Lower Prothrombin Time Research Articles

Clinical utility of serum fucosylated hemopexin in Japanese patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common clinical problem all over the world. Fucosylated hemopexin (Fuc-Hpx) is a newly reported glycoprotein for the diagnosis of HCC, however, its clinical implications are unclear. The aim of this study was to elucidate the clinical utility of Fuc-Hpx in Japanese patients with HCC. The sera from 331 HCC patients, 45 with liver cirrhosis (LC), 85 with chronic hepatitis (CH) and 22 healthy people were examined for the expression of Fuc-Hpx; the level was compared with clinical parameters as well as hemopexin (Hpx) expression. The expressions of Fuc-Hpx in 12 HCC tissues and corresponding adjacent non-cancerous liver tissues were also examined. No correlation was observed between Hpx and Fuc-Hpx level. The median Fuc-Hpx levels in healthy people and CH, LC and HCC patients were 3.8, 3.7, 6.1 and 7.6 AU/mL, respectively (CH vs LC, P = 0.002; CH vs HCC, P < 0.001; LC vs HCC, P = 0.02). Multivariate analysis revealed that low albumin, low prothrombin time and the presence of HCC were significantly correlated with high Fuc-Hpx (P = 0.013, =0.001 and <0.001, respectively). Among the HCC patients, albumin was correlated with high Fuc-Hpx; however, none of the tumor factors, such as tumor size, tumor number and tumor stage, was correlated with Fuc-Hpx level. The expression of Fuc-Hpx in cancer tissue was not different from that in non-cancerous tissue. Fuc-Hpx is a valuable biomarker for HCC but it might be a marker for hypercarcinogenic liver rather than a marker for tumor-bearing liver.

Targeted molecular therapies (cetuximab and bevacizumab) do not induce additional hepatotoxicity: Preliminary results of a case–control study

Aims To analyse the effects of the preoperative targeted molecular therapy (cetuximab (cetu) or bevacizumab (beva)) on non-tumorous liver parenchyma, and the clinical and biological outcome after liver resection for colorectal liver metastases (CLM). Methods Between January 2005 and December 2007, 36 patients receiving preoperatively cetu ( n = 15) or beva ( n = 21) were, respectively, matched to a control group of patients who did not receive targeted molecular therapy. They were matched on the basis of age, gender, body mass index, extent of hepatectomy, and type and number of neoadjuvant chemotherapy. Liver function tests, postoperative outcome and histopathology of the resected liver were compared. Results There was no mortality. Postoperative morbidity and perioperative bleeding rates were similar in both groups. In the beva group, liver function tests showed higher serum bilirubin level on postoperative day (POD) 1 ( p = 0.001) and POD 3 ( p = 0.01), higher serum aspartate aminotransferase on POD 1 ( p = 0.004), and lower prothrombin time on POD 5 ( p = 0.02). In both groups, cetu and beva, the postoperative peaks of γ-glutamyl transpeptidase and alkaline phosphatase were statistically higher than in the control groups. Interestingly, the prevalence of sinusoidal injury and fibrosis was lower in patients receiving cetu ( p = 0.04), while the prevalence of steatohepatitis was lower in patients receiving beva ( p = 0.04). Conclusion The addition of beva or cetu to the neoadjuvant chemotherapy regimens does not appear to increase the morbidity rates after hepatectomy for CLM. The pathological examination did not show additional injury to the non-tumorous liver parenchyma.

Exchange Transfusion as a Possible Therapy for Neonatal Hemochromatosis

Exchange Transfusion as a Possible Therapy for Neonatal Hemochromatosis

Preoperative risk factors for mortality after relaparotomy: analysis of 254 patients

The aim of this work was to analyze preoperative mortality risk factors after relaparotomy for abdominal surgery in a unit of General Surgery at a University Hospital. A total of 314 relaparotomies in 254 patients were performed between February 2004 and February 2008. We analyzed data about past medical history, first operation, as well as clinical and biochemical parameters previous to reoperation. Indications for relaparotomy were peritonitis, bleeding, abscess, exploratory laparotomy, and evisceration. Overall mortality was 22%. Mortality of the patients with a single relaparotomy was 20% vs. 44% if they were reoperated upon twice. Mortality was associated with age, past history of cardiovascular disease, active neoplasm, previous treatment with platelet anti-aggregant drugs, first surgery American Society of Anesthesia score, and the presence of an anastomosis. Preoperative data associated with mortality were the number of systemic inflammatory response syndrome criteria, suture dehiscense, ileus, positive blood cultures, mechanical ventilation, artificial nutrition, antibiotics or vasoactive drugs, tachycardia, and abnormal body temperature. High white blood cell count or bilirrubin levels and low albumin or prothrombin time were also associated with mortality. Multivariate logistic regression analysis isolated age (P = 0.02), abnormal body temperature (P = 0.02), and the need of mechanical ventilation (P = 0.004) as independent preoperative variables predictive for mortality after relaparotomy. Advanced age, the presence of either fever or hypothermia, and the need of mechanical ventilation are preoperative risk factors associated with mortality after relaparotomy and should be considered when planning reintervention.

Soy Protein Isolate versus Meat‐Based Low‐Protein Diet for Dogs with Congenital Portosystemic Shunts

Both presurgical preparation and long-term support of nonoperable dogs with congenital portosystemic shunts (CPSS) require optimal dietary management. Studies suggested that protein source may play an important role, with vegetable and dairy protein sources having better effects on hepatic encephalopathy (HE) than meat proteins. Determine whether a low-protein test diet with soy as its main protein source results in better scores than a control diet with the same composition but with poultry as its main protein source in dogs with CPSS. In a double-blind cross-over study, 16 dogs received each diet for 4 weeks. Dogs in group T first received the test diet and then the control diet, whereas dogs in group C were fed the diets in the opposite order. Different variables (body weight, body condition score, HE score, fecal score, CBC, plasma tests of liver function including NH3, and coagulation tests) were measured at the start of the study and after completion of each diet. One-way repeated measures ANOVA was performed. Plasma NH3 was significantly lower after the test diet than after the control diet. The test diet also resulted in significantly higher fibrinogen concentrations and lower prothrombin times. The HE score improved with both diets, with no significant difference between the 2 diets. Both diets achieved a significant improvement in HE score. The influence of the soy-based diet on plasma NH3 concentration and coagulation parameters suggests that such a diet decreases the risk for HE and gives better support of liver function.

Urinary Stone Disease in Adults With Celiac Disease: Prevalence, Incidence and Urinary Determinants

Intestinal diseases may cause urinary stone disease via hyperoxaluria or diarrhea induced hyperconcentrated acidic urine. Data are missing on urinary stone disease in celiac disease, a common malabsorptive disorder. In this study we analyzed urinary stone disease and urine composition in adults with celiac disease. Study patients were 18 years or older, untreated, and newly diagnosed with celiac disease by serum markers and jejunal biopsy. Clinical presentation of celiac disease was assessed focusing on 5 disorders of diarrhea, and deficiency of calorie (low body mass index or weight loss), lipid (low prothrombin time or low serum lipids), iron (low hemoglobin or low serum ferritin) and calcium (low serum calcium or low bone densitometry). Urinary stone disease history was assessed by questionnaire (imaging, stone excretion, stone disruption/removal). Urinary variables were measured in a 24-hour collection in a subgroup of patients. Under untreated conditions (baseline) urinary stone disease was independent of celiac disease presentation and more prevalent in patients with celiac disease than in a population sample used as a control (608 and 3,540, 7.9% and 5.0%, sex and age adjusted odds ratio 4.0, 95% CI 2.7-5.9). Excluding from analysis individuals with baseline urinary stone disease, the incidence of urinary stone disease history was not significantly different between the treated celiac disease (gluten-free diet) and control population (458 and 3,003, 2.4% vs 3.9%). The urine of untreated patients with celiac disease differed from that of healthy volunteers with 120% higher oxalate and 43% lower calcium (in 45 and 45, p <0.001). A gluten-free diet corrected urinary abnormalities (p <0.01). Urinary stone disease risk is high in untreated patients with celiac disease independent of overt malabsorption. Hyperoxaluria is likely the underlying disorder. A gluten-free diet reduces urinary stone disease risk and oxaluria.

Complications of Laser Ablation for Hepatocellular Carcinoma: A Multicenter Study

To retrospectively and prospectively determine the rate and type of complications and their association with clinical or technical factors after percutaneous laser ablation (LA) for hepatocellular carcinoma (HCC). The institutional research board of each center approved the study and all patients provided informed consent. By using an Internet liver tumor database of nine Italian centers, 520 patients were included with HCC nodules of any size (small, 0-3 cm; intermediate, >3-5 cm; large, >5 cm). Postprocedural complications were related to clinical or percutaneous LA factors by using the Student t and chi(2) tests. Follow-up was carried out with computed tomography (CT) at 1, 3, 6, 9, and 12 months, and primary effectiveness rate was defined as the percentage of HCCs completely ablated after percutaneous LA. A total of 353 men and 147 women (age range, 24-86 years; Child-Pugh score A = 63.4%, B = 30.8%, C = 5.9%) with 647 nodules (mean diameter, 3.2 cm +/- 1.7) were treated by 1004 percutaneous LA sessions. There were four (0.8%) deaths in 520 patients; 15 (1.5%) of 1004 sessions presented major complications without any seeding. Major complications were associated with excess energy (10 520 J +/- 7073 vs 7474 J +/- 3803; P = .001) and high-risk location (P = .05). Sixty-two (6.2%) sessions resulted in minor complications associated with excess energy (P = .001), high bilirubin level (1.74 mg/dL +/- 1.10), and low prothrombin time (P = .01). Primary effectiveness rates were 60% in all HCCs and 81% in HCCs smaller than 3 cm. Percutaneous LA may be considered a safe treatment for small HCCs.

Use of recombinant activated factor VII for massive postpartum hemorrhage

We hypothesised that patients with massive postpartum hemorrhage (PPH), defined as blood loss >1,500 ml,may benefit from the use of activated recombinant factor VII (rFVIIa). Design. Retrospective cohort study. Setting.Department of Obstetrics & Gynaecology, Dow University of Health Sciences. Thirty-four women with a diagnosis of massive PPH. All patients with PPH who were admitted to the Department of Obstetrics &Gynecology and Surgical Intensive Care Unit of Civil Hospital Karachi, Pakistan, were included in the study. From March 2005 to October 2006, 34 patients fulfilled the criteria of massive PPH, of which 18 received rFVIIa to control bleeding, and 16 patients did not. Availability and cost of rFVIIa were the factors in drug allocation. Main outcome measures. Maternal mortality, correction of coagulopathy, the amount of blood products transfused and preservation of fertility. Patients receiving rFVIIa had lower maternal mortality (5/18, 28% versus 8/16, 50%, OR: 0.04 (0.002, 0.83)), and received a lower number of packed red cell transfusions (4.0 ± 4.46 versus 9.61 ± 6.7, p value 0.007), against the comparison group. Patients receiving rFVIIa had lower activated partial thromboplastin (median: 13.0; 25-75th percentile: -25.0, -8.0, signed rank p<0.0001), and lower prothrombin times (median: -8.8; 25-75th percentile: -24.2, -4.8), after administration of drug.There was no significant difference in the rate of hysterectomy between the 2 groups (11/18 (61%) versus 6/16 (38%)). No adverse event attributable to rFVIIa was observed in the study. Activated recombinant factor VII can be a lifesaving drug in patients with massive PPH.

Hepatic steatosis is a risk factor for postoperative complications after major hepatectomy: a matched case-control study.

To assess the impact of microsteatosis (MiS) and macrosteatosis (MaS) on major hepatectomy. While steatosis of a liver graft is an established risk factor in transplantation, its impact on major hepatectomy remains unclear. Fifty-eight steatotic patients who underwent major hepatectomy were matched 1:1 with patients with normal liver according to age, gender, ASA score, diagnosis, extent of hepatectomy, and need of hepaticojejunostomy. Steatosis was evaluated quantitatively and qualitatively. Primary endpoints were mortality and complications. Pure MaS and MiS were present in only 10 and 3 patients, respectively, while mixed steatosis was noted in 45 patients. Forty-four patients had mild (10%-30%) and 14 moderate/severe (>30%) steatosis. Steatotic patients had significantly higher serum transaminase and bilirubin levels, and lower prothrombin time. Blood loss (P = 0.04) and transfusions (P = 0.03), and ICU stay (P = 0.001) were increased in steatotic patients. Complications were higher in steatotic patients when considered either overall (50% vs. 25%, P = 0.007) or major (27.5% vs. 6.9%, P = 0.001) complications. Patients with pure MaS had increased mortality (MaS: 20% vs. MiS: 6.6% vs. mixed: 0%; P = 0.36) and major complications (MaS: 66% vs. MiS: 50% vs. mixed: 24%; P = 0.59), but not significantly. Preoperative cholestasis was a highly significant risk factor for mortality in patients with hepatic steatosis. Steatosis per se is a risk factor for postoperative complications after major hepatectomy and should be considered in the planning of surgery. Caution must be taken to perform major hepatectomy in steatotic patients with preexisting cholestasis.

Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan

In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.

Severe Alcoholic Hepatitis with Extremely High Neutrophil Count Successfully Treated by Granulocytapheresis

We report a severe alcoholic hepatitis (SAH) patient with an extremely high WBC count, high serum bilirubin and low prothrombin time (PT) successfully treated with granulocytapheresis. After neutrophil-elastase inhibitor failed to reduce WBC count, methylprednisolone pulse therapy was performed. However, WBC count continued to be elevated to 97,190/microl (neutrophils 97.0%) despite improvement of total bilirubin and PT. After 5 sessions of granulocytapheresis and ulinastatin administration, increased serum IL-6, IL-8, neutrophil-elastase and WBC count gradually decreased. We could conclude that granulocytapheresis and ulinastatin can be very effective in reducing cytokines and neutrophil-elastase, and in improving the general status of SAH patients.

The effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm

N-acetylcysteine (NAC) may offer renal and hepatic protection during surgery, but in experimental studies it has been shown to impair coagulation. Since very little is known about the effects of NAC on blood coagulation in surgical patients, we studied its effects during abdominal aortic reconstruction. NAC (a bolus of 150 mg/kg followed by a continuous 24-h infusion of 150 mg/kg) or the same volume of placebo was given intravenously, in a randomized double-blinded fashion, to 20 patients undergoing abdominal aortic aneurysm repair. The haematocrit, platelet count, prothrombin time, thromboelastometry, and platelet aggregation were studied during and after surgery. Total blood loss was also measured. The median (25th-75th percentiles) decrease of the prothrombin time value was 33.0% (30-37%) after NAC treatment and 6.5% (4-8%) after placebo (P<0.001). Postoperative prothrombin time values remained lower in the patients receiving NAC. In thromboelastometry tracings the coagulation time was more prolonged after the bolus of NAC (P=0.02). Platelet aggregation induced with adenosine diphosphate decreased after NAC but not after placebo. Low prothrombin time values before and after bolus infusions were associated with increased blood loss (P=0.008 and P=0.015, respectively). NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery. This abnormal haemostatic activity should be considered when NAC is administered to patients with increased bleeding risk.

The "50-50 criteria" on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy.

To standardize the definition of postoperative liver failure (PLF) for prediction of early mortality after hepatectomy. The definition of PLF is not standardized, making the comparison of innovations in surgical techniques and the timely use of specific therapeutic interventions complex. Between 1998 and 2002, 775 elective liver resections, including 69% for malignancies and 60% major resections, were included in a prospective database. The nontumorous liver was abnormal in 43% with steatosis >30% in 14%, noncirrhotic fibrosis in 43%, and cirrhosis in 12%. The impact of prothrombin time (PT) <50% and serum bilirubin (SB) >50 micromol/L on postoperative days (POD) 1, 3, 5, and 7 was analyzed. The lowest PT level was observed on postoperative day (POD) 1, while the peak of SB was observed on POD 3. These 2 variables tended to return to preoperative values by POD 5. The median interval between hepatectomy and postoperative death was 15 days (range, 5-39 days). Postoperative mortality significantly increased in patients with PT <50% and SB >50 microml/L. The conjunction of PT <50% and SB >50 micromol/L on POD 5 was a strong predictive factor of mortality. In patients with significant morbidity, this "50-50 criteria" was met 3 to 8 days before clinical evidence of complications. The association of PT <50% and SB >50 microml/L on POD 5 (the 50-50 criteria) was a simple, early, and accurate predictor of more than 50% mortality rate after hepatectomy. This criteria could be identified early enough, before clinical evidence of complications, for specific interventions to be applied in due time.

Predictive Factors for the Distant Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation of Hepatocellular Carcinoma

Purpose: Radiofrequency ablation (RFA) therapy for hepatocellular carcinoma (HCC) has made good local control possible. After the local control, however, distant recurrences are frequently observed in remnant liver. In this study the efficacy of RFA is evaluated and predictive factors for the distant recurrence are revealed. Methods: 135 patients with initial HCC who underwent RFA in our hospital (Male/Female = 100/35) were selected for this study. After transecatheter airterial embolization, RFA was performed under the real-time CT guided. Safety margins of more than 5mm around tumors were confirmed by dynamic CT after the RFA with all those patients. The mean age is 66.9 years old, HBV/HCV/HBV+HCV/NBNC = 10/109/1/15, Child-Pugh(A/B/C) = 96/35/4, the average follow-up period is 21.8 months (3–54months). We studied local and distant recurrence rates, predictive factors for the distant recurrence of HCC, and treatment performed for the recurrence. Results: After RFA for the initial HCC, survival rates are 84.5%, 82.4% and 62.8% for two, three and four years respectively. The recurrence rates after RFA are 5% and 12% in two and four years respectively for local, and 41.4% and 67.7% in two and four years respectively for distant. RFA could be performed again for 76% of the patients with distant recurrence. The study of predictive factors for cumulative distant recurrence rates by Kaplan-Meier method shows significant high recurrence rates in cases of initial multi-occurrence, low albumin level, high AST level, low platelet count and low prothrombin time (PT). The predictive factors for cumulative distant recurrence after RFA by Cox proportional hazard regression model are low albumin level and high AST level. Conclusions: While RFA enables good local control for the initial HCC without remarkably worsening liver functions, distant recurrences in remnant liver are observed at high rates in the cases with low albumin, platelet and PT level. Low albumin and high AST level are predictive factors for the distant recurrence, and it is possible to control distant recurrence by caring nutrition and lowering AST after RFA.

Predictors of Mortality in Trauma Patients

The purpose of this study was to ascertain risk factors for death from trauma. The large cohort allows for simultaneous evaluation of known mortality risk factors along with controlling for factors to assess the influence of each independently. Individually, base deficit, temperature, hypotension, age, and injury severity have been shown to be associated with an increased risk of death. However, in the English literature, there is no data on the independent predictive power and interaction of these risk factors. A review of trauma registry parameters from 1995 to 2000 was used. Demographics, injury severity, physiological and hematological parameters, and time data were evaluated in a univariate analysis. Variables significantly associated with mortality were entered into a stepwise backward multiple logistic regression. There were 1276 deaths (8.9%) with 25 per cent of the deaths within 3 hours. The top four predictors of mortality in this group were partial thromboplastin time (OR 3.37, 95% CI: 2.51-4.52), positive head computed tomography result (OR, 2.47; 95% CI, 1.95-3.04), initial hemoglobin (OR, 1.69; 95% CI, 1.23-2.31), base deficit (OR, 1.62; 95% CI, 1.29-2.04), and trauma resuscitation bay systolic blood pressure (OR, 1.45; 95% CI, 1.11-1.88). We conclude that prognostic indicators of all-cause mortality after trauma, which remain independent in the presence of all other factors and are potentially treatable, included low hemoglobin, elevated prothrombin and partial thromboplastin time, low scene and trauma bay systolic pressure, and elevated base deficit. The independent indicators of mortality, which are untreatable, included head injury, increasing age, and Injury Severity Score.

Major hepatic resection for hilar cholangiocarcinoma: analysis of 46 patients.

Major hepatectomy, bile duct resection, and regional lymphadenectomy for hilar cholangiocarcinoma are associated with actual long-term (>5 years) survival. Retrospective outcome study. Single tertiary referral institution. Between 1979 and 1997, 46 consecutive patients had resection of hilar cholangiocarcinoma by major hepatectomy, bile duct resection, and regional lymphadenectomy. Overall survival and tumor recurrence were correlated to clinicopathological factors, operative morbidity, and mortality. Twenty-five patients underwent left hepatectomy, 17 underwent right hepatectomy, and 4 had extended right hepatectomy. Eighteen patients underwent resection of segment 1. Negative (R0) resection margins were achieved in 37 patients (80%). The operative mortality rate was 9%, and the surgical morbidity rate was 52%. Actual 1-year, 3-year, and 5-year survival rates were 80%, 39%, and 26%, respectively. Factors adversely associated with patient survival rates included: male sex, lymph node metastases, tumor grade 3 or 4, elevated direct serum bilirubin level at diagnosis, elevated preoperative activated partial thromboplastin time, and more than 4 U of red blood cells transfused perioperatively. Tumor size and R0 resection approached significance for survival. Factors associated with tumor recurrence included: male sex, tumor grade 3 or 4, a low hemoglobin level both at diagnosis and preoperatively, and a low preoperative prothrombin time and low alkaline phosphatase level at diagnosis and preoperatively. Median time to recurrence was 3.6 years. Tumor recurrence was predominantly local and regional. The actual 5-year survival rate of 26% justifies major partial hepatectomy, bile duct resection, and regional lymphadenectomy for hilar cholangiocarcinoma. The high frequency of local and regional recurrence warrants investigation of adjuvant therapy.

Central nervous system alterations in liver cirrhosis: the role of portal-systemic shunt and portal hypoperfusion.

The role of portal-systemic shunting and portal liver hypoperfusion in the pathophysiology of central nervous system dysfunction (CNSD) of cirrhosis is not yet well defined. It is well known that one of the most important collateral vessels (CVs) is a patent paraumbilical vein (PUV), but there is controversy regarding its clinical significance. We have evaluated the relationships between neuropsychological and EEG alterations, ammonia plasma level (NH4), hepatic function, and portal hemodynamics (Doppler Ultrasound) in 95 cirrhotic patients. Patency, diameter, or flow of PUV or the presence of other CVs were not related to an increased prevalence of neuropsychological or EEG abnormalities. Patients with effective portal flow (EPF = portal flow - PUV flow) lower than 692 mL/min (median) had a significantly higher risk of failing the neuropsychological test, or of having an altered EEG. Low EPF and prothrombin time (<50%), and high NH4 (51 micromol/L) were independent predictors of an abnormal EEG. Considering both low EPF and the numerosity of CVs, only low EPF was found to explain EEG alterations. In conclusion, portal liver hypoperfusion and decreased liver function were associated with an increased risk of CNSD in cirrhotic patients, whereas PUV patency per se was not.

Central nervous system alterations in liver cirrhosis: the role of portal-systemic shunt and portal hypoperfusion.

The role of portal-systemic shunting and portal liver hypoperfusion in the pathophysiology of central nervous system dysfunction of cirrhosis is not yet well defined. It is well known that one of the most important collateral vessels (CV) is a patent paraumbilical vein (PUV) but there is controversy regarding its clinical significance. We have evaluated the relationships between neuropsychological and EEG alterations, ammonia plasma level (NH4), hepatic function, and portal hemodynamics (Doppler Ultrasound) in 95 cirrhotic patients. Patency, diameter, or flow of PUV or the presence of other CV were not related to an increased prevalence of neuropsychological or EEG abnormalities. Patients with effective portal flow (EPF = portal flow - PUV flow) lower than 692 mL/min (median) had a significantly higher risk of failing the neuropsychological test, or of having an altered EEG. Low EPF and prothrombin time (<50%), and high NH4 (> or = 51 micromol/L) were independent predictors of an abnormal EEG. Considering both low EPF and the numerosity of CV, only low EPF was found to explain EEG alterations. In conclusion, portal liver hypoperfusion and decreased liver function were associated with an increased risk of central nervous system dysfunction in cirrhotic patients, whereas PUV patency per se was not.

The deleterious effect of donor high plasma sodium and extended preservation in liver transplantation. A multivariate analysis.

The aim of this study was to analyze the donor risk factors associated with second orthotopic liver transplantation (reOLT) and graft loss after OLT within 1 month. A total of 649 OLTs performed in 11 centers in Spain during the period from 1992 to 1993 were analyzed retrospectively. Eleven donor and recipient variables were studied. Biochemical evolution of the OLT, biliary and arterial complications, patient status (alive, retransplanted, or dead), and follow-up were also recorded. Bivariate study demonstrated that extended preservation ( > 12 hr) was associated with increased biliary complications (P = 0.02), and lower prothrombin time (P = 0.04). In a logistic model regression for biliary complications, ischemia > 12 hr was an independent risk factor (odds ratio = 2.2, 95% confidence interval [CI] = 1.1-4.3). The multivariate Cox proportional model of potential risk factors showed that only urgent reOLT (relative risk [RR] = 2.7, 95% CI = 1.4-5.4) was independently associated with higher 30-day mortality. Donor plasma sodium > 155 mmol/L (RR = 1.4, 95% CI = 1.0-2.2) and incompatible ABO graft (RR = 3.2, 95% CI = 1.3-7.9) were independently associated with increased rate of reOLT before 30 days. Donor plasma sodium > 155 mmol/L (RR = 2, 95% CI = 1.1-3.6) and incompatible graft (RR = 3.3, 95% CI = 1.4-8.2) were independently associated with graft loss (death or reOLT) before 1 month. We conclude that cold ischemia should be kept less than 12 hr in order to avoid biliary complications. Donors over 60 years old or with plasma sodium > 155 should be carefully evaluated before OLT.

The role of dynamic and morphological studies in the assessment of potential liver donors.

In a prospective study, 66 donor livers were evaluated by monoethylglycinexylidide (MEGX) dynamic clearance and semiquantitative scoring of pathological changes in liver biopsies. The median MEGX level in 63 donors was 89 mcg/L (range 16-250 mcg/L); fifteen had MEGX levels < 50 mcg/L, 17 between 50 and 90 mcg/L, and 31 > 90 mcg/L. There were no cases of primary nonfunction, and no deaths were related to poor graft function. There was no statistically significant difference in peak aspartate aminotransferase (AST), day 5 AST, peak bilirubin, or lowest prothrombin time among the 3 groups. Liver biopsies were assessed in 61 donors: 33 (54%) were normal and 17 (28%) showed mild, 8 (13%) showed moderate, and 3 (5%) showed severe steatosis. Postperfusion biopsy assessing the extent of preservation injury was essentially normal or showed minimal change in 16 (26%), mild change in 29 (48%), moderate in 13 (21%) and severe abnormalities in 3 (5%). The latter 3 biopsies all had severe steatosis. There was no significant difference in early graft function or outcome between moderate/severe groups and normal/minimal groups, although the former had a higher peak AST (P < 0.02) and peak bilirubin (P < 0.004). This detailed prospective analysis suggests that MEGX and the morphological studies may assist in the assessment of potential liver donors but they do not provide a basis on which grafts should be discarded.