Cumulative methotrexate dose is not associated with liver fibrosis in patients with a history of moderate-to-severe psoriasis.

BACKGROUND: There are established risk factors for liver fibrosis (LF), but data on the impact of methotrexate on LF in patients with psoriasis are lacking. OBJECTIVES: This cross-sectional study aimed to determine the prevalence of LF in patients with psoriasis and to evaluate the relationship between LF, cumulative methotrexate dose and other LF risk factors. METHODS: Adults with a history of moderate-to-severe chronic plaque psoriasis were recruited between June 2020 and March 2021. Patients underwent transient elastography to evaluate LF. Three values for liver stiffness measurement (LSM) were assessed, indicating mild or worse LF (≥ 7 kPa), moderate or worse LF (≥ 7.9 kPa) and advanced LF (≥ 9.5kPa). Cumulative methotrexate dose and other potential risk factors for LF were assessed. RESULTS: Overall, 240 patients were recruited and 204 participants with valid LSM values were included in the analysis [median age 48 years [interquartile range (IQR) 37-57]; 51% female sex; 56% body mass index (BMI) ≥ 30 (kg m-2) and a median Alcohol Use Disorders Identification Test (AUDIT) score of 4 (IQR 1-7, 23% score ≥ 8)]. In total, 91% had received methotrexate [median duration 36 months (IQR 14-78)]. Prevalence of LF was 36%, 25% and 17% using LSM ≥ 7 kPa, ≥ 7.9 kPa and ≥ 9.5 kPa, respectively. There was no association between cumulative methotrexate dose [median 2.16 (IQR 0.93-5.2)] and continuous LSM values [unstandardized coefficient 0.16, 95% confidence interval (CI) -0.49 to 0.82, P = 0.626] or using the categorical LSM cutoff values: ≥ 7 kPa [unadjusted odds ratio 1.06 (95% CI 0.97-1.15), P = 0.192], ≥ 7.9 kPa [unadjusted odds ratio 1.03 (95% CI 0.94-1.12), P = 0.577] and ≥ 9.5 kPa (unadjusted odds ratio 1.01, 95% CI 0.91-1.12; P = 0.843). The following risk factors were associated with higher LSM values: BMI (P ≤ 0.001), waist circumference (P ≤ 0.001), metabolic syndrome (P ≤ 0.001), AUDIT score (P = 0.020) and FIB-4 score (P = 0.03). BMI ≥ 28, diabetes and metabolic syndrome were shown to be better predictors of LF compared with FIB-4 score. CONCLUSIONS: This study confirms a high prevalence of significant LF in patients with psoriasis. Cumulative methotrexate dose was not associated with LF. Patients with BMI ≥ 28, metabolic syndrome and diabetes are at higher risk for LF. These risk factors may help to identify when a more detailed liver health assessment is needed.

Psoriasis is a common inflammatory skin disease affecting 3% of the UK population. People with psoriasis appear to have higher rates of liver fibrosis (scarring in the liver from injury or inflammation) compared with people without psoriasis. There are several risk factors for increasing chances of developing liver fibrosis, including obesity, alcohol and diabetes; however, there have been some concerns that methotrexate (a medicine used to treat psoriasis) could also contribute to liver fibrosis. The majority of people needing systemic therapy (such as oral medicines) will try methotrexate first as per National Institute for Health and Care Excellence (NICE) guidance. In this study carried out in the UK, we aimed to look at the relationship between the cumulative dose (total over time) of methotrexate and liver fibrosis and the relationship between other risk factors and liver fibrosis (e.g. body mass index (BMI) (a measure that uses your height and weight to work out whether your weight is healthy), diabetes, alcohol intake and metabolic syndrome (a combination of diabetes, high blood pressure and obesity)). Liver fibrosis was measured using transient elastography, which is a non-invasive technique similar to an ultrasound. We also aimed to find out whether the clinical risk factors for liver fibrosis and a simple test called a 'FIB-4 score' (measured using blood test values and age) can predict a person's chance of developing liver fibrosis, in order to determine which people will benefit most from transient elastography. From our results, we were able to confirm that liver scarring is prevalent in our patients with psoriasis. We did not find an association between cumulative methotrexate and liver scarring. However, BMI, diabetes, metabolic syndrome and FIB-4 score were associated with liver scarring. We found that BMI ≥ 28, metabolic syndrome and diabetes can be used to identify patients who require a liver health assessment. Overall, the study findings suggest that cumulative methotrexate dose is not associated with liver fibrosis in people with a history of moderate-to-severe psoriasis.

Associations between early infections and childhood cognition in the Newcastle Thousand Families Study birth cohort.

Childhood infections have been shown to stunt growth, contribute to malnutrition and reduce cognition in early adulthood. This study aimed to assess relationships between early life infections and childhood cognition at age 11 years in the Newcastle Thousand Families Study (NTFS). The analysis included 741 members from the NTFS who had complete data for infections between birth and 5 years, and the 11-plus examinations. School records from the 11-plus examinations showed cognitive (IQ), English (EQ) and arithmetic (AQ) abilities. Housing conditions, overcrowding, birth order and social class were recorded at birth. Helicobacter pylori seropositivity was measured at age 49-51 years. Multivariable linear regression was used to examine relationships between infections and cognition. The total number of infections in the first 5 years of life was not significantly associated with IQ, EQ or AQ, nor were there significant relationships between cognitive outcomes and most infections. Tonsillitis did display a positive, significant association with IQ after adjustment for confounders (b = 6.43, 95% CI 0.92, 11.94, p = 0.022). Lower respiratory tract infections (LRTIs) showed significant negative relationships with all cognitive outcomes. H. pylori seropositivity at age 50 exhibited negative, significant relationships with EQ (p = 0.014) and AQ (p = 0.024) after adjustment for confounders. Although no significant relationship between overall infections and cognition were found, there were indications that LRTIs and gastrointestinal system infections may limit cognitive development. Given these infections remain prevalent, further research regarding severity and recurrence of infections and how they affect childhood cognition is needed.

Differences Between Self-Reported and Objectively Measured Hearing Loss at Age 61-63 Years: The Newcastle Thousand Families Birth Cohort.

PURPOSE: Hearing loss is most prevalent among older adults, yet underestimated by patients, clinicians, and research communities. This study aimed to assess the accuracy of self-reported hearing difficulties among a group of adults aged 61-63 years, against audiometric measures. METHOD: The analysis used a sample (N = 346) of the Newcastle Thousand Families Study birth cohort. Data from audiological examinations and self-reported hearing difficulties were used to compare subjective and objective hearing. Hearing aid use was also assessed. RESULTS: Over 40% of the participants had some level of hearing loss (n = 155, 44.8%), and 31% (n = 133) of these reported having hearing problems during subjective assessment. Only 18 (10%) of those with objectively measured hearing loss reported using hearing aids. CONCLUSIONS: There was an inconsistency between measured and self-perceived hearing loss among adults aged 61-63 years in this cohort. The small number of hearing aid users in the cohort is a concern, in that people in this age group appear not to be getting the help they need. The data also add to the research evidence that people at this age underestimate their hearing loss.