Complement System as a Target for Therapies to Control Liver Regeneration/Damage in Acute Liver Failure Induced by Viral Hepatitis.

The complement system plays an important role in innate immunity inducing liver diseases as well as signaling immune cell activation in local inflammation regulating immunomodulatory effects such as liver damage and/or liver regeneration. Our aim is to evaluate the role of complement components in acute liver failure (ALF) caused by viral hepatitis, involving virus-induced ALF in human subjects using peripheral blood, samples of liver tissues, and ex vivo assays. Our findings displayed low levels of C3a in plasma samples with high frequency of C3a, C5a, and C5b/9 deposition in liver parenchyma. Meanwhile, laboratory assays using HepG2 (hepatocyte cell line) showed susceptibility to plasma samples from ALF patients impairing in vitro cell proliferation and an increase in apoptotic events submitting plasma samples to heat inactivation. In summary, our data suggest that the complement system may be involved in liver dysfunction in viral-induced acute liver failure cases using ex vivo assays. In extension to our findings, we provide insights into future studies using animal models for viral-induced ALF, as well as other associated soluble components, which need further investigation.

Changes in cellular proliferation and plasma products are associated with liver failure.

AIM: To study the differences in immune response and cytokine profile between acute liver failure and self-limited acute hepatitis. METHODS: Forty-six patients with self-limited acute hepatitis (AH), sixteen patients with acute liver failure (ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced self-limited AH and ALF. Thus, we worked with five groups: Hepatitis A virus (HAV)-induced self-limited acute hepatitis (HAV-AH), HAV-induced ALF (HAV-ALF), non-viral-induced self-limited acute hepatitis (non-viral AH), non-viral-induced acute liver failure (non-viral ALF), and healthy subjects (HC). Comparisons among HAV and non-viral-induced AH and ALF were performed. RESULTS: The levels of mitochondrial DNA (mtDNA) and the cytokines investigated [interleukin (IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology (P < 0.05). High plasma mtDNA and IL-10 were the best markers associated with ALF [mtDNA: OR = 320.5 (95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8 (95%CI: 1.38-257.94), P = 0.028] and death [mtDNA: OR = 12.1 (95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01 (95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NKbright, NKT and regulatory T cells (TReg) predominated in virus-specific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION: mtDNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.

Diretrizes para avaliação e validação do potencial doador de órgãos em morte encefálica / Guidelines for the assessment and acceptance of potential brain-dead organ donors

RESUMO O transplante de órgãos é a única alternativa para muitos pacientes portadores de algumas doenças terminais. Ao mesmo tempo, é preocupante a crescente desproporção entre a alta demanda por transplantes de órgãos e o baixo índice de transplantes efetivados. Dentre as diferentes causas que alimentam essa desproporção, estão os equívocos na identificação do potencial doador de órgãos e as contraindicações mal atribuídas pela equipe assistente. Assim, o presente documento pretende fornecer subsídios à equipe multiprofissional da terapia intensiva para o reconhecimento, a avaliação e a validação do potencial doador de órgãos.

ABSTRACT Organ transplantation is the only alternative for many patients with terminal diseases. The increasing disproportion between the high demand for organ transplants and the low rate of transplants actually performed is worrisome. Some of the causes of this disproportion are errors in the identification of potential organ donors and in the determination of contraindications by the attending staff. Therefore, the aim of the present document is to provide guidelines for intensive care multi-professional staffs for the recognition, assessment and acceptance of potential organ donors.

Right gastroepiploic artery as an alternative for arterial reconstruction in living donor liver transplantation.

Background. An adequate blood flow is directly related to graft survival in living donor liver transplantation. However, in some cases, unfavorable conditions prevent the use of the hepatic artery for arterial reconstruction. Herein, we report a case in which the recipient right gastroepiploic artery was used as an option for arterial reconstruction in adult-to-adult living donor liver transplantation. Case Report. A 62-year-old woman, with cirrhosis due to hepatitis B associated with hepatocellular carcinoma, was submitted to living donor liver transplantation. During surgery, thrombosis of the hepatic artery with intimal dissection until the celiac trunk was observed, which precluded its use in arterial reconstruction. We decided to use the right gastroepiploic artery for arterial revascularization of the liver graft. Despite the discrepancy in size between donor hepatic artery and recipient right gastroepiploic artery, anastomosis was performed successfully. Conclusions. The use of the right gastroepiploic artery as an alternative for arterial revascularization of the liver graft in living donor liver transplantation should always be considered when the hepatic artery of the recipient cannot be used. For performing this type of procedure, familiarity with microsurgical techniques by the surgical team is necessary.

Portal vein embolization using an adapted hysterosalpingography catheter.

BACKGROUND: Portal vein embolization is an accepted procedure that provides hypertrophy of the future remnant liver in order to reduce post-hepatectomy complications. AIM: To present a series submitted to portal vein embolization using an adapted hysterosalpingography catheter via transileocolic route. METHODS: Were performed right portal branch embolization in 19 patients using hysterosalpingography catheter. For embolizing the vessel, was used Gelfoam(r) powder with absolute alcohol solution. Indications for hepatectomy were colorectal liver metastases in all cases. RESULTS: An adequate growth of the future remnant liver was achieved in 15 patients (78.9%) and second time hepatectomy could be done in 14 (73.7%). In one patient (5.2%), tumor progression prevented surgery. One patient presented acute renal failure after portal embolization. CONCLUSIONS: The hysterosalpingography catheter is easy to handle and can be introduced into the portal vein with a wire guide. There were no major post-embolization complication. Its use is safe, cheap and effective.

Portal vein embolization using an adapted hysterosalpingography catheter / Embolização portal utilizando cateter adaptado de histerossalpingografia

BACKGROUND: Portal vein embolization is an accepted procedure that provides hypertrophy of the future remnant liver in order to reduce post-hepatectomy complications. AIM: To present a series submitted to portal vein embolization using an adapted hysterosalpingography catheter via transileocolic route. METHODS: Were performed right portal branch embolization in 19 patients using hysterosalpingography catheter. For embolizing the vessel, was used Gelfoam(r) powder with absolute alcohol solution. Indications for hepatectomy were colorectal liver metastases in all cases. RESULTS: An adequate growth of the future remnant liver was achieved in 15 patients (78.9%) and second time hepatectomy could be done in 14 (73.7%). In one patient (5.2%), tumor progression prevented surgery. One patient presented acute renal failure after portal embolization. CONCLUSIONS: The hysterosalpingography catheter is easy to handle and can be introduced into the portal vein with a wire guide. There were no major post-embolization complication. Its use is safe, cheap and effective. .

RACIONAL: Embolização da veia porta é procedimento consagrado para estimular a hipertrofia do fígado remanescente, a fim de reduzir as complicações pós-hepatectomia. OBJETIVO: Apresentar série de casos submetidos à embolização da veia porta usando cateter adaptado de histerossalpingografia, por via transileocólica. MÉTODOS: Foi realizada embolização do ramo portal direito em 19 pacientes utilizando cateter de histerossalpingografia. Foi usado Gelfoam(r) em pó com solução de álcool absoluto, como material embolizante. As indicações para hepatectomia foram metástases hepáticas colorretais em todos os casos. RESULTADOS: Hipertrofia adequada do fígado remanescente foi alcançada em 15 pacientes (78,9%) e a hepatectomia foi realizada em 14 (73,7 %). Em um (5,2 %), a progressão do tumor impediu a realização da operação. Um paciente apresentou insuficiência renal aguda após embolização portal. CONCLUSÕES: O cateter de histerossalpingografia é fácil de ser manuseado e pode ser introduzido na veia porta com um fio guia. Não houve complicação grave pós-embolização. Seu uso é seguro, barato e eficaz. .

Is there any difference between right hepatectomy and left lateral sectionectomy for living donors? as much you cut, as much you hurt?

BACKGROUND: The worldwide rising demand for cadaveric donors in liver transplantation is an important incentive for the development of alternative transplantation options, such as living donors. A precise evaluation of surgical complications is, therefore, considered to be an important issue in this setting. AIM: Present a retrospective analysis of 126 living donors hepatectomies undertaken at our centre. METHODS: From December 2002 to August 2009, 126 living donors were submitted to hepatectomy. Donors' complications were stratified according to Clavien's scoring system to compare the morbidity of right hepatectomy (RH) (Group 1) and left lateral sectionectomy (LLS) (Group 2). RESULTS: Thirty-nine complications were observed in 35 patients. Sixty LLS, 3 left (LH) and 63 RH were performed. The complications were classified as: Clavien grade 1-11 (28.2%), grade 2-12 (30.7%), grade 3A-13 (33.3%), grade 3B-2 (5.1%) and grade 4A-1 (2.5%). When Group 1 (63 patients) and Group 2 (60 patients) were compared, there was no significant difference between the number of complications: 20 (31%) and 14 (23%), respectively (P > 0.3). CONCLUSIONS: Hepatectomy for living donor liver transplantation (LDLT) was a safe procedure, regardless of the type of liver resection undertaken. We found no difference in morbidity between RH and LLS, which suggests that complications may occur despite the amount of liver retrieved.

Fulminant hepatitis failure in adults and children from a Public Hospital in Rio de Janeiro, Brazil

Fulminant hepatic failure (FHF) is characterized by massive hepatocellular injury, whose physiopathology is still unclear. Hepatitis B (HBV) is probably the most common viral cause of FHF, while hepatitis A (HAV) virus seem occurs less frequently. However, the host and viral factors that determine the outcome of these infections are poorly understood. In the present study, viral load and genotyping determining regions of HAV and HBV genomes were sequenced. Eight FHF patients and one patient with severe acute hepatitis (SAH) were included. Liver and blood samples were collected during liver transplantation or necropsy procedures. HAV-RNA and HBV-DNA were extracted from serum, biopsy and paraffin liver. Nucleotide sequencing of HAV-RNA was performed from VP1/2A and HBV-DNA from PreS/S region. The amplified samples were quantified by Real-Time PCR. The cases of HAV infection were due to subgenotype IA. The cases of HBV infection were due to genotype A2 and D4. The case of HAV/HBV coinfection was infected by genotype IA and D3. Hepatitis A and B infection were associated with genotypes most prevalent in Brazil. In hepatitis A infection the mean of period evolution was 13 days. In hepatitis B, FHF patients infected by genotype D have a shorter period of evolution than FHF patients infected by genotype A (mean 15 v. 53 days). There was no association with genotype-determining region with the severity of hepatitis, however nucleotide differences and high viral load could be observed among FHF.

Eosinophils involved in fulminant hepatic failure are associated with high interleukin-6 expression and absence of interleukin-5 in liver and peripheral blood.

BACKGROUND/AIMS: Although eosinophils are considered to play an important role in the pathogenesis of various parasitic, allergic and autoimmune digestive diseases, their role in fulminant hepatic failure (FHF) is unknown. Our contribution was to identify and quantify eosinophils and cytokine levels [interleukin (IL)-6, IL-5 and macrophage inflammatory protein (MIP)-1alpha] in liver parenchyma and peripheral blood from FHF patients at pre- and post-transplantation steps. METHODS: Histochemical methods were used to identify/quantify eosinophils in liver samples. Liver and plasma cytokine levels were quantified using immunofluorescence methods. RESULTS: Fulminant hepatic failure patients showed a high number of intrahepatic eosinophils concomitant with an increased expression of IL-6, besides the IL-6-positive eosinophils associated with the lack of IL-5. Also, an increased number of eosinophils and soluble IL-6 and MIP-1alpha with a low expression of IL-5 in peripheral blood at the pretransplantation step was observed. CONCLUSIONS: The increased number of intrahepatic eosinophils, besides the high production of IL-6, may be involved in liver dysfunction. In addition, the low presence of IL-5 in liver and peripheral blood may represent a particular pattern of eosinophil behaviour in human liver failure, which may also involve MIP-1alpha. Further ex vivo studies are necessary to evaluate the specific role of eosinophils in FHF.

Fulminant hepatitis failure in adults and children from a Public Hospital in Rio de Janeiro, Brazil.

Fulminant hepatic failure (FHF) is characterized by massive hepatocellular injury, whose physiopathology is still unclear. Hepatitis B (HBV) is probably the most common viral cause of FHF, while hepatitis A (HAV) virus seem occurs less frequently. However, the host and viral factors that determine the outcome of these infections are poorly understood. In the present study, viral load and genotyping determining regions of HAV and HBV genomes were sequenced. Eight FHF patients and one patient with severe acute hepatitis (SAH) were included. Liver and blood samples were collected during liver transplantation or necropsy procedures. HAV-RNA and HBV-DNA were extracted from serum, biopsy and paraffin liver. Nucleotide sequencing of HAV-RNA was performed from VP1/2A and HBV-DNA from PreS/S region. The amplified samples were quantified by Real-Time PCR. The cases of HAV infection were due to subgenotype IA. The cases of HBV infection were due to genotype A2 and D4. The case of HAV/HBV coinfection was infected by genotype IA and D3. Hepatitis A and B infection were associated with genotypes most prevalent in Brazil. In hepatitis A infection the mean of period evolution was 13 days. In hepatitis B, FHF patients infected by genotype D have a shorter period of evolution than FHF patients infected by genotype A (mean 15 v. 53 days). There was no association with genotype-determining region with the severity of hepatitis, however nucleotide differences and high viral load could be observed among FHF.

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.