Recent Advances in Locoregional Therapy of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is responsible for 90% of primary hepatic cancer cases, and its incidence with associated morbidity and mortality is growing worldwide. In recent decades, there has been a revolution in HCC treatment. There are three main types of locoregional therapy: radiofrequency ablation, transarterial chemoembolisation, and transarterial radioembolisation. This article summarises recent advances in locoregional methods

PCRRT Expert Committee ICONIC Position Paper on Prescribing Kidney Replacement Therapy in Critically Sick Children With Acute Liver Failure

Management of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in the pediatric population can be challenging. Kidney manifestations of liver failure, such as hepatorenal syndrome (HRS) and acute kidney injury (AKI), are increasingly prevalent and may portend a poor prognosis. The overall incidence of AKI in children with ALF has not been well-established, partially due to the difficulty of precisely estimating kidney function in these patients. The true incidence of AKI in pediatric patients may still be underestimated due to decreased creatinine production in patients with advanced liver dysfunction and those with critical conditions including shock and cardiovascular compromise with poor kidney perfusion. Current treatment for kidney dysfunction secondary to liver failure include conservative management, intravenous fluids, and kidney replacement therapy (KRT). Despite the paucity of evidence-based recommendations concerning the application of KRT in children with kidney dysfunction in the setting of ALF, expert clinical opinions have been evaluated regarding the optimal modalities and timing of KRT, dialysis/replacement solutions, blood and dialysate flow rates and dialysis dose, and anticoagulation methods

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background &amp; Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p &lt;0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p &lt;0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.</p

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. Homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC), in contrast to patients with two predicted protein truncating mutations (PPTM). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n=31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n=30), and with two PPTMs (BSEP3/3; n=77). We compared presentation, native liver survival (NLS), and effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (P<0.001). Without siEHC in their follow-up, NLS of BSEP1/3 was similar to BSEP3/3 patients, but considerably lower than BSEP1/1 patients (at age 10 years: 38%, 30%, and 71%, resp; P=0.003). After siEHC, BSEP1/3 and BSEP3/3 patients had similarly low NLS, while this was much higher in BSEP1/1 patients (10 years after siEHC, 27%, 14%, and 92%, resp.; P<0.001). Conclusions: BSEP deficiency patients with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as patients with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment

Robotic donor hepatectomy: a niche advancement or the way forward? A perspective from the world’s largest center

The application of minimally invasive liver surgery (MILS) in the field of living donor hepatectomy has been exceedingly slow, and its impact is limited to a handful of centers worldwide. Widespread adoption has been primarily hampered by the technical limitations of laparoscopy, namely rigid instrumentation, suboptimal optics, and a seemingly steep learning curve. These deficiencies are magnified in the donor hepatectomy operation wherein the parenchyma and vasculature must be handled atraumatically to produce a pristine allograft fit for implantation. Donor safety concerns and medicolegal ramifications are also cited as impediments to MILS in donor surgery. In 2013, our institution embraced a purely laparoscopic approach to living donor left lateral sectionectomy, and it quickly became our default technique. However, with donor hemi-hepatectomy, we gravitated to the robotic surgical system as our preferred modality. Herein, we describe our experience with minimally invasive donor hepatectomy, which we now universally offer to all living donors. Our extensive familiarity with robotic donor hepatectomy will provide the reader with an instructive perspective on the attributes and merits of the robotic approach. With appropriate collaboration and proctorship, we believe that the robotic platform will actualize a more rapid and widespread adoption than that experienced with the purely laparoscopic technique

Use or Misuse of Albumin in Critical Ill Patients

Since 1940 albumin has been used worldwide and is widely available commercially since this time. However, a meta-analysis in 1998 challenged the use of albumin and identified a trend toward higher mortality in critically ill patients who had received albumin. Since then, many studies including multicenter randomized controlled trials have been carried out investigating the safety and efficacy of albumin treatment in different patient cohorts. In this context, patient cohorts that benefit from albumin were identified. However, particularly in non-liver patients, the use of albumin remains controversial. In our comprehensive review, we would like to highlight the most important studies in the recent 20 years and therefore offer an evidence-based outlook for the use of albumin for patients treated in the ICU

Invasive aspergillosis caused by Aspergillus terreus in a living donor liver transplant recipient successfully treated by caspofungin

Invasive aspergillosis is one of the most severe complications after liver transplantation characterised by early dissemination of disease and high mortality. Recent data show that the prognosis is diminishing even further when Aspergillus terreus, a strain resistant to standard treatment with amphotericin, is isolated. We report a high risk liver transplant recipient with multiple co-morbidities including renal failure and allograft dysfunction in whom pulmonary aspergillosis due to A. terreus was successfully treated by the echinocandin antifungal agent caspofungin

First fully laparoscopic donor hepatectomy for pediatric liver transplantation using the indocyanine green near-infrared fluorescence imaging in the Middle East : a case report

Living donor liver transplantation (LDLT) is a well-established treatment modality for several pediatric end-stage liver diseases owning excellent long-term results. Left lateral sectionectomy (LLS) through an open approach is a well-standardized procedure. This technique has been modified for a fully laparoscopic approach and gaining more and more interest worldwide. We report herein the first fully laparoscopic LLS for pediatric LDLT in the Middle East with the use of indocyanine green dye and near-infrared fluorescence imaging to identify the biliary ducts intraoperatively. The recipient was a 2-year-old. girl affected by glycogen storage disease type IV. The mother, aged 21 years, was her donor. The surgical technique, key-points of this procedure, and outcome are hereby discussed

Splitting of the middle hepatic vein in full-right full-left splitting of the liver

Full-right/full-left splitting of the liver offers a chance to overcome the severe shortage of donor organs. During this procedure, the splitting surgeons are always faced with the question of how to share the middle hepatic vein (MHV), since this vein drains parts of both halves of the liver. Consequently, we developed a procedure that splits the MHV, thus creating an MHV on both grafts. In this short article, we report on this splitting technique and our first initial experience