Partial Liver Transplantation Research Articles

Auxiliary xenotransplantation as an in vivo bioreactor—Development of a transplantable liver graft from a tiny partial liver

We established a completely novel method of auxiliary xenogeneic partial liver transplantation and examined whether liver grafts procured from Syrian hamsters regenerated in nude rats, which were used as in vivo bioreactors. The hamsters and the rats were all males (n=10). Partial liver grafts from hamsters were transplanted into nude rats in an auxiliary manner. We evaluated liver graft injury, rejection, and regeneration during 7days after auxiliary xenogeneic partial liver transplantation. All rats survived until sacrifice on post-operative day (POD) 1, 3, and 7. HE-staining showed normal at POD1, mild periportal edema, and slight bile duct and venous endothelial inflammation at POD3, and moderate acute cellular rejection at POD7 without parenchymal necrosis. The liver regeneration rates at POD3 and 7 were 1.54±0.23 and 2.54±0.43, respectively. The Ki-67 labeling index was also elevated at POD3 (27.5±4.1%). Serum HGF and VEGF were elevated at POD1 and 3. ATP levels of liver grafts recovered at POD7. These results revealed that with appropriate immunosuppressive therapy, partial liver graft regeneration occurred in a xenogeneic animal, which suggests liver grafts regenerated in xenogeneic environments, such as an in vivo bioreactor, have potential to be transplantable liver grafts for humans.

6. Auxiliary Partial Orthotopic Liver Transplantation for Selected Non Cirrhotic Metabolic Liver Disease

Background and Aims: Auxiliary Partial Orthotopic Liver Transplantation (APOLT) in selected non-cirrhotic metabolic liver diseases (NCMLD) is a viable alternative to orthotopic liver transplantation as it supplements the function of the native liver with the missing functional protein. APOLT for NCMLD is not universally accepted due to concerns of increased technical complications and long-term graft atrophy. Methods: Review of a prospectively collected database of all paediatric patients (age ≤16 years) who underwent liver transplant for non-cirrhotic MLD (NCMLD), from August 2009 up to June 2017 was performed. Patients were divided into two groups; Group 1 underwent APOLT and group 2 orthotopic liver transplant (OLT). Results: Eighteen OLT and 12 APOLT were performed for NCMLD during the study period. There was no significant difference in the age and weight of the recipients in both groups. All APOLT patients needed intra-operative portal flow modulation. Intraoperative peak and end of surgery lactate were significantly higher in the OLT group, and Cold ischemia time (CIT) was longer in the APOLT group. There were no differences in postoperative liver function tests apart from higher peak INR in the OLT group. The incidence of postoperative complications, duration of hospital stay and 1 & 5 year survivals were similar in both groups. Conclusions: We present the largest series of APOLT for NCMLD. APOLT is a safe and effective alternative to OLT, and may even be better than OLT due to lesser physiological stress, and smoother postoperative period for selected patients with NCMLD. The authors have none to declare.

Loco-regional intervention for hepatocellular carcinoma

Anatomic location/size and number of lesions, inadequate volume of future liver remnant, or poor coexisting premorbid conditions preclude surgery in the majority of patients with hepatocellular carcinoma (HCC). Liver transplantation can cure some patients with poor liver function, but few patients are eligible because of scarcity of donors. Without specific anti-cancer treatment, the prognosis of HCC is poor. Various locoregional therapies are used to treat patients who are not candidates for surgery, and have emerged as tools for palliation, tumor down-staging, and bridging therapy prior to liver transplantation. Currently, local ablative therapy even competes with partial hepatectomy and liver transplantation as a primary treatment for small HCC. HCC is well suited to treatment with loco-regional therapy because it has a tendency to stay within the liver, with distant metastasis generally occurring late in the course of disease. This suggests that an effective local-regional therapy can have a great impact on HCC patients who are not candidates for surgical treatment. Loco-regional therapy can further be justified because patients with HCC usually die of liver failure consequent to intrahepatic growth resulting in liver tissue destruction, rather than extrahepatic metastases.

Application of 3-Dimensional Printing in Pediatric Living Donor Liver Transplantation: A Single-Center Experience.

Three-dimensional (3D) printing has been used to support organ transplantations. However, whether it helps remains unclear. This study aimed to present and assess the application of 3D-printed liver models in pediatric living donor liver transplantation (LDLT). The 3D images were printed to touchable liver models with transparent liver parenchyma, specifically colored hepatic vessels, and biliary structures. A total of 30 consecutive recipients were enrolled in the study: 10 were operated on with the support of 3D printing (3D-printing group) and 20 (control group) were operated on without it. Detailed photographs and data of the cases in the 3D-printing group were presented. One patient underwent auxiliary partial orthotopic liver transplantation using the left lobe graft, in which the abdominal cavity model was also printed to test whether the planned graft fit the recipient's abdominal cavity. The 3D-printed models facilitated surgical planning and procedures, particularly in the management of hepatic veins and in the prevention of large-for-size syndrome. The operative time of donors in the 3D-printing group was significantly shorter compared with the control group (2.3±0.4 versus 3.0±0.4 hours; P<0.001). Inpatient costs for donors in the 3D-printing group were 17.1% lower than those in the control group (34.6±6.6 versus 41.7±10.4 thousand ¥; P=0.03). In conclusion, in small infants and complicated pediatric LDLT patients, 3D-printed models can help minimize the risk of large-for-size syndrome and graft reduction. The 3D-printed models may be conducive to liver graft procurement and intraoperative assistance in pediatric LDLT.

Glycine protects partial liver grafts from Kupffer cell-dependent ischemia-reperfusion injury without negative effect on regeneration.

Donor preconditioning with glycine prevents Kupffer cell-dependent reperfusion injury to liver grafts. Partial liver grafts need to regenerate and grow in size after transplantation; however, glycine inactivates Kupffer cells, which are important for hepatic regeneration. Thus, this study was designed to evaluate the impact of donor preconditioning with glycine after partial liver transplantation (pLTx). PLTx was performed in 28 female Sprague-Dawley rats. Glycine (1.5ml, 300mM; i.v.) was given to 14 live donors before organ procurement. Liver enzymes and histology were investigated 8h after reperfusion to index liver injury and leukocyte infiltration. Hepatic microperfusion and leukocyte-endothelium interaction were assessed using the in vivo fluorescence microscopy method. Ki-67 and TNF-α were detected by immunohistochemistry for regeneration and Kupffer cell activation. Glycine significantly increased survival from 0% in controls to 40%, while both liver enzyme levels and necrosis were decreased to about 50% of controls (p < 0.05). Sinusoidal blood flow increased by 40-80%, while leukocyte-endothelium interaction decreased to 30% of control values (p < 0.05). While Kupffer cell-derived TNF-α decreased to 70% of controls, there was no difference between groups in Ki-67 expression. Data presented here clearly demonstrate that glycine protects partial liver grafts from reperfusion injury without effects on regeneration.

Portojejunostomy in Split Liver Transplantation as a Rescue Technique for Challenging Biliary Reconstruction: A Case Report

Cadaveric split liver transplantation (SLT) is a valid option to increase the pool of cadaveric organs, obtaining 2 functioning grafts from a single donor. Typically, SLT is performed for 1 adult and 1 pediatric recipient. However, on the heels of great results achieved in living donor liver transplantation, splitting cadaveric liver into full right graft and full left graft for 2 adults has become a feasible idea. The rate of biliary complications remains the “Achilles heel” in partial graft liver transplantation, either from cadaveric or living donors. In cases of biliary complications, interventional radiology and/or endoscopic procedures are the cornerstone of management. Surgical revision is left as the last option. When surgical revision fails, retransplantation becomes the only rescue option. Herein we describe the case of a cadaveric SLT, complicated by biliary leakage in the presence of multiple bile ducts. A duct-to-duct anastomosis was not feasible. Therefore, a hepaticojejunostomy was performed and resulted in a high-output biliary leak from different sources. Given the anatomy of the biliary tree, radiologic interventional measures were not feasible to address the leak. The idea of performing a portoenterostomy to restore bilioenteric continuity proved to be successful. Portoenterostomy should not be performed in lieu of other alternatives, but rather as the last option to avoid retransplantation in cases of complicated biliary reconstruction after partial graft liver transplant.

Staged biliary reconstruction after liver transplantation: A novel surgical strategy for high acuity pediatric transplant recipients

IntroductionBiliary complications after pediatric orthotopic liver transplantation remain causes of significant patient morbidity. Staged operative approach in complex hepatobiliary surgery has improved postoperative outcomes but has not been evaluated in pediatric orthotopic liver transplantation. We sought to analyze the outcomes of staged biliary reconstruction after orthotopic liver transplantation in high acuity patients. MethodsA retrospective analysis of 43 pediatric orthotopic liver transplantations at our center (January 2013 through December 2017). Median follow-up was 25 months. Variables were compared for group I: 1-stage orthotopic liver transplantation with biliary anastomosis (n = 6) versus group II: staged biliary reconstruction orthotopic liver transplantation (n = 37). ResultsComparing groups I and II, median age (7.3 vs 4.8 years), weight (27 vs 19 kg), proportion of urgent orthotopic liver transplantation (50% vs 65%), partial graft orthotopic liver transplantation (33% vs 35%), and intraoperative red blood cell transfusion volume (11 vs 21 mL/kg) were comparable. Roux-en-Y hepaticojejunostomy was performed in 67% (group I) and 49% (group II). There was no biliary complication in both groups. For groups I and II, 3-year survival rates for graft (100% vs 92%, P = .477) and patient (100% vs 97%, P = .679) were comparable. ConclusionOur study showed excellent outcomes with staged biliary reconstruction orthotopic liver transplantation in high acuity pediatric transplant recipients. This is the first report showing clinical applicability of staged biliary reconstruction orthotopic liver transplantation in children.

MiR-155 Aggravates Liver Ischemia/reperfusion Injury by Suppressing SOCS1 in Mice

Liver ischemia/reperfusion injury (IRI) occurs during partial liver resection and liver transplantation. Activation of Toll-like receptors (TLRs) is a key event triggered by a range of proinflammatory cytokines during liver I/R. Although it has been reported that miR-155 takes part in both innate and adaptive immune responses, the potential role of miR-155 in liver IRI remains unknown. In this study, we found that expression of miR-155 was upregulated during liver I/R by many inflammatory cytokines, and forced expression of miR-155 aggravated hepatocyte injury following liver I/R both in vivo and in vitro. Mice transfected with Ago-miR-155—a chemically modified miR-155—showed enhanced liver severity compared to those transfected with negative control miRNA by inhibiting the expression of SOCS1, the target of miR-155. Thus by the inhibition of SOCS1, the overexpression of miR-155 promoted activation of NF-κB, and elevating the production of proinflammatory cytokines, such TNF-α and IL-6. In conclusion, miR-155 aggravates liver I/R injury in vivo and hepatocyte hypoxia/reoxygenation injury by suppressing the expression of SOCS1.

Macroporous Dual-compartment Hydrogels for Minimally Invasive Transplantation of Primary Human Hepatocytes.

Given the shortage of available organs for whole or partial liver transplantation, hepatocyte cell transplantation has long been considered a potential strategy to treat patients suffering from various liver diseases. Some of the earliest approaches that attempted to deliver hepatocytes via portal vein or spleen achieved little success due to poor engraftment. More recent efforts include transplantation of cell sheets or thin hepatocyte-laden synthetic hydrogels. However, these implants must remain sufficiently thin to ensure that nutrients can diffuse into the implant. To circumvent these limitations, we investigated the use of a vascularizable dual-compartment hydrogel system for minimally invasive transplantation of primary hepatocytes. The dual-compartment system features a macroporous outer polyethylene glycol diacrylate/hyaluronic acid methacrylate hydrogel compartment for seeding supportive cells and facilitating host cell infiltration and vascularization and a hollow inner core to house the primary human hepatocytes. We show that the subcutaneous implantation of these cell-loaded devices in NOD/SCID mice facilitated vascular formation while supporting viability of the transplanted cells. Furthermore, the presence of human serum albumin in peripheral blood and the immunostaining of excised implants indicated that the hepatocytes maintained function in vivo for at least 1 month, the longest assayed time point. Cell transplantation devices that assist the anastomosis of grafts with the host can be potentially used as a minimally invasive ectopic liver accessory to augment liver-specific functions as well as potentially treat various pathologies associated with compromised functions of liver, such as hemophilia B or alpha-1 antitrypsin deficiency.

Auxiliary partial orthotopic liver transplantation for acute liver failure in mice

Auxiliary partial orthotopic liver transplantation for acute liver failure in mice

A Survey of Molecular Heterogeneity in Hepatocellular Carcinoma.

Understanding the heterogeneity of dysregulated pathways associated with the development of hepatocellular carcinoma (HCC) may provide prognostic and therapeutic avenues for disease management. As HCC involves a complex process of genetic and epigenetic modifications, we evaluated expression of both polyadenylated transcripts and microRNAs from HCC and liver samples derived from two cohorts of patients undergoing either partial hepatic resection or liver transplantation. Copy number variants were inferred from whole genome low‐pass sequencing data, and a set of 56 cancer‐related genes were screened using an oncology panel assay. HCC was associated with marked transcriptional deregulation of hundreds of protein‐coding genes. In the partially resected livers, diminished transcriptional activity was observed in genes associated with drug catabolism and increased expression in genes related to inflammatory responses and cell proliferation. Moreover, several long noncoding RNAs and microRNAs not previously linked with HCC were found to be deregulated. In liver transplant recipients, down‐regulation of genes involved in energy production and up‐regulation of genes associated with glycolysis were detected. Numerous copy number variants events were observed, with hotspots on chromosomes 1 and 17. Amplifications were more common than deletions and spanned regions containing genes potentially involved in tumorigenesis. Colony stimulating factor 1 receptor (CSF1R), fibroblast growth factor receptor 3 (FGFR3), fms‐like tyrosine kinase 3 (FLT3), nucleolar phosphoprotein B23 (NPM1), platelet‐derived growth factor receptor alpha polypeptide (PDGFRA), phosphatase and tensin homolog (PTEN), G‐protein‐coupled receptors‐like receptor Smoothened (SMO), and tumor protein P53 (TP53) were mutated in all tumors; another 26 cancer‐related genes were mutated with variable penetrance. Conclusion: Our results underscore the marked molecular heterogeneity between HCC tumors and reinforce the notion that precision medicine approaches are needed for management of individual HCC. These data will serve as a resource to generate hypotheses for further research to improve our understanding of HCC biology. (Hepatology Communications 2018; 00:000‐000)

Comparison between Cadaveric Whole Liver and Live Donor Partial Liver Transplantation in High Risk Patients with MELD Score more than 40

Comparison between Cadaveric Whole Liver and Live Donor Partial Liver Transplantation in High Risk Patients with MELD Score more than 40

Impact of Donor Age on Recipient Survival in Adult-to-Adult Living-donor Liver Transplantation.

To investigate the influence of donor age on recipient outcome after living-donor partial liver transplantation (LDLT). Donor age is a well-known prognostic factor in deceased donor liver transplantation; however, its role in LDLT remains unclear. We retrospectively analyzed 315 consecutive cases of primary adult-to-adult LDLT in our center between April 2006 and March 2014. Recipients were divided into 5 groups according to the donor age: D-20s (n = 60); D-30s (n = 72); D-40s (n = 57); D-50s (n = 94); and D-60s (n = 32). The recipient survival and the association with various clinical factors were investigated. Recipient survival proportions were significantly higher in D-20s compared with all the other groups (P = 0.008, < 0.001, < 0.001, and = 0.006, vs D-30s, -40s, -50s, and -60s, respectively), whereas there was no association between recipient survival and their own age. There are 3 typical relationships between donors and recipients in adult-to-adult LDLT: from child-to-parent, between spouses/siblings, and from parent-to-child. The overall survival in child-to-parent was significantly higher than in spouses/siblings (P = 0.002) and in parent-to-child (P = 0.005), despite significantly higher recipient age in child-to-parent [59 (42-69) years, P < 0.001]. Contrastingly, parent-to-child exhibited the lowest survival, despite the youngest recipient age [26 (20-43) years, P < 0.001]. In addition, younger donor age exhibited significantly better recipient survival both in hepatitis C virus-related and in non-hepatitis C virus diseases. Univariate and multivariate analyses both demonstrated that donor age and graft-type (right-sided livers) are independent prognostic factors for recipient survival. Donor age is an independent, strong prognostic factor in adult-to-adult LDLT.

A pooled analysis of treatment and prognosis of hepatic angiosarcoma in adults

BackgroundHepatic angiosarcoma is a rare malignant vascular tumor presenting unique treatment challenges. The aim of the present study was to determine the treatment and prognosis of this entity. Data sourcesA systematic literature search was conducted using PubMed, Embase and Chinese Biomedical Literature database, to identify articles published from January 1980 to July 2017. Search terms were “hepatic angiosarcoma” and “liver angiosarcoma”. Additional articles were retrieved through manual search of bibliographies of the relevant articles. Pooled individual data concerning the prognosis following various therapeutic modalities were analyzed. ResultsA total of 75 articles involving 186 patients were eligible for inclusion. The median overall survival (OS) was 8 months, with 1-, 3-, and 5-year OS rates of 36.6%, 22.3%, and 12.0%, respectively. The median OS after partial hepatectomy (n = 86), chemotherapy (n = 36), liver transplantation (n = 17), and supportive care (n = 46) were 15, 10, 5 and 1.3 months, respectively. Small tumor size (<10 cm) was the only significant favorable factor for OS after partial hepatectomy (P = 0.012). ConclusionsDespite the dismal prognosis, partial hepatectomy could prolong the survival of hepatic angiosarcoma patients, particularly those with tumors <10 cm. Chemotherapy could be an option for unresectable disease. Liver transplantation is not a recommendable option for the management of this malignancy.

Exogenous melatonin protects small-for-size liver grafts by promoting monocyte infiltration and releases interleukin-6.

Defective regeneration of small-for-size (SFS) liver remnants and partial grafts remains a key limiting factor in the application of liver surgery and transplantation. Exogenous melatonin (MLT) has protective effects on hepatic ischemia-reperfusion injury (IRI), but its influence on graft regeneration is unknown. The aim of the study is to investigate the role of MLT in IRI and graft regeneration in settings of partial liver transplantation. We established three mouse models to study hepatic IRI and regeneration associated with partial liver transplantation: (I) IR+PH group: 60minutes liver ischemia (IR) plus 2/3 hepatectomy (PH); (II) IR+exPH group: 60minutes liver IR plus extended hepatectomy (exPH) associated with the SFS syndrome; (III) SFS-LT group: Arterialized 30% SFS liver transplant. Each group was divided into MLT or vehicle-treated subgroups. Hepatic injury, inflammatory signatures, liver regeneration, and animal survival rates were assessed. MLT reduced liver injury, enhanced liver regeneration, and promoted interleukin (IL) 6, IL10, and tumor necrosis factor-α release by infiltrating, inflammatory Ly6C+ F4/80+ monocytes in the IR+PH group. MLT-induced IL6 significantly improved hepatic microcirculation and survival in the IR+exPH model. In the SFS-LT group, MLT promoted graft regeneration and increased recipient survival along with increased IL6/GP130-STAT3 signaling. In IL6-/- mice, MLT failed to promote liver recovery, which could be restored through recombinant IL6. In the IR+exPH and SFS-LT groups, inhibition of the IL6 co-receptor GP130 through SC144 abolished the beneficial effects of MLT. MLT ameliorates SFS liver graft IRI and restores regeneration through monocyte-released IL6 and downstream IL6/GP130-STAT3 signaling.

Re-Arterialized Rat Partial Liver Transplantation with an in vivo Vessel-Oriented 70% Hepatectomy.

Split liver transplantation and living liver donor liver transplantation were developed in the clinic to utilize liver organs in a more efficient manner. To better understand the mechanism behind these surgical procedures, a rat partial liver transplantation (PLTx) model was established for relevant surgical studies. Because of the complexity of the rat PLTx model, a protocol with detailed descriptions is required. An article published previously reported a protocol in which ex vivo hepatectomy was used to achieve 50% rat PLTx. In contrast to this protocol, we introduced a re-arterialized PLTx with an in vivo 70% hepatectomy. An updated vessel-oriented hepatectomy was incorporated into the rat PLTx to refine the microsurgical procedure. The portal veins and hepatic arteries of the left lateral lobe and the median lobe were individually dissected and ligated before removal of the liver parenchyma, thereby decreasing the probability of bleeding in the remnant liver stump. Furthermore, an end-to-side vessel anastomosis between the common hepatic artery and the enlarged proper hepatic artery was introduced to re-arterialize the hepatic artery. By using this end-to-side vessel anastomosis technique, the diameter of the anastomosis was enlarged, thereby decreasing the difficulty of hand suture and maintaining a high rate of anastomotic patency. Moreover, the cuff anastomosis of the infrahepatic vena cava was slightly modified. A section of circumferential liver parenchyma around the vena cava of a recipient was preserved during cuff anastomosis to maintain the three-dimensional shape of the vascular lumen. This section of liver parenchyma was removed after completing the anastomosis. With this modification, the step involving placement of stay sutures was omitted, thereby further shortening the cuff anastomosis time. By using this protocol of rat PLTx, a low liver enzyme level, an intact liver lobular architecture and a high survival rate were achieved after microsurgery.

Effect of Hepatic Preconditioning with the Use of Methylene Blue on the Liver of Wistar Rats Submitted to Ischemia and Reperfusion

BackgroundThe liver may be injured in situations where it is submitted to ischemia, such as partial hepatectomy and liver transplantation. In all cases, ischemia is followed by reperfusion and, although it is essential for the reestablishment of tissue function, reperfusion may cause greater damage than ischemia, an injury characterized as ischemia-reperfusion (I/R) damage. The aim of this work was to analyze the effect of ischemic preconditioning with the use of methylene blue (MB; 15 mg/kg) 5 or 15 minutes before I/R (IRMB5′ and IRMB15′, respectively) on the hepatic injury occurring after I/R. MethodsTwenty-eight male Wistar rats were used, and liver samples submitted to partial ischemia (IR) or not (NI) were obtained from the same animal. The samples were divided into 7 groups. Data were analyzed statistically by means of the nonparametric Mann-Whitney test and Wilcoxon Matched test, with the level of significance set at 5% (P < .05). ResultsThe rate of oxygen consumption by state 3 mitochondria was inhibited in all ischemic groups compared with the sham group (SH vs IR: P = .0052; SH vs IRMB5′: P = .0006; SH vs IRMB15′: P = .0048), which did not occur in the nonischemic contralateral portion of the same liver (SH vs NI: P = .7652; SH vs NIMB5′: P = .059; SH vs NIMB15′: P = .3153). The inhibition of the rate of oxygen consumption by state 3 mitochondria was maintained in the presence of MB (IR vs IRMB5′: P = .4563; IR vs IRMB15′: P = .9021). The respiratory control ratio was reduced in all ischemic groups compared with the sham group, owing to the inhibition of oxygen consumption in state 3 (SH vs IR: P = .0151; SH vs IRMB5′: P = .005; SH vs IRMB15′: P = .0007). ConclusionsMethylene blue had no effect on the mitochondrial respiratory parameters studied, but was able to reduce lipid peroxidation, preventing the production of reactive oxygen species (SH vs IRMB15′: P = .0210).

Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies.

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma‐glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP‐common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP‐other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP‐common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP‐other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP‐other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations. (Hepatology Communications 2018;2:515‐528)

Treatment of hypersplenism in patients with portal hypertension of hepatic cirrhosis

Hypersplenism is a common clinical manifestation of portal hypertension in hepatic cirrhosis. Clinical treatment of hypersplenism includes splenectomy, partial splenic embolization and liver transplantation. Splenectomy and partial splenic embolization are effective for hypersplenism, but the main complications are portal / splenic vein thrombosis (PSVT) and infection. Liver transplantation is an ideal method for the treatment of hypersplenism caused by cirrhosis, but patients with liver transplantation may still have persistent hypersplenism. Simultaneous splenectomy or partial splenic embolization which is performed with liver transplantation is a therapy of persistent hypersplenism. It can improve the function of graft but also increase the risk of infection. Key words: Hypersplenism; Splenectomy; Partial splenic embolization; Liver transplantation

Significance of presence of microvascular invasion in specimens obtained after surgical treatment of hepatocellular carcinoma.

Partial hepatectomy and liver transplantation are potentially curative treatments in selected patients with hepatocellular carcinoma (HCC). Unfortunately, a high postoperative tumor recurrence rate significantly decreases long-term survival outcomes. Among multiple prognostic factors, the presence of microvascular invasion (MVI) has increasingly been recognized to reflect enhanced abilities of local invasion and distant metastasis of HCC. Unfortunately, MVI can only currently be identified through histopathological studies on resected surgical specimens. Accurate preoperative tests to predict the presence of MVI are urgently needed. This paper reviews the current studies on incidence, pathological diagnosis, and classification of MVI; possible mechanisms of MVI formation; and preoperative prediction of the presence of MVI. Furthermore, focusing on how the postoperative management can be improved on histopathologically confirmed patients with HCC with MVI, and the potential roles of using predictive tests to estimate the risk of presence of MVI, helps in preoperative therapeutic decision-making in patients with HCC.