Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice

Interleukin (IL)-17 signaling has been implicated in lung and skin fibrosis. We examined the role of IL-17 signaling in the pathogenesis of liver fibrosis in mice.

Predictors of short term treatment outcome in patients with achalasia following endoscopic or surgical therapy

Pneumatic balloon dilation and surgical myotomy are the most effective treatments for achalasia. While there is controversy which method is best, the aim of the current study was to identify predictors of symptom recurrence after endoscopic or surgical therapy.

Endoscopy for repeatedly ingested sharp foreign bodies in patients with borderline personality disorder: an international survey

The general guidelines on the management of ingested foreign bodies (FBs) do not address specific aspects raised by psychiatric patients, particularly in patients with borderline personality disorders (BPD) who repeatedly ingest FBs. The aim of this survey was to collect data on experience and opinions on the management of FBs in psychiatric patients with BPD and to review the relevant literature.

Impedance-pH reflux patterns can differentiate non-erosive reflux disease from functional heartburn patients

Symptom association is important to distinguish non-erosive reflux disease [NERD; abnormal oesophageal acid exposure time (AET) and/or positive symptom association] from functional heartburn (FH; normal AET and negative symptom association). Asymptomatic patients during reflux monitoring are challenging as symptom association cannot be assessed.

Transient Benign Hyperphophatasemia - A Systematic Review of The Literature

BACKGROUND:: Sometimes, a temporary increase in alkaline phosphatase level is found in healthy infants and toddlers without evidence of liver or bone disease. The condition is customarily termed transient benign hyperphosphatasemia of infancy and early childhood. Most textbooks do not refer to the condition. METHODS:: We completed a systematic review of the literature using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS:: The 142 reports retained for analysis included 813 cases (male:female ratio = 1.1:1.0): 80 in subjects >18 years and 733 in subjects ≤18 years of age. The alkaline phosphatase ratio, calculated by dividing the measured level by the upper normal limit, was ≥5.0 in ≈70% and the duration of the elevation ≤4 months in 80% of the cases. Transient benign hyperphosphatasemia often followed a benign infection but available data fail to demonstrate a causal link. The prevalence of transient benign hyperphosphatasemia ranged 1.1-3.5% in infants 2 to 24 months of age. CONCLUSIONS:: Transient benign hyperphosphatasemia is likely the most common cause of hyperphosphatasemia among healthy infants and toddlers. Sometimes, it also occurs in older children and adults, indicating that the traditional term transient benign hyperphosphatasemia of infancy and early childhood might not be correct. The elevation in alkaline phosphatase persists for >4 months in ≈20% of the cases. Recognition of this benign condition is crucial to avoid unnecessary investigations.

Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis

BACKGROUND ; AIMS: Nonalcoholic steatohepatitis (NASH) is a frequent liver disease that can progress to cirrhosis and for which there is no recognized therapy. UDCA and vitamin E have been considered separately as therapeutic options and have not been shown to be effective. This study tested their combination. METHODS: Patients with elevated aminotransferase levels and drinking less than 40 g alcohol/week with biopsy-proven NASH were randomly assigned to receive UDCA 12-15 mg.kg-1.day-1 with vitamin E 400 IU twice a day (UDCA/Vit E), UDCA with placebo (UDCA/P), or placebo/placebo (P/P). After 2 years, they underwent a second liver biopsy. Biopsy specimens were collected, blinded, and scored by a single liver pathologist. RESULTS: Forty eight patients were included, 15 in the UDCA/Vit E group, 18 in the UDCA/P group, and 15 in the P/P group; 8 patients dropped out, none because of side effects. Baseline parameters were not significantly different between the 3 groups. Body mass index remained unchanged during the study. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels diminished significantly in the UDCA/Vit E group. Neither the AST nor the ALT levels improved in the P/P group and only the ALT levels in the UDCA/P group. Histologically, the activity index was unchanged at the end of the study in the P/P and UDCA/P groups, but it was significantly better in the UDCA/Vit E group, mostly as a result of regression of steatosis. CONCLUSIONS: Two years of treatment with UDCA in combination with vitamin E improved laboratory values and hepatic steatosis of patients with NASH. Larger trials are warranted.

Efficiency and safety of bosentan in child C cirrhosis with portopulmonary hypertension and renal insufficiency

Bosentan has lately been described as a successful therapeutic agent for portopulmonary hypertension consecutive to child A cirrhosis. This is the first report of the effect of this substance with advanced liver cirrhosis (child C) and renal insufficiency. Low doses of bosentan (initially twice 31.25 mg/day and then 62.5 mg/day) increased cardiac output and allowed correction of renal insufficiency; it allowed one to stop the requirement of oxygen and not only improved the 6-min walking test by more than 400 m, but also decreased the severity of the liver cirrhosis to child B stadium. This suggests that patients, who would be excluded from a liver transplantation program because of their portopulmonary hypertension, could profit from a careful therapy with bosentan.

Hint2, a mitochondrial apoptotic sensitizer down-regulated in hepatocellular carcinoma

BACKGROUND ; AIMS: Hints, histidine triad nucleotide-binding proteins, are adenosine monophosphate-lysine hydrolases of uncertain biological function. Here we report the characterization of human Hint2. METHODS: Tissue distribution was determined by real-time quantitative polymerase chain reaction and immunoblotting, cellular localization by immunocytochemistry, and transfection with green fluorescent protein constructs. Enzymatic activities for protein kinase C and adenosine phosphoramidase in the presence of Hint2 were measured. HepG2 cell lines with Hint2 overexpressed or knocked down were established. Apoptosis was assessed by immunoblotting for caspases and by flow cytometry. Tumor growth was measured in SCID mice. Expression in human tumors was investigated by microarrays. RESULTS: Hint2 was predominantly expressed in liver and pancreas. Hint2 was localized in mitochondria. Hint2 hydrolyzed adenosine monophosphate linked to an amino group (AMP-pNA; k(cat):0.0223 s(-1); Km:128 micromol/L). Exposed to apoptotic stress, fewer HepG2 cells overexpressing Hint2 remained viable (32.2 +/- 0.6% vs 57.7 +/- 4.6%), and more cells displayed changes of the mitochondrial membrane potential (87.8 +/- 2.35 vs 49.7 +/- 1.6%) with more cleaved caspases than control cells. The opposite was observed in HepG2 cells with knockdown expression of Hint2. Subcutaneous injection of HepG2 cells overexpressing Hint2 in SCID mice resulted in smaller tumors (0.32 +/- 0.13 g vs 0.85 +/- 0.35 g). Microarray analyses revealed that HINT2 messenger RNA is downregulated in hepatocellular carcinomas (-0.42 +/- 0.58 log2 vs -0.11 +/- 0.28 log2). Low abundance of HINT2 messenger RNA was associated with poor survival. CONCLUSION: Hint2 defines a novel class of mitochondrial apoptotic sensitizers down-regulated in hepatocellular carcinoma.

Acute partial Budd-Chiari syndrome and portal vein thrombosis in cytomegalovirus primary infection: a case report

BACKGROUND: Splanchnic vein thrombosis may complicate inherited thrombotic disorders. Acute cytomegalovirus infection is a rare cause of acquired venous thrombosis in the portal or mesenteric territory, but has never been described extending into a main hepatic vein. CASE PRESENTATION: A 36-year-old immunocompetent woman presented with acute primary cytomegalovirus infection in association with extensive thrombosis in the portal and splenic vein. In addition, a fresh thrombus was evident in the right hepatic vein. A thorough evaluation for a hypercoagulable state was negative. The clinical course, biological evolution, radiological and histological findings were consistent with cytomegalovirus hepatitis complicated by a partial acute Budd-Chiari syndrome and portal thrombosis. Therapeutic anticoagulation was associated with a slow clinical improvement and partial vascular recanalization. CONCLUSION: We described in details a new association between cytomegalovirus infection and acute venous thrombosis both in the portal vein and in the right hepatic vein, realizing a partial Budd-Chiari syndrome. One should be aware that this rare thrombotic event may be complicated by partial venous outflow block.

Serological and DNA-based evaluation of Chlamydia pneumoniae infection in inflammatory bowel disease

OBJECTIVES: Chlamydia has been associated with autoimmune diseases, but a link between chlamydial infection and the aetiopathogenesis of inflammatory bowel disease (IBD) remains controversial. In this study we assessed the relationship between chlamydial infection and IBD, as evidenced by serological measurement and DNA analysis of mucosal biopsy specimens. PATIENTS AND METHODS: The sera of 78 patients with Crohn's disease (CD), 24 patients with ulcerative colitis (UC), 73 healthy family members, and 20 healthy controls were tested for anti-C. pneumoniae IgG titres. A subgroup consisting of 13 UC and 39 CD patients was screened for the presence of chlamydial DNA on 42 inflamed versus 30 non-inflamed biopsy specimens and for mutations of their NOD2/CARD15 gene. RESULTS: Anti-C. pneumoniae IgG antibodies were found in the sera of 32 (41%) patients with CD, 11 (46%) patients with UC, 35 (48%) of unaffected family members, and nine (45%) unrelated healthy controls. Thirty-five percent of the control, 18% CD and 24% UC biopsy specimens contained C. pneumoniae DNA. In CD, however, C. pneumoniae DNA was significantly more frequently found in inflamed (27%) versus non-inflamed (8%) biopsy specimens (P < 0.05, Fisher's exact test). The frequencies of NOD2/CARD15 mutations were 33% for CD patients with C. pneumoniae DNA compared to 47% for CD patients without C. pneumoniae DNA. CONCLUSION: We found no marked differences in respect to anti-C. pneumoniae serum IgG or C. pneumoniae DNA between healthy controls and patients with IBD. However, in CD patients, inflamed tissue specimens contained significantly more likely C. pneumoniae DNA compared with biopsies from unaffected areas. Thus C. pneumoniae is unlikely to be of pathogenic importance in IBD while it may still influence local clinical manifestations.

Intraoperative three-dimensional fluoroscopic cholangiography

Precise intraoperative assessment of the architecture of the biliary tree could reduce lesions to intra- or extrahepatic bile ducts. The aim of this study was to test feasibility of intraoperative three-dimensional imaging during liver resections. Isocentric C-arm fluoroscopy acquires three-dimensional images during a 190 degrees orbital rotation. The bile ducts were displayed three-dimensionally by realtime rotational projections or multiplanar reconstructions. The technique was established ex vivo in a preserved cadaveric human liver. Intraoperative three-dimensional cholangiography was performed in five patients with centrally located liver malignancies. Complete data acquisition in 3 patients depicted precise anatomical details of the architecture of the biliary tree up to third order divisions. Biliary imaging can be improved by the application of real-time intraoperative three-dimensional cholangiography. For the development of computer-aided navigation in hepatobiliary procedures, this technique could be an important prerequisite for defining landmarks of the liver in a three-dimensional space.