Oval cells in hepatitis B virus-positive and hepatitis C virus-positive liver cirrhosis: histological and ultrastructural study

AIMS: It is still not clear whether oval cells demonstrate diverse morphology, immunophenotype or quantity in different human liver diseases. The aim of this study was to investigate these differences in hepatitis B virus (HBV)-positive and hepatitis C virus (HCV)-positive human liver cirrhosis (HLC). METHODS AND RESULTS: Thirty-eight cases of HBV+ HLC and 32 cases of HCV+ HLC were investigated by light microscopy and immunohistochemistry for Hepatocyte, CK19, stem cell factor (SCF) and CD34. Five cases were also examined by transmission electron microscopy. Oval cells of similar morphology could be found in proliferating bile ductules in both groups. These cells coexpressed CK19 and Hepatocyte, but did not express SCF or CD34. Some of these cells exhibited a trend towards differentiation. There was no difference in the amount of oval cells between the two groups. The oval cell number was found to increase significantly with the progression of inflammation. A similar stem-like cell was not seen in the normal liver. CONCLUSIONS: There are bipotential oval cells in both HBV+ and HCV+ HLC. The lack of difference in oval cells between the two groups suggests that they might play a similar biological role in the histogenesis of different liver diseases.     

Safety of donor in adult-to-adult living donor liver transplantation using right lobe graft

BACKGROUND: The growing gap between the number of patients awaiting liver transplantation and available organs has continued to be the primary issue facing the transplant community. To overcome the waiting list mortality, living donor liver transplantation has become an option, in which the greatest concern is the safety of the donor, especially in adult-to-adult living donor liver transplantation (A-A LDLT) using a right lobe liver graft. OBJECTIVE: We evaluated the safety of donors after right lobe liver donation for A-A LDLT performed in our center. METHODS: From January 2002 to March 2006, 26 patients underwent A-A LDLT using right lobe liver grafts in our center. Seven donors were men and 19 were women (range, 19-65 years; median age, 38 years). The right lobe liver grafts were obtained by transecting the liver on the right side of the middle hepatic vein without interrupting the vascular blood flow. The mean follow-up time for these donors was 9 months. RESULTS: These donor residual liver volumes ranged from 30.5% to 60.3%. We did not experience any donor mortality. Two cases (7.69%) experienced major complications: intra-abdominal bleeding and portal vein thrombosis in one each and three (11.54%), minor ones: wound steatosis in two, and transient chyle leak in one. All donors were fully recovered and returned to their previous occupations. CONCLUSIONS: A-A LDLT using a right lobe liver graft has become a standard option. The donation of right lobe liver for A-A LDLT was a relatively safe procedure in our center.     

Microalbuminuria and urinary albumin excretion: French clinical practice guidelines

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.     

Peroxisome proliferator-activated receptor alpha reduces cholesterol esterification in macrophages

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor activated by fatty acid derivatives and hypolipidemic drugs of the fibrate class. PPARalpha is expressed in monocytes, macrophages, and foam cells, suggesting a role for this receptor in macrophage lipid homeostasis with consequences for atherosclerosis development. Recently, it was shown that PPARalpha activation promotes cholesterol efflux from macrophages via induction of the ABCA1 pathway. In the present study, the influence of PPARalpha activators on intracellular cholesterol homeostasis was investigated. In human macrophages and foam cells, treatment with fibrates, synthetic PPARalpha activators, led to a decrease in the cholesteryl ester (CE):free cholesterol (FC) ratio. In these cells, PPARalpha activation reduced cholesterol esterification rates and Acyl-CoA:cholesterol acyltransferase-1 (ACAT1) activity. However, PPARalpha activation did not alter ACAT1 gene expression, whereas mRNA levels of carnitine palmitoyltransferase type 1 (CPT-1), a key enzyme in mitochondrial fatty acid catabolism, were induced. Finally, PPARalpha activation blocked CE formation induced by TNF-alpha, possibly due to the inhibition of neutral sphingomyelinase activation by TNF-alpha. In conclusion, our results identify a role for PPARalpha in the control of cholesterol esterification in macrophages, resulting in an enhanced availability of FC for efflux through the ABCA1 pathway.     

Factors associated with hospital mortality in community-acquired legionellosis in France

The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age <60 yrs (p = 0.02), general symptoms (p = 0.006), intensive care unit (ICU) stay (p<0.001), and class II-III Pneumonia Severity Index score (p = 0.004). Six predictors of death were identified by multivariate analysis: age (per 10-yr increment) (relative hazard (RH) 1.50, 95% CI 1.21-1.87), female sex (RH 2.00, 95% CI 1.08-3.69), ICU admission (RH 3.31, 95% CI 1.67-6.56), renal failure (RH 2.73, 95% CI 1.42-5.27), corticosteroid therapy (RH 2.54, 95% CI 1.04-6.20) and C-reactive protein (CRP) >500 mg · L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.     

Accidents vasculaires cérébraux ischémiques transitoires récurrents chez une jeune patiente secondaire à un fibroélastome papillaire de la valve mitrale et une hyperhomocystéïnémie. À propos d’une observation

We describe a case of a young patient admitted for recurrent ischemic stroke caused by a papillary fibroelastoma of the mitral valve and a hyperhomocysteinemia. A papillary fibroelastoma is a benign cardiac tumor which can be associated with serious embolic complications. A moderate plasma level of hyperhomocysteinemia is considered as a risk factor of ischemic stroke. The authors suggest that this association increases the risk of ischemic stroke in their patient. The tumor was surgically removed to avoid new embolic events associated with a vitamin B supplementation. After surgery and acid folic supplementation, no recurrence was observed.     

Possible small-bowel neoplasms: contrast-enhanced and water-enhanced multidetector CT enteroclysis

PURPOSE: To prospectively evaluate the sensitivity and specificity of contrast material-enhanced and water-enhanced multidetector computed tomographic (CT) enteroclysis in depicting small-bowel neoplasms in symptomatic patients, with endoscopic, tissue, and follow-up findings as reference standards. MATERIALS AND METHODS: The study protocol was approved by the Human Research Committee of the institution, and all patients gave written informed consent. Two hundred nineteen patients (108 male, 111 female; age range, 17-98 years; mean, 53.1 years) with clinical suspicion of small-bowel neoplasm underwent contrast- and water-enhanced multidetector CT enteroclysis after normal findings of upper and lower gastrointestinal endoscopy. The prospective interpretations of CT enteroclysis results include evaluation of focal bowel wall thickening, small-bowel masses, small-bowel stenosis, mesenteric stranding, enlarged mesenteric lymph nodes, and visceral metastasis. Positive enteroclysis findings were compared with results of pathologic examination after surgical (n = 35) or endoscopic (n = 20) procedures. Negative results were compared with results of surgery (n = 8), enteroscopy (n = 15), capsule endoscopy (n = 14), and clinical follow-up (n = 127). Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated on a per-patient basis with 95% confidence intervals. RESULTS: Findings of CT enteroclysis were positive in 55 cases and negative in 164. The overall sensitivity and specificity in identifying patients with small-bowel lesions were 84.7% and 96.9%, respectively. The negative and positive predictive values were 94.5% and 90.9%, respectively. Findings of pathologic examination confirmed small-bowel tumor in 50 patients with carcinoid tumor (n = 19), adenocarcinoma (n = 7), lymphoma (n = 5), jejunal adenoma (n = 9), stromal tumor (n = 5), ectopic pancreas (n = 2), angiomatous mass (n = 2), or metastasis (n = 1). Five examinations resulted in false-positive findings. CONCLUSION: Contrast- and water-enhanced multidetector CT enteroclysis had an overall accuracy of 84.7% for depiction of small-bowel neoplasms.     

HCV genotype 3 is associated with a higher hepatocellular carcinoma incidence in patients with ongoing viral C cirrhosis

Liver steatosis is a main histopathological feature of Hepatitis C (HCV) infection because of genotype 3. Steatosis and/or mechanisms underlying steatogenesis can contribute to hepatocarcinogenesis. The aim of this retrospective study was to assess the impact of infection with HCV genotype 3 on hepatocellular carcinoma (HCC) occurrence in patients with ongoing HCV cirrhosis. Three hundred and fifty-three consecutive patients (193 men, mean age 58 ± 13 years), with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC between 1994 and 2007. Log-rank test and Cox model were used to compare the actuarial incidence of HCC between genotype subgroups. The patients infected with a genotype 3 (n = 25) as compared with those infected with other genotypes (n = 328) had a lower prothrombin activity [78 (interquartile range 60-85) vs 84 (71-195) %, P = 0.03] and higher rate of alcohol abuse (48%vs 29%, P = 0.046). During a median follow-up of 5.54 years [2.9-8.6], 11/25 patients (44%) and 87/328 patients (26%) with a genotype 3 and non-3 genotype, respectively, develop a HCC. HCC incidences were significantly different among the genotype subgroups (P = 0.001). The 5-year occurrence rate of HCC was 34% (95% CI, 1.3-6.3) and 17% (95% CI, 5.7-9.2) in genotype 3 and non-3 genotype groups, respectively (P = 0.002). In multivariate analysis, infection with a genotype 3 was independently associated with an increased risk of HCC occurrence [hazard ratio 3.54 (95% CI, 1.84-6.81), P = 0.0002], even after adjustment for prothrombin activity and alcohol abuse [3.58 (1.80-7.13); P = 0.003]. For patients with HCV cirrhosis and ongoing infection, infection with genotype 3 is independently associated with an increased risk of HCC development.     

Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: A short-term, randomized, double-blind controlled, cross-over study with long-term follow up

Abstract In order to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with primary biliary cirrhosis, a short-term, randomized, double-blind controlled, cross-over study was done with long-term follow up. In the first part of the study, 12 patients were randomly chosen to receive either UDCA 600 mg/day for 3 months followed by a placebo for 3 months or a placebo for 3 months followed by UDCA for 3 months. The clinical symptoms of pruritus improved when the patients were receiving UDCA but became worse when receiving a placebo. Mean serum levels of alkaline phosphatase (ALPase), γ-glutamyl transferase (γ-GT), total bilirubin, cholesterol, alanine aminotransferase (ALT) and aspartate aminotransferase all decreased below the baseline values when receiving UDCA treatment and all increased above the baseline values when receiving the placebo. The difference was statistically significant. In the second part of the study, 19 patients received long-term UDCA treatment (mean 20 months). The clinical symptoms of pruritus improved in 90% of the pruritic patients. Serum levels of ALPase, γ-GT and ALT fell significantly from the pretreatment values 6, 12 and from the mean 20 months after UDCA treatment. Serum levels of total bilirubin fell significantly 6 and 12 months after UDCA treatment but did not reach statistical significance at the last follow up. No patient lost antimitochondrial antibody and elevated immunoglobulin levels did not improve significantly, but the Mayo clinical risk score improved significantly after long-term UDCA treatment. Treatment failure was noted in three patients: two patients in the histologic stage IV with clinical overt jaundice died of complications 4 and 5 months after UDCA treatment, respectively; another patient underwent a liver transplantation 1 year after the UDCA treatment due to progressive jaundice. No severe adverse reaction was noted during UDCA treatment, only one patient suffered from a mild allergic reaction. In conclusion, UDCA is safe and effective in the treatment of Chinese PBC patients in stages I—III.