probiotic supplementation) were performed to measure serum TMAO concentrations through UHPLC-MS/MS. Stable outpatients living with HIV on highly active antiretroviral treatment with no major cardiovascular disease were enrolled. Non-parametric tests (bivariate and paired tests) and a multivariate linear regression analysis were used. RESULTS: A total of 175 participants were enrolled in the study. Median serum TMAO concentrations were 165 (103-273) ng/mL. An association with age, serum creatinine, number of antiretrovirals, multimorbidity and polypharmacy was observed; at linear logistic regression analysis, multimorbidity was the only independent predictor of TMAO concentrations. Carotid intima media thickness (IMT) was 0.85 (0.71-1.21) mm, with a trend towards higher TMAO concentrations observed in patients with IMT >0.9 mm (P=0.087). In the 25 participants who received probiotic supplementation, TMAO levels did not significantly change after 24 weeks (Wilcoxon paired P=0.220). CONCLUSION: Serum TMAO levels in PLWH were associated with multimorbidity, higher cardiovascular risk and subclinical atherosclerosis and were not affected by 6 months of high-dose probiotic supplementation.

Treatment with direct-acting antiviral agents of hepatitis C virus infection in injecting drug users: A prospective study.

In this prospective study, we evaluated the effectiveness and tolerability of novel therapies against hepatitis C virus (HCV) in a cohort of PWID enrolled at our centre from April 2015 to July 2016. In this analysis, a total of 174 patients were included: eleven (6.3%) were treated with pegylated interferon (PEG-IFN) and ribavirin (RBV) containing regimens, 163 (93.7%) with IFN-free treatments. RBV has been used in 70 patients (40.2%); 59 (33.9%) patients were in opioid substitution therapy (OST) with methadone or buprenorphine. Overall, sustained virological response (SVR) has been observed in 162 subject (93.1%), breakthrough (BT) in three (1.7%), relapse in one (0.6%) and dropout in eight (4.6%). Treatment was interrupted for clinical conditions in seven patients: six (3.4%) had hepatic decompensation and one died for hepatocellular carcinoma (HCC). In multivariate analysis, predictive factors of treatment failure were as follows: albumin level below 3 g/dL (OR=7.190; 95% IC=1.236-41.837; P<.001), MELD score >10 (OR=5.886; 95% IC=1.411-35.994; P<.001) and years of HCV infection >20 (OR=1.286; 95% IC=0.556-9.455; P=.016). In conclusion, treatment with DAAs was effective and well tolerated in PWID; cirrhotic subjects with MELD > 10 and albumin low level showed a higher risk of developing serious adverse events and treatment failure.

Diagnosis and Management of Hepatic Artery Complications After Liver Transplantation.

BACKGROUND: We assessed the usefulness of color Doppler imaging in diagnosis and monitoring hepatic artery complications after liver transplantation. METHODS: Subjects were 421 liver transplant recipients who underwent serial ultrasound (US) color Doppler evaluations of the hepatic arteries after surgery. RESULTS: We saw 4 hepatic arterial complications after liver transplantation (13 thrombosis, 29 stenosis, 2 kinking, 2 pseudo-aneurysm, and 2 pseudo-aneurysm rupture). All subjects underwent US color Doppler examination periodically after surgery. In 6 cases of early thrombosis, hepatic arterial obstruction was diagnosed with absence of Doppler signals; in the other 7 cases (late hepatic artery thrombosis), thrombosis was suspected for the presence of intra-parenchymal "tardus-parvus" waveforms. In all of the cases, computed tomography angiography showed obstruction of the main arterial trunk and the development of compensatory collateral circles (late hepatic artery thrombosis). In 10 of the 29 cases of stenosis, Doppler ultrasonography examination revealed stenotic tract and intra-hepatic tardus-parvus waveforms; in 17 stenosis cases, the site of stenosis could not be identified, but intra-parenchymal tardus-parvus waveforms were recorded. In 2 patients, hepatic artery stenosis occurred with ischemic complications. CONCLUSIONS: The use of US color Doppler examination allows the early diagnosis of hepatic arterial complications after liver transplantation. Tardus-parvus waveforms indicated severe impairment of hepatic arterial perfusion from either thrombosis or severe stenosis. The presence of these indirect signs enhanced the accuracy of color Doppler diagnosis, and detection should prompt therapy.

Acute Liver Failure in an Adult, a Rare Complication of Alagille Syndrome: Case Report and Brief Review.

Alagille syndrome (AS) is an autosomal-dominant, multisystem disorder affecting the liver, heart, eyes, skeleton, and face. The manifestations are predominantly pediatric. Diagnosis is based on findings of a paucity of bile ducts on liver biopsy combined with ≥3 of 5 major clinical criteria. Orthotopic liver transplantation (OLT) is the only option for treating patients who developed liver failure, portal hypertension, severe itching, and xanthomatosis. It is difficult to establish clear criteria for OLT; indications are controversial because of the wide variety of clinical symptoms and the multisystem involvement. Generally, AS-associated liver disease is never an acute illness. We report the case of a 28-year-old woman with AS who underwent urgent OLT for acute liver failure. At 24 months posttransplant, the patient is in good clinical condition and with normal hepatic and renal function.

Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients: a randomized, controlled, pilot study (the REYAGEN study).

BACKGROUND: Atazanavir without ritonavir, despite efficacy and tolerability, shows low plasma concentrations that warrant optimization. METHODS: In a randomized, controlled, pilot trial, stable HIV-positive patients on atazanavir/ritonavir (with tenofovir/emtricitabine) were switched to atazanavir. In the standard-dose arm, atazanavir was administered as 400 mg once daily, while according to patients' genetics (PXR, ABCB1 and SLCO1B1), in the pharmacogenetic arm: patients with unfavourable genotypes received 200 mg of atazanavir twice daily. EudraCT number: 2009-014216-35. RESULTS: Eighty patients were enrolled with balanced baseline characteristics. The average atazanavir exposure was 253 ng/mL (150-542) in the pharmacogenetic arm versus 111 ng/mL (64-190) in the standard-dose arm (P < 0.001); 28 patients in the pharmacogenetic arm (75.7%) had atazanavir exposure >150 ng/mL versus 14 patients (38.9%) in the standard-dose arm (P = 0.001). Immunovirological and laboratory parameters had a favourable outcome throughout the study with non-significant differences between study arms. CONCLUSIONS: Atazanavir plasma exposure is higher when the schedule is chosen according to the patient's genetic profile.

Influence of single-nucleotide polymorphisms on deferasirox C trough levels and effectiveness.

Deferasirox (DFX) is the only once-daily oral chelator for iron overload and its pharmacokinetic has been related with response to therapy. Our aim was to evaluate DFX plasma concentrations according to single-nucleotide polymorphisms in genes involved in its metabolism (UGT1A1, UGT1A3, CYP1A1, CYP1A2 and CYP2D6) and elimination (MRP2 and BCRP1). Further aim was to define a plasma concentration cutoff value predicting an adequate response to therapy. Plasma concentrations were determined at the end of dosing interval (C trough) using an high-performance liquid chromatography-ultraviolet method. Allelic discrimination was performed by real-time PCR. C trough levels were influenced by UGT1A1C>T rs887829, CYP1A1C>A rs2606345, CYP1A2A>C rs762551, CYP1A2C>T rs2470890 and MRP2G>A rs2273697 polymorphisms. A DFX plasma efficacy cutoff value of 20,000 ng ml(-1) was identified; CYP1A1C>A rs2606345 AA and CYP1A2C>T rs2470890 TT genotypes may predict this value, suggesting a negative predictive role in therapy efficacy. Our data suggest the feasibility of a pharmacogenetic-based DFX dose personalization.

Etravirine plasma exposure is associated with virological efficacy in treatment-experienced HIV-positive patients.

Etravirine is a non-nucleoside reverse transcriptase inhibitor used in combination with other antiretrovirals for the treatment of HIV infection. Given previous conflicting results aim of this study was to investigate whether etravirine plasma exposure was associated with virological outcome. Adult HIV-positive patients starting etravirine with detectable HIV viral loads were included if highly adherent (<90% of the doses) and if steady-state plasma concentrations were available (measured through a validated HPLC-PDA method). Virological success was defined as reaching and maintaining viral suppression (HIV RNA <50copies/mL) during follow up. Fifty-nine (84.7% male) patients were included: baseline CD4+ T-lymphocyte and HIV RNA were 276cells/µL (101-419) and 3.99Log10copies/mL (3.11-4.91), respectively. Darunavir/ritonavir (n=21, 35.6%) and raltegravir plus maraviroc (n=33, 55.9%) were the most common associated antiretrovirals. 240 trough samples were available (3-7 per patient); etravirine trough concentrations (Ctrough) and weighted genotypic inhibitory quotients (wgIQ) were 426ng/mL (266-763) and 408ng/mL/mutation (227-663), respectively. Virological success was observed in 49 patients (83.1%). Genotypic sensitivity of associated drugs (GSS) ⩾2 (p=0.03), etravirine Ctrough >300ng/mL (p=0.02) and etravirine wgIQ >276ng/mL/mutation (p=0.02) were associated with virological success; at multivariate Cox proportional analysis etravirine wgIQ <276ng/mL/mutation (p=0.012) and baseline CD4 <200cell/µL (p=0.043) were independently associated with virological failure. In a cohort of experienced patients etravirine exposure as well as immune status were associated with virological success; two cut off values (300ng/mL and 276ng/mL) were proposed for etravirine Ctrough and wgIQ and need to be confirmed in prospective studies.

Incidence of upper aerodigestive tract cancer after liver transplantation for alcoholic cirrhosis: a 10-year experience in an Italian center.

INTRODUCTION: The aim of this study was to evaluate the incidence, clinical characteristics, treatment, and outcome of de novo tumors (DNT) of the upper aerodigestive tract in patients with alcoholic cirrhosis after orthotopic liver transplantation (OLT). METHODS: Among 225 consecutive OLT performed between January 2002 and January 2012, a total of 205 patients received a first liver allograft. Eleven (4.9%) patients developed DNT (lung, pancreas, bowel, esophagus, larynx, tongue, tonsil, and lymphoma). Among these, we observed 5 patients with DNT of the upper aerodigestive tract. RESULTS: The 5 patients with DNT of the upper aerodigestive tract underwent OLT for alcoholic cirrhosis. There were 4 men and 1 woman with a mean age at transplantation of 47 years. The mean period of alcohol abuse was 90 months. The tumors occurred after a mean post-transplantation time of 39 months. The immunosuppressive regimen included Tacrolimus, mTOR, mycophenolate mofetil (MMF), and low-dose steroids. We observed 2 cases of squamous cell carcinoma of the esophagus, 1 case of tonsillar cancer, 1 case of larynx carcinoma, and 1 case of tongue carcinoma. All patients underwent surgical excision. After surgery, 4 patients received chemotherapy and 2 patients radiotherapy. At present, among the 5 patients with DNT of the upper aerodigestive tract, only 2 are alive without disease and 1 is alive with a local recurrence. CONCLUSION: The incidence of DNT of the upper aerodigestive tract after OLT is higher among patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of post-transplantation immunosuppression in patients exposed to alcohol before transplantation. We suggest a careful post-transplantation follow-up and more attention to improve early diagnosis.

Low values of left ventricular ejection time in the post-anhepatic phase may be associated with occurrence of primary graft dysfunction after orthotopic liver transplantation: results of a single-centre case-control study.

BACKGROUND: Previous investigations on risk factors for orthotopic liver transplantation (OLT) surgery have not analyzed hemodynamic aberrations in great detail. Moreover, the usefulness of esophageal Doppler monitoring has not been extensively studied in this clinical setting. The aim of this study was to evaluate if the occurrence of primary graft dysfunction (PGD) may be anticipated by hemodynamic indexes measured by esophageal Doppler (ED) monitoring system as well as by pulmonary artery catheter (PAC) in patients undergoing OLT. MATERIALS AND METHODS: 38 OLT recipients were studied. Patients with acute liver failure or having non treated esophageal varices and those transplanted with marginal donors were excluded from the study. The haemodynamic data - measured by ED monitoring system (HemosonicTM 100, Arrow, OK, USA) and PAC - collected at the following 3 time points were considered for statistical analysis: 30 minutes after the induction of anesthesia but before skin incision, T0; 20 minutes after liver dissection, T1; at the beginning of biliary reconstruction, T2. On the basis of early outcome (72 hours after OLT), patients were distinguished into two groups: those with PGD (grade III-IV of Toronto classification) and those without PGD (grade I-II). RESULTS: LVETc (left ventricular ejection time) values, registered at the beginning of biliary reconstruction (T2), were lower in patients with PGD compared to those without PGD (p < 0.000), while there were no differences in hemodynamic parameters derived from PAC between the two groups. CONCLUSIONS: Since LVETc is related to preload, the results of this study would suggest that normovolemia could be the end point of a fluid replacement strategy in OLT setting.

Short-term additional enfuvirtide therapy is associated with a greater immunological recovery in HIV very late presenters: a controlled pilot study.

OBJECTIVES: To evaluate whether the addition of enfuvirtide to standard highly active antiretroviral therapy (HAART) could confer immunovirological benefits in human immunodeficiency virus (HIV)-infected very late presenters. The current study is an open comparative therapeutic trial of standard protease inhibitor (PI)-based HAART ± additional enfuvirtide in treatment-naïve deeply immunologically impaired HIV-positive patients. METHODS: Very late presenters (CD4 <50/mm(3)), without tuberculosis and neoplasms, were alternatively allocated to two nucleoside reverse transcriptase inhibitors (NRTIs) and lopinavir/ritonavir without (control arm, CO) or with (ENF arm) enfuvirtide 90 mg bid. Enfuvirtide was administered until the achievement of viral load <50 copies/ml and for at least 24 weeks. The primary objective was the magnitude of CD4+ cell recovery at 6 months. HIV RNA was intensively monitored in the first month, and, thereafter, monthly, as for CD4+ cell count and percentage, clinical data, and plasma drug concentrations. RESULTS: Of 22 enrolled patients (11 per arm), 19 completed the study (10 in the ENF arm). Baseline CD4+ cell counts and % were comparable, with 20 CD4+/mm(3) (12-37) and a percentage of 3.3 (1.7-7.1) in the ENF arm, and 16 CD4+/mm(3) (9-29) and a percentage of 3.1 (2.3-3.8) in the CO arm, respectively. The baseline viral load was also comparable between the two arms, with 5.77 log10 (5.42-6) and 5.39 log10 (5.06-6) in the ENF and CO arms, respectively. Enfuvirtide recipients had higher CD4+ percentage at week 8 (7.6 vs. 3.6%, p = 0.02) and at week 24 (10.7 vs. 5.9%, p = 0.02), and a greater CD4+ increase at week 24 (207 vs. 134 cells/mm(3), p = 0.04), with 70% of enfuvirtide intakers versus 12.5% of controls who achieved a CD4+ cell count >200/mm(3) (p = 0.01). At 48 weeks, patients in the ENF arm had CD4+ cell counts higher than controls (251 vs. 153cells/mm(3), p = 0.04) and were also found to be faster in reaching a CD4 cell count over 200/mm(3): 18 (8-24) versus 48 (36-108) weeks (p = 0.01). Viral load decay at week 4 was greater in the ENF arm (-3 vs. -2.2 log, p = 0.04), while the proportion of patients with viral load <50 copies/ml at week 24 was comparable. CONCLUSIONS: In this pilot study, the addition of enfuvirtide to a lopinavir-based HAART was shown to be associated with a significantly faster and greater immunological recovery in newly discovered HIV-positive patients with very low CD4+ cell counts. Induction strategies using an enfuvirtide-based approach in such subjects warrant further investigation.

Late development of splenic artery aneurysm after orthotopic liver transplantation: a case report.

Splenic artery aneurysm (SAA) is a rare complication after orthotopic liver transplantation (OLT). Although SAAs are often incidental findings, in some cases they present with signs and symptoms of abdominal mass or intra-abdominal hemorrhage. The diagnosis requires Doppler ultrasound and confirmation with computed tomography, magnetic resonance, or angiography. Endovascular techniques are preferred to surgery for the treatment of most SAAs. A variable interval from 6 days to 11 years has been reported between OLT and the diagnosis of SAA, justifying a lifelong scheduled surveillance of abdominal vessels by ultrasound after OLT. Herein we have reported a case of SAA that developed 16 years after OLT. This pathological condition was totally asymptomatic. Only routine abdominal ultrasound allowed its detection and subsequent successful treatment.

Molecular adsorbent recirculating system (Mars) in patients with primary nonfunction and other causes of graft dysfunction after liver transplantation in the era of extended criteria donor organs.

Liver dysfunction is an important cause of morbidity and mortality after orthotopic liver transplantation (OLT). The Molecular Adsorbent Recirculating System (MARS) is an albumin-based dialysis system designed to enhance the excretory function of a failing liver. MARS has been successfully used in patients affected by advanced liver disease and presenting with severe cholestasis. The aim of this study was to evaluate the safety and clinical efficacy of MARS in patients with liver dysfunction after OLT. Seven patients (primary nonfunction, 2 patients; graft dysfunction, 5 patients) fulfilled the inclusion criteria of serum bilirubin level >15 mg/dL and least 1 of the following clinical signs: hepatic encephalopathy (HE) > or = grade II, hepatorenal syndrome (HRS), and intractable pruritus. Graft and patient survival rates at 6 months were 42.8% and 57.1%, respectively. All patients tolerated MARS treatment, with no adverse event. In all patients, a decrease in serum bilirubin (P < .05), bile acids (P < .05), serum creatinine, and ammonia levels was observed after treatment with MARS. A considerable improvement of HE, as well as renal and synthetic liver functions, was observed in 4 of 5 patients with graft dysfunction, but not among those with primary nonfunction. The patients with intractable pruritus showed significant improvement of this symptom after MARS therapy. Thus, MARS is a safe, therapeutic option for the treatment of liver dysfunction after OLT. Further studies are necessary to confirm whether this treatment is able to improve both graft and patient survival.

Use of an esophageal echo-Doppler device during liver transplantation: preliminary report.

Determination of cardiac output (CO) is crucial for perioperative monitoring of orthotopic liver transplant (OLT) recipients. A pulmonary artery catheter (PAC) has always been considered the "gold standard" of hemodynamic monitoring. The aim of this study was to evaluate the suitability of a transesophageal echo-Doppler device (ED) as a minimally invasive device to measure CO in OLT. ED was compared with the standard PAC technique taking into account the disease severity of OLT recipients as defined by the model for end-stage liver disease (MELD) score. We enrolled 42 cirrhotic patients scheduled for OLT 3 thermodilution CO measurements were taken by a PAC and the most recent ED measurement (CO(ED)) was also recorded. Paired measurements of CO were performed at standard times, unless there were additional clinical needs. Recipients were stratified into 3 groups according to MELD score: MELD score < or = 15 (14 patients); MELD score between 16 and 28 (17 patients); and MELD score > or = 29 (11 patients). We performed 495 paired measurements of CO. Mean bias was 0.34 +/- 0.9 L/min and limits of agreement were -1.46 and 2.14 L/min. In patients with MELD score <15, the bias was 0.12 +/- 0.55. The ED results were not interchangeable with PAC, because of the large limits of agreement. However, in cirrhotic patients with MELD scores <15, the precision of the new method was similar to that of PAC; therefore, in this subset of patients, it may represent a reliable alternative to PAC.

Successful use of extended criteria donor grafts with low to moderate steatosis in patients with model for end-stage liver disease scores below 27.

Liver transplantation may be performed using extended criteria donor grafts (ECDg). The characteristics of ECDg include age >60 years, long intensive care unit (ICU) stay, history of malignancy or steatosis. Grafts are often discarded due to steatosis, which can be macrovesicular (MaS) or microvesicular (MiS). MaS is the variety most frequently involved with unfavorable outcomes due to primary nonfunction (PNF) or primary dysfunction (PDF). As of January 2000, all livers referred to our institution were considered potentially transplantable. Steatosis was defined as the presence of fat droplets in more than 5% of hepatocytes. We observed 35 steatotic grafts. Grafts were stratified according to MaS and MiS as follows: low steatosis (5%-15%), mild steatosis (16%-30%), moderate steatosis (31%-60%), or severe steatosis (>60%). Fifteen grafts with moderate (n = 2) or severe (n = 13) MaS were discarded. Twenty grafts were harvested: 18 of them were transplanted at our institution, the remaining 2, discarded by our donor team, were transplanted by other Italian centers. Low MaS was detected in 10 grafts (50%), mild MaS in 4 (20%), and moderate MaS in 2 (10%). Low MiS was detected in 8 grafts (40%), mild MiS in 5 (25%), and moderate MiS in 1 (5%). Steatotic grafts were transplanted only into recipients with model for end-stage liver disease (MELD) scores <27. The 6-month graft survival was 80%; the PNF rate was 10%; and the PDF rate was 15%. The careful use of ECDg with low to moderate steatosis is possible if particular care is taken to avoid additional risk factors related to the recipient.

Donor risk index and organ patient index as predictors of graft survival after liver transplantation.

In liver transplantation the identification of risk factors and the risk quantification for each single case represent a field of great interest. There are donor-related and recipient-related risk factors. Donor risk index (DRI) was retrospectively calculated in 223 liver transplant cases. We did not include patients with preoperative diagnosis of hepatocarcinoma and retransplants. The cases were stratified into two classes according to the DRI (low risk, DRI<1.7, and high risk, DRI >or= 1.7). A new index, namely the organ patient index (OPI) was calculated adding the Model for End-stage Liver Disease (MELD) score to the DRI. Patients were stratified into two classes according to the OPI (low risk, OPI 2.85). The cases with low DRI (n=144) showed better survival than the cases with high DRI (n=82; P< .02). The cases with low OPI (n=173) showed better survival than cases with high OPI (n=50; P< .01). The OPI predicted outcomes better than DRI, increasing the gap in the long-term graft survival between the low- and the high-risk class. The inclusion of the MELD in the new index allowed better prediction of graft survival.

Treatment of chronic hepatitis C virus infection with pegylated interferon and ribavirin in cirrhotic patients awaiting liver transplantation.

Successful treatment of chronic hepatitis C virus (HCV) infection can prevent reinfection after orthotopic liver transplantation (OLT). Pegylated interferon (PEG-IFN) may ameliorate virological response (VR), making the risk-to-benefit ratio of therapy favorable in waiting list patients. From January 2001 to April 2006, we treated 15 HCV cirrhotics with PEG-IFN alpha-2b (1.5 microg/kg/week) and ribavirin (RIBA; >or=10.6 mg/kg/d). Their mean age was 51.5 years. There were 9 men. In 6 cases the genotype was 1b. With Child-Pugh scores >or=9 (range 9-12) and Model for End-Stage Liver Disease (MELD) scores >or=14 (range, 14-22). Adverse events occurred in all subjects: thrombocytopenia (<40,000/microL) in 8; neutropenia (<700/microL) in 10; anemia (Hb <8.5 g/dL) in 1; grade III hepatic encephalopathy in 2; pelvic infection in 1; variceal hemorrhage in 1; and hepatocellular carcinoma (HCC) recurrence in 1. Adverse events caused treatment withdrawal in 6 (40.0%) and RIBA and/or PEG-IFN dose reduction in 10 (66.6%). Early VR (EVR) was obtained in 9 subjects (60.0%), end-of-treatment (EOT) VR in 7 (46.6%), and sustained VR (SVR) in 3 (20.0%). Three subjects--2 nonresponder and 1 breakthrough--were transplanted at 25, 23, and 16 months after the EOT, respectively. Three subjects died at 6, 8, and 15 months after the EOT due to HCC, spontaneous bacterial peritonitis, and liver failure. Nine patients are awaiting OLT. The risk-to-benefit ratio is against PEG-INF and RIBA treatment of severely decompensated cirrhotics infected with genotype 1 awaiting OLT, but therapy is probably beneficial in genotype 2 subjects, due to an expected SVR rate of more than 40%. However, one must carefully consider the high risk for severe adverse events.

Donor-recipient MELD-based match in a patient who required three liver grafts in the era of nonstandard donors: case report.

In recent studies, nonstandard donors and high Model for End-stage Liver Disease (MELD) values have been indicated as risk factors for both graft survival and patient survival. A recent debate concerns which donor and recipient match guarantees the best results in terms of early and late survival. To emphasize the role of the donor-recipient match, we have reported herein a complex case of a patient who changed his preoperative risk status, being transplanted three times using donors of different risk levels. At each transplant, the patient moved to a higher MELD class: first transplant MELD=22; second transplant MELD=37; third transplant MELD=38. Only at the third transplant did the patient recover. Besides the liver, almost all his organs (kidneys, heart, lungs) recovered in a few weeks, as well. Unfortunately, severe cortical and subcortical brain damage remained a crucial limiting impairment, leading to death 5 months later, due to pulmonary infection, yet with a perfectly working liver. We underlined the role of donor factors to predict the outcome after liver transplantation in the MELD era.