Efficacy and Economic Evaluation of Nonbiological Artificial Liver Therapy in Acute-on-chronic Hepatitis B Liver Failure
Journal of clinical and translational hepatology. 2023;11(2):433-440
BACKGROUND AND AIMS Nonbiological artificial liver (NBAL) is frequently used as a first-line treatment for hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). This study aimed to compare the therapeutic efficacy and cost-effectiveness ratio (CER) of comprehensive medical treatment, plasma exchange (PE), and double plasma molecular adsorption system (DPMAS) plus half-dose PE (DPMAS+PE) in patients with HBV-ACLF. METHODS A total of 186 patients with HBV-ACLF randomly received comprehensive medical treatment, PE, or DPMAS+PE and were prospectively evaluated. Patients were divided into four subgroups based on the pretreatment prothrombin activity (PTA): Group I (PTA>40%), group II (PTA 30-40%), group III (PTA 20-30%), and group IV (PTA<20%). The main outcome measures were 28 day effectiveness; 90 day liver transplantation-free survival; change of biochemical parameters; and CER. RESULTS DPMAS+PE treatment was associated with significantly higher 28 day effectiveness and 90 day liver transplantation-free survival compared with PE treatment in patients with group I liver failure. Clearance of serum total bilirubin (TBIL), AST, and creatinine (Cr) were significantly higher in the DPMAS+PE group than in the PE group. For subjects with group I liver failure, DPMAS+PE treatment had advantages of lower CER values and better cost-effectiveness. CONCLUSIONS Compared with comprehensive medical treatment and PE alone, DPMAS with half-dose sequential PE treatment more effectively improved TBIL, AST, and Cr in HBV-ACLF patients, improved 28 day effectiveness and 90 day survival rates in patients with group I liver failure, and was more cost effective. DPMAS+PE is a viable NBAL approach for treatment of HBV-ACLF.
A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design
Frontiers in nephrology. 2023;3:1181076
BACKGROUND Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. METHODS We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. DISCUSSION Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.
Rituximab or plasmapheresis for prevention of recurrent focal segmental glomerulosclerosis after kidney transplantation: A systematic review and meta-analysis
World journal of transplantation. 2021;11(7):303-319
BACKGROUND Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases leading to renal failure. FSGS has a high risk of recurrence after kidney transplantation. Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results. AIM: To assess the risk of recurrence of FSGS after transplantation using prophylactic rituximab with or without plasmapheresis, and plasmapheresis alone compared to the standard treatment group without preventive therapy. METHODS This meta-analysis and systematic review were performed by first conducting a literature search of the MEDLINE, EMBASE, and Cochrane databases, from inception through March 2021; search terms included 'FSGS,' 'steroid-resistant nephrotic syndrome', 'rituximab,' and 'plasmapheresis,'. We identified studies that assessed the risk of post-transplant FSGS after use of rituximab with or without plasmapheresis, or plasmapheresis alone. Inclusion criteria were: Original, published, randomized controlled trials or cohort studies (either prospective or retrospective), case-control, or cross-sectional studies; inclusion of odds ratio, relative risk, and standardized incidence ratio with 95% confidence intervals (CI), or sufficient raw data to calculate these ratios; and subjects without interventions (controls) being used as comparators in cohort and cross-sectional studies. Effect estimates from individual studies were extracted and combined using a random effects model. RESULTS Eleven studies, with a total of 399 kidney transplant recipients with FSGS, evaluated the use of rituximab with or without plasmapheresis; thirteen studies, with a total of 571 kidney transplant recipients with FSGS, evaluated plasmapheresis alone. Post-transplant FSGS recurred relatively early. There was no significant difference in recurrence between the group that received rituximab (with or without plasmapheresis) and the standard treatment group, with a pooled risk ratio of 0.82 (95%CI: 0.47-1.45, I (2) = 65%). Similarly, plasmapheresis alone was not associated with any significant difference in FSGS recurrence when compared with no plasmapheresis; the pooled risk ratio was 0.85 (95%CI: 0.60-1.21, I (2) = 23%). Subgroup analyses in the pediatric and adult groups did not yield a significant difference in recurrence risk. We also reviewed and analyzed post-transplant outcomes including timing of recurrence and graft survival. CONCLUSION Overall, the use of rituximab with or without plasmapheresis, or plasmapheresis alone, is not associated with a lower risk of FSGS recurrence after kidney transplantation. Future studies are required to assess the effectiveness of rituximab with or without plasmapheresis among specific patient subgroups with high-risk for FSGS recurrence.
Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review
World journal of gastroenterology. 2020;26(2):219-245
BACKGROUND Acute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant. Other cohort studies demonstrated potential improvement in survival in patients with ACLF. AIM: To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation. METHODS Databases MEDLINE via PubMed, and EMBASE were searched and relevant publications up to 30 March, 2019 were assessed. Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange, with or without another alternative non-bioartificial liver assist device. RESULTS Three hundred twenty four records were reviewed, of which 62 studies were found to be duplicates. Of the 262 records screened, 211 studies were excluded. Fifty-one articles were assessed for eligibility, for which 7 were excluded. Twenty-nine studies were included for ALF only, and 9 studies for ACLF only. Six studies included both ALF and ACLF patients. A total of 44 publications were included. Of the included publications, 2 were randomized controlled trials, 14 cohort studies, 12 case series, 16 case reports. All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment (SMT) for ACLF, a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60 (95%CI 0.46-0.77, P < 0.01). CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high. Plasma exchange in ACLF improves survival at 30-and 90-d in non-transplanted patients. Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.
Adults and paediatric patients diagnosed with liver failure (44 studies).
Plasma exchange with or without other alternative liver support systems.
Standard medical treatment (SMT).
The acute liver failure (ALF) studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to SMT for acute-on-chronic liver (ACLF), a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60.
Effectiveness of combining plasma exchange and continuous hemodiafiltration in patients with postoperative liver failure
Artificial Organs. 2005;29((4):):324-8.
Nine patients with postoperative liver failure were treated with plasma exchange (PE) or PE and continuous hemodiafiltration (CHDF), and various biochemical parameters were determined before and after treatment. Although citrate levels increased significantly after treatment compared with pretreatment levels in both the PE group and the PE + CHDF group (P < 0. 0001 and P < 0. 0001, respectively), the percentage of the increase in citrate levels was significantly higher in the PE group than in the PE + CHDF group (P = 0. 0051). Total bilirubin (T-Bil) levels were significantly lower after treatment in both the PE and PE + CHDF groups (P < 0. 0001 and P = 0. 0001, respectively). There were no significant differences in T-Bil levels between the two groups (P = 0. 5181). There were no significant differences in interleukin (IL)-6 levels before and after treatment in both the PE and PE + CHDF groups (P = 0. 1281 and P = 0. 2273, respectively). IL-18 levels were significantly lower after treatment in both the PE and PE + CHDF groups (P < 0. 0001 and P = 0. 0002, respectively), but there were no significant differences in the removal rate of IL-18 in both the PE and PE + CHDF groups (P = 0. 8749). These results indicate that combining PE and CHDF in a series-parallel circuit is an effective modality for suppressing the elevation of blood citrate levels. This finding may have important implications for the development of an effective treatment for patients with postoperative liver failure.
Effect of plasmapheresis in kidney transplantation--a controlled study . German
Zeitschrift fur Urologie und Nephrologie. 1986;79((6):):311-6.
Until recently it has been controversial whether plasmapheresis is benefitial in graft rejection therapy. Here we present a controlled trial in 44 kidney transplanted patients with biopsy proven acute vascular rejection and specific anti-HLA-antibodies. 23 randomized patients were treated additionally with plasma exchange (group A), whereas the remaining 21 received drug therapy only (group B). 7 out of 23 (30%) lost their graft in group A and 17 out of 21 (81%) in group B. Mean serum creatinine and actuarial graft survival underline the significant effect of plasmaexchange therapy which appears especially benefitial when rejection occurs later than one month after surgery.
Plasma exchange in acute renal allograft rejection. A controlled trial
A controlled trial was carried out to assess the value of intensive plasma exchange in 27 renal transplant recipients with clinical and histological evidence of acute vascular rejection. In addition to standard immunosuppression, 13 patients received plasma exchange on six consecutive days at a mean exchange volume of 40.6 ml/kg of body weight each day using an intermittent cell separator. A further 14 patients received standard immunosuppression only. In addition, 10 patients exchanged prior to the controlled trial have been studied. Analysis of short-term benefit, as evidenced by a reduction in serum creatinine, and by subsequent graft survival revealed no significant difference in these parameters between the two groups in the controlled trial. This regimen of plasma exchange has not, therefore, been shown to modify acute renal allograft rejection.