Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection.

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

Time trends and geographic distribution of hepatocellular carcinoma in Brazil: An ecological study.

The incidence of hepatocellular carcinoma (HCC) is increasing globally, and HCC is the fourth leading cause of cancer-related death. This ecological study aimed to investigate the time trends and geographic distribution of HCC in Brazil. Data from the Brazilian Health Public System were retrospectively collected from January 2005 to December 2018. Hospitalization and intrahospital lethality rates for HCC were stratified by age and sex. Hospitalization rates and associated lethality per 100,000 inhabitants in each municipality were included in a worksheet to build maps displaying the estimates and the geographic distribution of HCC. From 2005 to 2018, a total of 75,466 admissions for HCC were registered and the mean hospitalizations increased from 2.1 to 5.8/100,000 inhabitants (176%). The greatest increase occurred among patients older than 50, particularly in males above 70 years old. Prevalence rates increased throughout the country, with the highest levels detected in the South and Southeast. However, the increase was proportionally higher in the Northeast (377%), especially in municipalities not integrated into metropolitan regions. The HCC lethality rate remained relatively stable in both sexes, ranging from 21% to 25% (19%), but it was higher among older patients. The length of hospital stay did not differ between survivors and nonsurvivors throughout the study period. HCC hospitalizations are rising, particularly above 50 years of age and in rural areas, not paralleled by lethality rates. This suggests ongoing changes in environmental and socioeconomic factors in Brazil.

Effectiveness of Direct-acting Agents After Liver Transplantation A Real-life Study in Rio de Janeiro.

BACKGROUND: Data concerning hepatitis C virus (HCV) treatment using direct-acting agents (DAAs) post liver transplantation (LT) remains scarce in low- and average-income countries. AIM OF THE STUDY: To evaluate the safety and efficacy of post-LT HCV treatment using DAAs in Rio de Janeiro (Brazil), and to assess the course of hepatic biomarkers after sustained virological response (SVR). METHODS: Data from LT recipients with recurrent HCV treated using DAAs was retrospectively analyzed. HCV was defined by detectable HCV-RNA with elevated aminotransferases and/or histological signs of infection on liver biopsy post LT. SVR was defined as undetectable HCV-RNA 12 weeks after the end of treatment. Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4) were calculated before treatment and after SVR. RESULTS: 116 patients (63% male, median age 62 years, 75% genotype 1 and 62% with hepatocellular carcinoma [HCC] prior to LT) were included. Cirrhosis was identified in the allograft of 21 subjects (18%). The overall SVR was 96.6% without differences in SVR proportion according to clinical/demographic characteristics, genotype or presence of cirrhosis. SVR rates were similar in individuals with and without HCC pre-LT (95.8% [95% CI: 87.6-98.7] vs. 97.7% [95% CI: 85.0-99.7%], p = 0.588). No serious adverse events were observed and the use of ribavirin was associated with at least one adverse event (OR = 8.71 [95% CI: 3.17-23.99]). SVR was associated with regression of APRI (OR = 26.00 [95% CI 4.27-1065.94]) and FIB-4 (OR = 15.00 [95% CI: 2.30-631.47]). CONCLUSION: Post-LT HCV treatment with DAAs was safe and effective and associated with a significant decrease in hepatic biomarker levels after SVR.

Survival and tolerance to sorafenib in Child-Pugh B patients with hepatocellular carcinoma: a prospective study.

Sorafenib has been widely used to treat unresectable hepatocellular carcinoma (HCC) but most studies have been done in Child-Pugh A (CP-A) patients with well-preserved liver function. We evaluated the overall survival (OS) and tolerance to sorafenib in a large cohort of Child-Pugh B (CP-B) HCC patients as compared to CP-A HCC patients. We prospectively studied 130 patients with advanced HCC who started sorafenib between January 2011 and December 2015. Patients were classified as CP-A (n = 65) or CP-B (n = 65). The average OS for all 130 patients was 10 months. CP-A patients had a median survival rate significantly longer than CP-B patients: 12 months vs. 6 months. The OS found in our group of CP-B patients was 6.5 months, which is higher than that found in most studies done so far. When stratified, our CP-B patients had better OS than ever reported. The dose of the drug was interrupted due to adverse events (AEs) in 38 (29%) of the patients, of whom 20 (30%) were CP-A patients and 18 (28%) were CP-B patients. This real-life cohort of CP-B HCC patients treated with sorafenib had a higher survival than that described in the literature, with a satisfactory safety profile. Despite the high prevalence of severe AEs in CP-B patients, there were fewer treatment interruptions in this group, indicating that Child-Pugh B patients can tolerate treatment and may benefit from sorafenib.

Hepatic artery reconstruction in pediatric living donor liver transplantation under 10 kg, without microscope use.

Arterial reconstructions are pivotal, particularly in pediatric LDLT. We describe microsurgical reconstruction technique with 6x loupes and the clinical course of the first 23 less than 10 kg recipients in an initial LDLT program at a developing country. From March 2002 to October 2008, 286 liver transplantation were performed in 279 patients at our unit. There were 73 children and 206 adults. Among the children, 23 weighing less than 10 kg were recipients from living donors. Arterial reconstructions were with end-to-end interrupted suture using a 6x magnification loupe, according to the untied suture technique. All patients were prospectively followed by color Doppler ultrasound protocol. In our initial experience there were no arterial complications. With mean 24 months of follow-up, 19 patients (82%) are alive with good graft function. Hepatic artery in LDLT can be safely reconstructed with microsurgical techniques without microscope using, with 6x loupe magnification, and can achieve good results in patients under 10 kg.

Selection of donors for living donor liver transplantation in a single center of a developing country: lessons learned from the first 100 cases.

The selection of donors for living donor liver transplantation (LDLT) is one of the most important features in this kind of surgery. The aim of this study is to describe our initial experience in the donor evaluation process. From December 2001 to January 2005, 104 donors were evaluated for 70 recipients (65 potential donors were evaluated for 39 adult recipients, and 39 donors for 31 pediatric recipients). Only 30 donors were able to donate: 13 for the adult group, and 17 for the pediatric one. In general, the utilization rate of potential donors was 28.8% (30/104). For the adult patients, 65 potential donors were seen to perform 13 LDLT, which represents a utilization rate of potential donors of 20%. For the pediatric patients, this rate was 43.6%. The exclusion criteria were clinical in 22 cases (21%), anatomical in 13 cases (13%), psychosocial in nine cases (9%), and others in 12 (12%). Death of recipients led to exclusion 18 of donors (17%). Thirty-three percent of adults and 55% of pediatric recipients who had at least one potential donor to start the evaluation process were able to identify a living donor. In conclusion, the first limit for LDLT is the rigorous donor evaluation.

Liver transplantation with monosegments. Technical aspects and outcome: a meta-analysis.

The shortage of organ donors for low-weight liver transplant recipients, especially small children, has led to the development of new surgical techniques to increase the donor pool. Almost all of these techniques use the left lateral segment (Couinaud's segments II and III), but even this graft could be too large for children under 10 kg, and further reduction could be necessary. Few articles address the issue of monosegmental liver transplantation. Available articles are with small sample sizes or even case reports, which makes it difficult to draw conclusions about indication and outcome for monosegmental grafts. A search of the MEDLINE databases using the terms "Liver Transplantation" and "Monosegmental" or "Monosegments" limited to title or abstract with publication in the English language was conducted. The data from each study were selected and analyzed, regarding donor status (living or cadaveric), donor weight, surgical techniques used in left lateral further reduction, recipient indication for liver transplantation, age and recipient weight, graft-to-recipient body weight ratio, segment utilized, type of abdominal closure, postoperative complications, and survival. Seven publications were identified from 1995 to 2004 and fulfilled the criteria. A total of 27 pediatric patients who received a monosegment transplant were identified, median age 211 days (range, 27 to 454 days) and median weight 4.6 kg (range, 2.45 to 7.4 kg). Segment III was utilized in 21 (78%) and segment II in 6 (22%). Patient survival was 85.2%. In conclusion, monosegment liver transplantation appears to be a satisfactory option for infants weighing less than 10 kg who require a liver transplant.

Liver transplantation with monosegment from a living donor.

The shortage of organ donors for low-weight liver transplant recipients, especially for small children, has led to the development of new surgical techniques to increase the donor pool. Almost all of these techniques use the left lateral segment (Couinaud's segments II and III), but even this graft could be too large for children under 10 kg. We report here the case of an 8-month-old boy, weighing 6.1 kg, who received a monosegmental graft (segment III) from his grandmother weighing 68 kg. The graft was reduced at the donor surgery, before clamping of the vessels. The donor was discharged on the fourth post-operative day; the recipient had an uneventful post-operative period and was discharged after 22 days.