Bridge Therapy before Liver Transplant for Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be considered. Bridge therapies have been introduced in order to limit this issue. The aim of this study is to evaluate if bridge therapies in advanced hepatocellular carcinoma can improve overall survival and reduce de-listing. We selected 185 articles. The search was limited to English articles involving only adult patients. These were deduplicated and articles with incomplete text or irrelevant conclusions were excluded. Sorafenib is the standard of care for advanced hepatocellular carcinoma and increases overall survival without any significant drug toxicity. However, its survival benefit is limited. The combination of transarterial chemoembolization + sorafenib, instead, delays tumor progression, although its survival benefit is still uncertain. A few studies have shown that patients undergoing transarterial chemoembolization + radiation therapy have similar or even better outcomes than those undergoing transarterial chemoembolization or sorafenib alone for rates of histopathologic complete response (89% had no residual in the explant). Also, the combined therapy of transarterial chemoembolization + radiotherapy + sorafenib was compared to the association of transarterial chemoembolization + radiotherapy and was associated with a better survival rate (24 vs. 17 months). Moreover, immunotherapy revealed new encouraging perspectives. Combination therapies showed the most encouraging results and could become the gold standard as a bridge to transplant for patients with advanced hepatocellular carcinoma.

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial.

Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6-12 ng/mL. The primary endpoint was the proportion of treated biopsy-proven acute rejection (tBPAR)-free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR-free (P = 0.09); composite endpoint-free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.

Safe pregnancy after liver transplantation: Evidence from a multicenter Italian collaborative study.

BACKGROUND: Women who have undergone liver transplantation (LT) enjoy better health, and possibility of childbearing. However, maternal and graft risks, optimal immunosuppression, and fetal outcome is still to clarify. AIM: Aim of the study was to assess outcomes of pregnancy after LT at national level. METHODS: In 2019, under the auspices of the Permanent Transplant Committee of the Italian Association for the Study of the Liver, a multicenter survey including 14 Italian LT-centers was conducted aiming at evaluating the outcomes of recipients and newborns, and graft injury/function parameters during pregnancy in LT-recipients. RESULTS: Sixty-two pregnancies occurred in 60 LT-recipients between 1990 and 2018. Median age at the time of pregnancy was 31-years and median time from transplantation to conception was 8-years. During pregnancy, 4 recipients experienced maternal complications with hospital admission. Live-birth-rate was 100%. Prematurity occurred in 25/62 newborns, and 8/62 newborns had low-birth-weight. Cyclosporine was used in 16 and Tacrolimus in 37 pregnancies, with no different maternal or newborn outcomes. Low-birth-weight was correlated to high values of AST, ALT and GGT. CONCLUSION: Pregnancy after LT has good outcome; however, maternal complications and prematurity may occur. Compliance with the immunosuppression is fundamental to ensure the stability of graft function and prevent graft-deterioration.

Pediatric T-tube in adult liver transplantation: Technical refinements of insertion and removal.

BACKGROUND: With the increasing use of extended-criteria donor organs, the interest around T-tubes in liver transplantation (LT) was restored whilst concerns regarding T-tube-related complications persist. AIM: To describe insertion and removal protocols implemented at our institution to safely use pediatric rubber 5-French T-tubes and subsequent outcomes in a consecutive series of adult patients. METHODS: Data of consecutive adult LT patients from brain-dead donors, treated from March 2017 to December 2019, were collected (i.e., biliary complications, adverse events, treatment after T-Tube removal). Patients with upfront hepatico-jejunostomy, endoscopically removed T-tubes, those who died or received retransplantation before T-tube removal were excluded. RESULTS: Seventy-two patients were included in this study; T-tubes were removed 158 d (median; IQR 128-206 d) after LT. In four (5.6%) patients accidental T-tube removal occurred requiring monitoring only; in 68 (94.4%) patients Nelaton drain insertion was performed according to our protocol, resulting in 18 (25%) patients with a biliary output, subsequently removed after 2 d (median; IQR 1-4 d). Three (4%) patients required endoscopic retrograde cholangiopancreatography (ERCP) due to persistent Nelaton drain output. Three (4%) patients developed suspected biliary peritonitis, requiring ERCP with sphincterotomy and nasobiliary drain insertion (only one revealing contrast extravasation); no patient required percutaneous drainage or emergency surgery. CONCLUSION: The use of pediatric rubber 5-French T-tubes in LT proved safe in our series after insertion and removal procedure refinements.

Effect of liver transplantation on intestinal permeability and correlation with infection episodes.

BACKGROUND: Liver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections. METHODS: LT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA). RESULTS: The median 51Cr-EDTA excretion was found to be higher in 35 LT recipients as compared with that in the healthy controls [4.77% (2.79-6.03) vs. 2.07% (1.57-2.42), p<0.0001], and comparable to that in the cirrhotic patients [3.69% (2.34-6.57), p = 0.445]. 51Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections [infection/no infection: 4.97% (3.14-7.03) vs 4.62% (2.79-5.82), p = 0.938]. CONCLUSION: LT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted.

Gallbladder agenesis: A case report and brief review.

Agenesis of the gallbladder and cystic duct represents one of the rarest anomalies of the biliary system, with a reported incidence of 0.007% to 0.027%. Almost half of the patients develop common duct stones and 23% of them manifest signs and symptoms that mimic biliary colic. We present the case of a woman presenting with symptoms of biliary colic. Based on the clinical findings and after abdominal ultrasonography, which showed hyperechoic material in the gallbladder fossa, a laparoscopic cholecystectomy was planned. Laparoscopy failed to reveal either gallbladder or cystic duct. The procedure was continued to further search for ectopic sites of gallbladder. A condition of gallbladder agenesis was hypothesized and the procedure was aborted without dissection of hepatic pedicle or conversion to laparotomy. Agenesis of gallbladder and cystic duct was confirmed via pos-operative magnetic resonance cholangiopancreatography. We report our experience with regard to the challenges associated with the diagnosis and management, and a brief review of the literature of this rare pathology.

Fibrolamellar hepatocellular carcinoma with biliary tumor thrombus: an unreported association.

Fibrolamellar hepatocellular carcinoma (FHCC) is a rare malignant tumor of hepatocyte origin occurring earlier in life than typical hepatocellular carcinoma (HCC). We describe a distinctive case of FHCC with biliary tumor thrombus (BTT) in a 25-year-old Caucasian patient, pointing out the imaging features supported by histopathology.