Zhuoyi Wang

A modified protocol with rituximab and intravenous immunoglobulin in emergent ABO-incompatible liver transplantation for acute liver failure

BACKGROUND The established procedure for ABO-incompatible liver transplantation (ABO-I LT) was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin (IVIG) for ABO-I LT in patients with acute liver failure (ALF). METHODS The data from 101 patients who had undergone liver transplantation (LT) for ALF were retrospectively analyzed. The patients were divided into two groups: ABO-compatible liver transplantation group (ABO-C LT, n=66) and ABO-I LT group (n=35). All the patients in the ABO-I LT group received a single dose of rituximab (375 mg/m2) and IVIG (0.4 g/kg per day) at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol. Quadruple immunosuppressive therapy including basiliximab, corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression. RESULTS The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%, respectively (P>0.05), and the graft survival rates were 80.0% and 86.3%, respectively (P>0.05). Two patients (5.7%) suffered from antibody-mediated rejection in the ABO-I LT group. Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups. CONCLUSIONS The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

Hepatitis E virus infection results in acute graft failure after liver transplantation: a case report

Hepatitis E virus (HEV) infection in most individuals is known as a self-limiting, acute, icteric hepatitis, but evidence shows HEV is responsible for choric hepatitis and rapid progressed liver cirrhosis in immuno-compromised patients. We present the case of a patient whose diagnosis of acute graft failure was due to a HEV infection 7 years after his first liver transplantation because of Wilsons disease. The process showed severe jaundice with fatigue, poor appetite and continually rising serum aminopherase. The blood serum was found positive for the anti-HEV IgG antibody but negative for anti-HEV IgM or other infections. Cholangiole cholestasis was detected in graft biopsy. Triple hepato-protective drugs (Transmetil, Polyene Phosphatidylcholine, and Compound Ammonium Glycyrrhetate S) alongside five times Artificial Liver Support System (ALSS) did not improve the patients condition, but the total bilirubin level rose to more than 900umol/L. So re-transplantation was performed. Blood testing shows normal liver enzymes and bilirubin with persisting anti-HEV IgG antibody positive at the 3-month follow-up.

A high frequency of CD8+CD28- T-suppressor cells contributes to maintaining stable graft function and reducing immunosuppressant dosage after liver transplantation

CD8+CD28-T cells (CD8Ts) exert immunosuppressive effects in various autoimmune diseases. The current study was designed to investigate the role of defects in CD8Ts in liver transplantation (LT). The proportion of CD8Ts in peripheral blood was determined by flow cytometry. The mean proportion of CD8Ts was 23.39% in recipients with stable graft function and 16.64% in those with graft dysfunction following LT compared with 19.86% in the healthy cohort. After receiving enhanced immunosuppressive therapy, patients in the rejection group who achieved recovery of graft function showed an increase in the proportion of CD8Ts (from 17.39% to 25.55%), but those in the group with refractory graft dysfunction showed no significant change (12.49% to 10.30%). Furthermore, in the first year after LT, recipients longer removed in time from the LT date exhibited a higher proportion of CD8Ts. Patients benefited most from tacrolimus concentrations of 5-10 ng/ml in the first year after LT and 0-5 ng/ml thereafter. Moreover, the change in the proportion of CD8Ts (ΔCD8Ts) was significantly higher in recipients with stable graft function than in those with graft dysfunction. These results suggest that a high frequency of CD8Ts prevents rejection and contributes to reduce immunosuppressant dosage and even induces tolerance.

In vivo therapeutic potential of Inula racemosa in hepatic ischemia–reperfusion injury following orthotopic liver transplantation in male albino rats

Hepatic ischemia–reperfusion (I/R) injury mainly occurs following hepatic resection and liver transplantation and cause severe liver damage, organ injuries, and dysfunction. Pro-inflammatory cytokines that promote injury are released when kupffer cell activates after getting induced by I/R. Repercussions of oxidative stress and cardiac function against isoproterenol based myocardial infarction are caused by flavonol glycosides which are found in high concentrations in Inula racemosa (Ir).The root was deemed to have analgesic and anti-inflammatory effects, and no report has been published about the liver-protective activity against hepatic I/R. Therefore, the present study was aimed to understand the therapeutic impact of Ir in hepatic I/R injury. Male albino, Wistar strain rats were used and were grouped into four total phenolic content, free radical scavenging activity and serum enzymes were determined. Histopathological and immunohistochemical analysis were also carried out. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6) and protein expression of p53, bax, and bcl-2 were determined. The administration of extracts of Ir significantly increased total phenolic and free radical scavenging activity. Altered cellular morphology, cytokines and aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were returned to near normal level. IL-6 and TNF-α levels were reduced more than 25% following treatment. Also, the protein expression of p53, bax, and bcl-2 were also returned to near normal level. Taking all these data together, it is suggested that the extracts of Ir may be a potential therapeutic agent for providing several beneficial effects in hepatic I/R injury.