Association between PNPLA3[G]/I148M variant, steatosis and fibrosis stage in hepatitis C virus - genetic matters.

There is an established correlation between the PNPLA3 rs738409 C > G single nucleotide polymorphism (SNP) and hepatic steatosis and fibrosis in hepatitis C virus (HCV) infected patients. However not all data is convergent regarding the exact impact of this SNP on the pattern of disease progression in different clinical settings. In this study, we aimed to further bridge the knowledge gap on this topic by investigating the role of the G allele in promoting steatosis, fibrosis and disease progression in relation to other metabolic and anthropometric host factors. Two hundred and fifty consecutive patients, previously diagnosed with chronic hepatitis C (CHC) underwent liver biopsy. Histology was assessed using the Metavir scoring system. Transient elastography was used for follow-up. Ninety-eight patients were genotyped for PNPLA3 rs738409 and followed up for fibrosis progression. PNPLA3 rs738409[G] allele was significantly correlated with severe steatosis (P = 0.04), severe fibrosis at the time of enrollment (P = 0.0005) and fibrosis progression with an OR of 10.31 (95% CI 1.06 - 99.59, P = 0.04), after a mean follow-up time of 62.85 (95%CI: 52.21 - 76.15) months. Severe steatosis at the time of enrollment had an OR of 11.02 (95% CI 1.48 - 82.09, P = 0.01) for the association with fibrosis progression. The HOMA-IR index was also positively correlated with severe fibrosis (P = 0.03) and fibrosis progression on univariate analysis (P = 0.02). PNPLA3 rs738409[G] allele is a reliable predictor for steatosis and fibrosis in CHC. The presence of G allele, along with severe steatosis and insulin resistance are significant predictors for fibrosis progression.

A novel pathophysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis.

Non-invasive biochemical markers are useful to distinguish between nonalcoholic steatohepatitis (NASH) and simple steatosis. The aim of this study was to test the diagnostic value of a panel of biomarkers derived from the pathophysiological events involved in the development of NASH. A total of 79 patients: 20 not-NASH and 59 NASH were included in the study. Definitive NASH was defined according to Kleiner's classification. In all subjects, parameters of the metabolic syndrome, insulin resistance (HOMA-IR), adiponectin, interleukin-6 (IL-6) and total cytokeratin-18 (M65 antigen) were determined. Univariate and multivariate analysis were used to identify independent predictors of NASH. In multivariate analysis three markers were independently predictors of NASH: adiponectin, IL-6 and M65 levels. In decreasing order, the independent predictors of NASH (NAS≥5) were M65 with an AUROC of 0.791, IL-6 with an AUROC of 0.727 and adiponectin with an AUROC of 0.709. The combination of two biomarkers yelded an AUROC of 0.828 for M65 and IL-6, 0.841 for adiponectin and M65 and 0.852 for adiponectin and IL-6. The best value was obtained by triple combination: adiponectin, M65 and IL-6 with and AUROC of 0.903, Sp=85.7% (PPV=94.2%) and Se=84.5% (NPV=66.7%). In conclusion, a novel pathophysiological - based panel of biomarkers combining total CK-18, IL-6 and adiponectin may be useful to predict NASH.

Acute diverticulitis--an unusual cause of liver abcesses in a young man: a case report.

Liver abscess is a rare complication of sigmoid diverticulitis and must be considered within the differential diagnosis. We report a case of a male patient, age 42, admitted to our hospital with chief complaints of a dull pain in upper right abdominal quadrant, fever, weakness, diarrhoea and weight loss of approximately 3 weeks duration. Physical examination on initial work-up revealed tenderness on palpation in upper right abdomen, and left iliac fosa and a 39 degrees C fever. Biochemistry showed marked inflammatory syndrome, leukocitosis, increased level of platelets, altered liver function. Ultrasound examination revealed inhomogeneous liver nodules and the thickening of the sigmoid wall. Further CT scan examination and MRI confirmed the lesions as beeing abscesses and also revealed trombosis of right portal vein. The sigmoid wall lesions proved to be an acute diverticulitis with perisigmoiditis, stenosis and abscess. Patient underwent a surgical treatment of sigmoid resection, but the punction of the abscesses revealed no pus at aspiration, making the surgical excision of the lesions unnecessary. After the surgery, during the antibiotic treatment, the patient developed pseudomembranous colitis treated with specific antibiotics. The evolution under this treatment was positive and the aspect of the liver lesions was improuved.

Hepatitis C virus infection is a risk factor for gallstone disease: a prospective hospital-based study of patients with chronic viral C hepatitis.

We evaluated the prevalence and the risk factors for gallstone disease in patients with chronic hepatitis C infection. We investigated 453 consecutively admitted patients with chronic infection with hepatitis C virus (HCV) (cirrhosis excluded) and 879 patients without liver disease (October 2006-April 2007). Gallstone disease was diagnosed if gallstones were present at ultrasonography or if there had been a previous cholecystectomy. Variables evaluated were age, gender, gallstone heredity, body mass index, waist circumference, parity, serum lipids, fatty liver, arterial hypertension, diabetes mellitus and metabolic syndrome (International Diabetes Federation criteria). Informed consent was obtained from all patients. We found that 88 of 453 (19%) patients with chronic HCV hepatitis (age 50.1 +/- 11.7 years) and 153 of 879 (17%) controls (age 60.6 +/- 12.6 years) had gallstone disease (GD). Abdominal obesity (OR = 2.108, 95% CI 1.287-3.452) and steatosis (OR = 3.699, 95% CI 2.277-6.008) were risk factors for GD in HCV patients. Gallstone heredity, dyslipidaemia, type 2 diabetes mellitus and metabolic syndrome increased the risk for GD in controls vs HCV patients. Our study shows that even HCV patients with chronic hepatitis but not cirrhosis have an increased prevalence of gallstones. Compared with controls, gallstones are present in HCV patients at a younger age and are associated with central obesity and liver steatosis, but not with gallstone heredity, dyslipidaemia, diabetes mellitus or metabolic syndrome. Although we could not establish a temporal relationship, the association between HCV infection and gall stone disease is real and appears to be causally linked, at least in predisposed individuals (obese and with liver steatosis).

Autoimmune chronic pancreatitis.

Autoimmune pancreatitis (AIP) is a new clinical entity recently described. Histologically it consists of a lymphoplasmacytic infiltration with diffuse fibrosis. Pancreatic imaging on US, CT and ERCP shows diffuse enlargement of the pancreatic gland and an irregular narrowing of the pancreatic duct. Hypergammaglobulinemia, increased serum levels of total IgG or IgG4, positive antilactoferrin and anti carbonic anhydrase II autoantibodies are quite frequently found in autoimmune pancreatitis. Laboratory data, pancreatic images and diabetes mellitus improve under oral steroid therapy.

The serum level of certain aminoacids in chronic liver diseases associated with impaired oral glucose tolerance.

We studied the plasma levels of some aminoacids and immunoreactive insulin in chronic liver diseases with impaired glucose tolerance during oral glucose tolerance test (OGTT). There are significant alterations of aminoacids levels and insulin in chronic hepatitis and liver cirrhosis, especially followed by impaired glucose tolerance.

The outpatient management of peripheral diabetic neuropathy.

Diabetic neuropathy is a common complication of diabetes. Its commonest form is the bilateral, distal sensorimotor neuropathy and this has been associated with increased risk of disability from foot ulceration, inadvertent injury leading to gangrene as well as to amputation. The economic implications of the treatment of diabetic neuropathy and its consequences are enormous. In spite of this, there is no universally accepted method of treating it and efforts are still underway to find an adequate form of therapy. The following is a review of the outpatient management of peripheral diabetic neuropathy.

Impaired glucose tolerance in the third trimester of pregnancy: associated factors to its persistence postpartum.

Glucose tolerance (75 g OGTT, according WHO) during the third trimester of pregnancy, in 302 women, has formerly been evaluated. Of these, 37 women were reinvestigated, with the same methodology, in absence of pregnancy and lactation, 2 years postpartum. According to oral glucose tolerance three groups were differentiated: group A (n = 14) with normal glucose tolerance (NGT) both in pregnancy and postpartum. Group B1 (n = 12) with impaired glucose tolerance (IGT) in pregnancy but NGT postpartum. Group B2 (n = 11) with IGT both in pregnancy and postpartum. B2 group had increased values (mean + SD) for age (37.0 +/- 6.6 years) versus B1 (30.2 +/- 5.5; p < 0.02) and A (29.5 +/- 5.9); p < 0.02) groups and BMI (32.5 +/- 4.2) versus 26.4 +/- 5.2; p < 0.01 and 23.3 +/- 4.4; p < 0.001 respectively). The ratio between basal insulinogenic indexes (microU IRI/mg BG) during pregnancy and 2 years postpartum has been significantly reduced in B1 (1.4 +/- 0.8) and B2 (1.5 +/- 0.6) as compared to A (2.5 +/- 1.1; p < 0.01) group suggesting, by comparison, the persistence of an increased level of insulin resistance postpartum in B1 and B2 groups. Insulinogenic index, after oral glucose was lower in B2 (34.4 +/- +/- 7.8) versus B1 (53.5 +/- 20.9; p < 0.01) group. These results suggest that, on an increased insulin resistance background, the decrease in glucose induced insulin response and increase in age and BMI are associated to deterioration of glucose tolerance early in the natural history of NIDDM.

[Nifedipine pharmacokinetics in liver cirrhosis patients after the administration of a single oral dose]. / Farmacocinetica nifedipinei la bolnavi cu ciroza hepatica dupa administarea unei doze unice oral.

The niphedipine pharmacokinetics was investigated in the patients with hepatic cirrhosis, in comparison with a group of healthy subjects, after administering unique doses of 10 mg per os. The niphedipine concentrations in serum were determined by a gas chromatography method. The niphedipine pharmacokinetics may be described in correspondence with the open pharmacokinetic model. The values of pharmacokinetic parameters of niphedipine in the patients with hepatic cirrhosis are significantly modified in comparison with those noticed in the healthy subjects. An increase in the level of the maximum concentrations (158 ng/ml versus 68 ng/ml), of the biological half time (11.9 hours versus 2.5 hours) and of the area under the curve of the drug concentrations in time (450 ng.ml-1.hour versus 205 ng.ml-1.hour) were found. The relative bioavailability [correction of biodisponibility] of niphedipine was double in the patients with hepatic cirrhosis versus the healthy subjects. The modified pharmacokinetics of niphedipine in the patients with hepatic cirrhosis and the great individual variations found, require a decrease of the dose in this category of patients and a surveillance of the clinical effect.