Evaluation of Liver Graft Recipient Workup in Predicting of Early Cardiovascular Events During Liver Transplantation: A Single-Center Experience.

BACKGROUND: Cardiovascular events (CVE) contribute to serious complications and death after liver transplantation (LT). Troponin I (TnI) level >0.07 mg/L and prior cardiac disease are known to be the independent predictors for posttransplant CVE. We evaluated single-center cardiac workup to predict early cardiovascular morbidity and mortality after LT. PATIENTS AND METHODS: We recruited 105 consecutive liver transplant recipients (male/female, 59/46; mean age, 51.66 ± 11.67 years). The cardiological assessment at evaluation for LT included medical history, electrocardiogram, echocardiography, Holter monitoring, and exercise test. We collected data regarding CVE including hypotonia with catecholamine usage, arrhythmia, sudden cardiac death, pulmonary edema, and myocardial infarction within 7 days after LT. RESULTS: CVE during LT occurred in 42 recipients (40%) and after LT in 9 patients (8.57%). Proposed cutoff level of TnI >0.07 mg/L did not correlate with CVE during operation (P = .73) or after LT (P = .47). CVE during LT was associated with arterial hypertension in medical history (P <.001), right ventricular systolic pressure (P< .05), and clinical scores: Child-Pugh (P = .04), Model for End-Stage Liver Disease (MELD) (P = .04), MELD incorporating serum sodium (P<.03), and integrated MELD score (P = .01). CVE after LT correlated only with arrhythmia (P<.001) and catecholamine usage (P < .05) perioperatively. Of interest, catecholamine usage during LT was associated with prolonged stay at the intensive care unit (P < .05). CONCLUSION: The single-center algorithm with noninvasive cardiac procedures without TnI assessment is optimal in evaluation before LT; however, medical history and severity of the liver disease are crucial for short-term cardiovascular morbidity after LT.

Risk Factors of Prolonged ICU Stay in Liver Transplant Recipients in a Single-Center Experience.

BACKGROUND: Prolonged initial intensive care unit (ICU) stay after liver transplantation (LT) is associated with prolonged total hospitalization, increased hospital mortality, and impaired patient and graft survival. Recent data suggested that model for end-stage liver disease (MELD) score at the time of LT and the length of surgery were the two independent risk factors for an ICU stay longer than 3 days after LT. We further identified factors influencing prolonged ICU stay in single-center liver graft recipients. PATIENTS AND METHODS: One hundred fifty consecutive LT recipients (M/F 94/56, median age 55 (range, 39-60), 36% with viral hepatitis, were prospectively enrolled into the study. Associations between clinical factors and prolonged ICU stay were evaluated using logistic regression models. Receiver operating characteristic curves were analyzed to determine the appropriate cutoffs for continuous variables. Threshold for significance was P ≤ .05. RESULTS: Highly prolonged (≥8 days) and moderately prolonged (≥6 days) postoperative ICU stay was noted in 19 (12.7%) and 59 (39.3%) patients, respectively. Serum bilirubin (P = .001) and creatinine concentrations (P = .011), international normalized ratio (P = .004), and sodium-MELD (P < .001) were all significantly associated with postoperative intensive care unit stay over or equal to 75th percentile (6 days). Sodium-MELD was significantly associated with postoperative care unit stay greater or equal to the 90th percentile (8 days; P = .018). CONCLUSIONS: Sodium-MELD might be a novel risk factor of prolonged ICU stay in this single-center experience.

Troponin I Is Not a Predictor of Early Cardiovascular Morbidity in Liver Transplant Recipients.

BACKGROUND: Cardiovascular events (CVE) might occur in 20% to 70% of liver transplant recipients, and major CVE are associated with poor long-term survival. Overall, the ability to identify patients at the highest risk of death after liver transplantation (LT) has been improved. Abnormal pretransplant troponin I (TnI) level is regarded as one of predictors of postoperative CVE. We evaluated the number of early CVE after LT and the impact of pretransplant TnI on cardiovascular morbidity. PATIENTS AND METHODS: We prospectively enrolled 110 consecutive liver transplant recipients (M/F 67/43, age 53.3 ± 10.4 years, 32.7% with hepatitis C virus). Seven of them (6.4%) were on urgent protocol and 3 patients (2.7%) had re-LT. TnI level was measured at listing for LT and directly after LT; clinical outcomes were observed within the first 7 days after LT. RESULTS: CVE during LT occurred in 51 recipients (46.4%). CVE after LT at the intensive care unit were noticed in 13 patients (11.8%). One patient (0.9%) died in the first 7 days after LT. The level of TnI >0.07 did not correlate with CVE during operation and 7 days after LT (P > .05), but the subgroup with TnI >0.07 before LT had a trend with higher TnI after LT (P = .065). Recipients with hepatitis C virus had a trend for higher TnI after LT (P = .061). CVE directly after LT correlated significantly with Child-Pugh (P = .01), Model for End-Stage Liver Disease (MELD), MELD incorporating serum sodium, and integrated MELD scales (P < .001). CONCLUSION: In our single-center algorithm, TnI with canonical cutoff value of 0.07 was not an effective predictor for cardiac outcomes shortly after LT in our population.

The effect of short term treatment with probiotic VSL#3 on various clinical and biochemical parameters in patients with liver cirrhosis.

The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation. In our study twenty patients with compensated and decompensated liver cirrhosis and ten healthy controls received probiotic VSL#3 daily for 28 days. Plasma levels of interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI), macrophage inflammatory protein 3/α (MIP-3 α/CCL20), monocyte chemotactic protein-1α (MCP-1/CCL2), human myeloperoxidase (MPO), nitric oxide (NO), prostaglandins, thromboxane (TXB2) and big-endothelin were measured at baseline, day 14 and 28 of probiotic administration. The incidence of hepatic encephalopathy was assessed with critical flicker frequency. Changes in clinical, biochemical and microbiological parameters were evaluated. The stage of liver cirrhosis correlated with an increase in plasma levels of pro-inflammatory cytokines (IL-6) and chemotactic chemokines involved in immune cell trafficking (MIP-3α/CCL20). Probiotic administration in patients with liver cirrhosis led to modulation of plasma levels of several molecules and compounds measured (MIP-3α/CCL20, NO, big-endothelin, TXB2 and MPO). The grade of encephalopathy during the course of probiotic supplementation remained unaffected in both groups of patients. VSL#3 treatment was well tolerated and safe in patients with liver disease. In patients with compensated and decompensated liver cirrhosis, VSL#3 manipulates selected plasma molecules and compounds involved in hyperdynamic circulatory dysfunction. Short term VSL#3 administration affects several clinical and biochemical parameters commonly altered in liver cirrhosis.

Relationship between pretransplantation liver status and health-related quality of life after grafting: a single-center prospective study.

BACKGROUND: Severity of liver disease evaluated with Model for End-Stage Liver Disease (MELD)/Child-Pugh-Turcotte (CPT) score is of importance in liver transplantation (LTx) assessment. The Medical Outcomes Study Short Form (SF-36) is a widely used generic questionnaire of health-related quality of life (HRQoL). This study was a prospective analysis of the effect of pretransplantation liver status on HRQoL after the procedure. MATERIALS AND METHODS: One hundred and seven (62 male, 45 female, median age 52 years) consecutive patients were included. MELD/CPT score and diabetes status were evaluated during LTx assessment. Patients were divided into 3 groups depending on the period after LTx: 6 to 12 months (group I), 13 to 36 months (group II), and >37 months (group III). They also were divided into 2 groups depending on the age at LTx: group I (<50 years) and group II (>50 years). SF-36 was used in the assessment of HRQoL. RESULTS: Correlation between pretransplantation MELD/CPT score and HRQoL was only seen in the general health domain of the SF-36 in patients from group I (r = 0.64; P = .004 and r = 0.61; P = .02, respectively). Diabetes exerted a significant effect on the physical component summary (P = .02), again in group I. No significant correlation was observed between MELD/CPT score and the presence of diabetes in groups II and III. Regarding age at LTx, no significant correlation between MELD/CPT score and HRQoL was seen. CONCLUSIONS: Liver status assessed with MELD and CPT scores before transplantation has a minor effect on HRQoL after LTx and exerts no significant effect in patients evaluated >12 months after LTx. Patients with diabetes seem to have worse quality of life early after surgery; however, diabetic and nondiabetic patients had comparable HRQoL scores later on after LTx.

Apolipoprotein E4 allele is associated with substantial changes in the plasma lipids and hyaluronic acid content in patients with nonalcoholic fatty liver disease.

Fat may affect progression of liver damage in patients with non-alcoholic fatty liver disease (NAFLD). In this study we characterize the state of lipid metabolism in 22 patients with NAFLD and different Apo-E variants. Total concentration of plasma total fatty acids was quantified by gas chromatography, while their derivatives by liquid chromatography/tandem mass spectrometry (LC ESI MS/MS). The ratio of plasma saturated fatty acid to monounsaturated fatty acid increased, whereas the ratio of polyunsaturated fatty acids to saturated fatty acids was reduced in Apo-E4 carriers. Simultaneously, the levels of individual plasma linoleic, arachidonic, and alpha linolenic acids significantly increased in subjects with the Apo-E4 allele. The 15-lipoxygenase metabolite, 13-hydroxyoctadecadienoic acid, was significantly higher in Apo-E3 carriers (p<0.006). 5-oxo-6,8,11,14-eicosatetraenoic acid was significantly elevated in Apo-E4 carriers (p<0.009). A significant difference in hyaluronic acid concentration (p<0.0016) as well as predicted advanced fibrosis (using the BARD scoring system) was found in Apo-E4 carriers (p<0.01). We suggest that a distinct mechanism of fibrosis between Apo E alleles. In Apo-E4 carriers, an elevation in 5-oxo-6,8,11,14-eicosatetraenoic acid synthesis and fatty acid dysfunction may induce fibrosis, while an inflammatory process may be the main cause of fibrosis in Apo-E3 carriers.

Ligation of oesophageal varices may increase formation of "deep" gastric collaterals.

BACKGROUND/AIMS: Endosonography (EUS) is rarely used in the routine diagnostic of portal hypertension in patients with cirrhosis even though it has significantly higher sensitivity for detection of varices than gastroduodenoscopy. The aim of this cross-sectional study was to assess the features of portal hypertension identified with EUS and to analyze the effect of variceal ligation on the prevalence of "deep" varices in subjects with cirrhosis. METHODOLOGY: A cohort of 121 patients was divided into 2 groups depending on whether they had a history of variceal bleeding treated with ligation or not. RESULTS: "Deep" oesophageal varices and large (> 5 mm) gastric varices occurred significantly more common in patients with previous banding. Also, large "deep" gastric varices occurred significantly more common in the banded group with no or small varices than in the not-banded group with similar endoscopy. Sixty percent of banded patients who had grade II/III oesophageal varices on endoscopy had large "deep" gastric varices comparing to 20% of not-banded with the same endoscopical findings (p = 0.04). CONCLUSION: Previous banding may increase the risk of the development of large "deep" oesophageal and gastric varices. Thus potential new indication for EUS in patients with cirrhosis could be a follow-up examination after successful eradication of varices.

Upper gastrointestinal endosonography in patients evaluated for liver transplantation.

BACKGROUND: Endosonography (EUS), which merges endoscopic and ultrasound examinations, is a useful modality to display abnormal vessels that develop in the intrinsic circulation, frequently called "deep" varices. If these pathological veins exceed of 5 mm diameter, they significantly increase the risk of bleeding among patients with cirrhosis. In the most recent pilot study EUS proved useful to assess children for orthotopic liver transplantation (OLT). AIM: We performed a cross-sectional study of EUS on 33 (22 males and 11 females) adult cirrhotic subjects being assessed for OLT. MATERIALS/METHODS: We used an echoendoscope at 7.5 MHz/12 MHz/20 MHz to evaluate the esophagus and stomach, including "deep" periesophageal/perigastric varices (adjacent to the muscularis propria) and paraesophageal/paragastric varices (outside the muscularis propria). "Deep" varices were considered to be large if >5 mm. RESULTS: On endoscopy, 26 (79%) patients showed esophageal varices (EV), including 11 (33%) with large (>5 mm) varices. Gastric varices (GV) were observed in 13 (39%) subjects, with 3 patients displaying large (>5 mm) varices. On EUS large "deep" EV (both para and periesophageal) were observed in 12 (36%) subjects, among whom 5 (42%) did not have large varices on endoscopy. Large "deep" GV were found on EUS in 12 (36%) subjects. On endoscopy 4 of them (33%) showed no varices and 3 (25%) had small GV. CONCLUSIONS: EUS offers a precise evaluation of portal hypertension in OLT candidates. "Deep" potentially dangerous varices, which are undetected with routine endoscopy, were noted in a significant proportion of patients. The role of EUS in prioritizing subjects for OLT must be evaluated in a prospective study.

Immunosuppression with low-dose daclizumab in liver transplant recipients with impaired kidney function: a single-center experience.

BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNI) may exert detrimental effects, particularly in orthotopic liver transplantation (OLT) patients with impaired kidney function. Immunosuppression with daclizumab permits delayed introduction of CNI, and may be preferred for patients with kidney dysfunction. This retrospective analysis of our experience using daclizumab was performed among patients who underwent transplantation with impaired kidney function. METHODS: We analyzed 168 patients. A serum creatinine (Cr) level >1.5 mg/dL was the indication for a protocol with low-dose daclizumab (50 mg intravenous [IV], day 0 and day 4), mycophenolate mofetil (MMF; 500 mg twice daily IV/orally), and tapering doses of prednisolone from day 0 after OLT. CNI were introduced at day 4-15 after OLT. Patients with a Cr level <1.5 mg/dL received immunosuppression with CNI+MMF+steroids or CNI+steroids. RESULTS: Fourteen patients fulfilled the criterion for daclizumab immunosupression. Their Cr and creatinine clearance (CrCl) values at OLT were 2.85 +/- 1.22 mg/dL and 19 +/- 11 mL/min, respectively. In the remaining 154 patients, Cr and CrCl results were 0.88 +/- 0.3 mg/dL and 107 +/- 82 mL/min, respectively. At discharge, the daclizumab group showed Cr and CrCl estimates of 0.97 +/- 0.45 mg/dL and 86 +/- 34 mL/min (P < .0001 for both, when compared with prior to OLT). Both Cr and CrCl levels at discharge were not different from those values of patients who underwent transplantation with normal kidney function. The incidence of acuterejection was 14% in the daclizumab group and 18% in the other recipients (P = not significant [NS]). CONCLUSIONS: Immunosuppression with low-dose daclizumab and delayed introduction of CNI was safe and did not increase the risk of an acute rejection episode, thus offerring an excellent therapeutic option for patients who undergo transplantation with impaired kidney function.

Assessment of a modified Child-Pugh-Turcotte score to predict early mortality after liver transplantation.

OBJECTIVE: The Model for End-Stage Liver Disease (MELD) predicts mortality on the transplant list; however, it has not been of much use to predict posttransplant outcomes. Several prognostic models have been tested among patients with cirrhosis; nevertheless, their predictive value has not been established in the posttransplant setting. We recently modified the Child-Pugh-Turcotte (CPT) score by adding creatinine levels (CPT + Cr), which has proven useful for patients with alcoholic cirrhosis. This retrospective analysis sought to predict early (1 month) mortality using CPT + Cr versus 5 other prognostic models in patients who underwent orthotopic liver transplantation (OLT) at our center. MATERIALS AND METHODS: We included 48 consecutive patients (30 males, 18 females, median age 51 years). The predictive values of CPT + Cr were compared with CPT scores without or with the Huo modification, CPT + Na, MELD, and MESO, which is the MELD to serum Na ratio. Pearson correlations and ROC curves as evidenced by the area under the curve (AUC) were determined for each index. P < .05 was considered to be significant. RESULTS: CPT + Cr showed the highest correlation with the risk of death (r = .368, P = .01); MELD and MESO were the lowest (r = .204, P = NS; and r = .254, P = NS, respectively). ROC analysis showed the best predictive value of CPT and CPT-Crea with AUC of 0.758 (P = .010) and 0.748 (P = .011) respectively, as compared to 0.689 for MESO and 0.659 for MELD (both NS). CONCLUSIONS: A modified CPT score with creatinine levels may be of value to predict early death after OLT. Its usefulness must be validated in a prospective study of a large patient cohort.

Modified Charlson Comorbidity Index in predicting early mortality after liver transplantation.

BACKGROUND: The Charlson Comorbidity Index for orthotopic liver transplantation (CCI-OLT) is a modified clinical score recently proposed to be useful for the assessment of long-term survival after OLT. It includes 9 associated conditions selected upon a multivariate analysis of a large cohort of transplant recipients. Its role in predicting early mortality after OLT has not yet been investigated. We sought to CCI-OLT as a potential predictor of 1-month mortality after OLT. MATERIALS/METHODS: One hundred ninety-seven OLT were performed in our center between March 2002 and February 2009. After exclusion of patients who underwent transplantation for fulminant hepatic failure or those who underwent regrafting, we included a group of 169 patients. Viral (39%) and alcohol-induced (23%) cirrhosis were the most common indications for OLT. The CCI-OLT index was assessed in all patients. RESULTS: In total, 146 (86%) subjects survived and 23 (14%) died within 1 month after LT. Fifty-one (30%) patients suffered at least 1 comorbidity that was included in the CCI-OLT. Direct comparison between survivor versus nonsurvivor groups showed no significant difference in terms of the total frequency of comorbidities (30.1% vs 30.4%; P > .99) or the number or the type of comorbidity. The most commonly associated condition in both groups was diabetes mellitus. CONCLUSION: Unlike the case of long-term survival, CCI-OLT did not seem to predict early (1-month) mortality after OLT.

Serological characterization of Streptococcus mutans serotype polysaccharide g and its different molecular weight forms.

The serotype polysaccharide g from Streptococcus mutans 6715 was found to cross-react with serotype polysaccharide a from S. mutans HS6 and serotype polysaccharide d from S. mutans B13. Double immunodiffusion experiments indicated that the serotype polysaccharide g consisted of the following: (i) the type-specific g site; (ii) a cross-reactive site g-a that was in common with polysaccharide a; (iii) a cross-reactive site g-d that was in common with polysaccharide d; and (iv) a cross-reactive site g-(a-d) that was in common with both polysaccharides a and d. Moreover, by a procedure involving several column chromatography steps, six polysaccharide-containing fractions showing reactivity with anti-g serum were found. By gel filtration, the molecular weight estimates of fractions LI, LII, LIII, SI, SII, and SIII were 2 X 10(6), 5 X 10(5), 6 X 10(4), 3 X 10(4), 1.4 X 10(4), and 1 X 10(4), respectively. Double immunodiffusion analysis indicated that LI, LII, and LIII contained the four antigenic sites of the putative polysaccharide g. LII also contained another additional immunodominant region, designated site x. The analysis also suggested that fraction SI lacked the type-specific site g, fraction SII lacked sites g and g-a, and fraction SIII lacked sites g, g-a, and g-d.