Liver and Hepatocyte Transplantation: What Can Pigs Contribute?

About one-fifth of the population suffers from liver diseases in China, meaning that liver disorders are prominent causative factors relating to the Chinese mortality rate. For patients with end-stage liver diseases such as hepatocellular carcinoma or acute liver diseases with life-threatening liver dysfunction, allogeneic liver transplantation is the only life-saving treatment. Hepatocyte transplantation is a promising alternative for patients with acute liver failure or those considered high risk for major surgery, particularly for the bridge-to-transplant period. However, the lack of donors has become a serious global problem. The clinical application of porcine xenogeneic livers and hepatocytes remains a potential solution to alleviate the donor shortage. Pig grafts of xenotransplantation play roles in providing liver support in recipients, together with the occurrence of rejection, thrombocytopenia, and blood coagulation dysfunction. In this review, we present an overview of the development, potential therapeutic impact, and remaining barriers in the clinical application of pig liver and hepatocyte xenotransplantation to humans and non-human primates. Donor pigs with optimized genetic modification combinations and highly effective immunosuppressive regimens should be further explored to improve the outcomes of xenogeneic liver and hepatocyte transplantation.

1MD LiverMD Review – Is LiverMD Liver Support Supplement Safe? v1

1MD LiverMD

Therapeutic plasma exchange in children with acute liver failure (ALF): is it time for incorporation into the ALF armamentarium?

Paediatric acute liver failure (PALF) is a rare but devastating condition with high mortality. An exaggerated inflammatory response is now recognised as pivotal in the pathogenesis and prognosis of ALF, with cytokine spill from the liver to systemic circulation implicated in development of multi-organ failure associated with ALF. With advances in medical management, especially critical care, there is an increasing trend towards spontaneous liver regeneration, averting the need for emergency liver transplantation or providing stability to the patient awaiting a graft. Hence, research is ongoing for therapies, including extracorporeal liver support devices, that can bridge patients to transplant or spontaneous liver recovery. Considering the immune-related pathogenesis and inflammatory phenotype of ALF, plasma exchange serves as an ideal liver assist device as it performs both the excretory and synthetic functions of the liver and, in addition, works as an immunomodulatory therapy by suppressing the early innate immune response in ALF. After a recent randomised controlled trial in adults demonstrated a beneficial effect of high-volume plasma exchange on clinical outcomes, this therapy was incorporated in European Association for the Study of Liver (EASL) recommendations for managing adult patients with ALF, but no guidelines exist for PALF. In this review, we discuss rationale, timing, practicalities, and existing evidence regarding the use of plasma exchange as an immunomodulatory treatment in PALF. We discuss controversies in delivery of this therapy as an extracorporeal device, and practicalities of use of plasma exchange as a ‘hybrid’ therapy alongside other extracorporeal liver assist devices, before finally reviewing outstanding research questions for the future.

589 Role of Liver Support Systems in The Management of Post Hepatectomy Liver Failure: A Meta-Analysis and Systematic Review of Literature

Aim Post hepatectomy liver failure (PHLF) is a rare but serious complication following liver resection. PHLF is associated with high mortality of up to 50% in severe cases. With limited treatment options available, there is a need to evaluate the role of systems that support the function of the liver as treatment modalities following PHLF development. Method The aim of this study was to review the literature and summarise the role of liver support systems (LSS) in the management of PHLF. Publications of interest were identified using systematically designed searches. Following screening, data from the relevant publications were extracted, pooled where possible, and analysed. Results Systematic review identified ten studies, which used either Plasma Exchange (PE) or Molecular Adsorbent Recirculating System (MARS) as LSS after PHLF development. The sample sizes of included studies were small, ranging from N = 2 to N = 13. Across all studies, the pooled 90-day mortality rate was 40% (95% CI: 15% - 68%). However, there was substantial heterogeneity (I2=64%), likely since the studies used a variety of definitions for PHLF and had different selection criteria for patient eligibility for LSS treatment. Conclusions Despite potential benefits, the current evidence is insufficient to recommend LSS for the routine management of severe PHLF, with the current literature consisting of only a limited number of studies. There is a definite need for larger, multicentre, prospective studies evaluating the conventional and newer modalities of support systems with a view to improve the outcomes in this group of patients.

Anti-tuberculosis drug-induced acute liver failure requiring transplantation in the second trimester of pregnancy: a case report

Background Treatment of tuberculosis (TB) during pregnancy can reduce maternal and foetal complications. However, it may also induce fatal liver injury. Case presentation We present a case of a 26-year-old pregnant woman who underwent orthotopic liver transplantation for anti-TB drug-induced fulminant hepatic failure (FHF). Her tuberculous pleurisy was treated with rifampin, isoniazid and pyrazinamide. An artificial liver support system (ALSS) was unable to reverse the liver injury while serving as a bridge to liver transplantation. She had a successful liver transplantation operation at 17 3/7 weeks of gestation. The foetal ultrasound scan showed mild foetal bilateral ventriculomegaly at 21 5/7 weeks of gestation, and labour was induced via double-balloon catheter as soon as the allograft function was stable. Despite immunosuppression, the TB was well controlled with linezolid, levofloxacin and pyridoxine at the 8 months follow-up. Conclusions Anti-TB drug-induced liver failure during pregnancy is rare. We present a case of successful treatment of FHF in which an artificial liver support system combined with liver transplantation. The FHF was caused by anti-TB drugs with difficulties due to pregnancy status and post-transplant anti-TB treatment. Mild foetal ventriculomegaly was found in our case. Further research is still needed to identify the risks of TB treatment and liver transplantation in pregnant women. A multidisciplinary team coordinated properly to optimize patient outcomes.

The Use of Extracorporeal Liver Support Systems In Acute Decompensated Liver Failure

The aim of the study: to evaluate the efficacy of extracorporeal liver support systems in patients with acute liver failure of various etiologies.Material and methods. The study included 117 patients with acute liver failure of various etiologies. The main group consisted of 71 patients who received complex intensive therapy, including MARS-therapy and hemodiafiltration. The comparison group included 46 patients who received albumin dialysis (24 patients) and hemodiafiltration (22 patients) alone. The mean age of the patients was 34±5.6 years, the majority (56.4%) were men. Dynamic assessment of patients' severity was performed using Sequential Organ Failure Assessment (SOFA) and Model for End-Stage Liver Disease (MELD) scales.Results. A more significant reduction of SOFA and MELD scores was noted as early as by day 10 of intensive therapy in the main group with sequential use of extracorporeal liver detoxification methods — to 2.7±0.2 vs. 8.3±0.5 points (P=0.021) on SOFA and to 16.7±0.4 vs. 23.4±1.4 points (P=0.023) MELD scales. The use of a comprehensive approach to extracorporeal detoxification in acute decompensated liver failure increased the regression rate of multiple organ failure from 51.2 to 74.6% and reduced mortality from 47.8 to 25.4% (χ2=6.266; df=1; P=0.013). At the same time, the cumulative proportion of survivors depending on the type of complication within 30 days was 88.4% in the main group and 69.0% in the comparison group (χ2=4.164; df=1; P=0.042).Conclusion. A comprehensive approach to extracorporeal detoxification is highly effective, providing a more significant reduction of SOFA and MELD scores, increasing the proportion of regression of multiple organ dysfunction and reducing mortality.