Variceal pressure is a strong predictor of variceal haemorrhage in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension. (57/5450)

BACKGROUND: Variceal pressure is a strong predictor for a first variceal bleed in patients with cirrhosis. AIMS: To evaluate whether variceal pressure is also a determinant of the risk of a first variceal bleed in patients with non-cirrhotic portal hypertension. METHODS: Variceal pressure was measured non-invasively in 25 patients with non-cirrhotic portal hypertension and large varices while receiving a stable therapeutic regimen. Factors predictive of bleeding were compared with those observed in 87 cirrhotics. RESULTS: The one year incidence of variceal bleeding was 32% (n=28) for the cirrhotic and 20% (n=5) for the non-cirrhotic patients. There was no difference in factors predicting the risk of bleeding between the groups, except for variceal pressure. For the same level of variceal pressure, the risk of variceal bleeding was lower in patients with non-cirrhotic portal hypertension. Multiple logistic regression analysis revealed the following variables as having a significant predictive power: variceal pressure (p=0.0001), red spots (p=0.004), and the time interval between the first observation of the varices and the moment of variceal pressure measurement (p=0. 0046). For the non-cirrhotics the risk of bleeding increased with higher Child-Pugh score (p=0.0024); this was not the case for the cirrhotic patients (p=0.9521). CONCLUSION: Variceal pressure is a major predictor of variceal bleeding in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension. The risk of bleeding in non-cirrhotics is less than in cirrhotics for the same level of variceal pressure. In patients with non-cirrhotic portal hypertension the risk of variceal bleeding increases more with advancing disease.  (+info)

Should hepatomas be treated with hepatic resection or transplantation? (58/5450)

BACKGROUND: The aim of this collaborative study was to compare the long term results of hepatic resection (Hx) with those of orthotopic liver transplantation (OLTx) in large numbers of cirrhotic patients with hepatocellular carcinoma (HCC) and to delineate the roles of these two surgical treatments. METHODS: The databases of the National Cancer Center Hospital in Japan and the University of Pittsburgh Medical Center in the U. S. were exchanged and 294 cirrhotic patients who underwent curative Hx and 270 cirrhotic patients who underwent curative OLTx were selected for comparison. RESULTS: The mortality rate within 30 days and that within 150 days after Hx were significantly lower than those after OLTx (P = 0.001 and P = 0.00007, respectively). Overall survival was similar between the Hx group and the OLTx group (P = 0.40). When compared in the HCC patients without macroscopic vascular invasion and lymph node metastases, the overall survival rate after OLTx was significantly higher than that after Hx (P = 0.006). However, this difference was not significant between the patients with Child-Pugh Grade A tumors in the Hx group and all patients (majority with Child-Pugh Grade C tumors) in the OLTx group (P = 0.25). Tumor free survival after OLTx was significantly higher than that after Hx (P < 0.0001), particularly in HCCs measuring 5 cm and those with macroscopic vascular invasion, the tumor free survival rate was similar between the Hx group and the OLTx group. CONCLUSIONS: In the face of organ shortage, HCC developing in a well compensated cirrhotic liver initially may be treated with Hx. However, the authors believe OLTx should be applied selectively to those patients with tumor recurrence and/or progressive hepatic failure.  (+info)

The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells. (59/5450)

The expression of the asialoglycoprotein receptor (ASGP-R) on human hepatocellular carcinoma (HCC) cells might be exploited to reduce the extrahepatic toxicity of DNA synthesis inhibitors by their conjugation with galactosyl-terminating peptides. In the present study we first assessed the frequency of ASGP-R expression in 60 HCCs. Secondly, we investigated whether the receptor was maintained on the plasma membranes of DNA synthesizing cancer cells. Needle biopsies of HCC were evaluated. Diagnosis and grading of HCC were performed on routine haematoxylin and eosin-stained sections according to Edmondson and Steiner (1953). Thirty-five tumours were grade I and II and were classified as well differentiated, while 25 tumours were grade III and IV and were classified as poorly differentiated. Sections from formalin-fixed, paraffin-embedded samples were incubated, after antigen retrieval, with an anti-ASGP-R monoclonal antibody revealed by secondary biotinylated antibody and streptavidin-biotin-peroxidase-diaminobenzidine reaction. A clear immunolabelling of plasma membranes of HCC cells was observed in 28 out of 35 (80%) well differentiated (grade I and II) and in five out of 25 (20%) poorly differentiated (grade III and IV) HCCs. The presence of the ASGP-R on the surface of DNA synthesizing cancer cells was also investigated after in vitro bromodeoxyuridine (BrdU) labelling of HCC samples by immunohistochemical visualization of both the ASGP-R and incorporated BrdU on the same section. The results obtained clearly demonstrated that DNA synthesizing cancer cells expressed the ASGP-R on their surface. The presence of ASGP-R on cell plasma membrane in the majority of differentiated HCCs and its maintenance on proliferating cells encourages studies in order to restrict the action of the inhibitors of DNA synthesis of HCC cells by their conjugation with galactosyl-terminating carriers internalized through this receptor.  (+info)

Associations between cellular immune effector function, iron metabolism, and disease activity in patients with chronic hepatitis C virus infection. (60/5450)

We studied the associations of macrophage activity, T-helper cell types 1 and 2 (Th-1/Th-2) responses, and iron status in 55 patients with hepatitis C virus (HCV)-related liver disease and 28 control patients with noninfectious liver disease. Serum concentrations of soluble tumor necrosis factor receptor type II (sTNFrec 75), a macrophage activation marker, were higher in cirrhotic than in noncirrhotic patients (P<.001) regardless of their HCV status, whereas levels of neopterin, interleukin (IL)-4 and IL-10 did not differ significantly. In HCV-positive patients, sTNFrec 75 levels and transferrin saturation (TfS) correlated positively with levels of aspartate transaminase (P<.001 for sTNFrec 75 and P=.028 for TfS) and alanine transaminase (P=.003 for sTNFrec 75 and P=.039 for TfS). Increased TfS correlated significantly with both advanced liver disease and a predominant Th-2 pattern in HCV patients. Our data suggest that an association exists between macrophage activation and hepatic dysfunction, and that iron status may affect the clinical course of HCV infection by modulating Th-1/Th-2 responses in vivo.  (+info)

Renal distal tubular handling of sodium in central fluid volume homoeostasis in preascitic cirrhosis. (61/5450)

BACKGROUND/AIMS: Patients with preascitic liver cirrhosis have an increased central plasma volume, and, for any given plasma aldosterone concentration, they excrete less sodium than healthy controls. A detailed study of the distribution of sodium reabsorption along the segments of the renal tubule, especially the distal one, is still lacking in preascitic cirrhosis. METHODS: Twelve patients with Child-Pugh class A cirrhosis and nine control subjects (both groups on a normosodic diet) were submitted to the following investigations: (a) plasma levels of active renin and aldosterone; (b) four hour renal clearance of lithium (an index of fluid delivery to the loop of Henle), creatinine, sodium, and potassium; (c) dopaminergic activity, as measured by incremental aldosterone response to intravenous metoclopramide. RESULTS: Metoclopramide induced higher incremental aldosterone responses, indicating increased dopaminergic activity in patients than controls, which is evidence of an increased central plasma volume (+30 min: 160.2 (68.8) v 83.6 (35.2) pg/ml, p<0.01; +60 min: 140.5 (80.3) v 36. 8 (36.1) pg/ml, p<0.01). Patients had increased distal fractional sodium reabsorption compared with controls (26.9 (6.7)% v 12.5 (3. 4)% of the filtered sodium load, p<0.05). In the patient group there was an inverse correlation between: (a) absolute distal sodium reabsorption and active renin (r -0.59, p<0.05); (b) fractional distal sodium reabsorption and sodium excretion (r -0.66, p<0.03). CONCLUSIONS: These data suggest that in preascitic cirrhosis the distal fractional tubular reabsorption of sodium is increased and critical in regulating both central fluid volume and sodium excretion.  (+info)

Genomic heterogeneity in synchronous hepatocellular carcinomas. (62/5450)

BACKGROUND: Hepatocellular carcinoma (HCC) arising in cirrhosis is frequently multifocal. Whether HCC develops monoclonally or multiclonally is an unresolved question. Of the multiple tumour nodules present in many patients, it has not been established whether the smaller lesions represent intrahepatic metastases or de novo cancers. AIMS: To assess the degree of genomic heterogeneity in synchronous HCCs in cirrhosis. METHODS: The arbitrarily primed polymerase chain reaction technique was utilised to compare the DNA fingerprint of HCCs and regenerative nodules (RNs) removed from cirrhotic explant livers. RESULTS: Polymorphic genomic heterogeneity was noted in 54 HCCs and 31 RNs microdissected. Even satellite nodules in close proximity within the same segment of the liver were found to have distinct genomic patterns. CONCLUSION: Such genomic heterogeneity in synchronous HCCs may explain poor patient survival after surgical resection. If the smaller tumours are de novo lesions rather than metastases (as these data suggest), then current concepts regarding liver resection as a curative treatment modality for HCC may require reassessment.  (+info)

Clinical usefulness of scintigraphy with 99mTc-galactosyl-human serum albumin for prognosis of cirrhosis of the liver. (63/5450)

Scintigraphy with 99mTc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is useful for evaluating hepatic functional reserve. We assessed the clinical usefulness of this technique, including its value in establishing a prognosis, in patients with cirrhosis of the liver. METHODS: Scintigraphy with 99mTc-GSA was performed in 10 healthy subjects, 42 patients with chronic hepatitis and 158 patients with cirrhosis. Computer acquisition of gamma camera data were started just before the injection of 99mTc-GSA. Time-activity curves for the heart and liver were generated from regions of interest (ROIs) for the heart and the entire liver. A receptor index was calculated by dividing the radioactivity of the liver ROI by that of the liver-plus-heart ROI 15 min after the injection. An index of blood clearance was calculated by dividing the radioactivity of the heart ROI at 15 min by that of the heart ROI at 3 min. RESULTS: The median receptor index was lower in patients with cirrhosis than in patients with chronic hepatitis or in healthy subjects, and the median index of blood clearance was higher. The receptor index was significantly lower when a complication (varices, ascites) was present. The index of blood clearance was significantly higher when a complication (varices and ascites) was present. Correlation of the two indices with classic indicators for functional reserve was significant. On the basis of the receptor index, the patients with cirrhosis were divided into two groups of roughly equal size: group A, receptor index over 0.85, and group B, receptor index 0.85 or less. On the basis of the index of blood clearance, the patients with cirrhosis were divided into two groups of roughly equal size: group A, index of blood clearance < 0.70, and group B, index of blood clearance > or = 0.70. The cumulative survival rates were lower in group B than in group A. CONCLUSION: Scintigraphy with 99mTc-GSA is clinically useful, especially in establishing the prognosis of patients with cirrhosis of the liver.  (+info)

Cirrhosis mortality and per capita consumption of distilled spirits, United States, 1949-1994: trend analysis. (64/5450)

OBJECTIVE: To describe, evaluate, and suggest interpretations for an observed aggregate-level relation between trends in mortality from cirrhosis and per capita consumption of distilled spirits in the United States. DESIGN: Trend analysis using data on US cirrhosis mortality and per capita alcohol consumption. RESULTS: There is a consistent long-term trend relation between mortality from cirrhosis and per capita consumption of distilled spirits in the United States from 1949 to 1994. Two instances of comparatively sharp drops in the consumption of spirits in the 1940s generated mixed results in predicting changes in cirrhosis mortality. CONCLUSIONS: An aggregate-level relation between trends in long-term cirrhosis mortality and the consumption of spirits falls considerably short of establishing a direct causal link between the two for individuals. Moreover, two sharp drops in the consumption of spirits generated only mixed results with respect to the short-term trend in cirrhosis. Nevertheless, the observed relation between the consumption of spirits and cirrhosis mortality merits further investigation.  (+info)