Jaundice Occurrence After a Large Area Burn Is a Possible Indication to Delay Surgery.

The mortality of burn patients with sepsis is higher than that of trauma patients. Sepsis causes liver dysfunction, which is an independent risk factor for multiple organ dysfunction syndrome and sepsis-induced death. We present the case of a 57-year-old female with burns covering 59% of her total body surface area and the presence of full-thickness burns. She was transferred to our burn center due to the appearance of fever and skin jaundice during the previous treatment. Based on the clinical manifestation, two main strategies were performed: debridement to remove necrotic wound tissue and treatment with a combination of drugs for liver protection. The patient's condition appeared stable for a period thereafter. Skin grafting to cover the wound was unexpectedly followed by a rapid deterioration in clinical manifestation. We can learn from this failed case that jaundice might be a sign of a systemic crisis. In such cases, surgery could aggravate the severity of the condition and cause multiple organ dysfunction syndrome. Therefore, jaundice may be a sign that skin surgery is not the best option. The optimal treatment should enhance liver protection or provide artificial liver support systems to facilitate the recovery of the liver from severe sepsis. This case suggests that skin graft surgery should not be conducted until jaundice is resolved in burn patients.

Traditional Medicine Doctor Kim Gwangjin's Battle against Jaundice during the Japanese Colonial Period.

This study aims to examine how traditional medicine doctors of the Japanese colonial period in Korea treated patients and their own diseases with traditional medicine and Western medicine by analyzing Clinical Cases and A Diary of Jaundice Treatment of Kim Gwangjin (1885-1940). Through this inquiry, this study aims to reveal that the Japanese colonial period was a time when the traditional medicine and the Western medicine coexisted, and that this period cannot be simply defined as a dualism between "Western medicine, Japanese colonial government" versus "traditional medicine, governed public." Kim Gwangjin's main method of medical treatment was traditional medicine. Clinical Cases include over 60 treatment cases, and they illustrate that he was a typical doctor at the time using traditional medical knowledge. In addition, Kim wrote A Diary of Jaundice Treatment from January 1939 to July 1940, a month before his death. The disease that led to his death was jaundice. He examined the changes in his abdomen every day, and recorded the changes in edema in upper extremities and testicles, urine and feces. While the treatment that Kim used in the early stages of jaundice were herbal medicines, he was not confined to the boundaries of the traditional medicine as he studied Western medicine to obtain a license of traditional medicine doctor from Japanese colonial government. He took a urine test to confirm whether his illness was jaundice or kidney disease and had X-ray imaging to check for pleurisy at a Western medical hospital in Daegu. Furthermore, he received a procedure to artificially drain bile, took a medicine to excrete bile into the feces, and had injection to treat neuralgia. Mostly, it was diarrhea that bothered Kim, who had been suffering from jaundice. Preventing diarrhea led to edema, and removing edema led to diarrhea again. He managed his symptoms by stopping the herbal medicine treatments and going on a raw food diet. Around this time, Kim relied the most on Ejisan. Ejisan was a type of new medicine mixed with traditional medicine and Western medicine that had the effect of treating edema and digestive disorders. Kim personally manufactured and took the drug until a month before his death, praising it as a necessary drug to treat jaundice. Kim was a traditional medical doctor during the Japanese colonial period. He also had the conventional wisdom that Western medicine was excellent in treating surgical diseases but not effective in internal medicine. However, he used both traditional medicine and Western medicine to treat symptoms of jaundice that have not been treated well and created a new medicine called Ejisan, which combined the two types of medicines. For him, Western medicine was a new medicine that improved the wrong aspects of traditional medicine or the old medicine, but there was still a realm of traditional medicine that Western medicine could not intervene. Furthermore, he published a new theory of traditional medicine called the Principle of Up and Down, which incorporates some Western medical knowledge. The Japanese colonial government required traditional medicine doctors to study Western medicine, and traditional medicine doctors had to learn Western medicine in order to survive. In the meantime, traditional medicine doctors such as Kim have brought about new changes by integrating the two medical treatments in the clinical field. The Japanese colonial government planned the demise of traditional medicine by forcing traditional medicine doctors to study the Western medicine, but the unexpected achievement brought about by traditional medicine doctors, who survived longer than the Japanese Empire and the colonial government, was an attempt to integrate Eastern and Western medicine.

Effect of combined ursodeoxycholic acid and glucocorticoid on the outcome of Kasai procedure: A systematic review and meta-analysis.

INTRODUCTION: Multiple studies have investigated the effect of ursodeoxycholic acid (UDCA) or glucocorticoid (GC) on the outcome of the hepatoportoenterostomy (Kasai procedure) in patients with biliary atresia (BA). However, the combined effect of these drugs (UDCA + GC) is little understood. METHODS: This meta-analysis specifically evaluated the effect of UDCA + GC after the Kasai procedure in patients with BA. A comprehensive literature search was conducted for all relevant articles in the electronic databases Medline, PubMed, Cochrane, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database on Disc (CBM-disc), and Vendor Information Pages (VIP). RESULTS: Eight studies with BA patients were finally included in our meta-analysis. The 8 identified studies consisted of 3 case-control, 3 cohort, and 2 randomized controlled trials (RCTs) with overall 530 subjects (144, 152, and 234 subjects, respectively). Among them, 312 patients were treated with UDCA + GC, while 218 received placebo or other intervention. The meta-analysis indicated that groups that received UDCA + GC had significantly lower rates of postoperative jaundice relative to the controls (pooled, odds ratio [OR] = 2.41; 95% confidence interval [CI] 1.44-4.04; Z = 3.34; P = .0008), while rates of cholangitis were similar (pooled, OR = 0.87; 95% CI 0.43-1.74; Z = 0.40; P = .69). CONCLUSIONS: Combined UDCA and GC intervention was superior to that of the control in accelerating the clearance of serum bilirubin in patients with BA after the Kasai procedure. However, this conclusion requires further confirmation using RCTs of high methodological quality.

Adjuvant steroid treatment following Kasai portoenterostomy and clinical outcomes of biliary atresia patients: an updated meta-analysis.

BACKGROUND: It is controversial whether adjuvant steroid treatment should be given to biliary atresia (BA) patients following a Kasai portoenterostomy (KPE). This study aimed to quantitatively and systematically evaluate the effect of adjuvant steroid therapy post-KPE in relation to major clinical outcomes of BA patients. METHODS: We systematically reviewed the literature in PubMed, Embase, the Cochrane Library, China Knowledge Resource Integrated Database, Wanfang Database, Scholarly and Academic Information Navigator and manually searched for relevant papers published before August, 2015. We extracted data on the effects of steroid treatment following KPE on clinical outcome, including jaundice free rate and native liver survival rate at 6 months, 1 or 2 years after KPE. The weighted overall relative risk (RR) and 95% confidence intervals (CIs) were calculated by using a random-effects model. RESULTS: Eight cohort studies and two randomized controlled trials (RCTs) were identified (n=998). Of them, 6 cohort studies and 2 trials investigated the effect of steroid treatment as compared to non-users or placebo (n=566), and 2 cohort studies compared the effects of high-dose to low-dose steroid treatment (n=432). Steroid usage increased the clearance rates of jaundice at 6 months (pooled RR: 1.32; 95% CI: 0.995-1.76; I 2=72.6%) and 1 year (pooled RR: 1.35; 95% CI: 1.12-1.61; I 2=0.0%), but not 2 years (pooled RR: 0.82; 95% CI: 0.55-1.22; I 2=0.0%) after KPE. There was no solid evidence supporting that steroid treatment would improve native liver survival rate at 6 months (pooled RR: 1.02; 95% CI: 0.90-1.15; I 2=0.0%), 1 year (pooled RR: 1.10; 95% CI: 0.91-1.34; I 2=35.2%) or 2 years (pooled RR: 1.00; 95% CI: 0.73-1.35; I 2=57.4%) after KPE. CONCLUSIONS: Adjuvant steroid treatment following KPE may improve short-term (≤1 year) clearance rate of jaundice, but no significant effects on long-term (≥2 years) clearance rate of jaundice and native liver survival rate. Studies on doses and duration of steroids, and long-term follow-up studies are warranted.

Treatment of unresectable extrahepatic cholangiocarcinoma using hematoporphyrin photodynamic therapy: A prospective study.

BACKGROUND: The available evidence of Photodynamic therapy (PDT) combined with stent placement treatment for unresectable extrahepatic cholangiocarcinoma (EHCC) is still insufficient. It also remains unclear whether PDT influences systemic inflammatory response. AIM: To explore the clinical efficacy and safety of the combination treatment and the systemic inflammatory response in patients with EHCC. METHODS: Patients with unresectable EHCC underwent either the combined treatment using Hematoporphyrin PDT and stent placement (PDT+stent group, n=12) or stent-only (stent group, n=27). The primary end-point was overall survival. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. Quality of life was assessed using the Karnofsky performance scale (KPS) every 3 months. RESULTS: Average survival time (13.8 vs. 9.6 months), and 6-month (91.7% vs. 74.1%), and 1-year (58.3% vs. 3.7%) survival rates of PDT+stent group were significantly increased compared with the stent group. KPS scores in the PDT+stent group were significantly improved. TNF-α and IL-6 levels were significantly increased in the PDT+stent group. CONCLUSION: Hematoporphyrin-PDT combined with stent placement is an effective and safe treatment for EHCC. The treatment might promote systemic inflammatory response.

Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein.

[A 61-year-old man with jaundice following stomach cancer]. / 61-jähriger Patient mit Ikterus bei Zustand nach Magenkarzinom.

A 61-year-old man with occlusion of the common bile duct due to metachronous metastases after surgery for adenocarcinoma of the stomach underwent a bile drainage intervention using endoscopic ultrasound (EUS). A self-expanding metal stent was inserted into the common bile duct of the liver via the esophagus. Successful drainage of the bile fluid into the duodenum was achieved for 14 months until the death of the patient. EUS interventions are becoming increasingly common. Although many questions such as the methodological details still remain, EUS interventions have the potential to become standard procedures especially in the situation of malignant stenoses of the bile or pancreatic duct.

Postoperative steroids after Kasai portoenterostomy for biliary atresia: a meta-analysis.

AIM: The aim of this systematic review and meta-analysis was to determine if adjunct steroids affect jaundice-free, cholangitis, and survival rates after Kasai portoenterostomy. METHODS: The literature was searched using the following terms: biliary atresia, portoenterostomy, steroids, glucocorticoids, dexamethasone, prednisolone, and hydrocortisone. The primary outcome was the jaundice-free rate. Secondary outcomes were cholangitis and survival rates. RESULTS: Ten studies were included in the systematic review and 8 in the meta-analyses. Steroid treatment regimens were inconsistent between studies. The pooled odds ratio (OR) for the jaundice-free rate did not significantly favor steroid over non-steroid treatment (1.95; 95% confidence interval [CI]: 0.91-4.11; P = 0.087), nor did the pooled OR for the cholangitis rate (0.75; 95% CI: 0.48-1.17; P = 0.202). Overall survival ranged from 58 to 95% in the steroid group and from 36 to 96% in the control group. Native liver survival ranged from 30 to 56% in the steroid group and from 31 to 48% in the control group. The survival data were not suitable for meta-analysis. CONCLUSIONS: Although these results imply that adjunct steroids after Kasai portoenterostomy for BA may not improve jaundice-free or cholangitis rates, the quality of available evidence is limited and therefore not definitive. Additional high quality studies are needed.

Whole-liver radiotherapy concurrent with chemotherapy as a palliative treatment for colorectal patients with massive and multiple liver metastases: a retrospective study.

The purpose of this study was to investigate whether whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases. From January 2007 to December 2012, 19 patients who exhibited massive (with a longest diameter > 5 cm) and invasive liver metastases and multiple metastases were treated with radiotherapy and concurrent chemotherapy. The total radiation dose was 53.4 Gy (range 38.8 Gy-66.3 Gy). All of the patients received a continuous intravenous dose of 5 fluorouracil (5-FU) 225 mg/m2 concurrently with radiation. The median survival time was 19 months. The 1- and 2- year overall survival rates were 78.3% and 14.3%, respectively. Of all of the patients who presented with abdominal pain, 100% experienced a decrease in pain. Decreases in the rates of ascites and jaundice were confirmed by ultrasound and bilirubin levels. No cases of Grade 4 or 5 acute or late toxicity were recorded. There were only two cases of Grade 3 toxicity (elevated bilirubin). These data provide evidence that whole-liver radiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases.

Comparable efficacy of low- versus high-dose induction corticosteroid treatment in autoimmune pancreatitis.

OBJECTIVE: The objective of this study was to compare efficacy of high versus low doses of prednisone for induction of remission in autoimmune pancreatitis (AIP). METHODS: This is a retrospective, multicenter study including patients diagnosed with AIP between May 1992 and August 2011. Clinical, laboratory and imaging findings were assessed before treatment and at 1, 3, and 6 months after starting treatment. RESULTS: A total of 65 patients (57 males; median age, 63 years) were treated with an initial low dose (10-20 mg/d, n = 14), a medium dose (30 mg/d, n = 15), or a high dose (40-60 mg/d, n = 36) of prednisone. There were no significant differences in baseline characteristics between the treatment groups including age, presenting symptoms and laboratory results. During a follow-up period of 6 months, in nearly all patients, symptoms (jaundice, weight loss) resolved completely. After 6 months, treatment response with respect to symptomatic, radiological, and laboratory improvement was comparable for the different dosage groups. CONCLUSIONS: Response to therapy was comparable for AIP patients treated with doses of prednisone in the range of 10 to 60 mg/d. A prospective trial should be conducted to confirm efficacy of lower-dose prednisone treatment.

Prophylactic gastrojejunostomy for unresectable periampullary carcinoma.

BACKGROUND: The role of prophylactic gastrojejunostomy in patients with unresectable periampullary cancer is controversial. OBJECTIVES: To determine whether prophylactic gastrojejunostomy should be performed routinely in patients with unresectable periampullary cancer. SEARCH METHODS: For the initial version of this review, we searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 3), MEDLINE, EMBASE and Science Citation Index Expanded until April 2010. Literature searches were re-run in August 2012. SELECTION CRITERIA: We included randomised controlled trials comparing prophylactic gastrojejunostomy versus no gastrojejunostomy in patients with unresectable periampullary cancer (irrespective of language or publication status). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and the random-effects models using Review Manager (RevMan). We calculated the hazard ratio (HR), risk ratio (RR), and mean difference (MD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. MAIN RESULTS: We identified two trials (of high risk of bias) involving 152 patients randomised to gastrojejunostomy (80 patients) and no gastrojejunostomy (72 patients). In both trials, patients were found to be unresectable during exploratory laparotomy. Most of the patients also underwent biliary-enteric drainage. There was no evidence of difference in the overall survival (HR 1.02; 95% CI 0.84 to 1.25), peri-operative mortality or morbidity, quality of life, or hospital stay (MD 0.97 days; 95%CI -0.18 to 2.12) between the two groups. The proportion of patients who developed long-term gastric outlet obstruction was significantly lower in the prophylactic gastrojejunostomy group (2/80; 2.5%) compared with no gastrojejunostomy group (20/72; 27.8%) (RR 0.10; 95%CI 0.03 to 0.37). The operating time was significantly longer in the gastrojejunostomy group compared with no gastrojejunostomy group (MD 45.00 minutes; 95%CI 21.39 to 68.61). AUTHORS' CONCLUSIONS: Routine prophylactic gastrojejunostomy is indicated in patients with unresectable periampullary cancer undergoing exploratory laparotomy (with or without hepaticojejunostomy).

Reingreso para fototerapia en recién nacidos con ictericia sin hemólisis / Readmission for phototherapy in jaundiced newborns without hemolysis

La presencia de elevados niveles de bilirrubina indirectaen el período neonatal se convirtió en un problema desalud pública en los últimos años asociados al alta antesde las 72 h de vida y la alimentación exclusiva a pecho.Con los objetivos de determinar la incidencia dereingreso para fototerapia de recién nacidos de edadgestacional igual o mayor a 35 semanas aparentementesanos sin hemólisis en el departamento de Florida,analizar qué factores se asociaron a la necesidad defototerapia y describir el tratamiento realizado en lainternación se realizó un estudio descriptivo y analítico decarácter retrospectivo. El período de estudio fue de dosaños desde el 1 de enero de 2008 al 31 de diciembre de2009.Resultados: se incluyeron 18 recién nacidos en elperíodo de estudio lo que representa el 16,2 por mil dereingresos. Trece fueron del sexo masculino (72.2%) y 5de sexo femenino (27,8%). Primigestas correspondieron a83,3% y fueron producto de segunda gestación o más un16,7%. La vía de parto fue en un 77,7% parto vaginal y enun 22.3% por cesárea. Tenían 37 semanas de edadgestacional o menor tiempo de gestación 9 (50%). Elporcentaje de pérdida de peso al momento del reingresovarió entre 10% y 14,8% del peso al nacer.Conclusiones: la ictericia es una causa importante dereingreso hospitalario, correspondiendo a 16,2 por milrecién nacidos vivos en el departamento de Florida. Lapresencia de ictericia se asoció a alta antes de las 72 h,sexo masculino, edad gestacional menor a 38 semanas,alimentación a pecho exclusivo y pérdida de peso mayoral 10% del peso al nacer. Es importante evaluaradecuadamente el riesgo de ictericia y la calidad de laalimentación para evitar el reingreso debido a esta causa.

Prognostic factors and prevention of radioembolization-induced liver disease.

UNLABELLED: Radioembolization (RE)-induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low-dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P<0.0001). Treatment efficacy was not jeopardized since 3-month disease control rates were virtually identical in both groups (66.7% and 67.2%, P=0.93). Exposure to chemotherapy in the 2-month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume<1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. CONCLUSION: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD.

Umbilical cord milking in term infants delivered by cesarean section: a randomized controlled trial.

OBJECTIVE: The study's objective was to compare hematocrit (Hct) levels at 36 to 48 h of age in term infants delivered by cesarean section exposed to immediate cord clamping or umbilical cord milking (UCM). STUDY DESIGN: In this randomized controlled trial, 24 women scheduled for elective cesarean section were randomized to either immediate clamping (<10 s) or UCM (milked × 5 by the obstetrical provider) at birth. RESULT: All subjects received their allocated intervention. The milking group had a smaller placental residual blood volume (13.2±5.6 vs 19.2±5.4 ml kg(-1), P=0.01) and higher Hct levels at 36 to 48 h (57.5±6.6 vs 50.0±6.4 %, P=0.01). Five infants (42%) in the immediate group had a Hct of ≤47%, indicative of anemia. CONCLUSION: UCM results in placental transfusion in term infants at the time of elective cesarean section with higher Hct levels at 36 to 48 h of age.

Dexamethasone-induced cytokine changes associated with diminished disease severity in horses infected with Anaplasma phagocytophilum.

Anaplasma phagocytophilum is the zoonotic cause of granulocytic anaplasmosis. We hypothesized that immune response, specifically gamma interferon (IFN-γ), plays a role in disease severity. To test this, horses were infected and IFNG expression was pharmacologically downregulated using corticosteroids. Eight horses were infected with A. phagocytophilum; 4 received dexamethasone on days 4 to 8 of infection. Clinical signs, hematologic parameters, and transcription of cytokine/chemokine genes were compared among treated and untreated horses. Infection was quantitated by msp2 real-time PCR and microscopy. As anticipated, there was significantly greater leukopenia, thrombocytopenia, and anemia in infected versus uninfected horses. The A. phagocytophilum load was higher for dexamethasone-treated horses. Dexamethasone reduced IFNG transcription by day 12 and IL-8 and IL-18 by days 7 to 9 and increased IL-4 on day 7. The ratio of IL-10 to IFNG was increased by dexamethasone on day 9. There were no hematologic differences between the infected horses. Dexamethasone suppression of proinflammatory response resulted in delayed infection-induced limb edema and decreased icterus, anorexia, and reluctance to move between days 6 and 9 and lower fever on day 7. These results underscore the utility of the equine model of granulocytic anaplasmosis and suggest that Th1 proinflammatory response plays a role in worsening disease severity and that disease severity can be decreased by modulating proinflammatory response. A role for Th1 response and macrophage activation in hematologic derangements elicited by A. phagocytophilum is not supported by these data and remains unproven.

Prophylactic gastrojejunostomy for unresectable periampullary carcinoma.

BACKGROUND: The role of prophylactic gastrojejunostomy in patients with unresectable periampullary cancer is controversial. OBJECTIVES: To determine whether prophylactic gastrojejunostomy should be performed routinely in patients with unresectable periampullary cancer. SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 3), MEDLINE, EMBASE and Science Citation Index Expanded until April 2010. SELECTION CRITERIA: We included randomised controlled trials comparing prophylactic gastrojejunostomy versus no gastrojejunostomy in patients with unresectable periampullary cancer (irrespective of language or publication status). DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and the random-effects models using Review Manager (RevMan). We calculated the hazard ratio (HR), risk ratio (RR), or mean difference (MD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. MAIN RESULTS: We identified two trials (of high risk of bias) involving 152 patients randomised to gastrojejunostomy (80 patients) and no gastrojejunostomy (72 patients). In both trials, patients were found to be unresectable during exploratory laparotomy. Most of the patients also underwent biliary-enteric drainage. There was no evidence of difference in the overall survival (HR 1.02; 95% CI 0.84 to 1.25), peri-operative mortality or morbidity, quality of life, or hospital stay (MD 0.97 days; 95%CI -0.18 to 2.12) between the two groups. The proportion of patients who developed long term gastric outlet obstruction was significantly lower in the prophylactic gastrojejunostomy group (2/80; 2.5%) compared with no gastrojejunostomy group (20/72; 27.8%) (RR 0.10; 95%CI 0.03 to 0.37). The operating time was significantly longer in the gastrojejunostomy group compared with no gastrojejunostomy group (MD 45.00 minutes; 95%CI 21.39 to 68.61). AUTHORS' CONCLUSIONS: Routine prophylactic gastrojejunostomy is indicated in patients with unresectable periampullary cancer undergoing exploratory laparotomy (with or without hepaticojejunostomy).

Transplantation of a fetal liver cell-loaded hyaluronic acid sponge onto the mesentery recovers a Wilson's disease model rat.

An auxiliary liver represents a promising alternative for liver transplantation. The use of a large amount of mature hepatocytes, however, despite their high function, is limited in a clinical setting. Here, we propose a novel transplantation system that dramatically improved a diseased animal by incorporating fetal liver cells (FLCs) as a cell source, the mesentery as a transplantation site and a hyaluronic acid (HA) sponge as a cell scaffold. We transplanted wild-type Long Evans Agouti rat FLCs embedded in HA sponges onto the mesentery of Long Evans Cinnamon (LEC) rats, an animal model for Wilson's disease. The FLC-loaded HA sponges successfully grafted and consequently prevented jaundice. Accordingly, the treated animals showed a significant reduction in blood copper concentration, which consequently led to significant decreases in serum total bilirubin and direct bilirubin, and to a significant increase in albumin productivity. Furthermore, haematoxylin and eosin staining of the host livers demonstrated that fibrosis at the periportal area was moderated in the treated animals. In conclusion, we transplanted FLC-loaded HA sponges onto the mesenteric blood vessels, leading to thick, liver-like tissue possessing blood vessels, and the liver tissue engineered thus exhibited a remarkable therapeutic effect on the copper metabolism deficiency of LEC rats.