Medicine (Austin & Northern Health) - Research Publications

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    Clinical outcomes of patients with two small hepatocellular carcinomas
    Anh, DP ; Vaz, K ; Ardalan, ZS ; Sinclair, M ; Apostolov, R ; Gardner, S ; Majeed, A ; Mishra, G ; Kam, NM ; Patwala, K ; Kutaiba, N ; Arachchi, N ; Bell, S ; Dev, AT ; Lubel, JS ; Nicoll, AJ ; Sood, S ; Kemp, W ; Roberts, SK ; Fink, M ; Testro, AG ; Angus, PW ; Gow, PJ (BAISHIDENG PUBLISHING GROUP INC, 2021-10-27)
    BACKGROUND: Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear. AIM: To define the outcomes of patients presenting with two small HCC. METHODS: Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC ≤ 3 cm between January 2000 and March 2018. Primary outcomes were overall survival (OS) and transplant-free survival (TFS). RESULTS: 104 patients were identified (male n = 89). Median age was 63 years (interquartile range 58-67.75) and the most common aetiology of liver disease was hepatitis C (40.4%). 59 (56.7%) had synchronous HCC and 45 (43.3%) had sequential. 36 patients died (34.6%) and 25 were transplanted (24.0%). 1, 3 and 5-year OS was 93.0%, 66.1% and 62.3% and 5-year post-transplant survival was 95.8%. 1, 3 and 5-year TFS was 82.1%, 45.85% and 37.8%. When synchronous and sequential groups were compared, OS (1,3 and 5 year synchronous 91.3%, 63.8%, 61.1%, sequential 95.3%, 69.5%, 64.6%, P = 0.41) was similar but TFS was higher in the sequential group (1,3 and 5 year synchronous 68.5%, 37.3% and 29.7%, sequential 93.2%, 56.6%, 48.5%, P = 0.02) though this difference did not remain during multivariate analysis. CONCLUSION: TFS in patients presenting with two HCC ≤ 3 cm is poor regardless of the timing of the second tumor. All patients presenting with two small HCC should be considered for transplantation.
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    A novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation
    Sood, S ; Haifer, C ; Yu, L ; Pavlovic, J ; Churilov, L ; Gow, PJ ; Jones, RM ; Angus, PW ; Visvanathan, K ; Testro, AG (WILEY, 2017-04)
    Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon γ (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. A total of 75 adult transplant recipients were prospectively monitored in a blinded, observational study; 55/75 (73.3%) patients experienced a total of 89 clinical events. Most events occurred within the first month. Low week 1 results were significantly associated with risk of early infection (area under the receiver operating characteristic curve [AUROC], 0.74; P = 0.008). IFNγ ≤ 1.30 IU/mL (likelihood ratio positive, 1.93; sensitivity, 71.4%; specificity, 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ ≤ 1.30 IU/mL. Moreover, an elevated week 1 result was significantly associated with the risk of rejection within the first month after transplant (AUROC, 0.77; P = 0.002), but no episodes of infection. On multivariate logistic regression, IFNγ ≥ 4.49 IU/mL (odds ratio, 4.75) may be an independent predictor of rejection (P = 0.05). In conclusion, low IFNγ suggesting oversuppression is associated with infections, whereas high IFNγ indicating undersuppression is associated with rejection. This assay offers the potential to allow individualization and optimization of immunosuppression that could fundamentally alter the way patients are managed following transplantation. Liver Transplantation 23 487-497 2017 AASLD.
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    Early viral-specific T-cell testing predicts late cytomegalovirus reactivation following liver transplantation
    Sood, S ; Haifer, C ; Yu, L ; Pavlovic, J ; Gow, PJ ; Jones, RM ; Visvanathan, K ; Angus, PW ; Testro, AG (WILEY, 2018-10)
    INTRODUCTION: Although antiviral prophylaxis is effective in preventing early cytomegalovirus (CMV) reactivation following liver transplantation (OLT), it predisposes patients to late CMV after prophylaxis has ceased. QuantiFERON-CMV (QFN-CMV, Qiagen, The Netherlands) measures an individual's viral-specific immune response. METHODS: Fifty-nine OLT recipients were prospectively monitored post-OLT in an observational cohort study. QFN-CMV was performed at regular time-points. An absolute QFN-CMV <0.1 IU/mL was considered non-reactive. RESULTS: 50/59 (84.7%) had a reactive QFN-CMV by M6. 38/59 (64.4%) had antiviral prophylaxis or treatment before M6, with 31/38 (81.6%) developing a reactive QFN-CMV by 6 months. Over 90% already had a reactive result as early as 3 months post transplant, 3 patients (5.08%) developed late CMV between 6-12 months (median 251 days)-all had a non-reactive M6 QFN-CMV. And 2/3 experienced CMV disease. Non-reactive M6 QFN-CMV was significantly associated with late CMV (OR = 54.4, PPV = 0.33, NPV = 1.00, P = .003). CONCLUSION: Although only 5% of recipients developed late CMV, 2/3 suffered CMV disease. M6 QFN-CMV has an excellent NPV for late CMV, suggesting patients who exhibit a robust ex vivo immune response at M6 can safely cease CMV monitoring. Furthermore, >90% already express viral-specific immunity as early as 3 months. Conceivably, antiviral prophylaxis could be discontinued early in these patients.
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    Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients
    Sood, S ; Yu, L ; Visvanathan, K ; Angus, PW ; Gow, PJ ; Testro, AG (BAISHIDENG PUBLISHING GROUP INC, 2016-12-18)
    AIM: To investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODS: Adult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1st February 2014. RESULTS: Cirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient's immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM < 214 IU/mL was associated with HR = 4.1 (P = 0.01) for infection. A very low QFM < 30 IU/mL was significantly associated (P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSION: QFM is lower in cirrhotics, allowing objective determinations of an individual's unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.