Use of perihepatic packing in the management of intraoperative hemorrhage in liver transplantation.
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Biomedical subjects
Publications and source records attributed to M Navasa.
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BACKGROUND/AIMS: Hepatopulmonary syndrome is defined as a clinical triad including chronic liver disease, abnormal pulmonary gas exchange resulting ultimately in profound arterial hypoxaemia, and evidence of intrapulmonary vascular dilatations. We report five patients with liver cirrhosis diagnosed with hepatopulmonary syndrome who had associated chronic obstructive or restrictive respiratory diseases. METHODS: Clinical, radiographic and constrast-enhanced echocardiographic findings, and systemic and pulmonary haemodynamic and gas exchange, including ventilation-perfusion distributions, measurements were assessed in all five patients. RESULTS: Echocardiography was consistent with the presence of intrapulmonary vasodilation without intracardiac abnormalities, and high resolution computed tomographic scan features were compatible with clinical (3 cases) or histopathological diagnoses (2 cases) of associated respiratory disorders. The most common prominent functional findings were moderate to severe arterial hypoxaemia, caused by moderately to severely increased intrapulmonary shunting and/or mild to moderate low ventilation-perfusion areas, and hypocarbia along with an increased cardiac output and a low pulmonary artery pressure and vascular resistance. CONCLUSIONS: These functional characteristics, classically reported in the setting of clinically stable, uncomplicated hepatopulmonary syndrome, conform to a distinctively unique, chronic gas exchange pattern. Equally important, these pulmonary haemodynamic-gas exchange hallmarks are not influenced by the co-existence of chronic cardiorespiratory disease states. These data may have clinical relevance for elective indication of hepatic transplantation in patients with life-threatening hepatopulmonary syndrome.
BACKGROUND: There are numerous studies concerning the natural history and prognostic factors in cirrhosis, the results of which are useful in selecting liver transplant candidates. However, little attention has been paid to the prognostic significance of hepatic encephalopathy despite the high frequency of this complication. METHODS: We reviewed the charts of 111 cirrhotic patients who developed a first episode of acute hepatic encephalopathy to determine their survival probability and to identify prognostic factors. RESULTS: During follow-up (12+/-17 months), 82 (74%) patients died. The survival probability was 42% at 1 year of follow-up and 23% at 3 years. With univariate analyses followed by a multivariate analysis, 7 out of 30 clinical and standard laboratory variables were significantly associated with poor prognosis: male sex, increased serum bilirubin, alkaline phosphatase, potassium and blood urea nitrogen, and decreased serum albumin and prothrombin activity. Patients were classified into two groups according to a prognostic index calculated from these 7 variables. Survival probability at 1 and 3 years was 73% and 38%, respectively, in patients with a low prognostic index, and 10% and 3% in patients with a high prognostic index. CONCLUSION: Hepatic encephalopathy is associated with short survival in cirrhotic patients. Although these patients can be classified into several groups with a different prognosis, the survival probability in every group is lower than that currently expected after liver transplantation. Therefore, cirrhotic patients developing a first episode of acute hepatic encephalopathy should be considered as potential candidates for this therapeutic procedure.
Major neuroendocrine tumors contain many somatostatin receptors. This feature allows for the localization of primary tumors and tumor metastases by scintigraphy with the radiolabeled somatostatin analog octreotide. We describe a patient with nonspecific clinical data and ultrasonography and CT that showed an isolated focal lesion in the liver. In-111 octreotide scintigraphy was essential in establishing the diagnosis of liver metastasis from a neuroendocrine tumor confirmed by pathologic findings. Because clinical symptoms recurred, ultrasonography and CT were performed a few months after surgery. Both were negative. However, In-111 octreotide scintigraphy suggested multiple bone metastases and established the diagnosis of bone metastases from a neuroendocrine tumor, which was confirmed by Tc-99m MDP bone scans and MRI.
The incidence of bacterial infections in cirrhotic patients admitted to hospital is very high. In several studies, 30% to 50% of cirrhotics presented bacterial infections at admission, or developed this type of complication during hospitalization. Most bacterial infections in cirrhotic patients are hospital-acquired. Between 15% to 35% of cirrhotics admitted to hospital develop nosocomial infections; these figures contrast sharply with the hospital-acquired infection rate in the general hospital population (5% to 7%). Urinary tract infections (12% to 29%), spontaneous bacterial peritonitis (7% to 23%), respiratory tract infections (6% to 10%) and bacteraemia (4% to 9%) are the most frequent bacterial infectious complications seen in cirrhotic patients. However, since spontaneous bacterial peritonitis is the most characteristic bacterial infection in cirrhosis, this report will focus (mainly) on this infectious complication.
Spontaneous bacterial peritonitis (SBP) is associated with an important production of inflammatory mediators. However, it is unknown whether there is a relationship between the abdominal production of these mediators and the development of renal impairment, one of the most important prognostic parameters in spontaneous bacterial peritonitis. We studied 52 cirrhotic patients at diagnosis and resolution of the infection, by measuring endotoxin, tumor necrosis factor (TNF), and interleukin-6 (IL-6) levels in plasma and ascitic fluid. Thirteen patients (25%) developed renal impairment. Patients developing renal impairment showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection than patients who did not (plasma TNF-alpha: 96.0+/-38.7 vs. 39.1+/-3.6 pg/mL, P=.0209; ascitic fluid TNF-alpha: 474.5+/-118.1 vs. 160.8+/-42.7 pg/mL, P=.0173; plasma IL-6: 6,635+/-2,897 vs. 458+/-109 pg/mL, P=.0004; ascitic fluid IL-6: 182,559+/-47,328 vs. 39,250+/-10,803 pg/mL, P=.0001). Independent predictors of development of renal impairment at diagnosis were: renal failure (blood urea nitrogen > 30 mg/dL or serum creatinine > 1.5 mg/dL) (P < .001), IL-6 levels in ascitic fluid (P < .001), and mean arterial pressure (P < .05). Ten of the 13 (77%) patients who developed renal impairment died during hospitalization, but only 2 of the 39 (5%) patients who did not (P=.0001). In addition, renal failure at diagnosis of the infection was the only independent predictor of hospital mortality (P < .001). In conclusion, the inflammatory response to the infection may be an important mechanism of renal impairment and the associated mortality in SBP.
Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.
BACKGROUND/AIM: The type of disease indicating liver transplantation is one of the most powerful predictors of postoperative survival. This may be an important problem in evaluating the prognostic significance of other factors when patients with liver diseases of very different nature are jointly studied. To minimize this bias, the present study aimed to investigate preoperative prognostic factors in liver transplantation only in patients with non-biliary cirrhosis. METHODS: Twenty-three preoperative standard clinical and laboratory variables were analyzed as possible prognostic factors in 162 patients receiving liver transplantation for non-biliary cirrhosis. Data for seven splanchnic and systemic hemodynamic variables were also analyzed in 55 patients. RESULTS: Using univariate analyses followed by a multivariate analysis, only preoperative blood urea nitrogen (BUN) reached statistical significance as an independent predictor of hospital survival; the survival rate at the end of hospitalization being 90% in patients with BUN< or =25 mg/dl and 65% in patients with BUN>25 mg/dl (p=0.0008). Similarly, preoperative BUN was the only variable independently predicting cumulative long-term survival, with an 87% survival probability at 1 year and 73% at 4 years in patients with BUN< or =25 mg/dl, and 61% and 49%, respectively, in patients with BUN>25 mg/dl (p=0.0014). CONCLUSIONS: Renal function parameters are the most powerful preoperative predictors of survival after liver transplantation in patients with non-biliary cirrhosis. It is suggested that liver transplantation is indicated in these patients before marked renal dysfunction develops.
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We studied the effect of endotoxin (LPS), and cytokines (TNF, IL-1, and IL-6) on hepatic microsomal triglyceride transfer protein (MTP) mRNA levels in vivo in Syrian hamsters and in vitro in HepG2 cells. LPS, interleukin-1 (IL-1), and to a lesser extent tumor necrosis factor (TNF) significantly decreased MTP mRNA levels in hamster liver. These effects required several hours. Furthermore, IL-1 and IL-6 significantly decreased MTP mRNA levels in HepG2 cells. This decrease appeared soon after IL-1 administration (8 h) and at very low doses (0.1 ng/ml). MTP activity and protein levels of the large subunit of MTP also decreased modestly in HepG2 cells with prolonged cytokine treatment. IL-1 reduced the expression of an MTP promoter luciferase construct to a similar degree as seen with MTP mRNA, indicating that transcriptional regulation plays a major role in the decrease of MTP gene expression. Deletional analysis of the MTP promoter identified the region -121 to -88 bp upstream to the coding sequence as the site of the negative regulation by IL-1. This region contains an insulin response element (IRE), activating protein 1 (AP-1), hepatic nuclear factor 1 (HNF-1) and hepatic nuclear factor 4 (HNF-4) consensus sequences; mutations of the IRE and HNF-4 sites did not affect the response to IL-1. In contrast, mutating AP-1 or HNF-1 sites led to a marked decrease in basal expression and the loss of the IL-1 effect, suggesting that an intact AP-1 and/or HNF-1 regulatory element are crucial for the IL-1 regulation of MTP gene expression. However, prolonged incubation with IL-1 did not alter HepG2 apolipoprotein B secretion suggesting that MTP mRNA down-regulation does not contribute significantly to the cytokine-induced effects on lipid metabolism.
Caroli's disease is an uncommon congenital disorder of the intrahepatic biliary tree. It is characterized by multiple and segmental dilatations of the bile ducts. The clinical course of Caroli's disease is often complicated by recurrent episodes of bacterial cholangitis that seriously impair the patient's quality of life. Despite wide spectrum antimicrobial agents, medical treatment of cholangitis is frequently unsuccessful in patients with Caroli's disease due to the persistence of bacteria in dilatated bile ducts. Other therapies, including internal or external biliary drainages and various surgical or endoscopic procedures, have been used in the treatment of Caroli's disease, with poor results. There are no previous reports in the literature of liver transplantation for recurrent cholangitis in patients with Caroli's disease. We present two such cases, in which cholangitis is resolved.
The results of orthotopic liver transplantation (OLT) in patients with alcoholic liver cirrhosis (ALC) are currently similar to those obtained in patients with other indications. However, the frequent association of ALC with hepatitis C virus (HCV) infection may impair these results. We retrospectively studied the consequences of HCV infection on survival and graft function in 59 patients with ALC undergoing OLT. Patients were classified into two groups depending on their HCV serology before transplantation: group 1 comprised 24 anti-HCV-positive patients, and group 2, 35 anti-HCV-negative patients. Patient and graft survival were similar in both groups. Liver function tests 1 and 4 years after OLT showed AST and ALT values that were significantly higher in group 1 patients and post-transplant histologically proven chronic hepatitis was found in 45% and 61% of these patients at 1 and 4 years, respectively. We conclude that pretransplant HCV infection in patients with ALC does not affect survival after OLT. However, one must bear in mind the high incidence of post-transplant chronic hepatitis secondary to recurrence of HCV infection and be cautious when drawing this conclusion.
The purpose of this study was to determine the prevalence of osteoporosis, to estimate the bone turnover and hormonal status, and to identify the factors associated with bone disease in patients with end-stage liver disease who were referred for orthotopic liver transplantation. A prospective study was performed on 58 cirrhotic patients (6 with primary biliary cirrhosis, 14 with alcoholic cirrhosis, and 38 with posthepatitic cirrhosis), who were referred for orthotopic liver transplantation. Patients, excluding those with primary biliary cirrhosis, were classified in Child-Pugh groups according to the severity of liver disease (class B [28 patients], class C [24 patients]). Biochemical parameters of bone mineral metabolism and standard liver function tests were measured in all patients. Additionally, serum osteocalcin, urinary hydroxyproline/creatinine ratio, serum intact parathyroid hormone, serum 25-hydroxyvitamin D, serum 1,25-dihydroxyvitamin D, follicle-stimulating hormone, and luteinizing hormone levels were determined in patients and controls within the same age range. Plasma testosterone, sex hormone-binding globulin levels, and free testosterone index were obtained for all men included in the study. Bone mass of the lumbar spine and femur were measured by dual X-ray absorptiometry (DPX-L), and were expressed as a standard deviation of mean values (Z-score) from a sex and age-matched control group. Spinal X-rays were obtained to assess vertebral fractures. Osteoporosis was considered as a factor in spinal bone mineral density with a Z-score below 2 or at least one vertebral fracture. Twenty-five patients (43%) had osteoporosis, with lower bone mass measurements in the lumbar spine than in the femoral neck (P < 0.005). Alcoholic and Child-Pugh C patients showed the lowest femoral bone mineral density values. Cirrhotic patients showed lower osteocalcin levels than controls (14.3 +/- 5.9 vs. 18.2 +/- 8.1 ng/ml; P < 0.05) and showed increased urinary hydroxyproline (125.1 +/- 51.5 vs. 107.9 +/- 26.6 nM/mg creatinine; P < 0.05). Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone levels were significantly lower in cirrhotic patients than in controls (10.3 +/- 9.1 vs. 23.1 +/- 26.6 ng/ml; P = 0.000), (12.9 +/- 9.1 vs. 48.3 +/- 11.5 pg/ml; P = 0.000), (16.6 +/- 9.2 vs. 27.9 +/- 8.2 pg/ml; P = 0.000), with no differences between Child-Pugh groups. Alcoholic Child-Pugh C patients showed the lowest 25-hydroxyvitamin D serum values (4.5 +/- 2.2 ng/ml; P < 0.05). Male patients had lower testosterone levels than controls (302.5 +/- 229.4 vs. 556.7 +/- 146.5 ng/dl; P = 0.000), with increased sex hormone-binding globulin values. Levels of testosterone and gonadotropin were related to Child-Pugh classification. No correlation was found between bone mass and hormonal values. A significant decrease in bone mass, particularly in the lumbar spine, is seen in end-stage cirrhotic patients. Reduced bone formation and significant disorders of bone mineral metabolism, such as vitamin D deficiency, reduced parathyroid hormone levels, and hypogonadism are involved. Moreover, severity and etiology of the liver disease are the main risk factors for developing bone loss and mineral metabolism disorders in patients referred for orthotopic liver transplantation.
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BACKGROUND/AIMS: Selective intestinal decontamination with norfloxacin is widely used to prevent spontaneous bacterial infections in cirrhosis. The study was performed to compare the spontaneous bacterial peritonitis occurring in patients with and without prophylactic norfloxacin. METHODS: Two hundred and twenty-nine consecutive episodes of spontaneous bacterial peritonitis, (193 in patients without (Group A) and 36 in patients with norfloxacin prophylaxis (Group B)), were retrospectively analyzed. In 100 episodes (86 and 14, respectively), the responsible organism was isolated in ascitic fluid. RESULTS: Clinical and laboratory data at diagnosis were comparable in both groups. There were marked differences (p < 0.001) between group A and B in the frequency of peritonitis caused by gram-negative (67.4% vs. 14.3%) and gram-positive (30.2% vs. 78.6%) bacteria. There were three polymicrobial episodes. Bacteria resistant to cefotaxime and gram-negative bacilli resistant to quinolones were isolated in ascitic fluid in nine (seven in Group A and two in Group B) and three episodes (all in Group A), respectively. No differences in the course of infection and patient survival were observed between groups. CONCLUSIONS: Spontaneous bacterial peritonitis in patients with and without prophylaxis with norfloxacin are not different in clinical features, response to treatment and prognosis. Spontaneous bacterial peritonitis caused by gram-negative organisms resistant to quinolones is extremely uncommon in patients with cirrhosis receiving prophylactic norfloxacin.
Most bacterial infections in cirrhotic patients are hospital-acquired. Urinary tract infections, spontaneous bacterial peritonitis (SBP), respiratory tract infections, and bacteremia are the most frequent bacterial infectious complications seen in cirrhotic patients. SBP is the most characteristic infectious complication of cirrhotic patients, and it is defined as the infection of a previously sterile ascitic fluid, with no apparent intra-abdominal source of infection. The incidence of SBP in cirrhotic patients admitted to hospital with ascites has been estimated to range between 7 and 23%. The diagnosis is established on the basis of clinical signs and symptoms and/or a polymorphonuclear cell count in ascitic fluid higher than 250/mm3. This diagnosis is confirmed by a positive culture in approximately 70% of the cases. The remaining 30% are considered culture-negative SBP but are empirically treated with antibiotics because severe peritonitis and death may follow if these patients are not treated. Early diagnosis, the routine use of diagnostic paracentesis in patients admitted to hospital with ascites, and, especially, the use of adequate antibiotics are very important tools in the treatment of SBP. Third-generation cephalosporins are the first-choice antibiotic treatment in SBP, although selected patients with SBP, those with normal renal function and without hepatic encephalopathy, shock, or gastrointestinal bleeding, may be treated with oral quinolones. Selective intestinal decontamination with norfloxacin is safe and useful in the primary and secondary prophylaxis of SBP, although the incidence of quinolone-resistant organisms is increasing and this may be a problem in the future.
The reintroduction of paracentesis has modified the way in which patients with ascites are treated. Transjugular intrahepatic portosystemic shunt can be an alternative treatment for patients with refractory ascites and for those patients with hepatorenal syndrome, although more studies are needed to clarify its usefulness and safety. The use of more potent and less nephrotoxic antibiotics together with an earlier diagnosis have improved the outcome of patients with spontaneous bacterial peritonitis (SBP). Oral antibiotics can be used in patients with SBP and good clinical conditions with an efficacy similar to that obtained with intravenous antibiotics. Prophylactic antibiotics in SBP should be restricted to cirrhotic patients at high risk, including bleeding cirrhotic patients, those with a past history of SBP, and those with low protein content in ascitic fluid. This chapter describes the management of ascites in patients with portal hypertension.