Long-term outcome of autologous peripheral blood CD34+ hematopoietic stem cell transplantation in the treatment of advanced liver cirrhosis

Abstract

Objective To investigate the long-term outcome of autologous peripheral blood CD34+ hematopoietic stem cell transplantation in the treatment of advanced liver cirrhosis. Methods The retrospective cross-sectional study was adopted. The clinical data of 42 patients with advanced liver cirrhosis who were admitted to the Sichuan Provincial People's Hospital between July 2010 and July 2015 were collected. The patients underwent autologous peripheral blood CD34+ hematopoietic stem cell transplantation. The 5 μg/kg colony-stimulating factors were injected subcutaneously daily for 3-5 days. The peripheral blood stem cells were collected and detected by flow cytometry, showing (1.8±1.7)×106/kg of CD34+ cell. Transfemoral superselective hepatic arterial implantation or catheterization via right gastroepiploic venous to main portal vein (PV) was performed by digital subtraction angiography (DSA) at 2 days after collection, and intraoperative portal venous pressure (PVP) was monitored. PVP was reduced after operation and liver and renal functions were protected. The patients underwent anticoagulation therapy at 3 days for preventing PV thrombosis. Observation indicators included (1) treatment: the basic conditions of patients after CD34+ hematopoietic stem cell transplantation and postoperative complications, (2) follow-up: survival rate of patients, Child score, model for end-stage liver disease (MELD) score, result of biopsy, Knodell score and health related quality of life (HRQL) score. The follow-up using outpatient examination, telephone interview and Email was performed to detect the liver and renal functions and coagulation function up to July 2015. Peritoneal effusion of patients was detected by B ultrasound and computed tomography (CT) examination. The patients received liver function Child-Pugh score, MELD score, percutaneous transhepatic biopsy guided by B ultrasound and HRQL score. Measurement data with normal distribution were presented as ±s, comparison between groups was analyzed by the matched t test. The survival curve was drawn by the Kaplan-Meier method. Measurement data with skewed distribution were presented as M (range). Results (1) Treatment: the symptoms of spirit, sleep, appetite, urination and defecation in 42 patients were improved after autologous peripheral blood CD34+ hematopoietic stem cell transplantation. Ten patients had postoperative complications, including 3 with upper gastrointestinal hemorrhage, 3 with grade I of hepatic encephalopathy, 2 dying of hepatorenal syndrome at postoperative month 1 and 3, 1 with PV thrombosis at postoperative month 6 and 1 with spontaneous peritonitis. Other patients were cured or improved by symptomatic treatment. (2) Follow-up situations: 42 patients were followed up for a median time of 57 months (range, 1-60 months), with 5-year survival rate of 95.23%. The Child score and MELD score were 7.1±1.1 and 14±4 at postoperative year 5, 9.4±1.8 and 19±5 before operation, respectively, with statistically significant differences (t=1.672, 3.773, P<0.05). The result of liver biopsy showed that disordered hepatic lobule structures were cut by fibers and ground-glass hepatic cells showed symptoms of edema and degeneration with spotty and piecemeal necrosis. Necrosis from portal regions to bridge connection were found, proliferation of fibrous tissue, invasion of moderate amount of lymphocytes and monocytes inside portal regions were also detected, and pseudolobule was formed. At postoperative year 5, hepatic lobule was increased obviously and the distribution tended to normal. Hepatic cells showed symptoms of edema and degeneration with small amounts of spotty necrosis and without piecemeal necrosis. Proliferation of fibrous tissue inside portal regions was improved markedly, fibrous tissues were obviously reduced and stain was significantly fade. Knodell score at postoperative year 5 and before operation was 9.9±2.7 and 14.1±4.1, showing a statistically significant difference (t=4.142, P<0.05). HRQL score at postoperative year 5 and before operation was 167±21 and 134±15, with a statistically significant difference (t=3.142, P<0.05). Conclusion Autologous peripheral blood CD34+ hematopoietic stem cell transplantation can effectively improve liver function and pathological histology of hepatic cirrhosis as well as quality of life in patients with advanced liver cirrhosis. Key words: End-stage liver diseases; Liver cirrhosis; Autologous peripheral blood CD34+ stem cell; Model for end-stage liver disease score; Health related quality of life score