Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

AIM: Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. RESULTS: CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P < 0.001 in all cases). Circulating levels of pro-inflammatory cytokine TNF-α were significantly increased in rats with liver fibrosis as compared with normal rats, while symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-ß, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. CONCLUSIONS: Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis.

Optimized contrast-enhanced ultrasonography for characterization of focal liver lesions in cirrhosis: A single-center retrospective study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of death amongst cirrhotic patients. Its diagnosis and discrimination from non-HCC malignant lesions in cirrhosis includes contrast enhanced computed tomography (CECT), contrast enhanced magnetic resonance imaging (CEMRI), or, in selected cases, liver biopsy. The role of contrast-enhanced ultrasonography (CEUS) is still controversial. AIMS: To evaluate whether, by selecting an appropriate 'time to wash-out' cut-off value, CEUS capability of discriminating between HCC and non-HCC malignancies in cirrhotic patients may be enhanced. METHODS: We enrolled 282 cirrhotic patients who underwent CEUS at our institute, from January 2008 to January 2012, for focal liver lesions (FLLs) detected at ultrasound (US). We used liver biopsy and subsequent histological evaluation as the gold standard for correct classification of FLLs. We calculated the area under receiver operator characteristic curves for CEUS to distinguish patients with HCC from those with non-HCC malignancies. The best 'time to wash-out' cut-off values were selected. RESULTS: HISTOLOGICAL DIAGNOSIS OF FLLS WAS AS FOLLOWS: 34 benign lesions (i.e. 25 regenerative nodules and 9 dysplastic nodules) and 248 malignant lesions (223 well-to-moderately differentiated HCCs; 7 poorly-differentiated HCCs; 5 intrahepatic colangiocellular carcinomas (ICCs); 5 primary non-Hodgkin B-cell lymphomas (NHBLs); and 8 metastatic liver tumors). A time to wash-out > 55 s identified patients with HCC with the highest level of accuracy (92.7%). Similarly, a time to wash-out ≤ 55 s correctly identified the vast majority of the non-HCC malignancies (100% sensitivity, 98.2% specificity and diagnostic accuracy of 98.3%). CONCLUSIONS: CEUS is an accurate and safe procedure for discriminating FLLs in cirrhotic patients, especially when a cut-off time to wash-out of 55 s is chosen as a reference value.

Ultrasound-guided percutaneous biopsy for diagnosis of gastrointestinal lesions.

BACKGROUND AND AIMS: Endoscopical examination is not always sufficient for the diagnosis of gastrointestinal masses. This study assessed the diagnostic accuracy and safety of ultrasound-guided percutaneous biopsy of gastrointestinal lesions. METHODS: This retrospective study evaluated 114 patients who underwent ultrasound-guided biopsy of gastrointestinal masses with a 18G needle. Thirty-two of these patients underwent a 22G fine-needle biopsy for cytology. Histology was compared with a composite standard of reference for diagnosis (i.e. post-surgery histological evaluation in 73 cases and computed tomography or magnetic resonance scan findings, together with a compatible clinical follow-up for at least 24 months, in the remaining 41 cases). Safety was assessed by recording side effects for up to 4h after the procedure. RESULTS: Of the 114 lesions evaluated, 112 were malignant (98.2%) and 2 benign (1.8%). Specimens were adequate for histology in all but one case. Specimens were obtained from the stomach (n=38; 33.3%), small bowel (n=36; 31.6%) and colon (n=40; 35.1%). Diagnosis was correct in 113/114 cases (99.1%). Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were 99.1%, 100%, 100%, 66%, and 99%, respectively. One of the 114 patients (0.9%) bled from a gastric GIST. CONCLUSIONS: Ultrasound-guided percutaneous biopsy of gastrointestinal lesions is a valid alternative when diagnosis of a gastrointestinal mass cannot be obtained with an endoscopical procedure.

Liver failure in an obese middle-aged woman after biliointestinal bypass.

Obesity is considered an emerging epidemic that is often associated with non-alcoholic fatty liver disease. Among the therapeutic options for morbid obesity, bariatric surgery plays an important role when conventional therapies fail. The effects of bariatric surgery on liver function and morphology are controversial in the literature. Liver failure has been reported after jejunoileal bypass (JIB), biliopancreatic diversion and gastric bypass. Biliointestinal bypass (BIB) is considered an effective procedure among recently introduced bariatric surgery techniques. It is a clinically safe, purely malabsorptive operation in which the blind intestinal loop of the JIB is anastomosed to the gallbladder, allowing a portion of bile to transit into excluded intestinal tract. BIB is the only procedure, to our knowledge, to have no liver side effects reported in the literature. We report the case of a young obese woman who developed liver failure 8 mo after BIB. She had a rapid weight loss (70 kg) with a reduction in body mass index of 41% from January to September 2012. Because of a severe hepatic decompensation, she was referred to a transplantation centre. We strongly believe that the most important pathogenetic mechanism involved in the development of liver injury is the rapid weight loss that produced a significant fatty liver infiltration.