Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

Kornberg, Arno

doi:10.4254/wjh.v7.i11.1494

Cited by 14 publications

(15 citation statements)

References 175 publications

(344 reference statements)

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“…Our study aimed to evaluate the efficacy and safety of Cytotect®CP in patients with CMV infection after allo-HCT. In fact, hyperimmune anti-CMV polyclonal antibodies activity has been explained in other clinical settings by its ability to counteract the virus with high avidity antibodies and possibly through cellular immunological reaction modulation mediated by cytokines, Fab-mediated actions, targeting Fc receptors, interactions with dendritic cells, B and T cell implication, and intracellular signal transduction blockade [22,38,39]. Interestingly, other studies concluded that this treatment, applied after allo-HCT, reduced the risk of CMV infection from 62 to 36% and may be effective in such patients [23,40,41].…”

Section: Discussionmentioning

confidence: 99%

Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study

Alsuliman

Kitel

Duléry

et al. 2018

Bone Marrow Transplant

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Cytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect®CP CMV-hyperimmune globulin is used as salvage therapy. This study aims to investigate the safety and efficacy of Cytotect®CP as a salvage therapy in patients with CMV infection after allo-HCT. Twenty-three consecutive patients received Cytotect®CP for CMV infection after prior CMV therapy. At the time of Cytotect®CP introduction, 17 patients (74%) had developed acute GVHD and 15 patients (64%) were receiving steroid treatment; Cytotect®CP was used as monotherapy (n = 7) and in combination (n = 16). Overall, response was observed in 18 patients (78%) with a median time of 15 days (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5 responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were due to causes unrelated to CMV. Estimated 100-day OS from the introduction of Cytotect®CP was 69.6%. No statistically significant difference was observed in 100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258). Cytotect®CP as salvage therapy is effective and well-tolerated. Given its safety profile, early treatment use should be considered.

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Section: Discussionmentioning

confidence: 99%

Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study

Alsuliman

Kitel

Duléry

et al. 2018

Bone Marrow Transplant

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“…Although antiviral prophylaxis by ganciclovir or valganciclovir is nowadays widely established in patients with high-risk CMV immunoglobulin (Ig) G donor (D)/recipient (R) seroconstellation (D+/R−), this is usually not applicable in severely immunocompromised allograft recipients due to intolerance against common side effects like renal dysfunction, leukopenia and thrombocytopenia [11]. That is why anti-CMV hyperimmunoglobulin (CMVIg) for passive immunization is meanwhile increasingly reconsidered in selected patients [12]. Although tolerability and antiviral efficacies of CMVIg have clearly been confirmed in the past [13], its use is currently not a recommended standard for antiviral prophylaxis or treatment in the LT setting [14].…”

Section: Introductionmentioning

confidence: 99%

“…Although tolerability and antiviral efficacies of CMVIg have clearly been confirmed in the past [13], its use is currently not a recommended standard for antiviral prophylaxis or treatment in the LT setting [14]. In recent years, there seems to be growing suggestive evidence that, apart from antiviral activities, CMVIg may provide anti-inflammatory and immunoregulatory properties that could be valuable to counteract CMV-related immune reactions [12,[15][16][17]. We hypothesized that critically ill liver recipients, who are particularly threatened by early inflammatory events, might benefit from these positive immunomodulatory capabilities.…”

Section: Introductionmentioning

confidence: 99%

Prophylactic Anti-Cytomegalovirus Hyperimmunoglobulin in Critically Ill Liver Transplant Patients: Impact on Early Immunology and Survival

Kornberg

Witt

Kornberg

et al. 2020

JCM

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Background: Anti-cytomegalovirus hyperimmunoglobulin (CMVIg) was shown to provide beneficial immunodulatory properties beyond antiviral efficacies. The aim of this retrospective study was to assess the impact of prophylactic CMVIg treatment on early outcome following liver transplantation (LT) in critically ill patients. Methods: Forty-three cirrhotic patients requiring pre-LT intensive care due to multiorgan failure were analyzed. Twenty-eight patients with enhanced CMV risk (D+/R+; D+/R−; D−/R+) received prophylactic CMVIg for a minimum of 7 days, while 15 patients (D−/R−) did not. Results: Post-transplantation rates of intra-abdominal infections (28% vs. 61.1%; p = 0.03), Epstein–Barr virus infections (0% vs. 33.3%; p = 0.034), allograft rejections (0% vs. 22.2%; p = 0.013) and sepsis-related mortality (4% vs. 27.8%; p = 0.026) were significantly lower, whereas incidence of CMV infections (4% vs. 22.2%; p = 0.066) tended to be lower in the CMVIg subset. In multivariate analysis, only pretransplant elevated serum lactate level (hazard ratio = 34.63; p = 0.009) and absence of CMVIg therapy (hazard ratio = 21.76; p = 0.023) were identified as independent promoters of 3-month mortality. Conclusion: Prophylactic treatment with CMVIg reduces predisposition for severe immunological and septic events and, thereby, early mortality in critically ill liver recipients.

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“…The recurrence was related to the presence of pre-transplantation HBV DNA, which in the past has been detected using a hybridization methodology. To date, the mechanism of action of immunoglobulins in the setting of transplantation has not been completely elucidated [3,4]. They could neutralize the circulating virus, prevent its linkage to the receptor on the surface of the hepatocytes, or even block the production/secretion of HBs [3,4].…”

Section: Introductionmentioning

confidence: 99%

Prophylaxis of Hepatitis B Virus (HBV) Re-Infection in Liver Transplantation: Is the Reappearance of Hepatitis B Surface Antigen (HBsAg) Significant?

Brancaccio

Gaeta

2020

Ann Transplant

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The recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) was in the past a primary cause of organ loss or mortality. Currently, post-OLT prophylaxis with anti-HBs immunoglobulins plus a nucleos(t)ide analogue has virtually abolished the risk of re-infection. Some studies have proposed to simplify prophylaxis by discontinuing immunoglobulins while continuing the analogue alone. This review analysed the available studies, focusing on the recurrence of HBsAg in serum and its biological effects. In all, 16 studies were retrieved, mainly observational or retrospective, each enrolling 14 to 80 patients. Our review of the literature found that HBsAg reappeared in 0% to 24% of the patients, generally with HBV DNA undetectable in plasma. One study measured HBsAg using a new ultra-sensitive method, which could allow a reappraisal of the incidence of recurrence. This review discusses the role of HBV surface proteins in inducing hepatocellular carcinoma, particularly when mutations in the C-terminal occur that induce stop-codons that cause defects of secretion and retention of truncated protein S, resulting in direct cell toxicity and cancer. The data on the suspension of immunoglobulins in the prophylaxis regimes of post-transplant re infection do not appear sufficiently robust for an extensive and safe application in clinical practice.

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Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

Abstract: Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing.

Cited by 14 publications

References 175 publications

Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study

Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study

Prophylactic Anti-Cytomegalovirus Hyperimmunoglobulin in Critically Ill Liver Transplant Patients: Impact on Early Immunology and Survival

Prophylaxis of Hepatitis B Virus (HBV) Re-Infection in Liver Transplantation: Is the Reappearance of Hepatitis B Surface Antigen (HBsAg) Significant?

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