Primary Sclerosing Cholangitis: Epidemiology, Genetics, Diagnosis, and Current Management.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-gochanour a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-interview-kowdley an interview with the author

Current perspectives into the evaluation and management of hepatitis B: a review.

Hepatitis B is a widespread disease which affects millions of people worldwide. Chronic hepatitis B (CHB) can lead to significant morbidity and mortality due to complications such as cirrhosis and hepatocellular carcinoma. The pathophysiology of hepatitis is critical to diagnosing CHB. Deciding which patients with CHB should be treated is an important decision as treatment can often lead to better outcomes in the appropriate patient population. The nucleos(t)ide analog inhibitors entecavir and tenofovir are currently the mainstay of treatment as they are able to successfully suppress the virus and lead to fewer complications. Novel therapies are currently being developed which may offer a potential cure for this disease in the future

Impact of body mass index on the incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis

Background: Pancreatitis is a potential major complication after endoscopic retrograde cholangiopancreatography (post-ERCP pancreatitis; PEP). Obesity has been associated with increased severity of acute pancreatitis. However, the correlation between obesity and PEP is controversial. Therefore, our study aimed to clarify the relationship between body mass index (BMI) and the incidence and severity of PEP. Methods: A retrospective cohort study was conducted to elucidate the relationship between BMI and PEP in all patients who underwent ERCP in a tertiary referral center between January 2009 and October 2016. Patient characteristics and procedure details were collected. PEP was defined by consensus criteria. Multivariate logistic regression was used to determine the association between BMI and PEP. Results: The analysis included 2236 patients whose BMI was recorded and had adequate follow up (921 with BMI≥30 kg/m2, 1315 with BMI<30 kg/m2). PEP was diagnosed in 107 (4.8%) patients. PEP was seen in 49 obese patients (5.3%) and 58 non-obese patients (4.4%). In the univariate and multivariate analysis BMI≥30 kg/m2 was not associated with PEP (odds ratio 1.2, 95%CI 0.8-1.8; P=0.32). A subgroup analysis of different BMI subcategories found that BMI was not associated with the incidence or severity of PEP. Conclusion: In the largest study to date, neither obesity nor low body weight increased the incidence or severity of PEP

Hepcidin Signaling in Health and Disease: Ironing Out the Details.

Hepcidin, a peptide hormone produced by hepatocytes, is the central regulator of systemic iron homeostasis through its interaction with ferroportin, the major cellular iron export protein. Hepcidin binding to ferroportin results in reduced iron export from macrophages and intestinal absorptive cells, leading to decreased serum iron levels. Hepcidin expression is influenced by several factors that include serum and liver iron stores, erythropoiesis, hypoxia, inflammation, and infection. Erythropoietic drive and hypoxia suppress hepcidin expression and promote red cell production. In contrast, inflammation and infection are associated with increased hepcidin production to sequester iron intracellularly as a means of depriving microorganisms of iron. Chronic inflammation may up-regulate hepcidin expression through the interleukin-6 (IL-6)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. The bone morphogenetic protein (BMP)-mothers against decapentaplegic homolog (SMAD) pathway is a major positive driver of hepcidin expression in response to either increased circulating iron in the form of transferrin or iron loading in organs. Hereditary hemochromatosis (HH) consists of several inherited disorders that cause inappropriately reduced hepcidin expression in response to body iron stores, leading to increased iron absorption from a normal diet. The most common form of HH is due to a mutation in the HFE gene, which causes a failure in the hepatocyte iron-sensing mechanism, leading to reduced hepcidin expression; the clinical manifestations of HFE-HH include increased serum transferrin-iron saturation and progressive iron loading in the liver and other tissues over time among patients who express the disease phenotype. In this article, we review the physiologic mechanisms and cellular pathways by which hepcidin expression is regulated, and the different forms of HH resulting from various mutations that cause hepcidin deficiency. We also review other drivers of hepcidin expression and the associated pathophysiologic consequences

Impact of body mass index on the incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis

Background: Pancreatitis is a potential major complication after endoscopic retrogradecholangiopancreatography (post-ERCP pancreatitis; PEP). Obesity has been associated withincreased severity of acute pancreatitis. However, the correlation between obesity and PEP iscontroversial. Therefore, our study aimed to clarify the relationship between body mass index(BMI) and the incidence and severity of PEP.Methods: A retrospective cohort study was conducted to elucidate the relationship between BMIand PEP in all patients who underwent ERCP in a tertiary referral center between January 2009and October 2016. Patient characteristics and procedure details were collected. PEP was definedby consensus criteria. Multivariate logistic regression was used to determine the associationbetween BMI and PEP.Results: The analysis included 2236 patients whose BMI was recorded and had adequate follow up(921 with BMI≥30 kg/m2, 1315 with BMI&lt;30 kg/m2). PEP was diagnosed in 107 (4.8%) patients.PEP was seen in 49 obese patients (5.3%) and 58 non-obese patients (4.4%). In the univariate andmultivariate analysis BMI≥30 kg/m2 was not associated with PEP (odds ratio 1.2, 95%CI 0.8-1.8;P=0.32). A subgroup analysis of different BMI subcategories found that BMI was not associatedwith the incidence or severity of PEP.Conclusion: In the largest study to date, neither obesity nor low body weight increased theincidence or severity of PEP

Serum miRNA profiles are altered in patients with primary sclerosing cholangitis receiving high-dose ursodeoxycholic acid

Background &amp; Aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease that can lead to end-stage liver disease and cholangiocarcinoma. High-dose ursodeoxycholic acid (hd-UDCA, 28–30 mg/kg/day) was evaluated in a previous multicentre, randomised placebo-controlled trial; however, the study was discontinued early because of increased liver-related serious adverse events (SAEs), despite improvement in serum liver biochemical tests. We investigated longitudinal changes in serum miRNA and cytokine profiles over time among patients treated with either hd-UDCA or placebo in this trial as potential biomarkers for PSC and response to hd-UDCA, as well as to understand the toxicity associated with hd-UDCA treatment. Methods: Thirty-eight patients with PSC were enrolled in a multicentred, randomised, double-blinded trial of hd-UDCA vs. placebo. Results: Significant alterations in serum miRNA profiles were found over time in both patients treated with hd-UDCA or placebo. Additionally, there were striking differences between miRNA profiles in patients treated with hd-UDCA compared with placebo. In patients treated with placebo, the changes in concentration of serum miRNAs miR-26a, miR-199b-5p, miR-373, and miR-663 suggest alterations of inflammatory and cell proliferative processes consistent with disease progression. However, patients treated with hd-UDCA exhibited a more pronounced differential expression of serum miRNAs, suggesting that hd-UDCA induces significant cellular miRNA changes and tissue injury. Pathway enrichment analysis for UDCA-associated miRNAs suggested unique dysregulation of cell cycle and inflammatory response pathways. Conclusions: Patients with PSC have distinct miRNAs in the serum and bile, although the implications of these unique patterns have not been studied longitudinally or in relation to adverse events related to hd-UDCA. Our study demonstrates marked changes in miRNA serum profiles with hd-UDCA treatment and suggests mechanisms for the increased liver toxicity with therapy. Impact and implications: Using serum samples from patients with PSC enrolled in a clinical trial comparing hd-UDCA with placebo, our study found distinct miRNA changes in patients with PSC who are treated with hd-UDCA over a period of time. Our study also noted distinct miRNA patterns in patients who developed SAEs during the study period

Serum miRNA profiles are altered in patients with primary sclerosing cholangitis receiving high-dose ursodeoxycholic acid.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease that can lead to end-stage liver disease and cholangiocarcinoma. High-dose ursodeoxycholic acid (hd-UDCA, 28-30 mg/kg/day) was evaluated in a previous multicentre, randomised placebo-controlled trial; however, the study was discontinued early because of increased liver-related serious adverse events (SAEs), despite improvement in serum liver biochemical tests. We investigated longitudinal changes in serum miRNA and cytokine profiles over time among patients treated with either hd-UDCA or placebo in this trial as potential biomarkers for PSC and response to hd-UDCA, as well as to understand the toxicity associated with hd-UDCA treatment. METHODS: Thirty-eight patients with PSC were enrolled in a multicentred, randomised, double-blinded trial of hd-UDCA RESULTS: Significant alterations in serum miRNA profiles were found over time in both patients treated with hd-UDCA or placebo. Additionally, there were striking differences between miRNA profiles in patients treated with hd-UDCA compared with placebo. In patients treated with placebo, the changes in concentration of serum miRNAs miR-26a, miR-199b-5p, miR-373, and miR-663 suggest alterations of inflammatory and cell proliferative processes consistent with disease progression CONCLUSIONS: Patients with PSC have distinct miRNAs in the serum and bile, although the implications of these unique patterns have not been studied longitudinally or in relation to adverse events related to hd-UDCA. Our study demonstrates marked changes in miRNA serum profiles with hd-UDCA treatment and suggests mechanisms for the increased liver toxicity with therapy. IMPACT AND IMPLICATIONS: Using serum samples from patients with PSC enrolled in a clinical trial comparing hd-UDCA with placebo, our study found distinct miRNA changes in patients with PSC who are treated with hd-UDCA over a period of time. Our study also noted distinct miRNA patterns in patients who developed SAEs during the study period