Steatotic liver disease is the most important somatic determinant of quality of life in patients with obesity: A cross-sectional study.

BACKGROUND AND AIMS: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are often comorbid and stigmatized. This can negatively affect quality of life (QOL). Other studies have primarily used the Chronic Liver Disease Questionnaire (CLDQ), which focuses on liver-related symptoms, to characterize QOL, but most MASLD patients have only mild liver disease, and CLDQ might overlook QOL issues pertaining to them. We aimed to determine the impact of metabolic dysfunction-associated steatohepatitis (MASH) on QOL in obese patients using a 136-item generic QOL questionnaire. METHODS: We included participants with BMI ≥ 35 kg/m2 who all fully answered the sickness impact profile (SIP, range 0-100, normal = 3.4, 100 = worst) and had a liver biopsy to diagnose MASLD. Sociodemographics, comorbidity and biometric data were obtained from all participants. RESULTS: Of 176 (mean age 45.9 years, 70% female, 12.6 years of education), 132 had no-MASH and 44 MASH. On stepwise multivariable regression analysis, divorce (p = .011), unemployment (p < .003) and hepatic steatosis (p = .01) were associated with poor overall QOL. No other somatic comorbidity was associated. MASH patients more frequently than no-MASH reported physical discomfort (48% vs. 30%, p = .04), inability to do daily activities (29% vs. 54%, p = .006) and attention problems (32% vs. 57%, p = .003). CONCLUSION: MASLD severity was the only somatic determinant of QOL in patients with obesity in this cohort, and a large fraction reported debilitating symptoms. Patients and caregivers should consider the limitations this poses when planning interventions.

Are Nonalcoholic Fatty Liver Disease and Bone Mineral Density Associated? - A Cross-Sectional Study Using Liver Biopsy and Dual-Energy X-Ray Absorptiometry.

There is controversy regarding the association between nonalcoholic fatty liver disease (NAFLD) and osteoporosis. Our study aim was to assess bone mineral density (BMD) in patients with biopsy-proven NAFLD and examine if the severity of NAFLD affects BMD. A total of 147 adult women (n = 108) and men (n = 39) aged 18-76 years (mean ± standard deviation [SD] age 45.3 ± 12.5) were recruited in this cross-sectional study and underwent a liver biopsy and dual-energy X-ray absorptiometry (DXA). NAFLD activity score (NAS) based on the degree of steatosis, lobular inflammation and hepatocellular ballooning was used to assess NAFLD severity. The majority of subjects, 53%, had steatosis, 25% had nonalcoholic steatohepatitis (NASH) whereas 23% served as control subjects with no evidence of NAFLD. There were no significant differences in the lumbar spine (1.09 ± 0.12, 1.11 ± 0.18, and 1.12 ± 0.15 g/cm2, p = 0.69, in controls, steatosis, and NASH, respectively) or hip BMD (1.10 ± 0.15, 1.12 ± 0.13, and 1.09 ± 0.13 g/cm2, p = 0.48, in controls, steatosis, and NASH, respectively) between the groups. Adjusting for age, gender, body mass index, and diabetes in multiple regression models did not alter the results. There was no correlation between NAS and neither lumbar spine BMD (r = 0.06, p = 0.471), nor hip BMD (r = -0.03, p = 0.716). In conclusion, BMD was similar across the spectrum of NAFLD in both genders and not related to the severity of the underlying histological lesions, suggesting that neither steatosis nor NASH exerts a detrimental effect on BMD in these relatively young patients. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Circulating TREM2 as a noninvasive diagnostic biomarker for NASH in patients with elevated liver stiffness.

BACKGROUND AND AIMS: Reliable noninvasive biomarkers are an unmet clinical need for the diagnosis of NASH. This study investigates the diagnostic accuracy of the circulating triggering receptor expressed on myeloid cells 2 (plasma TREM2) as a biomarker for NASH in patients with NAFLD and elevated liver stiffness. APPROACH AND RESULTS: We collected cross-sectional, clinical data including liver biopsies from a derivation ( n = 48) and a validation cohort ( n = 170) of patients with elevated liver stiffness measurement (LSM ≥ 8.0 kPa). Patients with NAFLD activity scores (NAS) ≥4 were defined as having NASH. Plasma TREM2 levels were significantly elevated in patients with NASH of the derivation cohort, with an area under the receiver operating characteristics curve (AUROC) of 0.92 (95% confidence interval [CI], 0.84-0.99). In the validation cohort, plasma TREM2 level increased approximately two-fold in patients with NASH, and a strong diagnostic accuracy was confirmed (AUROC, 0.83; 95% CI, 0.77-0.89; p < 0.0001). Plasma TREM2 levels were associated with the individual histologic features of NAS: steatosis, lobular inflammation, and ballooning ( p < 0.0001), but only weakly with fibrosis stages. Dual cutoffs for rule-in and rule-out were explored: a plasma TREM2 level of ≤38 ng/ml was found to be an optimal NASH rule-out cutoff (sensitivity 90%; specificity 52%), whereas a plasma TREM2 level of ≥65 ng/ml was an optimal NASH rule-in cutoff (specificity 89%; sensitivity 54%). CONCLUSIONS: Plasma TREM2 is a plausible individual biomarker that can rule-in or rule-out the presence of NASH with high accuracy and thus has the potential to reduce the need for liver biopsies and to identify patients who are eligible for clinical trials in NASH.

Only one-third of referrals for fatty liver disease are on time: real-world study reveals opportunities to avoid unnecessary and delayed referrals.

BACKGROUND AND AIMS: Fatty liver disease is a global health concern, but in the absence of specific guidelines, current referral patterns differ according to the preferences of the general practitioners. Outpatient Gastroenterology clinics spend futile resources on liver-healthy patients while diagnosing decompensated patients delayed. We aimed to describe referral patterns to a regional outpatient Gastroenterology clinic. METHODS: We reviewed 9684 referrals from primary care for suspected liver disease in the years 2016-2017, during two years. Data were extracted from the patients' hospital records to assess the clinical workup and patient outcomes until a mean of 43 months after the time of referral. Referrals were categorized as unnecessary (no signs of liver disease), timely (significant fibrosis/compensated cirrhosis), or delayed (decompensated cirrhosis). RESULTS: We included 375 patient referrals from primary care. The main reason for referral was elevated transaminases. More than half (54%) of patients had no signs of liver disease, being unnecessarily referred for evaluation, while 17% had decompensated liver disease and were thus referred too late. CONCLUSIONS: Only one-third of patients referred on suspicion of liver disease were referred on time, either before presenting with decompensated liver cirrhosis or with some evidence of significant liver disease, e.g., liver fibrosis. There is a huge unmet need for clinical referral pathways in primary care. Strengths and Limitations of this StudyA strength of this study is the complete mapping of all potential referrals to the outpatient clinic in the two-year period. Instead of retrieving the historic data by ICD-10 diagnosis codes, and reflecting only those patients where the GP clearly suspects liver disease, we have a strong reliance on our methods. We screened all potentially relevant referrals, e.g., referrals due to weight loss or fatigue, which may reflect symptoms of cirrhosis. Thereby we are confident that we have not missed any patients that originally were referred with unspecific symptoms, but after evaluation are diagnosed with liver disease.Another strength of our study is the long follow-up period, which allows us to fully evaluate the course for the individual patient, and the potential later coming diagnoses.Finally, it is a strength of the study that we were not exclusive to one liver disease etiology, both ALD and NAFLD etiology were included in the study.A limitation of this study is the use of historic data, and the fact that it is a single-center study, showing only the referral patterns in one outpatient Gastroenterology clinic.

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease-Current Knowledge, Mechanisms and Perspectives.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut-liver-brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.

Validation of a Simple Quality-of-Life Score for Identification of Minimal and Prediction of Overt Hepatic Encephalopathy.

Minimal hepatic encephalopathy (MHE) is underdiagnosed because most clinics refrain from psychometric testing. Diagnostic activities need to go up so patients with MHE can get the treatment their condition requires. The sickness impact profile questionnaire for covert hepatic encephalopathy (SIPCHE) score is based on quality-of-life outcomes and has been proposed as a simple, patient-administered diagnostic score for grade 1 and MHE. Validate the SIPCHE for MHE identification and overt hepatic encephalopathy (OHE) prediction. 110 patients with liver cirrhosis (age 60 years, Model for End-Stage Liver Disease score of 11.4, 80% blue-collar) provided information for SIPCHE scoring: gender, age, and four SIP statements: "I do not maintain balance (physically)," "I act irritable or impatient with myself," "I am not doing any of the usual physical recreation or activities," and "I am eating much less than usual." MHE was diagnosed using an abnormal continuous reaction time test and/or portosystemic encephalopathy syndrome test score. Patients were followed for 2.7 years on average. SIPCHE score positivity had high sensitivity (82%) but low specificity (38%) for MHE detection. Patients with an abnormal SIPCHE had a higher incidence of OHE during follow-up (35% vs. 14%, P = 0.05). OHE prediction sensitivity was 87% and exclusion sensitivity was 85%. The patients with an abnormal SIPCHE had twice as many subsequent episodes of OHE, and despite their high mortality, also a higher risk. An abnormal SIPCHE had a high sensitivity and low specificity for MHE identification. An abnormal SIPCHE was associated with a more than doubled risk of OHE, even with death as a competing event. SIPCHE could be used as a high-sensitivity, low-cost, surrogate marker of MHE in clinics without availability of psychometric tests and allow more patients to benefit from anti-MHE treatment.