Frequency and distribution of FCN2 and FCN3 functional variants among MBL2 genotypes.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The six types of pattern recognition molecules (PRMs) that initiate complement via the lectin pathway (LP) comprise collectins and ficolins. The importance of having various PRMs to initiate the LP is currently unclear. Mannan-binding lectin (MBL) is a collectin member of the LP PRMs. MBL deficiency is common with mild clinical consequence. Thus, the lack of MBL may be compensated for by the other PRMs. We hypothesized that variants FCN2 + 6424 and FCN3 + 1637delC that cause gene-dose-dependent reduction in ficolin-2 and ficolin-3 levels, respectively, may be rare in MBL-deficient individuals due to the importance of compensation within the LP. The aim of this study was to investigate the distribution and frequency of these variants among MBL2 genotypes in healthy subjects. The allele frequency of FCN2 + 6424 and FCN3 + 1637delC was 0.099 and 0.015, respectively, in the cohort (n = 498). The frequency of FCN2 + 6424 tended to be lower among MBL-deficient subjects (n = 53) than among MBL-sufficient subjects (n = 445) (0.047 versus 0.106, P = 0.057). In addition, individuals who were homozygous for FCN2 + 6424 were sufficient MBL producers. The frequency of FCN3 + 1637delC did not differ between the groups. The frequency of FCN2 + 6424 was similar in FCN3 + 1637delC carriers (n = 15) versus wild type (n = 498). Furthermore, subjects that were heterozygote carriers of both FCN2 + 6424 and FCN3 + 1637delC were sufficient MBL producers. In conclusion, FCN2 + 6424 carriers with MBL deficiency tend to be rare among healthy individuals. MBL-deficient individuals with additional LP PRM defects may be at risk to morbidity.Icelandic Research Fund Unversity of Iceland Research Fund Landspitali University Hospital Research Fun

A nationwide study on hepatocellular carcinoma.

To access publisher's full text version of this article click on the hyperlink belowBackground & aims: Population based studies on the epidemiology of HCC are scarce. We aimed to compare CG (cirrhotic HCC group) with NCG (non-cirrhotic HCC group), analyze incidence, etiology and survival among patients diagnosed in Iceland in a population-based cohort. A previous study from Iceland (1984-1998) showed an incidence of HCC of 1.1/100.000, mostly with NCG. Methods: A nationwide, population based retrospective study. Information on patients with HCC during 1998-2017 was obtained and medical records viewed. Results: Overall 152 patients with HCC were identified. The mean incidence was 1.7/100.000 and increased by 8% annually. Alcohol and hepatitis C combined was more common as a risk factor in CG than in the NCG (13 % vs. 2%, p = 0.03). Tumor size was larger in NCG (11 cm vs 5 cm, p < 0.01) and portal vein thrombosis less common (11 % vs. 30 %, p = 0.03). Overall, 44 % in NCG underwent surgical treatment vs. 23 % in CG (p = 0.02). The proportion of patients diagnosed by surveillance in 1998-2007 was 3% and 19 % in 2008-2017 (p = 0.03). The disease specific median survival for cirrhotic patients diagnosed by surveillance was 519 days and 86 days in other cirrhotic patients, hazard ratio 0.45 (p = 0.007, CI 0.25-0.81). Conclusions: A major increase in the incidence of patients with HCC has occurred. The non-cirrhotic HCC presented with larger size tumors, lower proportion of portal vein thrombosis and were more likely to be surgical candidates, although not affecting prognosis. Diagnosis by surveillance in patients with cirrhosis has increased and the survival of those patients is better compared to others. Keywords: Cirrhosis; Epidemiology; Hepatocellular carcinoma; Non-cirrhotic etiology

Abstinence from alcohol and alcohol rehabilitation therapy in alcoholic liver disease: a population-based study.

To access publisher's full text version of this article click on the hyperlink belowObjective: Abstinence from alcohol is recommended in patients diagnosed with alcoholic hepatitis (AH) and alcoholic cirrhosis (AC). We aimed to determine the impact of alcohol abstinence on prognosis of patients with AC and AH.Methods: All incident AC and AH patients in Iceland 2001-2016 were identified. Cirrhosis was confirmed clinically, biochemically, with imaging and histologically. Abstinence, alcohol rehabilitation and survival were analyzed.Results: Overall, 169 patients with AC and/or AH were identified. Eleven died during index hospitalization, leaving 158 patients for final analysis, median (IQR) age 56 years (48-65), 72% males. Over all 61 patients (39%) had AC, 40 (25%) AH and 57 (36%) features of both. Thirty-nine percent of patients remained abstinent during follow-up and 63% underwent alcohol rehabilitation. Moderate to severe ascites at diagnosis (odds ratio (OR): 3.05, 95% confidence interval (CI): 1.37-7.02) and lack of alcoholic rehabilitation (OR: 5.28, 95% CI: 2.24- 14.11) were independent predictors of abstinence. Abstinence at one year of follow-up was not related to increased survival. Patients surviving one year, abstinence during follow-up was related to increased survival for both groups.Conclusion: Abstinence from alcohol following AC/AH diagnosis was achieved in 39% of patients. Abstinence was not related to increased survival for alcoholic liver disease patients at one-year, which might partly indicate that this might be a marker that some patients were 'too sick to drink'. AC and AH patients who survived one year and remained abstinent had a favorable long-term prognosis

Increase in the incidence of alcoholic pancreatitis and alcoholic liver disease in Iceland: impact of alcohol consumption.

To access publisher's full text version of this article click on the hyperlink belowObjective: To analyze the incidence of acute alcoholic pancreatitis and of severe alcoholic liver disease (ALD) and its association with per capita alcohol consumption with identification of both alcoholic cirrhosis (AC) and severe alcoholic hepatitis (AH), in a population-based setting.Methods: A search was undertaken in diagnoses database for diagnostic codes in order to find patients hospitalized with incident acute alcoholic pancreatitis (AP) and alcoholic liver disease in Iceland in 2001-2015. Diagnoses were verified in all patients who were retrospectively reviewed. Those with ALD had either AC or AH. Alcohol sales during the study period were obtained from Statistics Iceland.Results: Overall, 273 patients with acute AP, mean age at diagnosis 50 (14) years, 74% males and 159 patients with ALD, mean age 57 (11) years, 73% males, were identified. Mean per capita alcohol consumption was 6.95 (0.4) liters and increased by 21% over the study period. The annual incidence of AP increased from 4.2 per 100.000 to 9.5 and ALD from 1.6 to 6.1 per 100.000. Trend analysis showed a significant annual increase of 7% (RR 1.07, 95%CI 1.04-1.10) for AP and an annual increase of 10.5% (RR 1.10, 95%CI 1.06-1.15) for ALD. The increase was only significant in males.Conclusions: Increase per capita alcohol consumption over a 15 year study period was associated with an increase in the incidence of severe alcoholic liver disease and alcohol-related acute pancreatitis in males but not in females