RESUMO
Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype (p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age (p = 0.02), neutrophil to lymphocyte ratio (p = 0.04) and TBX21 genotype CC (p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMF-based regimens have a favourable anti-apoptotic profile in vitro, supporting its use in case of LT recipients at high risk for liver graft fibrosis.
RESUMO
BACKGROUND: Hepatic resection is the only potentially curative treatment for primary liver tumors and hepatic metastases. The most frightening postoperative complication of extensive hepatectomies is liver failure due to insufficient future liver remnant (FLR). The ALPPS technique (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) effectively increased the resectability of otherwise inoperable liver tumors (primary or secondary malignant liver tumor) by achieving a rapid and an effective hypertrophy of the FLR, which lowers postoperative liver failure risk. AIM: To present the ALPPS classic right trisectionectomy and its technical variants which were invented to decrease the high rate of post-operative morbidity and mortality, reported in early case series. TECHNIQUE: ALPPS involves two stages. The first surgical procedure consists in the ligation of the right portal branch and the partition of the liver at the site of the falciform ligament (insitu splitting). In contrast to a classical hepatectomy, the tumoral hemiliver is left in situ and remains vascularized by the right hepatic artery only. The biliary and systemic venous drainages represented by the right biliary duct and respectively the hepatic veins, are preserved. The second step of the procedure is usually performed within 7 to 15 days after the firststage. The tumoral hemiliver is removed by sectioning the right hepatic artery, the biliary duct and the systemic venous pedicle. Conclusions: The ALPPS technique is a therapeutic method for inoperable liver tumors by standard methods of hepatectomy ± portal vein ligation (PVL). By careful patient selection and technical adjustment to the particular conditions of each case, better outcomes have been achieved, leading toan increasing number of surgeons who perform ALPPS.
