Gut microbiota of liver transplantation recipients.

The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients with end-stage liver disease. Here, we focused on the characteristics of intestinal fecal microbial communities in post-liver transplantation (LT) patients in comparison with those in the same individuals pre-LT and in healthy individuals. The fecal microbial communities were analyzed via MiSeq-PE250 sequencing of the V4 region of 16S ribosomal RNA and were then compared between groups. We found that the gut microbiota of patients with severe liver disease who were awaiting LT was significantly different from that of healthy controls, as represented by the first principal component (p = 0.0066). Additionally, the second principal component represented a significant difference in the gut microbiota of patients between pre-LT and post-LT surgery (p = 0.03125). After LT, there was a significant decrease in the abundance of certain microbial species, such as Actinobacillus, Escherichia, and Shigella, and a significant increase in the abundance of other microbial species, such as Micromonosporaceae, Desulfobacterales, the Sarcina genus of Eubacteriaceae, and Akkermansia. Based on KEGG profiles, 15 functional modules were enriched and 21 functional modules were less represented in the post-LT samples compared with the pre-LT samples. Our study demonstrates that fecal microbial communities were significantly altered by LT.

Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature.

Mesenchymal hamartomas of the liver (MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography (CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen included intraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg (dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.

Autoimmune hepatitis-primary biliary cirrhosis concurrent with biliary stricture after liver transplantation.

Although the development of de novo autoimmune liver disease after liver transplantation (LT) has been described in both children and adults, autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome has rarely been seen in liver transplant recipients. Here, we report a 50-year-old man who underwent LT for decompensated liver disease secondary to alcoholic steatohepatitis. His liver function tests became markedly abnormal 8 years after LT. Standard autoimmune serological tests were positive for anti-nuclear and anti-mitochondrial antibodies, and a marked biochemical response was observed to a regimen consisting of prednisone and ursodeoxycholic acid added to maintain immunosuppressant tacrolimus. Liver biopsy showed moderate bile duct lesions and periportal lymphocytes infiltrating along with light fibrosis, which confirmed the diagnosis of AIH-PBC overlap syndrome. We believe that this may be a case of post-LT de novo AIH-PBC overlap syndrome; a novel type of autoimmune overlap syndrome.

Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.

OBJECTIVE: The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. METHODS: Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. RESULTS: The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. CONCLUSION: A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.

Acquired factor V inhibitor after liver transplantation.

Acquired inhibitors against coagulation factor V (FV) occur rarely, the clinical symptoms vary to a great extent, from asymptomatic laboratory abnormalities to life-threatening bleeding. Coagulation factor V (FV) is a plasma-cofactor mostly existing in the plasma, and approximately 20-25% (Tracy et al. (1982), Kane (2006)) of FV exist in platelet granules. Patients' reaction is the prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT), but there is no exact reason, and that can not be corrected after normal plasma transfusion (Morris and Curris (2009), Lucia and Aguilar (2005)). We report here a case of the occurrence of FV inhibitors after orthotopic liver transplantation (OLT). With gastrointestinal bleeding, patient's haemostatic response was not achieved after using fresh frozenplasma (FFP), platelet concentrates (PC), prothrombin complex concentrates (PCC) or recombinant activated FVII (rFVIIa). After using high-dose intravenous immunoglobulin (IVIg) and change of immunosuppressant from tacrolimus (FK506) to cyclosporine, the bleeding stopped and better laboratory examination results was achieved thereafter.

Prognosis in liver transplantation recipients after hepatitis B virus recurrence.

BACKGROUND/AIMS: To analyze the data from hepatitis B virus (HBV) infected patients with HBV recurrence after orthotopic liver transplantation (OLT) to determine their prognosis and survival. METHODOLOGY: We retrospectively analyzed data from patients who experienced HBV recurrence following OLT at our center between January 2000 and September 2011. All patients were monitored until June 2012 or their death. RESULTS: The total number of cases of HBV recurrence after liver transplantation was 56. Of these cases, 21 had benign liver disease and 35 had hepatocellular carcinoma (HCC). The median follow-up time was 48.8 months (range: 5.0-138.1 months). The median time to recurrence following transplantation was 44.4 months (range: 0.3-116.3 months) and 12.2 months (range: 0.3-135.1 months) for patients with benign liver disease and HCC, respectively. Nine patients were diagnosed with HBV recurrence first (1.2-8.2 months prior to HCC recurrence), seven patients showed HCC recurrence first (0.4-27.1 months prior to HBV recurrence), and the remaining 5 patients had HBV and HCC recurrence at the same time. Correlation analysis demonstrated a strong correlation between HBV and HCC recurrence times. Of the 56 patients with HBV recurrence, 24 had died at the time of data cut off, and the main cause of death was HCC recurrence. In patients with malignant liver disease, the survival rates were 78.8%, 48.8%, and 40.1% at 1, 3, and 5 years, respectively, which were lower than those in patients with benign liver disease, which were 94.7%, 89.5%, and 77.5% at 1, 3, and 5 years, respectively, P=0.001. CONCLUSION: Patients with HBV recurrence and benign liver disease have a better prognosis than HCC patients. Treatment with the addition of adefovir and/or entecavir is necessary for patients with HBV recurrence. A correlation between HBV and HCC recurrence times was observed. Hepatitis B recurrence can be used as a warning signal for tumor recurrence.

Outcomes in children with biliary atresia following liver transplantation.

BACKGROUND: Congenital biliary atresia is a rare condition characterized by idiopathic dysgenesis of the bile ducts. If untreated, congenital biliary atresia leads to liver cirrhosis, liver failure and premature death. The present study aimed to evaluate the outcomes of orthotopic liver transplantation in children with biliary atresia. METHOD: We retrospectively analyzed 45 patients with biliary atresia who had undergone orthotopic liver transplantation from September 2006 to August 2012. RESULTS: The median age of the patients was 11.0 months (5-102). Of the 45 patients, 41 were younger than 3 years old. Their median weight was 9.0 kg (4.5-29.0), 34 of the 45 patients were less than 10 kg. Thirty-one patients had undergone Kasai portoenterostomy prior to orthotopic liver transplantation. We performed 30 living donor liver transplants and 15 split liver transplants. Six patients died during a follow-up. The median follow-up time of surviving patients was 11.4 months (1.4-73.7). The overall 1-, 2- and 3-year survival rates were 88.9%, 84.4% and 84.4%, respectively. CONCLUSION: With advances in surgical techniques and management, children with biliary atresia after liver transplantation can achieve satisfactory survival in China, although there remains a high risk of complications in the early postoperative period.

Successful percutaneous transluminal balloon dilatation for hepatic venous outflow obstruction after pediatric liver transplantation: A series of cases.

AIM: Whether percutaneous transluminal balloon dilatation (PTBD) or stent placement should be used in children with hepatic venous outflow obstruction (HVOO) is still controversial. The aim of the present study was to retrospectively describe experience in diagnosis and treatment of HVOO and to evaluate the outcome of PTBD in HVOO patients after pediatric liver transplantation (P-LT). METHODS: From January 2001 to January 2011, 54 children received P-LT at our center. The clinical features of children with HVOO analyzed included demography, type of donor and liver transplant, the new-onset symptoms, liver function test, interventional examination, and treatment and outcome. RESULTS: Three children were treated successfully with PTBD without stenting. All patients received percutaneous interventional management successfully. In the total of eight episodes of PTBD across the stenosis, the mean pressure gradient ± standard deviation was 16.6 ± 7.90 mmHg before PTBD and 6.8 ± 2.27 mmHg after PTBD. The difference was significant (P < 0.05). All of the three HVOO patients were still surviving with primary graft functioning normally until the last follow up. CONCLUSION: HVOO after P-LT should be taken seriously. PTBD is an effective and safe treatment for HVOO in younger patients subjected to P-LT and re-venoplasty is recommended even in patients with recurrent HVOO.

[Chemical constituents of Trichosanthes kirilowii Maxim].

To study the chemical constituents of Trichosanthes kirilowii Maxim., chromatographic methods such as D101 macroporous resin, silica gel column chromatographic technology, Sephadex LH-20, octadecylsilyl (ODS) column chromatographic technique and preparative HPLC were used and nine compounds were isolated from a 95% (v/v) ethanol extract of the plant. By using spectroscopic techniques including 1H NMR, 13C NMR, 1H-1H COSY, HSQC and HMBC, these compounds were identified as 5-ethoxymethyl-1-carboxyl propyl-1H-pyrrole-2-carbaldehyde (1), 5-hydroxymethyl-2-furfural (2), chrysoeriol (3), 4'-hydroxyscutellarin (4), vanillic acid (5), alpha-spinasterol (6), beta-D-glucopyranosyl-a-spinasterol (7), stigmast-7-en-3beta-ol (8), and adenosine (9), separately. Among them, compound 1 is a new compound, and compounds 3, 4 and 5 are isolated from the genus Trichosanthes kirilowii Maxim. for the first time.

[Prognosis analysis of hepatitis B virus recurrence after liver transplantation: a single-center study of 38 cases].

OBJECTIVE: To analyze the prognosis of hepatitis B virus (HBV) recurrence after liver transplantation. METHODS: Thirty-eight patients (37 males; 1 female) with HBV-related end-stage liver disease underwent liver transplantation at our institute between December 1998 and November 2009 and experienced HBV recurrence. Clinical data from pre-transplant and follow-up examinations were retrospectively retrieved from medical records, and included serologic indices of HBV (HBV DNA, markers of liver function) and histological findings from liver biopsy. RESULTS: The median follow-up time was 45.1 months. The median time to HBV recurrence after transplantation was 31.8 months (range: 0.3 to 72.8 months) for histologically benign cases and 13.7 months (range: 0.3 to 66.6 months) for malignant cases. HBV DNA gene mutations were detected in 21% (8/38) of cases. Eighteen patients were treated with entecavir or adefovir, with respect to gene mutations, and HBV DNA fell below 103 copies/ml and liver function became normal. Twenty-two patients died, and causes of death included hepatocellular carcinoma (HCC, n=18), organ failure (n=2), or infection (n=1). CONCLUSION: HBV gene mutations and HCC recurrence were important risk factors for HBV recurrence in our study population. In addition, patients with benign liver diseases who received salvage therapy with adefovir or entecavir achieved a satisfactory prognosis.

[Long-term complications after liver transplantation].

OBJECTIVE: To investigate the long-term complications after liver transplantation. METHODS: Totally 85 living patients who received liver transplantation from December 30th 1998 to May 28th 2002 in Tianjin First Central Hospital were followed up till October 2007. Liver and kidney functions, blood drug levels, blood pressure, blood sugar, and blood fat were recorded and ultrasound imaging was performed during follow-up. RESULTS: At the end of the study, most patients had experienced one or more complications of prolonged immunosuppressant treatment, including posttransplantation diabetes mellitus (21.18%, 18/85), hypertension (10.59%, 9/85), renal impairment (8.24%, 7/85), hyperlipemia (7.06%, 6/85), hyperuricaemia (7.06%, 6/85), denovo malignancy (2.35%, 2/85), new-onset hepatitis C (7.06%, 6/ 85), recurrent hepatitis B (5.56%, 4/72). CONCLUSION: Recipients of liver transportation often suffers long-term complications, which should be carefully managed to improve their quality of life.