Effect of liver transplants with retrograde reperfusion on early postoperative recovery of liver function and its risk factors.

BACKGROUND: The purpose of this study was to investigate effect of liver Transplants (LT) with retrograde reperfusion on early postoperative recovery of liver function and its risk factors. METHODS: We conducted a retrospective analysis of clinical data from 136 liver transplantation (LT) patients at the 900th Hospital of the Chinese People's Liberation Army Joint Support Army, covering the period from January 2015 to January 2021. All participants provided informed consent, adhering to medical ethics guidelines. Patients were stratified into two groups based on the liver perfusion technique used: retrograde reperfusion (RTR, n = 108) and initial portal reperfusion (IPR, n = 28). Our study focused on a subset of 23 patients from each group to compare postoperative liver function recovery. The final analysis included 86 RTR and 28 IPR cases after excluding 8 RTR patients who underwent initial hepatic artery reperfusion and 14 who received simultaneous hepatic artery and portal vein reperfusion. Further subdivision within the RTR group identified 19 patients with early hepatic allograft dysfunction (EAD) and 67 without, allowing for an assessment of the influence of preoperative and intraoperative parameters, as well as perfusion methods, on EAD incidence post-LT. RESULTS: Alanine aminotransferase (ALT) was 329 (211 ~ 548) and 176 (98 ~ 282) U/L on the 3rd and 7th day after RTR, respectively, which was significantly lower than 451 (288 ~ 918) and 251 (147 ~ 430) U/L in the IPR group (Z =-1.979, -2.299, P = 0.048, 0.021). Aspartate aminotransferase (AST) on postoperative days 3, 5, and 7 was 252 (193, 522), 105 (79, 163), and 93 (41, 135) U/L in the RTR group, respectively; it was also significantly lower than 328 (251, 724), 179 (129, 306), and 150 (91, 200)U/L in the IPR group (Z=-2.212, -3.221, -2.979; P = 0.027, 0.001, 0.003). Logistic regression analysis showed that MELD score was an independent risk factor for EAD after LT. CONCLUSION: RTR LT is more favorable for patients' early postoperative liver function recovery. For patients undergoing LT for RTR, preoperative MELD score was an independent risk factor for their postoperative development of EAD.

Hemostatic and liver function parameters as COVID-19 severity markers.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a disease newly discovered in December 2019 which affects coagulation cascade and liver functions. The aim of this study was to investigate the potential of hemostatic and liver function parameters as severity markers in COVID-19 patients. This study was an observational analytic with cohort retrospective design using total sampling method. Data were retrieved from medical record of COVID-19 patients admitted to provincial hospital in Banda Aceh, Indonesia from March 2020 to March 2022. There were 1208 data eligible for the study after applying certain criteria. Mann-Whitney, logistic regression, and receiving operating characteristic (ROC) analyses were used to analysis the data. Thrombocyte count (p<0.001), prothrombin time (p<0.001), activated partial thromboplastin time (p<0.001), D-dimer (p<0.001), fibrinogen (p<0.001), aspartate aminotransferase (p<0.001), and alanine transaminase (p<0.001) significantly increased in severe compared to mild COVID-19 patients. After being adjusted, age (odds ratio (OR); 1.026 (95% confidence interval (CI): 1.016-1.037) was the most significant factor in predicting COVID-19 severity. Fibrinogen (cut-off 526.5 mg/L) was the best parameter associated with COVID-19 severity with 70% sensitivity and 66.4% specificity. Meanwhile, D-dimer (cut-off 805 ng/mL) had a sensitivity of 72.3% and specificity of 66.4%. Combining the parameters resulted in improved sensitivity to 82.0% with a slight decline of specificity to 65.5%. In conclusion, fibrinogen and D-dimer level on admission could be used as biomarkers in predicting COVID-19 prognosis. Routine monitoring and evaluation of laboratory testing especially D-dimer and fibrinogen could be implemented in order to reduce morbidity and mortality rate of COVID-19.

Effect of high-dose intravenous iron injection on hepatic function in a rat model of cirrhosis.

OBJECTIVE: To investigate the hepatic effects of high-dose intravenous (IV) iron, including those on liver function and the degree of fibrosis, in a rat model of cirrhosis. METHODS: We evenly allocated 25 Sprague-Dawley rats into five groups: normal rats (control group), cirrhotic rats receiving IV normal saline (liver cirrhosis [LC] group), and cirrhotic rats receiving 20, 40, or 80 mg/kg IV ferric carboxymaltose (LC-iron20, LC-iron40, and LC-iron80 group, respectively). Biochemical parameters were compared at 0, 7, 14, 21, and 28 days. The degrees of hepatic fibrosis and iron deposition were evaluated. Inflammatory and oxidative stress markers were also compared. RESULTS: There were no significant differences in the 28-day serum alanine aminotransferase levels among the LC-iron20, LC-iron40, and LC-iron80 groups (69 ± 7, 1003 ± 127, 1064 ± 309, 919 ± 346, and 820 ± 195 IU/L in the control, LC, LC-iron20, LC-iron40, and LC-iron80 groups, respectively). Hepatic iron accumulation increased in a dose-dependent manner, but the degree of hepatic fibrosis was comparable among the groups. The inflammatory and oxidative stress marker levels did not differ significantly according to the IV iron dose. CONCLUSIONS: Administration of IV iron at various high doses appears safe in our rat model of cirrhosis.

Approximately 50% of acute intestinal failure (AIF) patients on short-term parenteral nutrition (PN) have intestinal failure-associated liver disease (IFALD) without effect on hospital length of stay and mortality.

INTRODUCTION: Patients with intestinal failure (IF) are often dependent on PN for provision of calories and nutrients for survival. Similar to chronic intestinal failure (CIF) patients, those who have AIF are also at risk of IFALD, which is a poorly understood but potentially fatal condition. The local incidence of IFALD amongst AIF patients is not known. OBJECTIVES: The primary objective of this study was to determine the incidence of IFALD in AIF patients on short-term PN. Secondary objectives were to analyse patient and PN risk factors of IFALD, and clinical outcomes of length of stay (LOS) and inpatient mortality. DESIGN: This was a retrospective cross-sectional cohort study of hospitalised adult patients with AIF prescribed with short-term PN. All adult patients aged 21 years and above who received PN for at least 5 consecutive days and had normal liver function tests (LFTs) at the time of PN initiation were included in this study. RESULTS: A total of 171 patients were enrolled in this study, with 77 (45%) having deranged LFTs at the end of PN therapy and categorised under the IFLAD group. The patient cohort was predominantly male (92 [54%]) and had a median age of 68 years (IQR 59-76). Patients with IFALD at the end of PN therapy had higher diabetes prevalence (36% vs 26%, p = 0.2) and were on PN for a longer duration (median [IQR]: 12 [8-17] vs 8 [6-15] days, p = 0.003) than those without IFALD. There were no significant differences in patient and PN characteristics between the IFLAD and non-IFALD group. The multivariable models showed that the IFALD cohort had longer hospital stays (HR 0.90, 95% CI 0.65-1.23) and lower odds of inpatient death (OR 0.75, 95% CI 0.12-4.60), though both findings are not statistically significant (p = 0.5, 0.7). CONCLUSION: In this study, IFALD is a common phenomenon in AIF and the incidence was found to be an estimated 50% amongst patients on short-term PN with similar clinical outcomes between the two groups.

Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome.

OBJECTIVE: This study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women. METHODS: This is a cross-sectional, population-based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL-C and triglyceride-glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]). RESULT: In the present study, there was no significant difference between the PCOS and the non-PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20-7.68], p < 0.05), high ALT (4.76 [3.07-7.36], p < 0.05) and high HSI (8.44 [1.82-39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL-C was associated with increased odds of elevated ALT (3.35 [2.21-5.06]) and HSI (6.55 [1.17-36.46]), whereas the second tertile of TG/HDL-C (OR = 2.65, CI 95%: 1.74-4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests. CONCLUSION: The highest tertile of TyG index and the TG/HDL-C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.

Hepatic function markers as prognostic factors in patients with acute kidney injury undergoing continuous renal replacement therapy.

Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), secondary to cardiovascular disease and sepsis, is associated with high in-hospital mortality. Although studies have examined cardiovascular disease and sepsis in AKI, the association between AKI and hepatic functional impairment remains unclear. We hypothesized that hepatic function markers would predict mortality in patients undergoing CRRT. We included 1,899 CRRT patients from a multi-centre database. In Phase 1, participants were classified according to the total bilirubin (T-Bil) levels on the day of, and 3 days after, CRRT initiation: T-Bil < 1.2, 1.2 ≤ T-Bil < 2, and T-Bil ≥ 2 mg/dL. In Phase 2, propensity score matching (PSM) was performed to examine the effect of a T-Bil cutoff of 1.2 mg/dL (supported by the Sequential Organ Failure Assessment score); creating two groups based on a T-Bil cutoff of 1.2 mg/dL 3 days after CRRT initiation. The primary endpoint was total mortality 90 days after CRRT initiation, which was 34.7% (n = 571). In Phase 1, the T-Bil, aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT (De Ritis ratio) levels at CRRT initiation were not associated with the prognosis, while T-Bil, AST, and the De Ritis ratio 3 days after CRRT initiation were independent factors. In Phase 2, T-Bil ≥1.2 mg/dL on day 3 was a significant independent prognostic factor, even after PSM [hazard ratio: 2.41 (95% CI; 1.84-3.17), p < 0.001]. T-Bil ≥1.2 mg/dL 3 days after CRRT initiation predicted 90-day mortality. Changes in hepatic function markers in acute renal failure may enable stratification of high-risk patients.

Relapse following withdrawal of D-penicillamine from combination (D-penicillamine + zinc) therapy in hepatic Wilson disease.

OBJECTIVES: Long-term D-penicillamine (D-pen) therapy in Wilson disease (WD) has numerous adverse effects which advocates its withdrawal, but with an inherent risk of relapse. This prospective observational study was conducted with the objective of evaluating incidence of relapse following withdrawal of D-pen from combination (D-pen + zinc) therapy in maintenance phase of previously symptomatic hepatic WD. METHODS: Hepatic WD patients <18 years of age and on combination therapy for >2 years with 6 months of biochemical remission were included. Biochemical remission was defined as achievement of (i) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times upper limit of normal (ULN), (ii) serum albumin >3.5 g/dL, international normalized ratio (INR) <1.5 and (iii) 24-h urinary copper excretion (UCE) <500 mcg/day, nonceruloplasmin-bound-copper (NCC) <15 mcg/dL. After D-pen withdrawal, monthly liver function test (LFT) and INR and 3 monthly UCE and NCC were done till 1 year or relapse (elevation of AST/ALT/both >2 times ULN or total bilirubin >2 mg/dL), whichever occurred earlier. RESULTS: Forty-five patients enrolled with median combination therapy duration of 36 months. Sixty percent of them had their index presentation as decompensated cirrhosis. Fourteen patients (31.8%) relapsed (cumulative incidence: 4 at 3 months, 11 at 6 months, and 14 at 12 months after D-pen discontinuation). All relapsers had index presentation as decompensated cirrhosis. On Cox-regression, ALT at D-pen withdrawal was an independent predictor of relapse (hazard ratio [HR]: 1.077, 95% confidence interval [CI]: 1.014-1.145, p = 0.017) with area under the receiver operating characteristic (AUROC) of 0.860. ALT ≥40 U/L predicted risk of relapse with 85.7% sensitivity, 70.9% specificity. CONCLUSION: Incidence of relapse after withdrawal of D-pen from combination therapy is 31.8% in hepatic WD. ALT ≥40 U/L, at the time of D-pen stoppage, predicts future relapse.

Association of liver function and prognosis in patients with severe fever with thrombocytopenia syndrome.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS. METHODS: A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks. RESULTS: 60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 µmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome. CONCLUSIONS: Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.

Using haematological indices to predict impaired liver function in DTC patients.

OBJECTIVE: In patients with normal liver function, patients with acute or chronic thyroid disease are more likely to develop liver dysfunction. Although the mechanisms underlying this process are not yet fully understood, it has been shown that hypothyroidism can lead to hepatic injury. We evaluated haematological function trends in patients with differentiated thyroid cancer (DTC) at baseline and approximately 4 weeks after l-thyroxine withdrawal before radioactive iodine ablation. SUBJECTS AND METHODS: This is a retrospective study, and 157 patients were enrolled. Logistic regression analysis was used to find significant predictors. Four weeks after LT4 withdrawal, 64 patients belonged to the group of liver injury, and 93 patients belonged to the group of normal liver function. RESULTS: Univariate analysis determined that platelet count (PC) (P=0.005), mean platelet volume (MPV) (P=0.013), platelet distribution width (PDW) (P=0.039) and absolute lymphocyte count (ALC) (P=0.008) were responsible risk factors for liver injury in DTC patients after withdrawal of levothyroxine (l-thyroxine). Multivariate analysis showed that slight increases in PC (OR: 2.243, P: 0.024) and ALC (OR: 0.398, P: 0.017) were closely associated with liver injury in DTC patients after 4 weeks LT4 withdrawal before radioactive iodine ablation. CONCLUSION: Our results suggest that PC and ALC are independent predictors of hypo-related liver injury. Our study is the first to suggest that haematological indices can be used for predicting the development and progression of hypo-related liver disorders.

Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS: A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS: Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.

Within-individual reproducibility of a dual sample oral cholate challenge test (DuO) and simplified versions of the HepQuant SHUNT test.

Current noninvasive liver tests measure fibrosis, inflammation, or steatosis and do not measure function. The HepQuant platform of noninvasive tests uniquely assesses both liver function and physiology through the hepatic uptake of stable isotopes of cholate. However, the prototypical HepQuant SHUNT test (SHUNT V1.0) is cumbersome to administer, requiring intravenous and oral administration of cholate and six peripheral venous blood samples over 90 min. To alleviate the burden of test administration, we explored whether an oral only (DuO) version, and other simplified versions, of the test could provide reproducible measurements of liver function. DuO requires only oral dosing and two blood samples over 60 min. The simplified SHUNT test versions were SHUNT V1.1 (oral and IV dosing but four blood samples) and SHUNT V2.0 (oral and IV dosing but only two blood samples over 60 min). In this paper, we describe the reproducibility of DuO and the simplified SHUNT tests relative to that of SHUNT V1.0; equivalency is described in a separate paper. Data from two studies comprising 236 SHUNT tests in 94 subjects were analyzed retrospectively by each method. All simplified methods were highly reproducible across test parameters with intraclass correlation coefficients >0.93 for test parameters Disease Severity Index (DSI) and Hepatic Reserve. DuO and SHUNT V2.0 improved reproducibility in measuring portal-systemic shunting (SHUNT%). These simplified tests, particularly DuO and SHUNT V2.0, are easier to administer and less invasive, thus, having the potential to be more widely accepted by care providers administering the test and by patients receiving the test.

Comparison of the efficacy of the gadoxetic acid MRI-derived relative enhancement index (REI) and functional liver imaging score (FLIS) in predicting liver function: validation with Albumin-Bilirubin (ALBI) grade.

PURPOSE: This study compared the predictive performance of the relative enhancement index (REI) derived from gadoxetic acid (GA)-enhanced MRI with that of the functional liver imaging score (FLIS) in estimating liver function among patients with chronic liver disease (CLD) or liver cirrhosis (LC) by validating them with the albumin-bilirubin (ALBI) grade. MATERIALS AND METHODS: We retrospectively examined 166 patients (79 women, 87 men; 57.4 years) who were diagnosed with LC or CLD and underwent GA-enhanced MRI between August 2020 and September 2023. The enhancement ratio (ER) is calculated using the formula: ER = [hepatobiliary phase liver signal (SI HBP20)-precontrast liver signal (SI pre)]/SI pre. The REI is calculated using the formula: REI = Liver Volume (LV) × ER. FLIS was assigned from the sum of three HBP image features, each scored between 0 and 2: liver parenchymal enhancement, biliary contrast excretion, and portal vein sign. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff values of ER, REI, and FLIS in differentiating between ALBI grades. The area under the curve (AUC), accuracy, sensitivity, and specificity were calculated for REI and FLIS to distinguish the ALBI grades. Spearman's rank correlation was used to evaluate the ER, REI, and FLIS correlations between the ALBI grades. To evaluate inter-reader reliability for LV, ER, REI, and FLIS, intraclass correlation coefficient (ICC) was used. RESULTS: ROC curve analysis showed that the optimal cutoff value of REI for predicting ALBI Grade 1 was 899-905 for readers 1 and 2 and 461-477 for ALBI Grade 3, respectively. REI performed best in predicting ALBI Grade 1, achieving an accuracy range of 94%-92.2%, sensitivity of 94.9%-94.1%, and specificity of 91.7%-87.5% for readers 1 and 2, respectively. All parameters showed high accuracy in distinguishing ALBI Grade 3 from other grades. However, REI outperformed the others, showing an accuracy range of 98.8%-97.6%, sensitivity of 94.4%-94.4%, and specificity of 99.3%-98% for readers 1 and 2, respectively. REI showed the best and very strong correlation with ALBI for both readers. CONCLUSION: REI showed a very strong correlation with the ALBI grades for assessing liver function. It outperformed FLIS in predicting the ALBI grades, indicating its potential as a radiologic tool comparable to or better than FLIS in predicting liver function, especially given its dependence on liver volume.

Hepatitis after gene therapy, what are the possible causes?

Hepatitis is a common adverse event following gene therapy for haemophilia, often associated with a loss of transgene expression. Investigating the potential causes and implications of this is crucial for the overall success of treatment. Gene therapy trials using adeno-associated virus (AAV) vectors have demonstrated promising results marked by increases in factor FVIII and FIX levels and reductions in episodes of bleeding. However, hepatocellular injury characterised by elevations in alanine aminotransferases (ALT) has been noted. This liver injury is typically transient and asymptomatic, posing challenges in determining its clinical significance. Proposed causes encompass immune-mediated responses, notably T cell cytotoxicity in response to the AAV vector, direct liver injury from the viral capsid or transcribed protein via the unfolded protein response and pre-existing liver conditions. Liver biopsy data conducted years post-gene therapy infusion has shown sinusoidal infiltration without significant inflammation. The overall safety profile of gene therapy remains favourable with no evidence drug-induced liver injury (DILI) based on Hy's Law criteria. Essential pre-therapy monitoring and identifying patients at high risk of liver injury should involve liver function tests and non-invasive fibroscans, while novel blood-based biomarkers are under exploration. Further research is required to comprehend the mechanisms underlying transaminitis, loss of transgene expression and long-term effects on the liver, providing insights for optimising gene therapy for haemophilia.

Correlation between urinary rare earth elements and liver function in a Zhuang population aged 35-74 years in Nanning.

BACKGROUND: Animal studies have shown that exposure to REEs can cause severe liver damage, but evidence from population studies is still lacking. Therefore, we investigated the relationship between REEs concentrations in urine and liver function in the population. METHODS: We conducted a cross-sectional study on 1024 participants in Nanning, China. An inductively coupled plasma mass spectrometer (ICP-MS) was used to detect the concentrations of 12 REEs in urine. The relationship between individual exposure to individual REE and liver function was analyzed by multiple linear regression. Finally, the effects of co-exposure to 5 REEs on liver function were assessed by a weighted sum of quartiles (WQS) regression model and a Bayesian kernel machine regression (BKMR) model. RESULTS: The detection rate of 5 REEs, lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), and dysprosium (Dy), is greater than 60%. After multiple factor correction, La, Ce, Pr, Nd, and Dy were positively correlated with serum ALP, Ce, Pr, and Nd were positively correlated with serum AST, while Ce was negatively correlated with serum TBIL and DBIL. Both WQS and BKMR results indicate that the co-exposure of the 5 REEs is positively correlated with serum ALP and AST, while negatively correlated with serum DBIL. There were potential interactions between La and Ce, La and Dy in the association of co-exposure of the 5 REEs with serum ALP. CONCLUSIONS: The co-exposure of the 5 REEs was positively correlated with serum ALP and AST, and negatively correlated with serum DBIL.

Hyperpolarized 15N caffeine, a potential probe of liver function and perfusion.

PURPOSE: To demonstrate hyperpolarization of 15N-caffeine and report exploratory findings as a potential probe of liver function and perfusion. METHODS: An amorphous formulation of [1,3-15N2]caffeine was developed for hyperpolarization via dissolution dynamic nuclear polarization. Polarizer hardware was augmented to support monitoring of solid-state 15N MR signals during the buildup of hyperpolarization. Liquid state hyperpolarized 15N MR signals were obtained in a preclinical 3T magnet by interfacing an external spectrometer console with home-built RF surface coils. 15N signal decay constants were estimated in H2O and in vivo in liver and brain regions of rats at 3 T. Decays were also measured at 9.4 T to assess the effect of B0, and in the presence of albumin to assess the impact of protein binding. RESULTS: Polarization levels of 3.5% and aqueous T1 relaxation times of nearly 200 s were attained for both N1 and N3 positions at 3 T. Shorter apparent decay constants were observed in vivo, ranging from 25 s to 43 s, with modest extensions possible by exploiting competitive binding of iophenoxate with plasma albumin. Downstream products of caffeine could not be detected on in vivo 15N-MR spectra of the liver region, even with metabolic stimulation by ß $$ \beta $$ -naphthoflavone treatment. Considering the high perfusion rate of brain, persistence of caffeine signal in this region is consistent with potential value as a perfusion imaging agent. CONCLUSION: These results establish the feasibility of hyperpolarization of hyperpolarized 15N-caffeine, but further work is necessary to establish the role of this new agent to probe liver metabolism and perfusion.