Unrecognized liver cirrhosis is common and associated with worse survival in hepatocellular carcinoma: A nationwide cohort study of 3473 patients.

BACKGROUND: Data on unrecognized liver cirrhosis in patients with hepatocellular carcinoma (HCC) are derived mainly from cohorts with a risk of selection bias. OBJECTIVES: In a population-based cohort study we aimed to determine the proportion, characteristics, and prognosis of HCC in patients with unrecognized cirrhosis. METHODS: Using the Swedish quality register for liver cancer and other nationwide registers, we identified all adults with HCC in Sweden between 2012 and 2018 (n = 3,473). RESULTS: The final study cohort comprised 2670 patients with established cirrhosis, of which 1033 (39%) had unrecognized cirrhosis at HCC diagnosis. These patients were more often male, older, and had larger tumors, multinodular cancer, portal vein thrombosis, and extrahepatic metastasis compared to patients with known cirrhosis with HCC and under surveillance (34%). Compared to surveilled patients, those with unrecognized cirrhosis had worse median survival (0.89 years, 95% confidence interval [CI] = 0.78-1.01 vs. 3.79 years, 95%CI = 3.19-4.39), and an adjusted hazard ratio of 2.36 (95%CI = 2.09-2.66). Patients with cirrhosis but not under surveillance (27%) and patients with unrecognized cirrhosis had similar characteristics, such as equal proportions diagnosed at late stage (79%). CONCLUSIONS: Cirrhosis is often not recognized in patients with HCC. Unrecognized cirrhosis is associated with more advanced HCC at diagnosis and a worse prognosis. More efforts are needed to diagnose cirrhosis at an earlier stage.

Prognosis and mortality within 90 days in community-acquired acute kidney injury in the Southwest of Sweden.

BACKGROUND: Community-acquired acute kidney injury (CA-AKI) is common among hospitalized patients and has a poor prognosis. Research is scarce on the impact of a CA-AKI episode among patients without preexisting kidney disease and has not previously been investigated in Sweden. The aim was to describe the outcomes of patients with normal pre-hospitalization kidney function, admitted with community-acquired AKI and to investigate the association between AKI severity with outcomes. METHODS: A retrospective population-based study was applied including patients with CA-AKI according to KDIGO classification, admitted via emergency department (ED) 2017-2019 and with a 90-day follow-up period from the ED-admission, collecting data from the Regional Healthcare Informative Platform. Age, gender and AKI stages, mortality and follow-up regarding recovery and readmission was registered. Hazard ratio (HR) and 95% confidence Interval (CI) for mortality was analyzed using Cox regression adjusted for age, comorbidities, and medication. RESULTS: There were 1646 patients included, mean age was 77.5 years. CA-AKI stage 3 occurred in 51% of patients < 65 years of age and 34% among those > 65 years. In this study, 578 (35%) patients died and 233 (22%) recovered their kidney function. Mortality rate peaked within the first two weeks and among those at AKI stage 3. Nephrology referral post discharge occurred in 3% and 29% were readmitted. HRs for mortality was 1.9 (CI 1.38-2.62) for those who are > 65 years, 1.56 (CI 1.30-1.88) for atherosclerotic-cardiovascular disease. Medication with RAASi related to a decreased HR 0.27 (95% CI 0.22-0.33). CONCLUSIONS: CA-AKI is associated with high mortality within 90 days, increased risk for developing chronic kidney disease (CKD) and only one fifth recover their kidney function after hospitalization with an AKI. Nephrology referral was sparse. Patient follow-up after a hospitalization with AKI should be carefully planned during the first 90 days and focused on identifying those with a higher risk of developing CKD.

Targeting population groups with heavier burden of hepatocellular carcinoma incidence: A nationwide descriptive epidemiological study in Sweden.

Contemporary European studies examining associations between socioeconomic status and hepatocellular carcinoma (HCC) incidence are scarce. We aimed to target population groups with a heavier burden of HCC by assessing associations of individual-level sociodemographic variables and neighbourhood deprivation with all-stage and stage-specific HCC incidence rates (IR). Patient and population data stratified by calendar year (2012-2018), sex, age (5-year groups), household income (low, medium and high), country of birth (Nordic, non-Nordic) and neighbourhood deprivation (national quintiles Q1-Q5) were retrieved from Swedish registers. HCC stages were defined by Barcelona Clinic Liver Cancer stages 0 to A (early-stage) and B to D (late-stage). IR (per 100 000 person-years) were estimated by Poisson regression models. Men had four times higher IR than women. IRs increased markedly with lower household income as well as with neighbourhood deprivation. Seven times higher IR was observed among people with a low household income living in the most deprived neighbourhoods (IR 3.90, 95% confidence interval [CI] 3.28-4.64) compared to people with a high household income living in the least deprived neighbourhoods (IR 0.58, 95% CI 0.46-0.74). The gradient across income categories was more pronounced for late-stage than early-stage HCC. IR reached 30 (per 100 000 person-years) for people in the age span 60 to 79 years with low income and 20 for 60 to 79 year old people living in the most deprived neighbourhoods (regardless of income). Men with low household income and/or living in the most deprived neighbourhoods might be considered as primary targets in studies evaluating the cost-effectiveness of screening for early-stage HCC detection.

Incidence, aetiology and related comorbidities of cirrhosis: a Swedish population-based cohort study.

BACKGROUND: The incidence of cirrhosis for individuals in Sweden has previously been reported as stable/low among European countries. However, Swedish population-based studies are scarce and none of them included data from the most recent decade (2010-2019). We aimed to describe the incidence and aetiology of cirrhosis in the Halland region from 2011 to 2018, and to describe the severity and prevalence of liver-related complications and other primary comorbidities at the time of cirrhosis diagnosis. METHODS: We conducted a retrospective cohort study of all patients with cirrhosis in Halland, which has a population of 310,000 inhabitants. Medical records and histopathology registries were reviewed. RESULTS: A total of 598 patients with cirrhosis were identified. The age-standardised incidence was estimated at 23.2 per 100,000 person-years (95% CI 21.3-25.1), 30.5 (95% CI 27.5-33.8) for men and 16.4 (95% CI 14.3-18.7) for women. When stratified by age, the highest incidence rates were registered at age 60-69 years. Men had a higher incidence rate for most age groups when compared to women. The most common aetiology was alcohol (50.5%), followed by cryptogenic cirrhosis (14.5%), hepatitis C (13.4%), and non-alcoholic fatty liver disease (5.7%). Most patients had at least one liver-related complication at diagnosis (68%). The most common comorbidities at diagnosis were arterial hypertension (33%), type 2 diabetes (29%) and obesity (24%). CONCLUSIONS: Based on previous Swedish studies, our results indicate that the incidence of cirrhosis in Sweden might be considerably higher than previously reported. It is uncertain if the incidence of cirrhosis has previously been underestimated or if an actual increment has occurred during the course of the most recent decade. The increased incidence rates of cirrhosis reported in Halland are multifactorial and most likely related to higher incidence rates among the elderly. Pre-obesity and obesity are common in cirrhosis and non-alcoholic fatty liver disease has become an important cause of cirrhosis in Halland.

Socioeconomic and marital status among liver cirrhosis patients and associations with mortality: a population-based cohort study in Sweden.

BACKGROUND: The importance of socioeconomic status for survival in cirrhosis patients is more or less pronounced within different populations, most likely due to cultural and regional differences combined with dissimilarities in healthcare system organisation and accessibility. Our aim was to study the survival of patients with cirrhosis in a population-based Swedish cohort, using available data on marital status, employment status, and occupational skill level. METHODS: We conducted a retrospective cohort study of 582 patients diagnosed with cirrhosis in the Region of Halland (total population 310,000) between 2011 and 2018. Medical and histopathologic data, obtained from registries, were reviewed. Cox regression models were used to estimate associations between survival and marital status (married, never married, previously married), employment status (employed, pensioner, disability retired, unemployed), and occupational skill level (low-skilled: level I; medium-skilled: level II; medium-high skilled: level III; professionals: level IV); adjusting for sex, age, aetiology, Model for End-stage Liver Disease (MELD) score, Child-Pugh class, and comorbidities. RESULTS: Alcohol was the most common aetiology (51%). Most patients were male (63%) and the median age was 66 years. Occupational skill level was associated with the severity of cirrhosis at diagnosis and the prevalence of Child-Pugh C gradually increased from professionals through low-skilled. The mean survival for professionals (6.39 years, 95% CI 5.54-7.23) was higher than for low-skilled (3.00 years, 95% CI 2.33-3.67) and medium-skilled (4.04 years, 95% CI 3.64-4.45). The calculated hazard ratios in the multivariate analysis were higher for low-skilled (3.43, 95% CI 1.89-6.23) and medium-skilled (2.48, 95% CI 1.48-4.12), compared to professionals. When aggregated, low- and medium-skilled groups also had poorer mean survival (3.79 years, 95% CI 3.44-4.14; vs 5.64 years, 95% CI 5.00-6.28) and higher hazard ratios (1.85, 95% CI 1.32-2.61) compared to the aggregated medium-high skilled and professional groups. Marital and employment status were not statistically significant predictors of mortality in the multivariate analysis. CONCLUSIONS: Occupational skill level was strongly associated with mean survival and mortality risk. Poorer prognosis among patients with low and medium occupational skill level could not be explained by differences in sex, age, marital status, employment status, MELD score, Child-Pugh class, or comorbidity.

Vertebral compression fractures at abdominal CT: underdiagnosis, undertreatment and evaluation of an AI algorithm.

Vertebral compression fractures (VCF) are common and indicate a high future risk of additional osteoporotic fractures. However, many VCFs are unreported by radiologists, and even if reported, many patients do not receive treatment. The purpose of the study was to evaluate a new artificial intelligence (AI) algorithm for the detection of VCFs, and to assess the prevalence of reported and unreported VCFs. This retrospective cohort study included patients over age 60 years with an abdominal CT between 18 January 2019 and 18 January 2020. Images and radiology reports were reviewed to identify reported and unreported VCFs, and the images were processed by an AI algorithm. For reported VCFs, the electronic medical records were reviewed regarding subsequent osteoporosis screening and treatment. Totally, 1112 patients were included. Of these, 187 patients (16.8%) had a VCF, of which 62 had an incident VCF and 49 had a previously unknown prevalent VCF. The radiologist reporting rate of these VCFs was 30% (33/111). For moderate and severe (Grade 2-3) VCF, the AI algorithm had 85.2% sensitivity, 92.3% specificity, 57.8% PPV and 98.1% NPV. Three of 30 patients with reported VCFs started osteoporosis treatment within a year. The AI algorithm had high accuracy for the detection of VCFs and could be very useful in increasing the detection rate of VCFs, as there was a substantial underdiagnosis of VCFs. However, as undertreatment in reported cases was substantial, to fully realize the potential of AI, changes to the management pathway outside of the radiology department are imperative.

Vertebral compression fractures (VCF) are the most common osteoporotic fractures. However, they often go undetected leading to a high risk of further fractures. In this study we tested a new artificial intelligence (AI) algorithm to detect VCFs in abdominal CT scans in patients over 60 years of age, and assessed how often VCFs were missed by radiologists. We found that VCFs were underreported, with only 30% being identified by the radiologists. The AI algorithm showed promising results and had high accuracy for detecting VCFs. However, many patients with a detected VCF still did not receive treatment. The results suggests that AI could increase the detection rate of VCFs, but also highlights the need for changes beyond radiology to ensure that patients with detected fractures are appropriately treated.

Association Between Vitamin D, Frailty, and Progression of Frailty in Community-Dwelling Older Women.

CONTEXT: Vitamin D (25OHD) is involved in many physiological functions that decline with age, contributing to frailty and increased risk for negative health outcomes. Whether 25OHD is a long-term risk marker for frailty over a longer time and whether it is consistent with advancing age is unclear. OBJECTIVE: To investigate the association between 25OHD and frailty in older women followed for 10 years. DESIGN AND SETTING: Prospective, population-based, cohort study in Malmö, Sweden. PARTICIPANTS: Community-dwelling women, age 75 years (N = 1044) with reassessments at ages 80 (n = 715) and 85 (n = 382) years. METHODS: Frailty was quantified using a 10-variable frailty index. Women were categorized as 25OHD insufficient (<50 nmol/L) or sufficient (≥50 nmol/L). RESULTS: At ages 75 and 80 years, women with insufficient 25OHD were frailer than women with sufficient 25OHD (0.23 vs 0.18, P < 0.001; and 0.32 vs 0.25, P = 0.001, respectively). At age 80 years, 25OHD insufficiency was associated with subsequent frailty 5 years later (0.41 vs 0.32; P = 0.011). Accelerated progression of frailty was not associated with lower 25OHD levels, and 25OHD level >75 nmol/L was not additionally beneficial with regard to frailty. No association between 25OHD and frailty was observed at age 85 years. Within the frailty index, variables associated with 25OHD were related to muscle strength and function. CONCLUSION: In this study, 25OHD insufficiency was associated with increased frailty in all but the oldest old. This study supports the value of maintaining sufficient 25OHD levels for healthy aging.

Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality.

CONTEXT: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear. OBJECTIVE: To describe normal PTH profiles over time and the association with mortality. DESIGN AND PARTICIPANTS: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years). MAIN OUTCOME MEASURES: PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality. RESULTS: At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082). CONCLUSIONS: Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.

Association Between Hypovitaminosis D in Elderly Women and Long- and Short-Term Mortality-Results from the Osteoporotic Prospective Risk Assessment Cohort.

OBJECTIVES: To investigate the association between low vitamin D levels (<50 nmol/L) and 10-year mortality in women aged 75 and older. DESIGN: Prospective with 15 years of follow-up. SETTING: Malmö, Sweden. PARTICIPANTS: Population-based cohort of 75-year-old women (N = 1,044). MEASUREMENTS: Serum 25-hydroxyvitamin D (25(OH)D) levels at age 75 (n = 1,011), 80 (n = 642), and 85 (n = 348) were categorized as low (<50 nmol/L), intermediate (50-75 nmol/L) and high (>75 nmol/L) at all ages. Hazard ratios (HRs) for all-cause mortality between ages 75 and 90 were calculated according to 25(OH)D category. RESULTS: Between ages 80 and 90, all-cause mortality (HR = 1.8, 95% confidence interval (CI) = 1.3-2.4, P < .001; adjusted for comorbidities (aHR) = 1.9, 95% CI = 1.4-2.6, P < .001) was significantly higher in women with low 25(OH)D levels than in those with high levels. Osteoporosis had the greatest effect on mortality, but even after excluding women with osteoporotic fracture during the risk of dying associated with low 25(OH)D remained greater (HR = 1.8, 95% CI = 1.2-2.7, P = .002; aHR = 1.7, 95% CI = 1.2-2.5, P = .006). CONCLUSION: In this observational study of women aged 75 and older, 25(OH)D levels of less than 50 nmol/L were associated with greater all-cause mortality for up to 10 years. This difference was at least partially independent of comorbidities and fracture, indicating that low 25(OH)D not only is an indicator of impaired health, but also plays a role in disease outcome.