Cardio-Hepatic Interaction in Cardiac Amyloidosis.

Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and 13C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDRpeak) related to hepatic congestion. Reduced PDRpeak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDRpeak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA.

Importance of breath tests for the evaluation liver function in patients with chronic kidney disease.

Breath tests for the evaluation liver metabolic function are a non-invasive diagnostic method with high sensitivity and specificity. Up today, the issue of liver damage in patients with chronic kidney disease has not been investigated sufficiently, although it might have significant clinical consequences. The following article describes the principles of breath tests, experiences with breath tests in patients with chronic kidney disease (CKD) and the results of our pilot study with methacetin breath tests in patients with CKD and in regular peritoneal dialysis treatment.

Body Fat Changes and Liver Safety in Obese and Overweight Women Supplemented with Conjugated Linoleic Acid: A 12-Week Randomised, Double-Blind, Placebo-Controlled Trial.

Preliminary evidence suggests that conjugated linoleic acid (CLA) may reduce body weight and affect body composition. The present study assessed the effect of CLA supplementation on body fat composition in overweight and obese women, while also evaluating the liver safety of CLA use. Seventy-four obese or overweight women were randomly assigned to receive 3 g/day CLA or placebo for 12 weeks. Body composition (dual-energy X-ray absorptiometry) and liver function (13C-methacetin breath test and serum liver enzymes) were assessed before and after the trial. Patients receiving CLA experienced a significant reduction of total body fat expressed as mass (p = 0.0007) and percentage (p = 0.0006), android adipose tissue (p = 0.0002), gynoid adipose tissue (p = 0.0028), and visceral adipose tissue (p = 4.2 × 10-9) as well as a significant increase in lean body mass to height (p = 6.1 × 10-11) when compared to those receiving a placebo. The maximum momentary 13C recovery changes and end-point values were significantly higher in the CLA group when compared to the placebo group (p = 0.0385 and p = 0.0076, respectively). There were no significant changes in alanine aminotransferase, asparagine aminotransferase, and gamma-glutamyl transpeptidase activities between the groups. In conclusion, CLA supplementation was well tolerated and safe for the liver, which shows beneficial effects on fat composition in overweight and obese women.

13C-methacetin breath test for evaluating of children's liver disorder / 中华实用儿科临床杂志

Objective To explore the clinical value of 13C-methacetin breath test for the assessment of liver disorder and to analyze its predictive value to the severity of liver function injury in children.Methods Eighteen healthy children served as healthy control group,and 40 patients with different etiology and severity served as experimental group,and then the latter were divided into 2 subgroups,28 patients in Child-Pugh classification A,and 12 cases in below B(11 cases in B and 1 case in C).An oral dose of 2 mg/kg tracer 13C-methacetin was administered to each subject for the 13 C-methacetin breath test.At the same time,serum liver function markers including serum transaminase,bilirubin,albumin and prothrombin time were measured.The acquired data were analyzed by SPSS 17.0 software.Results (1) Metabolisation velocity (MV) max30 and cumulated dose (CUM) 120 in experimental group (46.64 ± 27.93,59.29 ± 30.73) were much lower than those of the healthy control group(73.56 ± 26.03,102.97 ± 41.80) (t =2.450,3.165,all P ＜0.05);(2) MVmax30 and CUM120 were closely correlated with the liver function markers of albumin,total bilirubin,direct bilirubin,prothrombin time (P ＜ 0.05);(3) MVmax30 and CUM120 could predict liver diseases in children,especially the CUM120.With CUM120 =85.80 as a cut-off value to predict liver diseases,the Youden index was 0.578 at its maximum,and the sensitivity and specificity were 77.8％ and 80.0％;(4) Compared with the Child-Pugh classification A,the CUM120 in Child-Pugh classification B and lower B was significantly lower(P ＜ 0.001);(5) CUM120 could predict the severity of liver diseases.With CUM120 =56.15 as a cut off value to predict the severity of liver diseases,the Youden index was 0.857 at its maximum,and the sensitivity and specificity were 85.7％ and 100.0％.Conclusion 13C-methacetin breath test index of CUM120 could predict liver diseases in children and the severity of liver function.

Activity of cytochrome P450 1A2 in relation to hepatic iron accumulation in transfusion-dependent ß-thalassaemia major patients.

BACKGROUND: Cytochrome P450 1A2 (CYP1A2) is a cytochrome enzyme with a pivotal role in hepatic drug metabolism. Data from CYP1A2((-/-)) mouse suggest that CYP1A2 plays a role in aspects of hepatic iron toxicity. The aim of this study was to assess the activity of CYP1A2 in relation to hepatic iron load in patients with transfusion-dependent ß-thalassaemia major. METHODS: The (13) C-methacetin continuous breath test was performed on 30 consecutive patients with transfusion-dependent ß-thalassaemia major. CYP1A2 activity was measured by the rate at which the (13) C substrate is metabolized and exhaled expressed as percentage dose recovery (PDR) per hour. CYP1A2 activity was correlated with clinical and laboratory parameters and hepatic iron accumulation by T2* magnetic resonance imaging (T2*MRI). RESULTS: Cytochrome P450 1A2 activity in patients with transfusion-dependent ß- thalassaemia major was positivity correlated with plasma ferritin levels. No correlation was found with age, duration and amount of red blood cell transfusion and type of iron chelation therapy. Low CYP1A2 activity was negatively associated with hepatic iron accumulation (T2*MRI ≤ 6.3 ms); adjusted odds ratio (OR; 95% CI) for hepatic iron accumulation in patients with low CYP1A2 activity was 0.047 (0.003-0.72; P = 0.021). Of the six patients with decreased activity of CYP1A2, five had no hepatic iron accumulation and one had mild hepatic iron accumulation by T2*MRI. CONCLUSION: Activity of CYP1A2 is associated with hepatic iron accumulation in patients with transfusion-depended ß-thalassaemia major. Further studies are needed to assess the exact role of CYP1A2 in iron metabolism in human.

Role of the ¹³C-methacetin breath test in the assessment of acute liver injury in a rat model.

AIM: To evaluate the role of the (13)C-methacetin breath test ((13)C-MBT) in the assessment of acute liver injury in a rat model. METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine (D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group (n = 8) and five model groups (each n = 8), and acute liver injury was assessed at different time points (6, 12, 24, 48 and 72 h) after D-GalN injection. The (13)C-MBT, biochemical tests, 15-min retention rate of indocyanine green (ICGR15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the (13)C-MBT (Tmax, MVmax, CUM120 and DOBmax), biochemical tests, ICGR15 and liver necrosis score were also analyzed using Spearman's correlation analysis. RESULTS: Tmax, MVmax, CUM120 and DOBmax, as well as most of the traditional methods, correlated with the liver necrosis score (r = 0.493, P < 0.05; r = -0.731, P < 0.01; r = -0.618, P < 0.01; r = -0.592, P < 0.01, respectively). MVmax, CUM120 and DOBmax rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection (3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MVmax, CUM120 and DOBmax returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy. CONCLUSION: The (13)C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury.

The study of reserved liver function after TACE in hepatic carcinoma by 13C-methacetin breath test / 肿瘤研究与临床

Objective To investigate the changes of hepatic function before and after transcatheter arterial chemoembolization (TACE) in primary liver cancer patients with different quantifications and classifications using 13C-methacetin breath test (13C-MBT), and to provide risk predicts for TACE. Methods 28 cases of primary liver cancer patients and 10 cases of metastatic liver cancer patients were selected.General examination items of liver function and 13C-MBT detection were performed on all cases. Primary liver cancer was divided into 4 groups according to the results of 13C-MBT (group 1 was normal or pathological liver damage; group 2 was grade A; Group 3 was grade B; group 4 was grade C). 13C-MBT detection was carried out in week 1 and 4 after TACE. Results The three parameters of 13C-MBT is 13CO2 maximum excretion rate before 40 min/27 (MVmax40), 13CO2 cumulative excretion of 40 min/12 (CUM40), and than of 120 min/28(CUM120). Compared with the parameters [(0.628±0.191)%, (0.628±0.289)%, (0.577±0.286)%] before TACE in hepatic metastasis, there were no statistic effect between week 1 [(0.600±0.187)%, (0.559±0.189)%, 0.587±0.181)%] and week 4 [(0.700±0.230)%, (0.734±0.229)%, (0.724±0.252)%] after TACE. Conclusion The lower classification of 13C-MBT, the more impairment to liver function after TACE. This could provide an important diagnostic basis for TACE.

The value of studying liver function reserve in hepatic carcinoma by 13C-methacetin breath test / 中华内科杂志

Objective To investigate the characteristic of 13C-methacetin breath test (13C-MBT) as a tool to monitor the hepatic function of patients with hepatic carcinoma by comparing with Child-Pugh classification and general liver function. Methods Thirty-nine patients with primary liver cancer, 16 patients with hepatic metastasis and 14 healthy volunteers serving as controls were included in this study. According to Child-Pugh classification, the primary liver cancer patients were divided into A, B and C subgroups. All subjects received 13C-MBT and routine liver function tests after an overnight fast. The three major parameters of 13C-MBT i.e. maximum excretion rate before 40 min (Mwnax40), 13CO2 cumulative excretion of 40 min(CUM40) and that of 120 min(CUM120) were recorded and the two metabolism curves (DOB curve, MV curve) were made. Results (1) In the control, hepatic metastasis and primary liver cancer groups, both the DOB curve and MV curve were similar in shape; the peak time occurred at about 20 min after administration and then the curves lowered progressively. There were significant differences between the primary liver cancer group and the other two groups, but it was not statistically different between the hepatic metastasis group and the controls. The shape was obviously distinct in the groups A, B and C of primary liver cancer. The group A had a single sharp peak curve, group B a relatively flat peak curve with a lower level for a long time after the ascending phase and group C no clear excretion peak or even a negative curve. (2) As to the three parameters of 13C-MBT, there were statistical difference between the primary liver cancer group and the other two groups(P <0. 05). Between hepatic metastasis group and controls,there was statistical difference about CUM120 (P <0. 05), but no statistical difference about Mvmax40 and CUM40. While in the three groups with primary liver cancer groups, there was statistical difference between group A and B in Mvmax40 and CUM40 ( P < 0. 05 ), but no statistical difference between group B and C. As to CUM120, there was statistical difference only between group A and C. (3) Comparing the three parameters of 13C-MBT with routine liver function tests, there was negative correlation with TBA, positive correlation with Alb, PA, ChE and no correlation with ALT, AST, TBil, γ-GT, ALP and PT. (4) There was a good consistency between 13C-MBT and Child-Pugh classification in the evaluation of liver function of patients with liver cancer ( Kappa = 0. 647, P < 0. 05 ). Conclusion The value of the three parameters of 13C-MBT is decreased with severity of the liver disease and 13C-MBT may be used to evaluate the reserved hepatic function in patients with primary liver cancer with a diagnostic value equivalent to Child-Pugh classification. The study further confirms that 13C-MBT has correlation with TBA,AIb, PA and ChE.

Evaluation the liver reservation functions of patients with severe hepatopath of nonage treated with plasma exchange by 13C-methacetin breath test / 中国综合临床

Objective To judge the effect of plasma exchange (PE) to the patients with severe hepatopath of nonage according to evaluating the change of the liver function of reserve with 13C-methacetin breath test. Methods There are two groups: the case group and the control group. Each group has 30 patients. The patients in the case group were treated by PE. All the patients received 13C-methacetin breath test at before or one week after treatment. MVmax40, CUM40 and CUM120 were present. At the same time, clinical symptoms, glutamate-pyruvate transaminase (ALT), total bilirubin (TBiL) and prethrombin active (PTA) were observed. Results MVmax40, CUM40, CUM120 and PTA were higher, ALT and TBiL were lower in the case group after treatment (t=4.679, 4.752, 5.048, 5.413, 6.208, 7.413, P=0.000,P<0.01). After a week, MVmax40, CUM40, CUM120 and PTA were higher, ALT and TBiL were lower in the case group than that in the control group (t=2.260, 2.247, 2.476, 4.017, 3.250, 3.658, P<0.05). The total effective rates in the case group and the control group were 83.3 % (25/30) and 43.3 % (13/30),which are significant different(χ2 10.335,P<0.01). Conclusion PE can im-prove the liver reservation functionin the severe hepatopath of nonage.