Influence of insulin resistance on hepatic fibrosis and steatosis in hepatitis C virus (HCV) mono-infected compared with HIV-HCV co-infected patients.

BACKGROUND: Insulin resistance (IR), the major feature of the metabolic syndrome, is also common in patients with chronic HCV infection. Liver fibrosis and steatosis are known potential outcome of chronic hepatitis B or C infection. Studies have shown that HIV positive individuals co-infected with HCV have more rapid live disease progression than those with HIV alone. Few data have reported the influence of IR on steatosis and fibrosis in the context of HIV-HCV coinfection. AIM: To test the association among insulin resistance (IR), liver fibrosis and liver steatosis in HIV-HCV and HCV-infected patients. PATIENTS AND METHODS: A total of 170 HIV-HCV-infected patients matched by age, gender and genotype with 170 HCV mono-infected patients were included. Patients were considered to be IR when the homeostasis model assessment of IR >2. Significant fibrosis was considered if METAVIR >or=F2 and significant steatosis if >or=10%. RESULTS: Insulin resistance was independently associated in HCV patients with fibrosis [odds ratio (OR) = 2.04 (95% CI 1.02-4)], a body mass index (BMI) >25 kg/m(2) [OR = 3.33 (1.47-7.69)] and steatosis [OR = 3.33 (1.67-6.67)]. Fibrosis >or=F2 was associated in HCV patients with high liver activity grade (>or=A2) [OR = 8.33 (3.85-16.67)], male gender [OR = 3.03 (1.33-7.14)] and IR [OR = 2.44 (1.15-5)]. In HIV-HCV patients, >or=A2 [OR = 5.56 (1.64-20)] was associated with fibrosis. Steatosis >or=10% was associated in HCV patients with IR [OR = 3.13 (1.59-6.25) and >or=F2 (OR = 2.22 (1.15-4.17)]. In HIV-HCV, a BMI >25 kg/m(2) [OR = 3.85 (1.64-9.10)], >or=A2 [OR = 2.16 (1.02-4.55); P = 0.044] and nucleoside reverse transcriptase inhibitor [OR = 3.61 (1.19-10.96); P = 0.023] were independently associated with significant liver steatosis. CONCLUSIONS: Insulin resistance is associated with liver fibrosis and steatosis in HCV mono-infected, but not in HIV-HCV co-infected patients. Significant liver fibrosis is associated with IR independent of liver steatosis only in HCV mono-infected patients.

[Non-invasive evaluation of liver fibrosis in hepatitis C]. / Evaluation non-invasive de la fibrose hépatique au cours de l'hépatite C.

In 2007, the << Haute Autorité de Santé >> recommended FibroScan, FibroTest or liver biopsy for the initial diagnosis of fibrosis in patients with hepatitis C without co morbidities. These methods have to be interpreted according to the clinical situation, keeping in mind negative and positive false results. For FibroTest, hemolysis, Gilbert syndrome or acute inflammation can modify the result. Pre-analytical and analytical conditions of FibroTest have to be respected according to manufactory recommendations. For FibroScan, the numbers of measurements, the rate of successful measurements, and the interquartile range have to be correct. In case of suspicious results, FibroTest or FibroScan have to be done again. The liver biopsy, FibroTest, and FibroScan are less relevant for the distinction of two adjacent stages of fibrosis. However, their performances are excellent for the diagnosis of severe fibrosis or cirrhosis compared to moderate fibrosis.

A study by spectroelectrochemical FTIR and density functional theory calculations of the reversible complexing ability of an electroactive tetrathiafulvalene crown.

We report on the study of the electrochemically targeted complexation/expulsion of a metal cation (Ba2+) by a crown ether tetra(thiomethyl)tetrathiafulvalene derivative (crown-TTM-TTF). Real time, in situ FTIR spectroelectrochemistry was used to obtain spectroscopic evidence of this electrochemically triggered phenomenon. Density functional theory calculations allowed the spectral information collected to be assigned. Both experimental and theoretical results clearly show that neutral crown-TTM-TTF complexes well Ba2+. Complexation is evidenced by a significant downshift of the frequency corresponding to the asymmetric stretching of the C-O-C ether groups. Concerning the cation crown-TTM-TTF, the spectroscopic signal of the complex form was difficult to identify, first because of the rather low value of the complexation constant and second because the vibration modes involving the oxygen atoms (which are the most affected by the complexation) were found by calculation to occur in the lower spectral region (<1000 cm(-1)), which is not accessible in our experimental conditions. In the case of the dication crown-TTM-TTF, it is now clear that the complex form does not exist, which means that the electrochemical formation of the dication necessarily involves the expulsion of the barium ion.

Pretreatment symptoms and dosing regimen predict side-effects of interferon therapy for hepatitis C.

We analysed data from a multicentre interferon (IFN) treatment trial to evaluate symptoms in patients with chronic hepatitis C and to identify factors that might predict development of debilitating IFN side-effects. Two hundred and twenty-two patients (120 US, 102 French) received 3 or 5 million units (MU) of IFN-alpha three times weekly (t.i.w.) for 3 months. Those who had detectable hepatitis C virus (HCV) RNA, as detected by the branched DNA signal amplification (bDNA) assay, at 3 months were intensified to daily therapy, while patients who were bDNA negative continued t.i.w. dosing for the subsequent 3 months of treatment. Symptoms were assessed at baseline, and adverse effects were evaluated at 6 months of therapy. Prior to treatment, the most common symptom that interfered with daily functioning was fatigue, occurring in 25% of patients. The frequency of debilitating fatigue, myalgia, arthralgia, headache, the presence of dry eyes and dry mouth, and use of antidepressant medication increased significantly from baseline to 6 months of IFN therapy (all P < 0.01). In multivariate analysis, the development of a debilitating side-effect at 6 months of treatment was associated with the presence of that symptom prior to therapy in all cases. Symptoms and adverse effects varied by gender and country. Compared with patients maintained on t.i.w. dosing, those who were dose intensified to daily IFN reported more debilitating fatigue, malaise, myalgia, arthralgia, fever, nausea, and headache, and the presence of dry mouth (all P < 0.05). In conclusion, patient characteristics, including pretreatment symptoms, gender and nationality, as well as daily IFN dosing are associated with the development of debilitating adverse effects on IFN therapy.

Infection complicating percutaneous liver biopsy in liver transplant recipients.

There is controversy about the frequency of and risk factors for infectious complications of percutaneous liver biopsy in liver transplant recipients. The aim of this study was to identify the incidence and nature of complications associated with liver biopsy after orthotopic liver transplantation (OLT), with particular emphasis on infection. The medical records of all patients undergoing OLT between January 1990 and August 1994 were reviewed retrospectively to identify complications requiring hospitalization within one week of percutaneous liver biopsy. The nature and severity of complications were recorded and possible risk factors for infectious complications were examined. One hundred ninety-eight patients underwent 1,136 percutaneous liver biopsies. There were eleven complications (0.96%), including as follows: 7 infections, 3 bleeding episodes, and 1 vasovagal reaction. Infections after percutaneous liver biopsy included fever and bacteremia (n = 6), and fever without bacteremia (n = 1). All infections developed only in patients with underlying biliary tract abnormalities; the frequency of infection was higher (9.8%) in patients with choledochojejunostomy when compared with those with choledochocholedochostomy (1.4%). Bacteremia was more likely caused by skin flora in patients with choledochocholedochostomy (CDC) and by enteric bacteria in patients with choledochojejunostomy (CDJ). All infections were treated successfully with parenteral antibiotics. We conclude that biliary tract abnormalities are the primary risk factors for infection after percutaneous liver biopsy, although the risk is higher in patients with CDJ than with CDC. These data support the use of antibiotic prophylaxis before percutaneous liver biopsy in OLT recipients with biliary tract abnormalities.

Histological and clinical outcome after liver transplantation for hepatitis C.

Hepatitis frequently recurs after liver transplantation for hepatitis C. However, the histological progression of disease, predictors of recurrence and disease severity, and patient survival remain uncertain. Fifty-five patients with cirrhosis caused by chronic hepatitis C underwent liver transplantation between January 1990 and December 1993. Hepatitis C genotype was determined, and liver biopsies were performed at frequent intervals posttransplantation. The median follow-up time was 40.4 months. The cumulative rate of survival was no different in liver transplant recipients for hepatitis C than in liver transplant recipients for other chronic liver diseases (P = .62). Histological recurrent hepatitis C developed in 33 of 50 patients assessable for disease recurrence; the median recurrence-free survival time was 13.4 months. Histological activity and stage were mild in most cases. Only 2 patients developed cirrhosis, and no patient required a second transplantation for recurrent disease. Patients with acute cellular rejection had a shorter recurrence-free survival (P = .0141). In patients with recurrent hepatitis, rejection also was correlated with increased histological grade 2 years after transplantation (P = .0061). Recurrence-free survival was decreased in patients infected with genotype 1 (1a and 1b combined) compared with genotypes 2 and 3 combined (P = .02), whereas there was no difference between genotypes 1a and 1b (P > .80). Only patients infected with genotype 1a or 1b developed bridging fibrosis or cirrhosis. In addition, patients who had an early recurrence had a greater risk of progressing to bridging fibrosis or cirrhosis (hazard ratio, 5.1; P = .0473). In our experience, recurrent hepatitiS C after liver transplantation in most cases is mild and survival is unaffected. Both acute cellular rejection and infection with genotype 1 are independent risk factors for reduced recurrence-free survival, and early recurrence is associated with a higher risk of disease progression.

[Serum gastrin levels in colorectal cancers. Evolution after treatment]. / La gastrinémie dans les cancers colorectaux. Devenir après traitement.

Increased basal serum gastrin level has been described in patients presenting with colorectal cancer. The aim of this work was to study the evolution of serum gastrin levels after cancer treatment. We measured basal serum gastrin levels before and 1 to 2 months after treatment in 15 patients (7 men, 8 women; mean age: 61.6 years). There were 3 malignant polyps, 4 Dukes A, 3 Dukes B, 4 Dukes C and 1 Dukes D colonic cancers. Treatment included 3 endoscopic polypectomies, 2 laser photodestructions, and 10 surgical resections, Mean basal gastrin level after treatment (49.07 +/- 12.65 mIU/l) was significantly lower (P less than 0.002) than before treatment (104.47 +/- 26.98 mIU/l). In the 2 patients treated by laser therapy, recurrences were associated with reincreasing serum gastrin levels. These results suggest an "autocrine" secretion of gastrin.

[Mucinous cystadenocarcinoma of the appendix. A rare tumor of the right iliac fossa]. / Cystadénocarcinome mucineux de l'appendice. Une tumeur rare de la fosse iliaque droite.

An observation of a mucinous cystadenocarcinoma of the appendix, in the tumor form, revealed by a painful syndrome of the right iliac fossa in a 62-year man is reported. It is a rare malignant tumor as less than 0.5% of the appendicectomy parts present a malignant mucosecreting tumor. In our observation, the diagnosis was allowed by pre-operation imaging. An increase of the serous amount in the tumor markers (carcinoembryonic antigen) (CEA) and CA 19-9 was found before the intervention and the immunodetections performed on the operation part were positive for CEA and CA 19-9. The serous amounts of these markers were normalized after operation. To the author's knowledge, the interest of dosing the serous tumor markers in the observation of such a type of tumor is not mentioned in the literature. The recurrences are frequent and sometimes late even when the initial excision has been macroscopically satisfactory. A new increase of the serous amount of the markers could allow for an earlier detection of a recurrence during the patient follow-up. At present, the prognosis of these malignant forms remains very poor as the 5-year survival does not exceed 25%.