-
1.
Hepatobiliary disease after bone marrow transplant: A cross-sectional study of 377 patients
Dezan, M. G. F., Cavalcante, L. N., Silva, H. R. C., de Moura Almeida, A., Dos Santos de Assis, L. H., de Freitas, T. T., de Araújo, M. A. S., Cotrim, H. P., Lyra, A. C.
Alimentary pharmacology & therapeutics. 2023
Abstract
BACKGROUND Bone marrow transplantation (BMT) is a standard treatment for several haematologic conditions. Following BMT, patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischaemic hepatitis, and fulminant hepatitis. AIMS To evaluate the frequency, clinical characteristics, and outcomes of patients with hepatobiliary alterations associated with BMT in a tertiary referral centre. METHODS This was a cross-sectional study with data collected from the medical records of patients undergoing BMT between January 2017 and June 2022. We diagnosed hepatobiliary complications based on established criteria. RESULTS We included 377 patients; 55.7% had hepatobiliary complications. Female gender, pre-BMT hepatobiliary alteration, and haploidentical allogeneic transplantation were associated with increased risk with odds ratios (OR) of 1.8 (p = 0.005), 1.72 (p = 0.013) and 3.25 (p = 0.003), respectively. Patients with hepatobiliary complications spent longer in the hospital than those without (27.7 × 19.3 days, respectively; p < 0.001). Among 210 patients with hepatobiliary complications, 28 died compared to 5 of 167 without complications (OR 4.98; p = 0.001). CONCLUSIONS Hepatobiliary complications are frequent in patients undergoing BMT. There is a greater risk of their occurrence in women, people with pre-BMT liver alterations, and in haploidentical transplants. The occurrence of these complications increases the length of stay and is associated with a higher risk of death.
-
2.
Profile of Hepatobiliary Dysfunction in Hematopoietic Stem Cell Transplant Recipients - An Indian Perspective
Manrai, M., George, E., Kapoor, R.
Journal of clinical and experimental hepatology. 2021;11(1):14-20
Abstract
BACKGROUND/AIMS: Hematopoietic stem cell transplantation (HSCT) is an established curative modality for various hematological malignancies and other diseases. Hepatobiliary dysfunction and subsequent sequelae constitute a common cause of morbidity and mortality in post-transplant scenario. However, data among Indian HSCT recipients is lacking. METHODS One hundred and one HSCT recipients (37 prospective and 64 retrospective) were followed up for hepatobiliary dysfunction in the post-transplant period. The causes for hepatobiliary dysfunction were categorized as sinusoidal obstruction syndrome (SOS), formerly known as veno-occlusive disease (VOD); acute and chronic graft-versus- host disease (GVHD); drug-induced liver injury (DILI); viral infections and miscellaneous causes including bacterial, fungal and unknown causes based on clinical and laboratory evidence. RESULTS Among the 101 transplants, 56.44% (n = 57) were allogenic transplants, and 43.56% (n = 44) were autologous transplants. Hepatobiliary dysfunction was observed among 71 (70.30%) patients in first 30 days and overall, among 78 (77.23%) patients. Incidence of hepatobiliary dysfunction was higher among allogenic transplant patients compared to autologous transplants (91.23% vs. 59.09%, p < 0.001). The most common cause of hepatobiliary dysfunction reported was Drug-induced liver injury (DILI). In most cases, however, hepatobiliary dysfunction was multifactorial. Sinusoidal obstruction syndrome (15.79%), acute liver GVHD (31.58%), chronic liver GVHD (33.33%) and viral infection/reactivation (26.32%) were reported only in allogenic transplant patients. 15 (14.85%) patients died of which 14 patients had hepatobiliary dysfunction, commonest cause being infections. CONCLUSION Our study reported a higher incidence of hepatobiliary dysfunction among Indian population post HSCT and was associated with significant mortality. In majority of the cases, the cause is multifactorial and pose a diagnostic dilemma and challenges in therapy.
-
3.
Liver disease during and after hematopoietic stem cell transplantation in adults: a single-center Egyptian experience
Abdelbary, H., Magdy, R., Moussa, M., Abdelmoaty, I.
Journal of the Egyptian National Cancer Institute. 2020;32(1):11
Abstract
BACKGROUND Hepatic complications are a well-known cause of both early and late mortality and morbidity in hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis and management of hepatic complications is important in order to commence appropriate therapy. Conditioning regimens, acute and chronic graft versus host disease, sinusoidal obstruction syndrome, and infections among others represent major hepatic complications for the transplant recipient. We assessed liver function tests, viral markers, polymerase chain reaction, abdominal ultrasound, portal, and hepatic venous duplex in 88 patients underwent autologous and 102 patients underwent allogeneic transplant as well as liver biopsy in selected patients in this retrospective study and evaluated early and late hepatic complications and their impact on transplant outcome. RESULTS The major cause of hepatic injury in allogeneic patients is the conditioning regimen (38.8%) followed by acute GVHD (14.7%), after day +100 chronic hepatic GVHD is the primary cause of liver injury which occurred in about 40% of allogeneic patients. In autologous patients, the first cause of hepatotoxicity is also conditioning regimen involving 27.9% of patients followed by flare of viral hepatitis in 7.9% and sepsis in 6.3% of cases. The prevalence of HCV, HBV, and CMV is 19%, 16%, and 8%, respectively. CONCLUSION In our study, conditioning regimens, acute and chronic hepatic GVHD are frequent causes of hepatic injury following allogeneic HSCT while conditioning regimens, flare of viral hepatitis, and sepsis represent the most common causes of hepatic injury following autologous HSCT.
-
4.
Predicting hepatic complications of allogeneic hematopoietic stem cell transplantation using liver stiffness measurement
Karlas, T., Weisse, T., Petroff, D., Beer, S., Dohring, C., Gnatzy, F., Niederwieser, D., Behre, G., Mossner, J., Fischer, J., et al
Bone marrow transplantation. 2019
Abstract
Allogeneic hematopoietic stem cell transplantation is the only curative option for a variety of diseases. Despite advances, it is associated with considerable morbidity and mortality, often involving liver complications. Liver disease can be characterized using ultrasound-based liver stiffness measurement. To assess its prognostic value, consecutive patients undergoing allogeneic hematopoietic stem cell transplantation were prospectively evaluated in a single-center study. Endpoints included liver event-free survival and all-cause mortality at 1 year. Competing risk and Cox-regression were used for analysis. We evaluated 106 patients (42 female, age 57) and observed 33 life-threatening events (14 died) including 16 liver complications at 100 days. At 1 year, 36 patients had died, 20 with disease relapse. The hazard ratios for liver-related complications at 100 days were 3.2 (95% CI: 1.8-14.6, p = 0.0022) and 4.4 (95% CI: 1.6-11.9, p = 0.0042) for elevated transient elastography (n = 11) and shear-wave velocity (n = 31), respectively. Results were analogous for all-cause mortality at 1 year. Prior stem cell therapy and elevated gamma glutamyltransferase were also associated with outcome. This demonstrates that elastography is a promising and viable tool for risk prediction and should be included in upcoming multi-center trials to establish new means of guiding treatment and prophylaxis.
-
5.
Evaluation of liver tissue by ultrasound elastography and clinical parameters in children with multiple blood cell transfusions
Wurschi, G. W., Kentouche, K., Herrmann, K. H., Krumbein, I., Nold, M., Beck, J. F., Reichenbach, J. R., Mentzel, H. J.
Pediatric radiology. 2019
Abstract
BACKGROUND Children receiving multiple blood cell transfusions are prone to iron overload and successive tissue damage in liver parenchyma, making noninvasive screening options desirable. Ultrasound (US) elastography using acoustic radiation force impulse (ARFI) imaging enables evaluation of liver parenchyma stiffness, and MRI allows for quantification of liver iron concentration. OBJECTIVE The objective was to correlate US elastography with MRI in children who had undergone bone marrow transplantation and to evaluate the modification of liver tissue with US in combination with clinical parameters at follow-up. MATERIALS AND METHODS ARFI, T2*-weighted MRI and a clinical score (HepScore, based on parameters of liver function) were performed in 45 patients (24 male; mean age 9.7 years) before and 100 days and 365 days after transplantation. All received multiple blood transfusions (mean number 22.2 up until 1 year after transplantation). We correlated US findings and HepScore with MRI findings. RESULTS We observed signs of iron accumulation in 29/45 (64.4%) patients on MRI (T2*<10 ms) and 15/45 (33.3%) showed increased tissue stiffness (ARFI>5.5 kPa). Correlation of elastography and MRI was not significant (P=0.57; n=51 matched measurements). Comparing US elastography with HepScore in receiver operating characteristic (ROC) curve analysis indicated a cut-off for affected parenchyma if HepScore was >5 points (sensitivity 67%, specificity 68%). Simultaneous increases of both indicated tissue alteration. CONCLUSION Combining US and HepScore enabled detection of liver tissue alteration through iron overload, but we found no direct significant effect of estimated iron from MRI on ARFI imaging.
-
6.
Liver GVHD is Associated with Poor Survival Among Allogeneic Hematopoietic Stem Cell Transplant Recipients
Modi, D., Christine Ye, J., Surapaneni, M., Singh, V., Chen, W., Jang, H., Deol, A., Ayash, L., Alavi, A., Ratanatharathorn, V., et al
American journal of hematology. 2019
Abstract
Liver GVHD is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and "non-liver GVHD" group which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT 124 patients developed liver GVHD and 125 were in "non-liver GVHD" group. The incidence of acute and chronic liver GVHD at 1-year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (HR, 1.76; P=0.008) and related donor (HR, 1.68; P=0.004) as independent risk factors for liver GVHD. The time varying covariate cox regression analysis with competing risk event demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. Total 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting. This article is protected by copyright. All rights reserved.
-
7.
Hepatic focal nodular hyperplasia after pediatric hematopoietic stem cell transplantation: The impact of hormonal replacement therapy and iron overload
Cattoni, A., Rovelli, A., Prunotto, G., Bonanomi, S., Invernizzi, P., Perego, R., Mariani, A. M., Balduzzi, A.
Pediatric blood & cancer. 2019;:e28137
Abstract
BACKGROUND The advent of techniques for the assessment of iron overload (liver T2*-MRI) has led to the awareness that focal nodular hyperplasia (FNH) represents a possible incidental finding after hematopoietic stem cell transplantation (HSCT), though its pathogenesis is still unclear. METHODS We performed a retrospective analysis of the liver T2*-MRI scans performed between 2013 and 2018 in a single pediatric HSCT Unit and recorded the number of patients with FNH (group A). Patients incidentally diagnosed with FNH at imaging performed for different clinical indications were included in group B. RESULTS Nine of 105 (8.6%) patients from group A were diagnosed with FNH. Group B included three patients. Overall, 12 patients were diagnosed 4.4 +/- 3.1 years after HSCT. At univariate analysis, female gender (odds ratio [OR] 3.77, P = .03), moderate-to-severe iron overload (OR 6.97, P = .01), and hormone replacement therapy (HRT) administered for at least 6 months (OR 18.20, P = .0002) exposed patients to a higher risk of developing FNH. The detrimental effect of HRT was significant also at multivariate analysis (OR 7.93, P = .024). MRI-T2* values in affected patients were statistically lower than healthy controls (P < .001). CONCLUSIONS We confirm the high incidence of FNH among transplanted pediatric patients and demonstrate the potential pathogenic role of HRT and iron overload.
-
8.
Utility and safety of liver biopsy in patients with undetermined liver blood test anomalies after allogeneic hematopoietic stem cell transplantation, a monocentric retrospective cohort study
Ruggiu, M., Bedossa, P., Rautou, P. E., Bertheau, P., Plessier, A., de Latour, R. P., Robin, M., de Fontbrune, F. S., Pagliuca, S., Villate, A., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Liver blood test anomalies are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but their cause often remains difficult to identify. Our objective was to evaluate the safety and utility of liver biopsies in patients who underwent allo-HSCT. In a retrospective single center cohort study, we reviewed all cases of patients who underwent liver biopsy between June 2005 and July 2017. During this period, 54 biopsies were performed in 45 patients; 38 patients underwent allo-HSCT for malignant and seven for non-malignant hematological disorders. Median time between allo-HSCT and liver biopsy was 213 days. Seven biopsies were percutaneous and 47 transjugular. No adverse event related to the biopsy procedure occurred; 94.5% biopsies (51/54) led to identify a histological diagnose. Cholestatic graft versus host disease was histologically demonstrated in 16 biopsies (30%), hepatitis-like GvHD in nine biopsies (17%), non-alcoholic steatohepatitis in six biopsies (9%), regenerative nodular hyperplasia in four biopsies (5%), and drug-induced liver injury, sinusoidal obstruction syndrome and viral hepatitis each in three biopsies (5%). Association between clinical, laboratory, imaging and pathological features was poor. Only 34% of physicians' pre-biopsy hypotheses were confirmed by pathological findings. Patient management was influenced by liver biopsy results in 65% of cases, allowing us to identify a new diagnosis (n=13), rule out a differential diagnosis (n=14) or confirm the main hypothesis (n=6). In conclusion, liver biopsy is a safe and useful technique to investigate liver blood test anomalies following allo-HSCT.
-
9.
Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population-based cohort study of 32,839 one-year survivors
Bonnesen, T. G., Winther, J. F., Andersen, K. K., Asdahl, P. H., de Fine Licht, S., Gudmundsdottir, T., Sallfors Holmqvist, A., Madanat-Harjuoja, L. M., Tryggvadottir, L., Wesenberg, F., et al
International Journal of Cancer. 2018;142(4):702-708
Abstract
Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR=6.9) and leukaemia (HR=1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR=3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications.Copyright © 2017 UICC.
-
10.
Vanishing bile ducts in the long-term following paediatric haematopoietic stem cell transplantation
Maximova, N., Sonzogni, A., Matarazzo, L., Ghirardi, A., D'Antiga, L.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
There are no structured studies on liver histology following haematopoietic stem cell transplantation (HSCT). We aimed to prospectively describe the clinico-pathological features of liver disease in the long-term following HSCT in an observational, longitudinal study of liver histology in a consecutive cohort of children undergoing allogeneic HSCT. First liver biopsy was performed in presence of abnormal liver function tests and repeated per protocol thereafter. A previously reported semi-quantitative score evaluating inflammation, cholestasis and ductopenia (bile ducts to portal tracts ratio ≤0.5) was adopted. Graft-versus-host disease (GVHD) was diagnosed according to standard criteria. 131 biopsies taken in 50 HSCTs performed in 47 children (mean age 9.7+/-5.2 years) were evaluated. Pre-HSCT chemotherapy was administered to 36/50 (72%). GVHD was diagnosed in 17/50 (34%). Over time the overall score decreased from a mean of 6+/-2.7 to 3.25+/-0.96 (p<0.01), inflammation from 1.22+/-1.19 to 1+/-0 (p=ns), cholestasis from 3.9+/-2.08 to 1.5+/-0.58 (p<0.01). Ductopenia, diagnosed in 113/131 (93%), worsened from 0.63+/-0.35 to 0.16+/-0.14 (p<0.01). On multivariate analysis severe ductopenia (ratio ≤0.2) was associated with previous chemotherapy (p=0.04), and in particular with thiotepa, but not with history of GVHD. Vanishing bile duct syndrome after HSCT may be due to drug-induced liver disease. Longer follow up will reveal whether these patients are prone to late liver-related morbidity and mortality.