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An immunological landscape of the bile duct: The human bile duct can often be a site of inflammation and disease, but the underlying immune landscape in the context of disease is not well understood. To address this, Zimmer et al. used endoscopy-guided sampling of the biliary tree in patients with primary sclerosing cholangitis (PSC) and non-PSC controls. The authors found that patients with PSC had the most prominent changes in the neutrophil and tissue-resident T cell populations in the bile duct. Together, this study provides a promising resource for understanding the immune landscape of the human bile duct. The human biliary system, a mucosal barrier tissue connecting the liver and intestine, is an organ often affected by serious inflammatory and malignant diseases. Although these diseases are linked to immunological processes, the biliary system represents an unexplored immunological niche. By combining endoscopy-guided sampling of the biliary tree with a high-dimensional analysis approach, comprehensive mapping of the human biliary immunological landscape in patients with primary sclerosing cholangitis (PSC), a severe biliary inflammatory disease, was conducted. Major differences in immune cell composition in bile ducts compared to blood were revealed. Furthermore, biliary inflammation in patients with PSC was characterized by high presence of neutrophils and T cells as compared to control individuals without PSC. The biliary T cells displayed a CD103+CD69+ effector memory phenotype, a combined gut and liver homing profile, and produced interleukin-17 (IL-17) and IL-22. Biliary neutrophil infiltration in PSC associated with CXCL8, possibly produced by resident T cells, and CXCL16 was linked to the enrichment of T cells. This study uncovers the immunological niche of human bile ducts, defines a local immune network between neutrophils and biliary-resident T cells in PSC, and provides a resource for future studies of the immune responses in biliary disorders. [ABSTRACT FROM AUTHOR]

Patients with liver cirrhosis have high mortality, often estimated by the Child–Pugh or MELD scores. Etiologies of cirrhosis are rapidly shifting, and it is unclear if these scores perform similarly across subgroups of patients. Here, we describe the characteristics and outcomes of a large contemporary cohort of patients with cirrhosis. This was a cohort study with retrospectively collected data. All patients with a verified diagnosis of cirrhosis during 2004–2017 at the Karolinska University Hospital, Sweden, were identified. Data at baseline to calculate Child–Pugh, MELD and confounders for mortality was collected. Competing risk regression was used to estimate risk for outcomes, adjusted for age, sex, baseline Child–Pugh score, etiology of cirrhosis and type 2 diabetes. We identified 2609 patients, with a median age of 61 years, and 68% men. Etiologies of cirrhosis shifted during the study period, with a −29% relative decrease in hepatitis C-cirrhosis and a + 154% increase in cirrhosis due to non-alcoholic fatty liver disease. The highest overall mortality was seen in patients with alcohol-related cirrhosis. MELD and Child–Pugh scores predicted 3-month and 1 to 2-year mortality reasonably well, but with a lower predictive performance in alcohol-related cirrhosis. Men were more likely than women to receive a liver transplant (sHR = 1.39, 95%CI = 1.08–1.78). We confirm previous findings of a rapid shift in the etiologies of cirrhosis. Differences in sex in regard to access to liver transplantation deserve further attention. [ABSTRACT FROM AUTHOR]

Background: Alcohol is a major risk factor for liver cirrhosis. Recently, it was proposed that colder climate might causally lead to increased consumption of alcohol. Methods: We performed an ecologic study, using monthly updated data on mean temperature, sunlight hours and alcohol consumption from ten regions in Sweden, using publicly available data. A generalised additive model, adjusted for region, was applied to examine the association between mean temperature and mean sunlight hours with mean alcohol consumption. Results: We found a non-linear inverse association between mean monthly temperature and mean alcohol consumption, suggesting that warmer temperature was associated with increased alcohol consumption and colder temperature with a decreased consumption. We found no association between mean sunlight hours and alcohol consumption. Consumption was highest during public holidays. Conclusions: We found no association between a colder climate and increased alcohol consumption. Socio-economic factors are likely to explain the suggested association. [ABSTRACT FROM AUTHOR]

Background and aims: Detection of early cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) is challenging. The aim of this study was to evaluate the diagnostic accuracy of a stepwise approach to biliary brush cytology with sequential use of fluorescence in‐situ hybridization (FISH) for the detection of biliary malignancy in PSC. Method: We retrospectively studied consecutive patients with PSC who underwent biliary brushings at Karolinska University Hospital between 2009 and 2015 (n = 208). Brush samples were categorized as benign, equivocal (atypical or suspicious) and malignant. Equivocal cases were further analysed with FISH. Samples with a malignant cytology or positive FISH were considered positive. The diagnosis was determined after 12 months of follow‐up. Results: The diagnosis CCA was confirmed in 15 patients (7%), high‐grade dysplasia in three patients, and low‐grade dysplasia in five patients at follow‐up. Using the diagnostic algorithm, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for a diagnosis of CCA were 80% (95%CI 52%‐96%), 96% (95%CI 92%‐98%), 60% (95%CI 36%‐81%) and 98% (95% CI 95%‐100%). In patients with equivocal cytology (n = 61), the sensitivity for CCA diagnosis increased to 100% (95%CI 72%‐100%) with a lower PPV of 58% (95%CI 34%‐78%). The diagnostic accuracy for detection of CCA in all patients was 95% (95%CI 91%‐97%). Conclusion: Biliary brush cytology with sequential use of FISH in equivocal cases seems to be a highly predictive diagnostic test for CCA in PSC. These results support the use of FISH when cytology is equivocal for detection of biliary malignancy in PSC. [ABSTRACT FROM AUTHOR]

Background and study aims: The role of cholangioscopy in primary sclerosing cholangitis (PSC) using a single-operator peroral cholangioscopy direct visualization system is unknown. This study aimed to prospectively evaluate the clinical utility of the system in PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Patients and methods: Patients with PSC or suspicion of PSC and a clinical indication for ERCP were enrolled between September 2008 and May 2011. Patients underwent cholangioscopy with sampling from biliary strictures. Clinical data, technical information from the ERCP procedure, and results from sampling by brush cytology and miniforceps biopsy were collected. Long-term followup was conducted. Outcomes included technical success, sampling adequacy, and diagnostic accuracy of cholangioscopy-guided sampling for detection of cholangiocarcinoma (CCA). Results: A total of 47 patients with PSC were included in the study. Median follow-up time was 27 months (range 2-64 months). Technical success was achieved in 96% (45/47). In 9% (4/45), the target lesion could not have been reached without the cholangioscopic visualization of the bile duct, which enabled further advancement of the investigation. A total of 64 biliary strictures were evaluated. Sample quality was adequate in 98% (62/63) of the cytology brushings and in 95% (21/22) of the mini-forceps biopsies. Of the three patients with a final diagnosis of CCA, one was diagnosed at the time of the investigation. The sensitivity, specificity, accuracy, and negative predictive value were 33%, 100%, 96%, and 95%, respectively. Conclusion: Cholangioscopy and cholangioscopyguided sampling can be utilized successfully in patients with PSC. Cholangioscopy enabled targeted biopsies to be taken and was able to pass otherwise inaccessible strictures, making it potentially valuable for the management of biliary strictures in patients with PSC. [ABSTRACT FROM AUTHOR]

Studies from Western countries suggest that early-onset biliary tract cancer, a rare malignancy originating from the bile ducts (cholangiocarcinoma) or gallbladder, is increasing. We performed a population-based cohort study to outline age trends in biliary tract cancer incidence in Sweden. All patients with biliary tract cancer, excluding non-biliary chiefly hepatocellular histopathology, recorded in the Swedish Cancer Register in year 1993–2019 and at age 20–84 were included. Analyses were stratified by anatomical subtype; intrahepatic, gallbladder, perihilar, distal, and not specified. We analyzed absolute incidence rates by calendar period (1993–2001, 2002–2010, and 2011–2019) and annual percentage change (APC) including 95% confidence intervals (CI) across 1993–2019 for all ages and stratified into younger (20–54 years) and older (55–84 years) patients. Among 14,083 patients with biliary tract cancer, 1377 (9.8%) were younger. Gallbladder cancer incidence decreased (APC -2.82, 95% CI: −3.18–-2.46), while intrahepatic cholangiocarcinoma increased (APC 1.74, 95% CI: 1.30–2.18), and the latter surpassed gallbladder as the most common subtype during the study period. While both intrahepatic and perihilar cholangiocarcinoma increased in both age groups, the rise was most prominent in younger adults, APC 3.01, 95% CI: 1.84–4.20 and 3.93, 95% CI: 2.08–5.81, respectively. Intrahepatic and perihilar cholangiocarcinoma are increasing in Sweden and more so younger adults. Further studies are needed to elucidate the underlying reasons behind the observed trends. • This Swedish cohort study assessed biliary cancer age trends • Gallbladder cancer incidence has decreased over time in all age groups • Intrahepatic and perihilar cholangiocarcinoma are on the rise and chiefly in younger • With the shift in anatomical subtype distribution, the women predominance is offset [ABSTRACT FROM AUTHOR]