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Biomedical subjects

L S Belli

Publications and source records attributed to L S Belli.

At least 19 recordsLinked to original sources

Right hemiliver transplant: results from living and cadaveric donors.

UNLABELLED: Although right hemiliver transplant from living donors (LD) is gaining acceptance as a way to overcome the critical organ shortage, splitting a liver for two adults from cadaveric donor (CD) is still controversial. METHODS: From May 1999 to August 2004 we performed nine right hemiliver transplants using segments 5-6-7-8 from CD and 18 from LD. RESULTS: We compared the two procedures to evaluate both the technical aspects and the patients' outcomes. In the CD group, three recipients died (33%), two of whom were UNOS Status 2A. Patient and graft survivals were 67% (median follow-up: 23 months). Among the LD group, three recipients died (17%) and two were retransplanted; one because of arterial thrombosis and the other as a consequence of small-for-size syndrome. Patient and graft survivals were 83% and 72%, respectively (median follow-up: 8 months). There were five early complications in the CD group (55%) and five (27%) in the LD group. Two patients in the LD group experienced a late stenosis of the biliary anastomosis. DISCUSSION: Data from our early experience show that better results are achieved by right hemiliver transplants from LD; the morbidity and mortality are higher among the CD group. We believe that this finding is probably a consequence of better preoperative donor evaluation, shorter ischemia time, better logistics, and learning curve. Recipient selection is crucial; this kind of graft is at high risk of poor function, technical complications, and infections. Further experience will help to clarify the reliability of right hemiliver transplants from CD.

Adult↗

Combined therapy with interferon and low-dose ribavirin in posttransplantation recurrent hepatitis C: a pragmatic study.

Recurrent hepatitis C is a common problem after liver transplantation that can progress to liver cirrhosis of the graft. Preliminary reports of combination treatment with interferon (IFN) and ribavirin have been promising, but long-term follow-up data are not yet available. We report our experience with 1 year of combination therapy with IFN (3 million units thrice weekly) and low-dose ribavirin (600 mg/d), followed by long-term ribavirin monotherapy in 18 patients with moderate to severe recurrent hepatitis C and a median follow-up of 32 months after the completion of combined therapy. All patients were followed up clinically and histologically at regular intervals. Overall, in an intention-to-treat analysis, 15 patients had normal alanine aminotransferase levels (biochemical end-treatment response [ETR], 83%), and 8 patients were also hepatitis C virus RNA negative in serum (virological ETR, 44%) at the end of combined treatment. At last follow-up after the completion of combined therapy (median, 32 months; range, 18 to 73 months), 13 patients were biochemical responders (biochemical long term-sustained response [LT-SR], 72%), and 5 patients also maintained viral clearance (virological LT-SR, 27%). Comparison of liver biopsy specimens before and after 12 months of combined therapy showed improvement in grading scores of at least two points in the majority of the patients (73%). Notably, a trend toward fibrotic progression was only noted in nonresponders. Regarding side effects, despite the low dose of ribavirn, almost half the patients developed hemolytic anemia requiring dose reductions. In addition, long-term ribavirin monotherapy was not associated with iron accumulation. We conclude that combined therapy with low-dose ribavirin followed by long-term ribavirin monotherapy can be recommended because it favorably modifies the natural history of recurrent hepatitis C in most patients and possibly halts histological disease progression without causing iron accumulation.

Administration, Oral↗

Influence of immunogenetic background on the outcome of recurrent hepatitis C after liver transplantation.

In immunocompetent patients, specific human leukocyte antigen (HLA) class II alleles have been associated with the severity of hepatitis C virus (HCV)-related disease, in particular, HLA-DRB1*11 has been found to exert a protective effect. The authors have analyzed the role of HLA class I and II alleles in determining the frequency, timing, and progression of histologically proven recurrent hepatitis C in 89 patients who underwent a liver transplant for HCV-related cirrhosis. In addition, the influence of HLA mismatch between donor and recipient, HCV genotype, and use of steroid pulses was also evaluated. Median patient follow up was 35 months (range 4-119). HLA-DRB1 typing was performed by genomic analysis in all cases. Liver biopsies were obtained routinely and at least at yearly intervals. Histologically proven recurrent hepatitis was observed in 46 patients (52%), 10 patients progressing to stage 5-6 fibrosis in most cases within 2 years after transplant. By univariate analysis, 3 variables, HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch, showed a significant effect on time to recurrent hepatitis C disease. These parameters were included in a multivariate regression model along with HCV genotype, treatment with steroid pulses and DRB1*11. HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch were confirmed to provide a significant and independent contribution to the risk of hepatitic disease recurrence. As for the severity of the disease, none of the 10 patients with stage 5-6 hepatitis carried the HLA-DRB1*11 allele, in line with what was observed in nontransplant subjects. Our results suggest that in posttransplant recurrent hepatitis C, immunogenetic factors are relevant in determining HCV infection outcome.

Adult↗

Orthotopic liver transplantation in a patient with severe haemophilia A and with advanced liver cirrhosis.

A patient with severe haemophilia A underwent orthotopic liver transplantation because of changes correlated to end-stage liver cirrhosis due to hepatitis B, C and D infection. Replacement therapy was carried out for 4 days and the clinical course was uneventful. At the time of reporting the patient has a normal working life. FVIII plasma concentration is normal. The indirect hyperbilirubinaemia may be related to the Gilbert's anomaly of the donor.

Activities of Daily Living↗

Early cyclosporine monotherapy in liver transplantation: a 5-year follow-up of a prospective, randomized trial.

Maintenance of adequate immunosuppression and avoidance of side-effects are the goals of long-term management of all organ-transplanted patients. We here report the final results of a prospective, randomized trial comparing early cyclosporine monotherapy versus double-drug therapy (cyclosporine and steroids) in adult liver transplantation patients. One hundred four patients were randomized 3 months after transplantation either to continue (Group I = 50 patients) or to stop steroids (Group II = 54 patients). Patients on a double-drug regimen were maintained long term on methylprednisolone at a dose of 0.1 mg/kg/d. Target cyclosporine trough levels were between 150 and 250 ng/mL in both groups. Our main points of interest were the prevalence of acute and chronic rejections and steroid-related side-effects in the two groups of patients. Mean follow-up was 41 +/- 16 months (range, 4-68 months). Patient actuarial survival 2 and 5 years after randomization was similar in the two groups (82% vs. 83% and 82% vs. 77%). The prevalence of acute rejections after randomization was, respectively, 8% and 4%. A single episode of chronic rejection was observed only in a patient on long-term steroid therapy. Side-effects of steroid therapy were less frequent in patients weaned off steroids, and when considering hypertension and diabetes, the differences between the two groups were statistically significant. Early cyclosporine monotherapy is a safe undertaking in liver transplantation because it allows a significant reduction of steroid-related side-effects without increasing the risk of acute and chronic rejection. After 5 years, patient survival was similar in patients with or without steroids.

Adult↗

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization.

Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

Actuarial Analysis↗

Hepatitis C virus genotypes, hepatitis, and hepatitis C virus recurrence after liver transplantation.

Several genotypes of hepatitis C virus (HCV) have been recently identified by phylogenetic analysis, but their clinical relevance in the liver transplant setting is unknown. We evaluated the incidence and course of recurrent hepatitis C after transplantation in 50 patients who underwent transplantation for HCV-related liver disease. Liver biopsy specimens were obtained when clinically indicated and at yearly intervals; hepatitis was histologically graded and staged according to standard criteria. HCV-RNA was detected by nested reverse-transcription polymerase chain reaction (RT-PCR). HCV genotyping was performed by primer specific PCR. Follow-up was 6 to 62 months. HCV genotype distribution after transplantation of our 50 patients was as follows: 31 type 1b, 13 type 2a, 3 type 1a, 1 type 3a, 1 type 1b/2a, and 1, undetermined. Actuarial rates of recurrent hepatitis and of severe fibrosis or cirrhosis 5 years after transplantation were 56% and 20%, respectively, in patients infected by type 1b and 33% (P = .18) and 8% (P = .16) in those infected by 2a. In conclusion, this study provides evidence that in patients infected by HCV type 1b there is a trend for a more aggressive recurrent liver disease.

Genotype↗

Liver transplantation for hepatocellular carcinoma: prognostic factors associated long-term survival.

Between December 1985 and February 1995, 260 orthotopic liver transplantations (OLTX) were performed on 238 patients at Niguarda Hospital. Sixty-three patients had hepatocellular carcinoma (HCC); in 13 of the patients HCC was incidental. All patients had negative lymph nodes. According to the Child classification, 13 patients were Child A, 30 Child B, and 18 Child C. According to the TNM classification, 11 patients were stage I, 22 stage II, 15 stage III, and 15 stage IVa. Pre-OLTX chemoembolization was performed on 25 patients. The perioperative mortality rate was 27% (17 patients). Overall survival and disease-free actuarial survival rates at 1, 3, and 5 years were 94%, 76%, 76%, and 83%, 75%, 75%, respectively. Survival curves were compared for 16 different variables. No difference was observed for all parameters analyzed except tumor site, TNM stage, pre-OLTX AFP levels and vascular infiltration. These results seem to demonstrate that the OLTX for unresectable HCC can be considered in specifically selected cases as the treatment of choice. An adequate tumor staging is also necessary for a better patient selection in order to increase survival.

Adult↗

Is the use of marginal donors justified in liver transplantation? Analysis of results and proposal of modern criteria.

A discrepancy exists worldwide between the number of suitable liver donors and the increasing demand for transplantation. Thus many centers have considered widening their liver donor acceptance criteria and this may increase the incidence of primary dysfunction (PD) with negative effect on the results of transplantation. In order to reduce the incidence of PD and improve patient and graft survival it becomes important to identify those risk factors associated with its occurrence. In a retrospective univariate and multivariate analysis we evaluated several donor, preservation and recipient parameters and their correlation with PD. In our Department 282 orthotopic liver transplantations (OLT) were performed on 256 adult patients over a 10-year period. Excluded were 15 cases with early vascular problems and 4 intraoperative deaths. A complete series of donor, recipient and procedure-related data were analyzed. About 30% of donors showed abnormal values. In 70 cases of PD (26%) there was a 61.4% graft failure rate compared with 15% in the group with immediate function (P < 0.05). Univariate analysis showed donor age, steatosis, ischemia time, amines, oliguria, hypotension and ICU stay to be significantly associated with PD. Multivariate analysis showed steatosis, ischemia time and amine dosage to be independent risk factors for the development of primary non function. In conclusion, the acceptance of marginal donors worsened the results of transplantation, but the rejection of these donors would reduce by about 30% our transplant activity resulting in increased mortality in the waiting list. Combinations of risk factors when possible should be avoided, and ischemia time, as the only variable that can be controlled, should be kept as short as possible.

Adolescent↗

Prospective randomized trial of steroid withdrawal in liver transplant patients: preliminary report.

Although steroid withdrawal has been successfully performed in heart and kidney transplant recipients, no controlled studies of SW have been carried out in liver transplant patients. To evaluate this possibility a prospective controlled study was carried out in 46 liver transplant recipients operated on after may 1991. They all received a sequential quadruple immunosuppression consisting of 3 mg/kg antithymocyte globulins (RATG) for the first 5 postoperative days, cyclosporin A (starting from day 3-5 and maintaining parenteral whole-blood trough levels at 200-300 ng/ml during the first month and at 150-250 thereafter), azathioprine (1 mg/kg per day for the first month) and steroids. Prednisone was started at a dose of 200 mg per day 1 and then tapered to 20 mg/day over the first posteroperative week; this dose was maintained until day 90 when the patients were randomly allocated either to long-term steroid therapy (0.1 mg/kg per day) or to steroid withdrawal. Minimum follow-up after randomization was 6 months (6-27 months). Liver biochemistry was checked at regular intervals throughout the follow-up period. Liver biopsies were performed whenever clinically indicated and also in the first 19 patients during readmission for annual review. The incidence ot acute and chronic rejection 90 days from liver transplantation was 2.5% in patients maintained on long-term therapy. No patient in the steroid-withdrawal group had experienced either an acute or a chronic rejection episode so far. Steroid-related complications did not differ significantly between the two groups. The most recent interim analysis showed that steroid withdrawal is a safe undertaking in liver transplant recipients and may be successfully accomplished in almost all patients.

Adult↗