Stellate cells have only recently received attention in patients with primary biliary cirrhosis (PBC). We have used electron microscopy and morphometry to perform a qualitative and quantitative ...examination of lipid‐storing activity of stellate cells in liver biopsies of 26 patients with noncirrhotic and cirrhotic PBC. In parallel with this study, a comparative analysis of the morphology of stellate cells in 51 patients with livers of normal histology was performed. There was a marked increased in the total number of lipid vesicles in stellate cells in all PBC patients when compared with livers with normal histology. Multiple multivesicular stellate cells were seen in the livers of 21 of 26 patients with PBC. There were 11 to 28 lipid vesicles per multivesicular stellate cell in sizes of 1 µm to 5 µm in diameter per lipid vesicle. Hepatocytes showed little or no steatosis in 24 of 26 (92%) PBC patients. Multivesicular stellate cells were not seen in female patients with normal liver histology. These results suggest that there is an alteration in hepatic lipid storage that involves stellate cells in PBC that could be an early manifestation of this disease. Its significance remains to be elucidated.
: Background: The upper normal limit (ULN) of serum alanine‐aminotrasferase (ALT) normal range was recently challenged, because patients diagnosed with liver diseases may have ‘normal’ or ...near‐‘normal’ ALT levels, and because possible modulators are often ignored in determining normal range.
Aim: To estimate the ULN for serum ALT and to identify factors modulating it.
Subjects and methods: We reviewed medical records of subjects aged 15–90, who underwent standard panels of laboratory tests, including serum ALT, over 6 months at a central laboratory. Three groups were defined: Group 1, comprised total study population (N=272 273). Group 2 (N=87 020) comprised total study population, excluding those receiving potentially hepatotoxic drugs, or diagnosed with liver disease, or had any abnormal laboratory test results other than for triglycerides, cholesterol, glucose, or HbA1c. Group 3 (N=17 496) the ‘healthy’ population, from whose ALT values we established the new ULN, comprised Group 2 subjects with normal triglycerides, cholesterol, glucose, and HbA1c levels.
Results: The 95th percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1, 40, and 37.5 U/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/l), had ALT level above our new ULN. Linear and logistic‐regression analyses showed that ALT levels were significantly modified by gender, age, glucose, cholesterol, triglycerides, and overweight/obesity diagnosis. Significant interaction was found between gender, glucose and cholesterol levels.
Conclusions: In this first large‐scale study of ‘healthy’ population, serum ALT ULN was far lower than currently accepted value. Age and gender may be considered when determining the ULN for ALT.
Liver biopsy specimens (178 percutaneous and 39 transjugular) were assessed from 217 consecutive patients with alcoholic liver disease, 77 noncirrhotics and 140 cirrhotics, whose cases were followed ...for 5 yr. Cirrhotic patients were categorized into two groups, with and without "hepatitis" using a criteria to define "hepatitis" that included only degrees of inflammation, necrosis, and Mallory bodies that had a prognostic weight in terms of mortality in 1 yr. This classification resulted in a sharp separation between a group of 42 patients with cirrhosis without "hepatitis" and with low mortality, both at 1 yr (7.1% +/- 4.0%) and at 5 yr (31% +/- 7%), and another group of 98 patients with cirrhosis and "hepatitis" and a high mortality both at 1 yr (26.5% +/- 4.5%, p less than 0.01), and at 5 yr (47% +/- 5%, p less than 0.02). Importantly, the 1-yr mortality in patients with cirrhosis and no "hepatitis" was not statistically different from that of patients with no cirrhosis or "hepatitis" (most of whom had only fatty liver) both at 1 yr (6.9% +/- 3.3%) and at 5 yr (24% +/- 6%). There were marked differences in several variables between cirrhosis with and without "hepatitis" combined clinical and laboratory index: no "hepatitis": 4.9 +/- 0.7, with "hepatitis": 7.8 +/- 0.5, p less than 0.01; score of collagen in space of Disse: no "hepatitis": 2.1 +/- 0.4, with "hepatitis": 3.7 +/- 0.3, p less than 0.01; hepatocyte cross-sectional surface area: no "hepatitis": 682 +/- 51 micron 2, with "hepatitis": 841 +/- 31 micron 2, p less than 0.01. These findings were more severe in the transjugular group than in the percutaneous group. Collagen in the space of Disse and hepatocyte surface area were not statistically different when cirrhosis without "hepatitis" was compared with a similar no "hepatitis" group of patients having noncirrhotic alcoholic liver disease. In this patient sample the presence of parenchymal nodules and fibrous septa, per se, did not result in an increase in mortality with respect to alcoholic patients without cirrhosis and with no "hepatitis."
Cellular mechanisms for Na(+) retention in portal hypertension are undefined, but epithelial Na(+) channels (ENaC) may be involved. Under high-salt diet, ENaC are absent from distal colon of rat but ...can be induced by mineralocorticoids such as aldosterone. Presence of rat ENaC was determined by amiloride inhibition of (22)Na(+) uptake in surface colonocytes 7 and 14 days after partial portal vein ligation (PVL) or sham surgery. At both times, uptake inhibition was significantly increased in PVL rats. Presence of mRNA transcripts, determined by RT-PCR, demonstrated that channel alpha- and gamma-subunits were similarly expressed in both groups but that beta-subunit mRNA was increased in PVL rats. This confirms that there was induction of rat ENaC and indicates that beta-subunit has a regulatory role. Urinary Na(+) was decreased for 3 days after PVL but was not different at other times, and serum aldosterone levels were elevated at 7 days, at a time when urinary Na(+) output was similar to that of sham-operated rats. We conclude that PVL leads to induction of ENaC in rat distal colon. An increase in aldosterone levels may prevent natiuresis and is probably one of several control mechanisms involved in Na(+) retention in portal hypertension.
Background Systemic hypotension may result in postoperative renal failure in jaundiced patients. Attenuated responsiveness to eatecholamines and hypovolaemia has been reported in jaundiced animals ...and may be a mechanism contributing to the increased susceptibility of jaundiced patients to haemorrhagic shock. This suggests that an alternative to vasoactive amines to control perioperative hypotension could be desirable.
Methods This study evaluated the pressor response to vasopressin in normovolaemic 3‐day bile duct‐ligated rats and in 3‐day bile duct‐ligated rats after an acute controlled haemorrhage. It also evaluated the response after volume loading with 0.9 per cent saline, 7.5 per cent saline, colloid and mannitol before controlled haemorrhage. In addition, blood volume was measured using radiolabelled albumin. All the data obtained from bile duct‐ligated rats were compared with data from sham‐operatcd animals.
Results Attenuated pressor responses to vasopressin were not observed in either normotensive bile duct‐ligated rats or in bile duct‐ligated rats subjected to controlled haemorrhage. Volume loading with the four fluids over the dosing range 25–73 μl per g body‐weight in bile duct‐ligated rats reversed the susceptibility to haemorrhagic hypotension.
Conclusion Although no reduction in blood volume was demonstrated, bile duct‐ligated rats may have a reduced effective blood volume manifesting itself as a latent hypovolaemia and/or tendency to hypotension. Preoperative fluid loading could be beneficial because it corrects hypovolaemia and improves cardiovascular function, as well as improving the cardiovascular response to haemorrhage.
Objective: (i) to characterize the profile of tumor necrosis factor alpha (TNF α), interleukin-6 (IL-6), IL 10, Fas-ligand and transforming growth factor beta (TGF β), chronic hepatitis C (HCV) ...patients with genotype 1; (ii) to determine the influence of triple therapy (TT) with interferon α (IFN α) + ribavirin + ursodeoxycholic acid on these cytokines and (iii) to establish the relationship between the pro-inflammatory cytokines and the outcome of treatment.
Design and Methods: 22 patients infected with HCV - genotype 1 a/b and non responsive to IFN-α monotherapy were enrolled in the TT. The controls were 49 HCV naı̈ve patients with genotype 1 a/b. Cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA).
Results: The baseline TNF α values (pg/mL) in the sustained responders (SRs) (63±3) were significantly lower than non-responders (NRs) (140±16) (
p < 0.001). Baseline Fas (ng/mL) levels were also lower in SRs (4.3±0.2) than NRs (5.4±0.4) (
p < 0.05).
Conclusions: Fas and TNF α may be used as serological markers of inflammation and effectiveness of therapy.
Stellate cells have only recently received attention in patients with primary biliary cirrhosis (PBC). We used electron microscopy and morphometry to perform a qualitative and quantitative ...examination of lipid‐storing activity of stellate cells in liver biopsies of 26 patients with noncirrhotic and cirrhotic PBC. Parallel with this study, a comparative analysis of the morphology of stellate cells in 51 patients with livers of normal histology was performed. There was a marked increase in the total number of lipid vesicles in stellate cells in all PBC patients when compared to livers with normal histology. Multiple multivesicular stellate cells were seen in the livers of 21 out of 26 patients with PBC. There were 11 to 28 lipid vesicles per multivesicular stellate cell from 1 μmol/L to 5 μmol/L in diameter per lipid vesicle. Hepatocytes showed little or no steatosis in 24 out of 26 (92%) PBC patients. Multivesicular stellate cells were not seen in female patients with normal liver histology. These results suggest that there is an alteration in hepatic lipid‐storage that involves stellate cells in PBC, which could be an early manifestation of this disease. Its significance remains to be determined.
Background Appropriate use of orthotopic liver transplantation (OLT) requires continued assessment of the indications for transplantation as a number of diseases are associated with a poor prognosis. ...High‐risk patients are those who have a poor survival or high incidence of recurrent disease (patients with tumours, hepatitis B‐ or hepatitis C‐induced cirrhosis, fulminant hepatic failure or primary graft non‐function). In addition, retransplantation may be associated with a poor outcome.
Methods A retrospective review was made of the records of all adult patients undergoing OLT at this hospital between October 1985 and July 1994.
Results A total of 396 liver transplants were performed in 364 patients. The 1– and 3–year actuarial survival rates were 82 and 69 per cent respectively. The overall survival rate of high‐risk patients was significantly lower than that for all OLT recipients (P < 0.05). While no patients transplanted for hepatitis C have developed graft failure, recurrent hepatitis occurred in 15 of 35 patients.
Conclusion Strict selection criteria and appropriate perioperative investigations and interventions are required to improve the results of OLT in these high‐risk patients.
PDF
