Fibrous ring formation in cirrhotics treated with band ligation.

BACKGROUND/AIMS: We observed that the formation of a fibrous ring following variceal eradication appeared to be associated with less variceal recurrence. We aimed to evaluate this formally. METHODOLOGY: Twenty-one cirrhotic patients with a fibrous ring formation in the esophagus after eradication of varices (FR group) were compared with 21 controls of similar age, gender and liver function but without ring formation after eradication in terms of variceal recurrence, portal hypertension related bleeding and survival. RESULTS: Both groups were similar with regard to baseline demographic and clinical data. During a mean follow-up period of 28.8+/-18.3 (SD) months, variceal recurrence occurred in 2 (9.5%) patients in the FR group compared to 10 (47.6%) in the control group (p=0.005). Cox regression model revealed a significant difference in probability of variceal recurrence between the two groups (p=0.006). In the FR group 1 patient bled and 3 died vs. 2 and 6 patients in the control group respectively. The differences between the groups in relation to bleeding and death were not statistically significant. CONCLUSIONS: In cirrhotic patients undergoing band ligation for eradication of esophageal varices, the formation of a fibrous ring is followed by a lower variceal recurrence rate.

A newly detected mutation of the RET protooncogene in exon 8 as a cause of multiple endocrine neoplasia type 2A.

Multiple endocrine neoplasia type 2A (MEN2A) is a syndrome of familial neoplasias characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands. RET protooncogene mutations are responsible for MEN 2A. Mutations in exons 10 or 11 have been identified in more than 96% of patients with MEN 2A. We herein report for the first time a patient with MEN 2A harboring a mutation (Gly(533)Cys) in exon 8. A 66-year old male patient was referred to our department for bilateral adrenal nodules. The patient's family history was remarkable in that his mother had pheochromocytoma. Biochemical evaluation and findings of the magnetic resonance imaging of the adrenals were compatible with the diagnosis of bilateral pheochromocytomas. The patient underwent laparoscopic bilateral adrenalectomy and histological examination confirmed the preoperative diagnosis of pheochromocytoma. Absence of phenotypic characteristics of VHL or NF1 and elevated calcitonin levels both basal and post pentagastrin stimulation, raised the possibility of MEN 2A syndrome. Total thyroidectomy was performed and histological examination showed the presence of MTC. Direct sequencing of exon 8 from the patient's genomic DNA revealed the mutation c.1,597G-->T (Gly533Cys). Although this missense point mutation has been associated with familial MTC (FMTC), to the best of our knowledge mutations in exon 8 have not previously been identified in patients with MEN 2A. In conclusion, in patients with clinical suspicion of MEN 2A syndrome, analysis of RET exon 8 should be considered when the routine evaluation of MEN 2A-associated mutations is negative. Furthermore, patients with FMTC and exon 8 mutations should also be screened for pheochromocytoma.

An assessment of serum leptin levels in patients with chronic viral hepatitis: a prospective study.

BACKGROUND: The role of leptin in the course of liver disease due to chronic viral hepatitis (CVH) remains controversial. Our aims were to investigate the relationship between serum leptin concentrations and the severity of liver disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB) and C (CHC) and to analyze the effect of body composition, the leptin system and insulin resistance together with viral factors on virologic response to antiviral treatment. METHODS: We studied 50 (36 men) consecutive patients suffering from biopsy-proven CVH due to HBV (n = 25) or HCV (n = 25) infection. Thirty-two (17 men) healthy volunteers served as controls. Levels of serum leptin and insulin were determined by immunoassays at baseline and at the end of the treatment. RESULTS: A significant association between serum leptin levels and the stage of hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs 6028.5 pg/ml, p = 0.03), CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An inverse correlation between lower leptin levels and response to lamivudine monotherapy was noted in patients with CHB; those with a virologic response presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003) than non-responders. In genotype 1 CHC patients, insulin resistance played a significant role in the response to antiviral therapy. CONCLUSION: Our data clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin levels. Increased serum leptin levels represent a negative prognostic factor for response to lamivudine monotherapy in patients with CHB. In CHC patients insulin resistance strongly influences the response to antiviral treatment in patients infected with genotype 1.

Ultrasound-guided liver biopsy in real life: comparison of same-day prebiopsy versus real-time ultrasound approach.

BACKGROUND AND AIM: Currently, an increasing number of liver biopsies are performed by radiologists under real-time ultrasound control. A routine ultrasound assessment of a puncture site before performing percutaneous biopsy is reported to increase diagnostic yield and decrease complication rates. It is not clear if real-time ultrasound is superior to marking the puncture site before biopsy as regards reducing biopsy size and avoiding fragmentation and complications. The aim of this study was to compare ultrasound assessment of the puncture site before performing percutaneous liver biopsy with real-time ultrasound liver biopsy for suspected diffuse liver disease. METHODS: Consecutive percutaneous liver biopsies (n = 631) for diffuse liver disease were evaluated. Group A consisted of patients who had real-time guided-ultrasound biopsy performed by radiologists (241 patients; M/F, 35/106; median age 48 year [range, 17-76]; needle 18 G). Group B patients were assessed by radiologists using ultrasound of the puncture site on the same day that biopsies were performed by experienced gastroenterologists/hepatologists on the ward using the marked site (390 patients; M/F, 276/114; median age 43 year [range, 15-75]; needle 16 G). RESULTS: There were no differences in severity of liver disease, establishing a diagnosis (OR, 1.92 [95% CI, 0.84-4.34]; P = 0.12), length of liver biopsy specimens, number of fragments or complications. Two independent variables were significantly associated with a histological diagnosis: longer biopsy length (P < 0001) and fragment number of two or less (P < 0.001). CONCLUSION: Real-time ultrasound did not improve diagnostic yield or result in fewer complications. Marking the puncture site seems adequate and has the practical advantage that it takes up less of the radiologists' time.

A single alcohol ingestion does not affect serum hepatitis C virus RNA in patients with chronic hepatitis C.

BACKGROUND AND AIM: The safe level of alcohol ingestion in sporadic drinkers with hepatitis C is unknown. Our aim was to evaluate the effect of a single moderate alcohol intake on serum HCV RNA concentrations and hepatic function in patients with chronic HCV infection. METHODS: Twenty-one patients with chronic hepatitis C were randomly assigned to consume 50 g alcohol (group 1) or a non-alcoholic beverage (group 2). In both groups, serum ethanol, serum HCV RNA, transaminase and gamma-glutamyltranspeptidase (gamma-GT) levels were measured just before alcohol intake and after 1, 2, 8, 24 h and 1 week's time. RESULTS: The maximum concentration of ethanol in the blood was observed at the first hour after alcohol intake. No significant changes were observed in serum HCV RNA after alcohol intake. Repeated measurements of HCV RNA among the two groups revealed no difference (P = 0.215). Similarly, no difference was observed in transaminase and gamma-GT levels at different time points in each group or among the groups [(ALT (P = 0.082), AST (P = 0.33), gamma-GT (P = 0.538)]. CONCLUSIONS: In patients with chronic hepatitis C, a single intake of 50 g alcohol does not affect liver biochemistry and HCV RNA concentrations. Therefore, it is a matter of further research whether sporadic drinking of light or moderate amounts of alcohol should be avoided in patients with chronic hepatitis C.

Leptin in the field of hepatic fibrosis: a pivotal or an incidental player?

Leptin is a 16-kDa nonglycosylated protein primarily secreted from the adipocytes of white fat; minor levels of regulated leptin expression also occurs at other sites such as placenta, skeletal muscle, the stomach fundus, and culture-activated hepatic stellate cells (HSCs). Leptin is primarily involved in the regulation of food intake and body composition through a central feedback mechanism linking food ingestion, hypothalamus, and adipose tissue mass. In recent years, however, emerging evidence has suggested a critical role of leptin in hepatic inflammation and fibrogenesis and the influence of leptin on chronic liver disease has been an area of active research worldwide. In this review the data on the in vivo and in vitro actions of leptin on liver cells in experimental animal models of liver injury and the effects of leptin on human liver are discussed, with a focus on three distinct fields of chronic liver diseases: nonalcoholic steatohepatitis, alcoholic liver disease, chronic viral hepatitis, and, especially, hepatitis C.