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Autoimmune liver diseases are rare serious diseases causing chronic inflammation and fibrosis in the liver parenchyma and bile ducts. Yet, the prevalence and burden of autoimmune liver diseases are largely unexplored in Arctic native populations. We investigated the prevalence and management of autoimmune liver diseases in Greenland using nationwide cross-sectional register data and subsequent medical chart reviews validating diagnoses and extracting liver histology examinations and medical treatments. The overall prevalence of autoimmune liver diseases in Greenland was 24.6 per 100,000 (95% CI: 14.7-41.3). This was based on 7 patients with autoimmune hepatitis (AIH) (12.3 per 100,000), 3 patients with primary biliary cholangitis (PBC) (5.3 per 100,000), 4 patients with AIH/PBC overlap disease (7.0 per 100,000), and no patients with primary sclerosing cholangitis. All diagnoses were confirmed by liver histology examinations. Medical treatments adhered to internal recommendations and induced complete remission in most patients with AIH, and complete or partial remission in 1 patient with PBC and 3 patients with AIH/PBC overlap disease. One patient had established cirrhosis at the time of diagnosis, while 2 patients progressed to cirrhosis. In conclusion, the prevalence of autoimmune liver diseases was lower in Greenland than in Scandinavia and among Alaska Inuit.

Introduction: The increasing prevalence of obesity and type 2 diabetes mellitus has become a global healthcare concern spreading to indigenous Arctic populations. As non-alcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome, it has become a leading cause of chronic liver disease. However, data are sparse on the prevalence of NAFLD in indigenous Arctic populations who may have a different risk profile for diabetes complications., Methods: We conducted a systematic review to estimate the prevalence of NAFLD or signs of NAFLD in indigenous Arctic people inhabiting Greenland, Alaska, Canadian territories and Eastern Russia. Also, we wanted to discuss how Arctic research in metabolic disease such as NAFLD may move forward., Results: Through the pre-specified search of Ovid MEDLINE and Embase, 3,070 unique references were identified and six studies including 5,487 persons qualified for data extraction. The prevalence of NAFLD or signs of NAFLD varied between 21% and 65%. The risk of bias was considerable particularly due to the inclusion of small and heterogeneous studies., Conclusion: Only limited published research exists on NAFLD in indigenous Arctic populations. This review reports that the prevalence of NAFLD or signs of NAFLD in the indigenous Arctic populations residing in Arctic Regions may be similar to the global level, emphasising the need for further health research in indigenous Arctic populations., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide due to its close association to the metabolic syndrome of type 2 diabetes mellitus (T2DM), obesity and insulin resistance. However, the prevalence and severity of NAFLD in Greenland remain unexplored. We aimed to estimate the prevalence of liver steatosis and fibrosis among Greenlanders and Danes with T2DM living in Greenland using biochemical surrogate markers. We included 1409 Greenlanders and 182 Danes with T2DM in this register-based cross-sectional study. Greenlanders had higher BMI and plasma lipid levels and lower HbA1c levels compared with Danes (p<0.05). Their median alanine aminotransferase (ALAT) levels were similar. However, more Greenlanders had elevated ALAT levels (20.5% vs. 11.5%, p<0.05). Greenlanders had lower FIB-4 scores than Danes, 0.91 (IQR: 0.66-1.27) vs. 0.97 (IQR: 0.78-1.34), without difference in FIB-4 score categories (p=0.27). The prevalence of advanced fibrosis was low in both populations (1.7-2.6%). In conclusion, Greenlanders with T2DM had better glycaemic control despite higher BMI and plasma lipids. A larger proportion of Greenlanders had elevated plasma ALAT levels, while FIB-4 scores were lower than Danes. These findings suggest that Greenlanders with T2DM may be less likely to develop liver complications than Danes with T2DM in Greenland.

In-depth reviewing of all medical records and clinical databases concluded a 7-year shorter lifespan among Greenlanders infected with hepatitis B virus (HBV) compared with non-infected. Mortality did not associate with liver disease or any other specific disease entity. A possible mechanism for the reduced lifespan is subclinical inflammation that may be augmented by chronic viral infection. We hypothesized that chronic HBV infection contributes to this process causing a reduced life span. We added measurement of two markers of inflammation to the 10-year follow-up on our study of HBV among 50- through 69-years-old subjects in Greenland. The markers were YKL40 related to liver disease and hsCRP as a global marker of inflammation. Survival was evaluated using Cox regression with time until death entered as dependent variable and age, sex, smoking, alcohol intake, BMI, the presence of HBsAg and one marker of inflammation as explanatory variables. Forty-eight percent of participants with chronic HBV infection were alive after 10 years compared with 65% of participants without infection (p = 0.003). Survival associated with age (p < 0.001), BMI (p = 0.003) and both YKL40 and hsCRP (both, p < 0.001). Harbouring HBV influenced 10-year survival in the Cox regression after adjusting for age, sex, BMI, smoking, alcohol intake and inflammation. In conclusion, chronic low-grade inflammation and being infected with HBV were independent markers of mortality in otherwise healthy subjects. Thus, the 7-year shorter lifespan among Greenlanders with chronic HBV infection seems related to the long-lasting infection. Our findings call for caution in perceiving a chronic infection as benign., (© 2022 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Objective: This study aimed to provide the first data on the occurrence of thyroid autoimmunity among Inuit in Greenland, a distinct ethnic group who is not iodine deficient., Design: This study is a population-based cross-sectional study., Methods: Data were collected in Nuuk in West Greenland and in Ammassalik district in East Greenland. Information on lifestyle, diet and diseases was obtained using questionnaires. Thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) and thyroid-stimulating hormone (TSH) were measured in serum. Iodine and creatinine were measured in spot urine samples., Results: The participation rate was 95% with 434 Inuit participants; 75% were smokers. Iodine excretion was 169 µg/24 h in urban West Greenland, 224 µg/24 h in the main town and 228 µg/24 h in settlements in rural East Greenland. TPOAb, TgAb or either of these was measured in the serum from 3.7, 5.9 and 8.3% of participants, respectively. TPOAb or TgAb was found in 9.3% of Inuit women and 7.5% of men and more frequently, in East Greenland Inuit with the higher iodine excretion (P = 0.02). There was some evidence suggesting that thyroid autoimmunity was more frequent among non-smokers (12.5%) compared to smokers (7.0%). Harbouring a thyroid autoantibody was most frequent in participants with TSH above 3.6 mIU/L (P < 0.001)., Conclusion: Thyroid autoantibodies were rare among Greenland Inuit. While iodine nutrition was associated with autoimmunity similarly to other ethnic groups, the influence of sex and smoking was limited. This could suggest genetic component in Inuit, but the impact of cold, selenium and persistent organic pollutants needs to be elucidated.

Objective: Arctic living is influenced by cold winters, short summers, and excessive iodine intake from the traditional Inuit diet providing for habitation of the Arctic for centuries. This is changing and we surveyed thyroid function in populations living in Greenland. Design: Population-based cross-sectional study. Methods: Data were collected in the capital city in West Greenland and in rural East Greenland. Information on lifestyle, dietary habits, and medical history was obtained using questionnaires. Thyrotropin, free thyroxine, free triiodothyronine, thyroglobulin, and thyroglobulin antibody were measured in serum, iodine, and creatinine in spot urine samples. Results: One percent of the Greenlandic population was invited and 535 participated with an overall participation rate of 95%. Iodine excretion was 225 μg/24 hours in East Greenland and 169 μg/24 hours among West Greenland Inuit. Hyperthyroidism occurred in 10.7% of West Greenlandic Inuit (men/women: 4.3%/16.3%) and 7.8% of East Greenlandic Inuit (3.8%/12.8%). Hypothyroidism was found in 2.7% in West Greenland (0.0%/5.0%) and 5.6% (5.6%/5.6%) in East Greenland. Conclusion: Hyperthyroidism was frequent among Inuit and the occurrence of hypothyroidism was low. The pattern of hyper- and hypothyroidism among Greenlandic Inuit with adequate iodine intake was comparable with those seen in populations with iodine deficiency. Inuit may thus have adapted to excessive iodine intake over centuries, causing a need for a higher iodine intake to prevent iodine deficiency disorders.

Prevalence of hepatitis B virus (HBV) infections varies markedly with geography and is endemic in the Arctic. Travel and migration have increased markedly while the influence of migration to high endemic areas remains unknown. We surveyed subjects migrating from an area with a low prevalence of chronic HBV infection (Denmark, 0.01%) to an endemic HBV area (West- and East Greenland, 3% and 29%) in order to describe the prevalence of HBV exposure among migrants. We included 198 Caucasian Danes that had migrated to Greenland and repeated the cross-sectional investigation after 10 years. We performed thorough serological testing for HBV. None had ongoing HBV infection. Migrants to East Greenland were more frequently exposed to HBV than those in West Greenland (34.3% vs 10.3%; p < 0.01). This difference was reduced at 10-year follow-up (8.1% vs 5.7%; ns) and the overall number of participants with past HBV infection decreased over the 10-year period from 19.4% to 6.9% (p = 0.02). In conclusion, migration from very low prevalence to endemic HBV areas associated with a markedly increased risk of exposure to HBV. Lack of vaccination among migrants from Denmark to Greenland was frequent and it poses a continuing risk. All who migrate from low to high endemic HBV areas should be vaccinated., Abbreviations: HBV: Hepatitis B virus; HBV-DNA: Hepatitis B virus deoxyribonucleic acid; HBsAg: Hepatitis B surface antigen; Anti-HBs: Antibodies against hepatitis B surface antigen; Anti-HBc: Antibodies against hepatitis B core antigen; BMI: Body mass index.

Dietary iodine is important to human health, and both low and high iodine intake levels increase the risk of disease. Seaweed is rich in iodine and it is a common component in both Asian and in Arctic cuisines. While the intake and impact are known for Asian people, data are lacking for Arctic people. We aimed to (1) measure iodine content of dietary seaweeds in Greenland, (2) estimate iodine absorption, and (3) assess the impact on iodine intake in Arctic people. A hunter in East Greenland donated household seaweed for (1) measurement of iodine content and (2) ingestion of 45 g by each of eight individuals with subsequent urine collections. (3) In Ammassalik, 96% of 50-69-year-old Inuit reported on the frequency of intake of seaweed and provided a spot urine sample for iodine measurement. Seaweed species provided were Chondrus crispus and Ascophyllum nodosum . (1) The iodine content was 47 and 102 mg/g, respectively. (2) An estimated 1.1 and 1.9 mg of the ingested 2.1 and 4.6 of iodine in seaweed were excreted in the urine within 2 days. (3) More than two in three Inuit reported some dietary use, and 41% (109 of 268) reported a weekly intake of dietary seaweed, which was associated with iodine excretion. In conclusion, the iodine content of edible seaweeds in the Arctic is very high and bioavailable. Dietary intake contributed to the recommended iodine intake level, but marked variation in iodine excretion calls for evaluation of the impact on thyroid function.

Ca homoeostasis is important to human health and tightly controlled by powerful hormonal mechanisms that display ethnic variation. Ethnic variations could occur also in Arctic populations where the traditional Inuit diet is low in Ca and sun exposure is limited. We aimed to assess factors important to parathyroid hormone (PTH) and Ca in serum in Arctic populations. We included Inuit and Caucasians aged 50-69 years living in the capital city in West or in rural East Greenland. Lifestyle factors were assessed by questionnaires. The intake of Inuit diet was assessed from a FFQ. 25-Hydroxyvitamin D (25OHD2 and 25OHD3) levels were measured in serum as was albumin, Ca and PTH. The participation rate was 95 %, with 101 Caucasians and 434 Inuit. Median serum 25OHD (99·7 % was 25OHD3) in Caucasians/Inuit was 42/64 nmol/l (25, 75 percentiles 25, 54/51, 81) (P<0·001). Total Ca in serum was 2·33/2·29 mmol/l (25, 75 percentiles 2·26, 2·38/2·21, 2·36) (P=0·01) and PTH was 2·7/2·2 pmol/l (25, 75 percentiles 2·2, 4·1/1·7, 2·7) (P<0·001). The 69/97 Caucasians/Inuit with serum 25OHD <50 nmol/l differed in PTH (P=0·001) that rose with lower 25OHD levels in Caucasians, whereas this was not the case in Inuit. Ethnic origin influenced PTH (β=0·27, P<0·001) and Ca (β=0·22, P<0·001) in multivariate linear regression models after adjustment for age, sex, BMI, smoking, alcohol and diet. In conclusion, ethnic origin influenced PTH, PTH response to low vitamin D levels and Ca levels in populations in Greenland. Recommendations are to evaluate mechanisms underlying the ethnic influence on Ca homoeostasis and to assess the impact of transition in dietary habits on Ca homoeostasis and skeletal health in Arctic populations.

Background: Hepatitis B virus (HBV) infection is common in Arctic populations and high alcohol intake has been associated with an increased risk of a number of diseases. Yet, a description of the influence of alcohol intake in persons with HBV infection on liver biochemistry is lacking., Objective: We aimed to describe the association between reported alcohol intake and liver biochemistry taking into account also HBV infection, ethnicity, Inuit diet, body mass index (BMI), gender and age in an Arctic population., Design and Methods: Population-based investigation of Inuit (n=441) and non-Inuit (94) in Greenland and Inuit living in Denmark (n=136). Participants filled in a questionnaire on alcohol intake and other life style factors. Blood samples were tested for aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, albumin, hepatitis B surface antigen, hepatitis B surface antibody and hepatitis B core antibody. We also performed physical examinations., Results: Participation rate was 95% in Greenland and 52% in Denmark. An alcohol intake above the recommended level was reported by 12.9% of non-Inuit in Greenland, 9.1% of Inuit in East Greenland, 6.1% of Inuit migrants and 3.4% of Inuit in the capital of Greenland (p=0.035). Alcohol intake was associated with AST (p<0.001) and GGT (p=0.001), and HBV infection was associated with ALP (p=0.001) but not with AST, GGT, bilirubin or albumin in the adjusted analysis. Inuit had higher AST (p<0.001), GGT (p<0.001) and ALP (p=0.001) values than non-Inuit after adjustment for alcohol, diet, BMI and HBV exposure. Ethnic origin modified the association between alcohol and AST, while HBV infection did not modify the associations between alcohol and liver biochemistry., Conclusions: Non-Inuit in Greenland reported a higher alcohol intake than Inuit. Ethnic origin was more markedly associated with liver biochemistry than was alcohol intake, and Greenlandic ethnicity modified the effect of alcohol intake on AST. HBV infection was slightly associated with ALP but not with other liver biochemistry parameters.

Hepatitis B virus (HBV) infection is a disease with a highly variable course. Chronic HBV infection may cause end-stage liver disease including cirrhosis and hepatocellular carcinoma, which is the 3(rd) most common cause of cancer related death due to the poor prognosis. The prevalence of HBV infection is low in many countries. Still, it remains important due to the potential consequences of the disease. HBV is endemic in the Arctic with serologic markers of chronic HBV infection in up to 29% of the population in some areas in Greenland. Interestingly, Inuit populations rarely show signs of liver disease despite the fact that around half of all Inuit has been exposed to HBV and around 8% of Inuit are chronically infected with HBV. These findings have been consistent in surveys conducted for more than four decades among Arctic Inuit. We thus review HBV infection in the Arctic with focus on Greenland Inuit and compared with Inuit in Canada, Alaska and Siberia. The aspects described include epidemiology and monitoring of the disease, as well as treatment and the risk of liver cancer.