ALK7 expression in prolactinoma is associated with reduced prolactin and increased proliferation.

Prolactinoma represents the most frequent hormone-secreting pituitary tumours. These tumours appear in a benign form, but some of them can reach an invasive and aggressive stage through an unknown mechanism. Discovering markers to identify prolactinoma proliferative and invading character is therefore crucial to develop new diagnostic/prognostic strategies. Interestingly, members of the TGFß-Activin/BMP signalling pathways have emerged as important actors of pituitary development and adult function, but their role in prolactinomas remains to be precisely determined. Here, using a heterotopic allograft model derived from a rat prolactinoma, we report that the Activins orphan type I receptor ALK7 is ectopically expressed in prolactinomas-cells. Through immunohistological approaches, we further confirm that normal prolactin-producing cells lack ALK7-expression. Using a series of human tumour samples, we show that ALK7 expression in prolactinomas cells is evolutionary conserved between rat and human. More interestingly, our results highlight that tumours showing a robust expression of ALK7 present an increased proliferation as address by Ki67 expression and retrospective analysis of clinical data from 38 patients, presenting ALK7 as an appealing marker of prolactinoma aggressiveness. Beside this observation, our work pinpoints that the expression of prolactin is highly heterogeneous in prolactinoma cells. We further confirm the contribution of ALK7 in these observations and the existence of highly immunoreactive prolactin cells lacking ALK7 expression. Taken together, our observations suggest that Activin signalling mediated through ALK7 could therefore contribute to the hormonal heterogeneity and increased proliferation of prolactinomas.

Neoadjuvant chemotherapy response influences outcomes in non-colorectal, non-neuroendocrine liver metastases.

BACKGROUND: Indications for surgical resection of non-colorectal, non-neuroendocrine (NCNNE) liver metastases are unclear. This study analysed the influence of response to neoadjuvant chemotherapy and the presence of extrahepatic disease (EHD) on outcomes. METHODS: Patients who underwent hepatic resection for NCNNE liver metastases and who received neoadjuvant chemotherapy at a single centre between 1982 and 2016 were analysed retrospectively. Patients were classified as having no EHD, controlled EHD or non-controlled EHD. RESULTS: Hepatic resection was performed in 199 patients (81·2 per cent) after partial or complete response to chemotherapy or disease stabilization, and 46 patients (18·8 per cent) after tumour progression. Patients with progressive disease after chemotherapy had worse overall survival than those without (23 versus 50·4 per cent at 5 years; P = 0·004). Median survival was 63·6 (range 31·1-94·8) months for patients without EHD, 34·8 (19·2-49·2) months for those with controlled EHD and 7·2 (1·2-13·2) months for patients with non-controlled EHD (P = 0·004). In multivariable analysis, EHD (P = 0·004), response to chemotherapy (P = 0·004) and resection margins (P = 0·002) were all independent predictors of overall survival, regardless of primary tumour site. CONCLUSION: The prognosis of patients with NCNNE liver metastases is influenced by preoperative chemotherapy and resectability.

Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry.

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data.

Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry.

Between 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The same trend was observed with a total ischemia time (TIT) >12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was 89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (-), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL-1 tends to offer the best graft outcome.

Use of different coloured ovitraps in the surveillance of Aedes mosquitoes in an arid-urban area of western Rajasthan, India.

BACKGROUND & OBJECTIVES: In the absence of any commercially available dengue vaccine or antiviral therapy, controlling the primary mosquito vector, Aedes aegypti, is currently the only means to prevent dengue outbreaks. Ovitraps are being employed as a sensitive method for detecting the presence of Ae. aegypti. Size, colour, material, paddle and use of oviposition attractant have been reported as important factors influencing the efficacy of ovitraps. METHODS: For the study of coloured ovitraps baited with grass infusion, 24 households were randomly selected in a locality and five ovitraps/premises were installed. Weekly ovitrap surveys were conducted during the study for four times. Ovitrap data were analyzed on the basis of its location, day-wise percent positivity, presence of eggs laid and inference of different ovitrap parameters were drawn. RESULTS: Grass infusion, used in the ovitraps has highest attractiveness on Day 6 in comparison to other days. Percent positivity of different coloured ovitraps revealed that red coloured ovitraps have highest positivity (92.7%), followed by black and orange (91.7% each), green (76.3%) and transparent (45.8%). The individual colour-wise ovitrap positivity revealed that the highest ovitrap positivity on Day 1 was recorded for black colour (21.8%), which on D2 and D3, in case of red colour (37.5 and 26%). However, on D4, D5 and D6 highest number of positive ovitraps was recorded in orange coloured (12.5, 21.9 and 31.3%, respectively) and on D7 highest number of positive ovitraps were recorded in transparent (21.9%), followed by green coloured ovitrap (20.8%). The overall location-wise ovitraps positivity revealed that highest positivity was recorded among the ovitraps installed inside bathrooms (92.0%), followed by bedrooms (85.0%), lobby (66.7%) and stores (48.3%). INTERPRETATION & CONCLUSION: The study revealed that for immediate detection of the presence of gravid females in a particular locality during epidemics, the black coloured ovitraps may be useful, however, in normal situations for surveillance of the vector species, the orange coloured ovitraps might be more suitable. Bathrooms were found to be the highest positive location for pitching ovitraps.

Larvicidal potential of wild mustard (Cleome viscosa) and gokhru (Tribulus terrestris) against mosquito vectors in the semi-arid region of Western Rajasthan.

Cleome viscosa L. (Family: Capparaceae) commonly known as Tickweed or wild mustard and Tribulus terrestris L. (Family: Zygophyllaceae) commonly known as Gokhru, growing wildly in the desert areas in the monsoon and post monsoon season, are of great medicinal importance. Comparative larvicidal efficacy of the extracts from seeds of C. viscosa and fruits and leaves of T. terrestris was evaluated against 3rd or early 4th stage larvae of Anopheles stephensi (Liston), Aedes aegypti (Linnaeus) and Culex quinquefasciatus (Say) in different organic solvents. 24 and 48 hr LC50 and LC90 values along with their 95% fiducial limits, regression equation, chi-square (chi2)/ heterogeneity of the response was determined by log probit regression analysis. The 24 hr LC50 values as determined for seeds of C. viscosa were 144.1, 99.5 and 127.1 (methanol); 106.3, 138.9 and 118.5 (acetone) and 166.4, 162.5 and 301.9 mg l(-1) (petroleum ether extracts) for all the three mosquito species respectively showing that methanol and acetone extracts were a little bit more effective than the petroleum ether extracts. Experiments were carried out with fruits and leaves of T. terrestris with all the solvents and mosquito species. The 24 hr LC50 values, as determined for fruits of T. terrestris were 70.8, 103.4 and 268.2 (methanol); 74.0,120.5 and 132.0 (acetone) and 73.8,113.5 and 137.4 mg l(-1) (petroleum ether extracts) while the 24 hr LC50 values for leaves were 124.3, 196.8 and 246.5 (methanol); 163.4, 196.9 and 224.3 (acetone) and 135.8, 176.8 and 185.9 mg l(-1) (petroleum ether extracts) for all the three mosquito species respectively. The results clearly indicate that fruit extracts of T. terrestris were more effective as compared to leaves extracts in the three solvents tested. Larvae of An. stephensi were found more sensitive to both fruit and leaves extracts of T. terrestris followed by larvae of Ae. aegypti and Cx. quinquefasciatus. Extracts from the seeds of C. viscosa were found less effective as compared to the fruit extracts of T. terrestris indicating that active larvicidal principle may be present in the fruits of this plant species. The studywould be of great importance while formulating the control strategy, for vectors of malaria, dengue and lymphatic filariasis, based on alternative plant based insecticides in this semi-arid region.

Laboratory observations on the larvicidal efficacy of three plant species against mosquito vectors of malaria, dengue/dengue hemorrhagic fever (DF/DHF) and lymphatic filariasis in the semi-arid desert.

Comparative larvicidal efficacy of aqueous and organic solvent extracts from seeds, leaves and flowers of three desert plants viz. Calotropis procera (Aiton), Tephrosia purpurea (L.) Pers. and Prosopis juliflora (Sw.) DC. was evaluated against Anopheles stephensi (Liston), Aedes aegypti (Linnaeus) and Culex quinquefasciatus (Say). For this purpose larvae of all the three mosquito species were reared in the laboratory and studies carried out on late 3rd or early 4th instars using standard WHO technique. Based on concentration mortality data 24 and 48 hr LC50and LC90 values along with their 95% fiducial limits, regression equation, chi-square (chi2)/ heterogeneity of the response were determined by log probit regression analysis. Experiments were carried out with different solvent extracts of seeds of C. procera which revealed that methanol (24 hr LC50: 127.2, 194.8, 361.0) and acetone (229.9, 368.1,193.0 mg l(-1)) extracts were more effective with the three mosquito species, respectively. Petroleum ether extract was effective only on An. stephensi while aqueous extracts were not effective at all with any of the mosquito species (mortality < 10-30%). Tests carried out with methanol extracts of fresh leaves (24 hr LC50: 89.2, 171.2, 369.7) and flowers (24 hr LC50: 94.7,617.3, 1384.0 mg l-(-1)) of Calotropis showed that preparations from fresh parts were 2-3 times more effective as compared to the stored plant parts. Efficacy was less than 10-30% with both An. aegypti and Cx. quinquefasciatus while An. stephensi was still susceptible to extracts from both leaves and flowers even after two years of storage. The 24 hr LC50 values as observed for methanol extracts of seeds of T. purpurea and leaves of P. juliflora were 74.9, 63.2 and 47.0 and 96.2,128.1 and 118.8 mg l(-1) for the above three mosquito species, respectively. Experiments carried out up to 500 mg l-(1) with leaves (T. purpurea) and seeds (P. juliflora) extracts show only up to 10-30% mortality indicating that active larvicidal principle may be present only in the seeds of Tephrosia and leaves of Prosopis. In general, anophelines were found more susceptible than the culicines to the plant derived derivatives. More studies are being carried outon some other desert plants found in this arid region. The study would be of great importance while formulating vector control strategy based on alternative plant based insecticides in this semi-arid region.

Comparative larvicidal potential of different plant parts of Withania somnifera against vector mosquitoes in the semi-arid region of Rajasthan.

Larvicidal potential of the extracts from different parts viz. green and red fruits, seeds, fruit without seeds, leaves and roots of Withania somnifera in different solvents was evaluated against larvae of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, the important disease vectors prevalent in the semi-arid region. Experiments were carried out on late 3rd or early 4th instar larvae of these mosquitoes using standard WHO technique. 24 and 48 hr LC50 values along with their 95% confidence limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined by log probit regression analysis. The 24 hr LC50 values as observed for whole green fruits in water, methanol and petroleum ether were 350.9, 372.4, 576.9; 115.0, 197.1, 554.6; 154.9, 312.0, 1085.0 while corresponding values for red fruits were 473.5, 406.4,445.2; 94.7, 94.5, 1013.0; 241.8, 535.0, 893.3 mg l(-1) for An. stephensi, Ae. aegypti and Cx. quinquefasciatus respectively showing that methanol extracts were more effective against anophelines as compared to culicines when whole fruits were taken. The 24 hr LC50 values as observed for seeds in acetone, methanol and petroleum ether were 188.1, 777.5, 822.5; 245.5, 769.0, 1169.0; 140.3, 822.9, 778.4 and for fruit without seeds were 80.2, 97.6, 146.6; 88.4, 404.4, 1030.0; 30.0, 44.5, 54.2 mg l(-1) for the above mosquito species respectively showing that extract of fruit without seeds were most effective in petroleum ether followed by acetone and methanol extracts. However, experiments conducted with methanol extracts of leaves and roots of this plant species did not show any appreciable larvicidal activity and a 20-40% mortality was observed up to 500 mg l(-1) of the extracts. Overall larvae of anophelines were found more susceptible as compared to culicines to all the extracts tested. Petroleum ether extract of fruit without seeds was found most effective against all the mosquito species showing that active ingredient might be present in this part of the plant species. The study would be of great importance while planning vector control strategy based on alternative plant derived insecticides.

Short- and long-term donor morbidity in right lobe living donor liver transplantation: 91 consecutive cases in a European Center.

The lack of use of a common grading system in reporting morbidity impedes estimation of the true risk to a right lobe living donor (RLLD). We report outcomes in 91 consecutive RLLD's using the validated 5-tier Clavien grading and a quality of life (QOL) questionnaire. The median follow-up was 79 months. The donors were predominantly female (66%), 22 (24%) received autologous blood transfusions. Fifty-three complications occurred in 43 donors (47% morbidity), 19 (37%) were ≥ Grade III, biliary fistula (14%) was the most common. There was no donor mortality. Two intraoperative complications could not be graded and two disfiguring complications in female donors were graded as minor. Two subgroups (first 46 vs. later 45 donors) were compared to study the presence if any, of a learning curve. The later 45 donors had lesser autologous transfusions, lesser rehospitalization and no reoperation and a reduction in the proportion of ≥ Grade III (major) complications (24% vs. 50%; p = 0.06). In the long term, donors expressed an overall sense of well being, but some sequelae of surgery do restrain their current lifestyle. Our results warn against lackadaisical vigilance once RLLD hepatectomy becomes routine.

Ondansetron is as effective as diphenhydramine for treatment of morphine-induced pruritus after cesarean delivery.

BACKGROUND: Subarachnoid (SA) morphine, highly effective for the management of pain after a cesarean delivery, is associated with a significant incidence of pruritus in up to 80% of patients. No previous study has compared the effectiveness of ondansetron (5-HT(3) antagonist) vs. diphenhydramine (H(1) receptor blocker) for the treatment of this side effect. METHODS: In this randomized, double-blind study, 113 patients with a pruritus score 3 or 4 (1=absent; 2=mild, no treatment required; 3=moderate pruritus, treatment required; and 4=severe pruritus) after SA morphine 0.2 mg were assigned to group ondansetron, which received 4 mg intravenously (i.v.) ondansetron, and group diphenhydramine, which received 25 mg i.v. diphenhydramine. Patients who continued to have pruritus > or =3, 30 min after the study drug were considered treatment failures and were treated with naloxone 0.04 mg i.v. repeatedly, as well as patients who relapsed. Pain scores, nausea, vomiting, and sedation were determined before and 30 min after the study drugs were administered. Patients were followed up for 24 h. RESULTS: The success rate was comparable between the two groups [40/57 (70%) and 38/56 (70%), P=0.79, in group ondansetron and group diphenhydramine, respectively]. Among the successfully treated patients, the recurrence rates of moderate to severe pruritus were 11/40 (28%) in group ondansetron and 13/38 (35%) in group diphenhydramine, P=0.52. The side effect profile was similar between the two groups. CONCLUSION: Ondansetron is as effective as diphenhydramine in relieving pruritus caused by SA morphine in patients undergoing a cesarean delivery. However, up to 50% of patients required naloxone either for primary failure or for recurrence.

Liver transplantation for alcoholic liver disease in Europe: a study from the ELTR (European Liver Transplant Registry).

Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation (LT). Long-term outcome after LT for ALD versus other etiologies is still under debate. The aim of this study was to compare outcome after LT of patients with ALD, viral (VIR), and cryptogenic cirrhosis. Donor, graft and recipient ELTR variables were analysed in transplants for alcoholic and nonalcoholic cirrhosis (1988-2005) and were correlated with patient survival. Causes of death and/or graft failure were compared between groups. Nine thousand eight hundred eighty ALD, 10,943 VIR, 1478 ALD+VIR and 2410 cryptogenic (CRYP) liver transplants were evaluated. One, 3, 5 and 10 years graft survival rates after LT in ALD patients were 84%, 78%, 73%, 58%, significantly higher than in VIR and CRYP (p=0.04, p=0.05). By multivariate analysis, ALD+VIR (RR 1.14) and viral alone (RR 1.06) were significant risk factors for mortality. De novo tumors, cardiovascular and social causes were causes of death/graft failure in higher percentage in ALD groups versus other etiologies. LT for ALD cirrhosis has a favorable outcome, however, hepatitis C virus co-infection seems to eliminate this advantage. Screening for de novo tumors and prevention of cardiovascular complications are essential to provide better long-term results.

Larvicidal activity of the extracts from different parts of the plant Solanum xanthocarpum against important mosquito vectors in the arid region.

Larvicidal efficacy of the aqueous and methanol extracts from green unripe and yellow ripe fruits, seeds, leaves and roots of the plant Solanum xanthocarpum was evaluated against Anopheles culicifacies, Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, the important mosquito vectors prevalent in the arid region. Studies were carried out on late 3rd orearly 4th instarlarvae of these species using standard WHO technique. Based on concentration mortality data LC50 and LC90 values along with their fiducial limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined bylog probit regression analysis. The 24 hr LC50 values as observed for aqueous extracts for green unripe and yellow ripe fruits were 112.7, 498.2 and 846.3 mg l(-1) and 104.7, 267.7and 832.2 mg l(-1) for Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus respectively. However, the 24 hr LC50 values formethanol extracts of yellow ripe fruits and seeds were 51.6, 52.2, 118.3 and 157.1 mg l(-1) and 66.9, 73.7, 123.8 and 154.9 mg l(-1) for the above four vector species respectively. The results showed that larvae of anophelines were much more susceptible as compared to culicines to both the aqueous and methanol extracts from fruits and seeds of the plant tested. The methanol extracts were found 2-5 times more effective as compared to the aqueous extracts. The chi-square values calculated during the analysis did not show any heterogeneity of the response. Experiments conducted with aqueous and methanol extracts from leaves and roots of this plant species didn't show any larvicidal activity against any of the mosquito species tested. The study would be of great importance while formulating vector control strategy based on alternative plant based insecticides.

Evaluation of larvicidal efficacy of Solanum xanthocarpum storage against vector mosquitoes in north - western Rajasthan.

Efficacy of the methanol extracts from fruits without seeds, whole yellow ripe fruits and seeds of the plant Solanum xanthocarpum was evaluated against larvae of Anopheles culicifacies, Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, the important vector mosquitoes prevalent in the arid region. Experiments were carried out on late 3rd or early 4th instar larvae of these mosquitoes using standard WHO technique. 24 and 48 hr LC50 and LC90 values along with their fiducial limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined by log probit regression analysis. The 24 hr LC50 values as observed for fruit without seeds, whole fruits and seeds after six months were 79.6, 91.7 and 131.7; 131.4, 186.9 and 195.6; 273.4, 290.9 and 377.6 and 384.9, 450.6 and 520.0 mg l(-1) for An. culicifacies, An. stephensi, Ae. aegypti and Cx. quinquefasciatus respectively. However, the 24 hr LC50 values for fresh yellow ripe fruits and seeds determined previously were 51.6 and 66.9; 52.2 and 73.7; 118.3 and 123.8 and 157.1 and 154.9 mg l(-1) for the above four vector species respectively showing that the efficacy was decreased two to three times more after six months of storage. The 24 hr LC50 values were also determined after one year of storage for fruit without seeds, whole fruits and seeds. The values were 103.3, 120.1 and 195.7; 146.3, 224.3 and 251.2; 316.9, 336.5 and 426.2 and 393.0, 500.3 and 656.7 mg l(-1) as compared to the 24 hr LC50 values of 47.4, 51.6 and 66.9; 52.3, 52.2 and 73.7; 108.0, 118.3 and 123.8 and 141.1, 157.1 and 154.9 mg l(-1) of all the three fresh preparations for the above four vector species respectively showing that the efficacy was further decreased after one year of storage. Further the extracts should be used when they have been prepared from the fresh plant parts instead of the old stored parts. Larvae of anophelines were found more susceptible as compared to culicine. HPLC and IR studies showed that active component might be present in the fruits and seeds of this plant species. The study would be of great importance while planning vector control strategy based on alternative plant derived insecticides.

Relative susceptibility of some common mosquito vector larvae to synthetic insecticidal compounds in north-western Rajasthan.

Relative susceptibility of three important mosquito vector larvae viz., Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, prevalent in the arid region was determined against four organophosphates (malathion, fenitrothion, fenthion, temephos) and three synthetic pyrethroid (alphamethrin, deltamethrin and fanvalerate) compounds. Studies were carried out on late 3rd or early 4th instar larvae of these species using standard WHO technique. Based on concentration mortality data LC50 and LC90 values along with their fiducial limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined by log probit regression analysis. LC50 values as observed for the above seven insecticides were 0.8097, 0.0398. 0.0432, 0.0035, 0.0025, 0.0092, 0.1006; 1.2370, 0.0531, 0.0655, 0.0076, 0.00004, 0.00004, 0.0046 and 1.4980, 0.0719, 0.0817, 0.0056, 0.00021, 0.00073, 0.0112 mg/l for the above three mosquito species respectively Among the four organophosphates tested temephos was the most effective followed by fenitrothion, fenthion and malathion. In general, Anopheles was found more susceptible as compared to the other two culicines to the above four compounds. The results also showed that larvae of Ae. aegypti were most susceptible followed by Cx. quinquefasciatus and An. stephensi to all the three pyrethroids tested. Among the three compounds tested alphamethrin was found to be the most toxic followed by deltamethrin while fanvalerate was the least toxic. The study would be of great importance while planning use of these insecticides for the control of different vector species in this area.

Adult liver transplantation: the Paul Brousse experience.

During the past 3 decades, more than 2,250 liver transplants were performed at Paul Brousse Hospital. Overall patient survival was 82% at one year, 71% at 5 years and 64% at 10 years. Our group has developed a variety of approaches to liver transplantation, including: 1. Anti HBs immunoglobulin prophylaxis for the prevention of HBV recurrence. Combination prophylaxis with lamivudine and anti HBs immunoglobulins reduced the rate of HBV re-infection to 20%. 2. Transplantation of HIV-HCV and HIV-HBV infected patients. These transplants are feasible and we achieved 2- year survival rates of 70% and 90%, respectively. The main problem was HCV recurrence which was more severe in HIV co-infected patients. 3. Transplantation for hepatocellular carcinoma on a cirrhotic liver with a single tumor <5 cm or <3 tumors <3 cm. 4. Transplantation for familial amyloidotic polyneuropathy (FAP). The 5- and 10-year survival rates were 76% and 72%, respectively. More than 100 livers obtained after hepatectomy from FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with a 5-year survival rate of 64%. In some domino recipients, symptoms of FAP disease occurred more rapidly than expected and this could be an indication for a second transplantation of a non FAP-liver. 5. Split-liver transplantation for pediatric patients. This has increased the number of transplantable livers for children by 28%. 6. Split-liver transplantation for 2 adults. The grafts were prepared by ex-vivo or in-situ splitting and the overall 5-year survival rate was 56%. 7. Adult -to-adult living-related liver transplantation. There has been no mortality nor late complications in donors and the overall 5-year survival rate among recipients was 73%. 8. Liver retransplantation with good results in the elective situation. Retransplantation should be used with discretion in the emergency setting.