Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.
Since its initial description in 1964, research has transformed spontaneous bacterial peritonitis (SBP) from a feared disease (with reported mortality of 90%) to a treatable complication of decompensated cirrhosis, albeit with steady prevalence and a high recurrence rate. Bacterial translocation, the key mechanism in the pathogenesis of SBP, is only possible because of the concurrent failure of defensive mechanisms in cirrhosis. Variants of SBP should be treated. Leucocyte esterase reagent strips have managed to shorten the 'tap-to-shot' time, while future studies should look into their combined use with ascitic fluid pH. Third generation cephalosporins are the antibiotic of choice because they have a number of advantages. Renal dysfunction has been shown to be an independent predictor of mortality in patients with SBP. Albumin is felt to reduce the risk of renal impairment by improving effective intravascular volume, and by helping to bind pro-inflammatory molecules. Following a single episode of SBP, patients should have long-term antibiotic prophylaxis and be considered for liver transplantation.
Microscopic colitis (MC) is considered an "umbrella term", comprising two subtypes, i.e., collagenous colitis (CC) and lymphocytic colitis (LC). They are classically associated with normal or unremarkable colonoscopy. In the last few years, reports have been published revealing findings that are thought to be characteristic or pathognomonic of MC, especially CC. A systematic electronic and manual search of PubMed and EMBASE (to December 2010), for publications on distinct endoscopic findings in MC, resulted in 42 relevant reports for inclusion in this review. Eighty eight patients with collagenous colitis were presented. Only one publication describing a distinct endoscopic pattern in LC was found. Typical findings in CC are alteration of the vascular mucosal pattern, mucosal nodularity, a sequence of change from mucosal defects to mucosal cicatricial lesions, and perhaps (although of doubtful relevance) mucosal pseudomembranes. A causal connection of mucosal defects with the use of lansoprazole seems to exist. Adoption of the proposed lesion description herein is recommended in order to improve homogeneity of future reports.
Chronic infection with the hepatitis B virus (HBV) is a frequent cause of cirrhosis and liver cancer. Targeted HBV screening is recommended by the Centre for Disease Control (CDC) and Prevention for subjects born in countries with >2% HBV prevalence. However, there are no UK guidelines. Here, we applied the (CDC) recommendations to the British-Chinese and British-South Asian community of North-East (NE) England. British-Chinese and South Asian subjects were invited to attend for HBV education and screening sessions held in community centres. Hepatitis B surface antigen (HBsAg) and hepatitis B core total antibody (HBcAb) were tested with dry blood spot tests. South Asians were also tested for hepatitis C antibody (HCVAb). A total of 1126 subjects (606 Chinese and 520 South Asian) were screened. Sixty-two (5.5%) were HBsAg positive. Ten of these reported a previous diagnosis of HBV. The prevalence of HBsAg positivity was 4.6% when previously diagnosed individuals were excluded. The HBsAg prevalence was significantly higher in the Chinese subjects compared with South Asians (8.7% VS. 1.7% P < 0.001). In Chinese subjects, HBsAg positivity was highest in subjects born in Vietnam (17.4%), followed by China (11%), Hong Kong (7.8%) and the UK (6.7%). Subjects from Pakistan had the highest HBsAg and HCV Ab prevalence in the South Asians (3.1% and 1.8%, respectively). Ten percentage of HBsAg positive patients who had follow-up assessment had active disease requiring antiviral treatment. Undiagnosed HBV infection was above the 2% threshold for screening suggested by the CDC in the British-Chinese and Pakistani community of NE England, which provides evidence for a UK HBV-targeted screening programme.
The reported incidence of spontaneous bacterial peritonitis (SBP) is 7-30% per annum in cirrhotic patients. Timely diagnosis and treatment is crucial to reduce mortality owing to this infection. Recently, leucocyte esterase reagent strips have been tested in the diagnosis of infection in the ascitic fluid. The objective was to evaluate the diagnostic value of leucocyte esterase reagent strips in SBP in cirrhotic patients with ascites, by systematically reviewing the evidence from prospective clinical studies. We performed a comprehensive literature search in Medline up to July 2007 for adult human prospective clinical studies. Two reviewers independently checked all identified studies for fulfillment of predefined inclusion criteria, extracted data and assessed methodological quality of included studies. We had decided a priori to pool the studies via meta-analysis, only if statistical heterogeneity was found to be nonsignificant (P>0.10). Seventeen studies were included. Statistical heterogeneity among studies was found to be highly significant (P<0.001) in all analyses, precluding pooling of data for meta-analysis. Compared with the manual polymorphonuclear count ('gold standard'), leucocyte esterase reagent strips were found to have sensitivity ranging from 45 to 100%, specificity ranging from 81 to 100%, positive predictive value ranging from 42 to 100% and negative predictive value ranging from 87 to 100%. Despite the wide variation in sensitivity and positive predictive value between studies, the consistently high negative predictive value of leucocyte esterase reagent strips in SBP diagnosis should gain it a place in the ascitic tap diagnostic algorithm.
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