Minimal hepatic encephalopathy is associated with a higher risk of overt hepatic encephalopathy and poorer survival.

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a frequent complication in patients with liver cirrhosis. Its impact on predicting the development of overt hepatic encephalopathy (OHE) and survival has not been studied in large multicenter studies. METHODS: Data from patients recruited at eight centers across Europe and the United States were analyzed. MHE was detected using the psychometric hepatic encephalopathy score (PHES). A subset was also tested with the simplified animal naming test (S-ANT1). Patients were followed for OHE development and death/liver transplantation (LTx). RESULTS: A total of 1462 patients with a median model of end-stage liver disease of 11 were included (Child-Pugh (CP) stages: A 47%/B 41%/C 12%). Median follow-up time was 19 months, during which 336 (23%) patients developed an OHE episode and 464 (32%) reached the composite end point of death/LTx (369 deaths, 95 LTx). In multivariable analyses, MHE (defined by PHES) was associated with the development of OHE (subdistribution hazard ratio 1.74, p < 0.001) and poorer LTx-free survival (hazard ratio 1.53, p < 0.001) in the total cohort as well as in the subgroup of patients without a history of OHE. In subgroup analyses, MHE (defined by PHES) was associated with OHE development in patients with CP B, whereas there was no association in patients with CP A or C. In the subgroup of patients with available S-ANT1, MHE (defined by S-ANT1) was independently associated with OHE development. Combined testing (PHES+S-ANT1) was superior to single testing for predicting OHE and poorer LTx-free survival. CONCLUSIONS: This large multicenter study demonstrates that screening for MHE is a useful tool for predicting OHE and poorer survival.

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.

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.

Prevalence of Minimal Hepatic Encephalopathy in Patients With Liver Cirrhosis: A Multicenter Study.

INTRODUCTION: The prevalence of minimal hepatic encephalopathy (MHE), in particular in different subgroups, remains unknown. This study aimed to analyze the prevalence of MHE in different subgroups to identify patients at high risk and to pave the way for personalized screening approaches. METHODS: In this study, data of patients recruited at 10 centers across Europe and the United States were analyzed. Only patients without clinical signs of hepatic encephalopathy were included. MHE was detected using the Psychometric Hepatic Encephalopathy Score (PHES, cut-off < or ≤-4 depending on local norms). Clinical and demographic characteristics of the patients were assessed and analyzed. RESULTS: In total, 1,868 patients with cirrhosis with a median model for end-stage liver disease (MELD) of 11 were analyzed (Child-Pugh [CP] stages: A 46%, B 42%, and C 12%). In the total cohort, MHE was detected by PHES in 650 patients (35%). After excluding patients with a history of overt hepatic encephalopathy, the prevalence of MHE was 29%. In subgroup analyses, the prevalence of MHE in patients with CP A was low (25%), whereas it was high in CP B or C (42% and 52%). In patients with a MELD score <10, the prevalence of MHE was only 25%, but it was 48% in patients with a MELD score ≥20. Standardized ammonia levels (ammonia level/upper limit of normal of each center) correlated significantly, albeit weakly with PHES (Spearman ρ = -0.16, P < 0.001). DISCUSSION: The prevalence of MHE in patients with cirrhosis was high but varied substantially between diseases stages. These data may pave the way for more individualized MHE screening approaches.

Closing spontaneous portosystemic shunts in cirrhosis: Does it make sense? Does it work? What does it take?

Spontaneous portosystemic shunts (SPSS) are an often neglected cause of hepatic encephalopathy associated with cirrhosis. Nowadays, SPSS are considered as radiological biomarkers of clinically significant portal hypertension rather than the previous dogmatic perceived decompressive vessels. SPSS are not rare as they can be diagnosed in over 60% of the patients with cirrhosis by mere contrast-enhanced CT. Moreover, they are clinically relevant since they impact on all portal hypertensive related complications, in particular medically refractory HE, and represent an independent predictor of decompensation and mortality in cirrhosis, irrespective of the type of SPSS. Taken together, these elements warrant strategies to target these shunts directly which is currently is achieved via interventional radiology embolization. In this review, we discuss why it makes sense to tackle SPSS, how to do it and what it takes to do it right based on aggregated literature.

Knowledge needs in patients with Liver Disease: a qualitative study.

BACKGROUND: Knowledge is essential for patients' disease management strategies and a critical component of healthcare. The importance of increasing patients level of knowledge has become more widely acknowledge in liver disease management in recent years, but further studies are needed to address patients experiences of unmet knowledge needs to develop appropriate patient education strategies. Therefore, the aim of this study was to explore knowledge needs in patients' with liver disease of different etiology and severity. METHODS: A qualitative study was designed and an inductive method was chosen. Thirty-three patients with liver disease of different etiology and severity were interviewed using a semi-structured interview guide. Content analysis was used as an inspiration to describe and compare patients' needs for knowledge across disease etiology and severity. The reporting followed consolidated criteria for reporting qualitative research. RESULTS: The analysis generated three categories and nine subcategories. In general, the patients described lack of knowledge related to their liver disease, which made it difficult for them to manage their disease. Patients wished to be more involved in care and treatment of the liver disease. However, patients' had difficulties to assess and understand the importance of the information they received from healthcare professionals. Due to lack of knowledge, patients' had a misconception of the liver disease. Patients' had variation in knowledge needs depending on liver disease etiology and severity. CONCLUSION: Within liver disease management, knowledge of patients' experiences is vital to meet patients' knowledge needs and to develop appropriate patient education strategies. Therefore, it is important to ascertain a patient-centered approach to accommodate patients' individual knowledge needs, involve patients in care and treatment, and insure understanding to strengthen their self-management and give the patients the necessary skills to manage their disease and everyday life. REGISTRATION NUMBER: Open Science Framework registration DOI https://doi.org/10.17605/OSF.IO/W28RC .

Psychometric methods for diagnosing and monitoring minimal hepatic encephalopathy -current validation level and practical use.

Hepatic encephalopathy (HE) is cerebral dysfunction caused by liver failure and inflicts 30-40% of patients with liver cirrhosis during their disease course. Clinically manifest HE is often preceded by minimal HE (MHE) - a clinically undetectable cognitive disturbance closely associated with loss of quality of life. Accordingly, detecting and treating MHE improve the patients' daily functioning and prevent HE-related hospital admissions. The scope of this review article is to create an overview of the validation level and usage of psychometric tests used to detect MHE: Portosystemic hepatic encephalopathy test, continuous reaction time test, Stroop EncephalApp, animal naming test, critical flicker frequency test, and inhibitory control test. Our work is aimed at the clinician or scientist who is about to decide on which psychometric test would fit best in their clinic, cohort, or study. First, we outline psychometric test validation obstacles and requirements. Then, we systematically approach the literature on each test and select well-conducted studies to answer the following questions:• Which percentage of patients with cirrhosis does the test deem as having MHE?• Is the test able to predict clinically manifest HE?• Is there a well-known test-retest variation and inter-observer variation?• Is the test able to detect a treatment response?• Is the test result affected by age, educational level, gender, or comorbidities?

Cognitive impairment in stable Wilson disease across phenotype.

In Wilson disease (WD), mutations in the gene encoding the ATP7B copper transport protein causes accumulation of copper especially in liver and brain. WD typically presents with hepatic and/or neuropsychiatric symptoms. Impaired cognition is a well-described feature in patients with neurological WD, while the reports on cognition in hepatic WD patients are fewer and less conclusive. We examined cognition in a cohort of WD patients with both phenotypes. In this cross-sectional pilot study, we investigated cognition in 28 stable Danish WD patients by the PortoSystemic Encephalopathy (PSE) and the Continuous Reaction Time (CRT) tests. Half of the patients were female, and their median age was 35.5 years (IQR 24.5). Their phenotype was hepatic in 14 (50%), neurologic in 10 (36%) and mixed in 4 (14%). The duration of treatment was > 2 year in all patients, and their condition was stable as judged by urinary copper excretion, liver enzymes, and clinical assessment. The hepatic patients did not show signs of liver failure. In total, 16 (57%) patients performed worse than normal in the PSE and/or the CRT tests. The two tests were correlated (rho = 0.60, p = 0.0007), but neither correlated with phenotype, MELD-, Child-Pugh score, 24 h-U-Cu, or treatment type. Measurable cognitive impairment was present in more than half of the stable WD patients independent of phenotype. Thus, our data questions the existence of a purely hepatic phenotype.

Opposite effects of sleep deprivation on the continuous reaction times in patients with liver cirrhosis and normal persons.

The continuous reaction times (CRT) method describes arousal functions. Reaction time instability in a patient with liver disease indicates covert hepatic encephalopathy (cHE). The effects of sleep deprivation are unknown although cirrhosis patients frequently suffer from sleep disorders. The aim of this study was to determine if sleep deprivation influences the CRT test. Eighteen cirrhosis patients and 27 healthy persons were tested when rested and after one night's sleep deprivation. The patients filled out validated sleep quality questionnaires. Seven patients (38%) had unstable reaction times (a CRTindex < 1.9) compatible with cHE. In these patients, the wakefulness improved or normalized their reaction speed and CRTindex (p = 0.01). There was no change in the other patients' reaction speed or stability. Seven patients (38%) reported poor sleep that was not related to their CRT tests before or after the sleep deprivation. In the healthy participants, the sleep deprivation slowed their reaction times by 11% (p < 0.0001) and in 7 persons (25%) destabilized them. The acute sleep deprivation normalized or improved the reaction time stability of the patients with a CRTindex below 1.9 and had no effect in the patients with a CRTindex above 1.9. There was no relation between reported sleep quality and reaction time results. Thus, in cirrhosis patients, sleep disturbances do not lead to 'falsely' slowed and unstable reaction times. In contrast, the acute sleep deprivation slowed and destabilized the reaction times of the healthy participants. This may have negative consequences for decision-making.

Prevalence of Obesity-Related Disease in a Danish Population - The Results of an Algorithm-Based Screening Program.

Purpose: The prevalence of obesity continues to rise. People with obesity are at increased risk of several diseases. We tested an algorithm-based screening program for people with a BMI above 30 kg/m2 and present data on the prevalence of previously undiagnosed obesity-related diseases. Patients and Methods: Seven hundred and sixty-nine persons with BMI > 30 kg/m2 and age 18-60 years were screened for diabetes (assessed by glycosylated hemoglobin and oral glucose tolerance test at HbA1c 43-48 mmol/mol), sleep apnea (screened by questionnaires and assessed by cardiorespiratory monitoring at indication of sleep disorder), liver steatosis or liver fibrosis (assessed by biochemistry and fibroscan) and arterial hypertension (assessed by both office and 24-hour blood pressure measurement). A reference group of people with a BMI of 18.5-29.9 kg/m2 was established. Results: Of those referred, 73.0% were women. We identified new diabetes in 4.2%, prediabetes in 9.1%, moderate-to-severe sleep apnea in 25.1%, increased liver fat and increased liver stiffness in 68.1% and 17.4%, respectively, and hypertension or masked hypertension in 19.0%. The prevalence of diseases was much higher among men and increased with BMI. Except for hypertension, we found few participants with undiagnosed disease in the reference group. Conclusion: An algorithm-based screening program is feasible and reveals undiagnosed obesity-related disease in a large proportion of the participants. The disproportional referral pattern calls for a tailored approach aiming to include more men with obesity. Trial Registration: Inclusion of the non-obese group was approved by the Scientific Ethics Committee of The Region of Southern Denmark (project identification number: S-20210091), and the study was reported at clinicaltrials.gov (NCT05176132).

The number of people with obesity is going up, and they are at a higher risk for various diseases. We tested a screening program for people referred with a BMI over 30 kg/m² and presented the prevalence of diseases related to obesity. We screened 769 people aged 18 to 60 years with a BMI over 30 kg/m² for diabetes (biochemistry and glucose tolerance test), sleep apnea (both questionnaires and home monitoring), liver disease (biochemistry and liver scan) and high blood pressure (office and 24-hour readings). We also tested a reference group of people with BMI 18.5-30 kg/m². Among those screened, 73.0% were women. We found new cases of diabetes in 4.2%, prediabetes in 9.1%, sleep apnea in 25.1%, increased liver fat in 68.1%, increased liver stiffness in 17.4%, and hypertension or masked hypertension in 19.0%. The diseases were more common in men and increased with both higher BMI and age. Except for hypertension, we found few cases in the reference groups. The screening program uncovered undiagnosed obesity-related diseases in a large group of individuals. The uneven distribution of referrals suggests we need a customized approach to include more men with obesity.

PHES scores have limited impact on the risk of overt HE in patients with minimal HE.

BACKGROUND: Minimal hepatic encephalopathy, defined by the portosystemic hepatic encephalopathy score (PHES), is associated with a higher risk of subsequent OHE. It remains unclear if there is a stepwise increase in OHE risk with worse PHES results. METHODS: In this multicenter study, patients with minimal hepatic encephalopathy, as defined by abnormal PHES, were followed for OHE development. RESULTS: In all, 207 patients were included. There was no stepwise increase in OHE risk with worse PHES results. CONCLUSIONS: Abnormal PHES is associated with a higher OHE risk, but we found no stepwise increase in OHE risk with worse PHES results below the established cutoff.

Mental Health, Quality of Life, and Stigmatization in Danish Patients with Liver Disease.

The mental health of patients with liver diseases is often overlooked when assessing their overall health and planning care and treatment. The aim of this study was to assess anxiety, depression, hopelessness, quality of life, and the perception of stigmatization in a large cohort of patients with chronic liver disease of different aetiology and severity, as well as to identify predictors associated with mental health disorders. A total of 340 patients completed a survey assessing mental health using the Beck Anxiety Inventory, the Beck Hopelessness Scale, and the Major Depression Inventory. Quality of life was measured with the Chronic Liver Disease Questionnaire and the European Quality-of-Life visual analogue scale. To assess stigmatization, validated questions from the Danish Nationwide Survey of Patient Experiences were used. Predictors associated with anxiety, hopelessness, and depression were analysed using univariable and multivariable logistic regression analyses. Overall, 15% of the patients had moderate or severe anxiety, 3% had moderate or pronounced hopelessness, and 8% had moderate or severe depression. The prevalence of all three was highest in patients with cirrhosis and was associated with a low quality of life. More patients with cirrhosis had perceived stigmatization compared to patients with liver disease without cirrhosis, which affected their self-perception, and more than one-third of the patients refrained from telling others about their liver disease. The results emphasize the need for increased focus on mental health problems and awareness on preventing the discrimination of patients with liver disease.

Post-Transjugular Intrahepatic Portosystemic Shunt (TIPS) Hepatic Encephalopathy-A Review of the Past Decade's Literature Focusing on Incidence, Risk Factors, and Prophylaxis.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension and its' complications in liver cirrhosis, yet the development of hepatic encephalopathy (HE) remains a significant concern. This review covers the reported incidence, risk factors, and management strategies for post-TIPS HE over the past decade. Incidence varies widely (7-61%), with factors like age, liver function, hyponatremia, and spontaneous portosystemic shunts influencing risk. Procedural aspects, including TIPS timing, indication, and stent characteristics, also contribute. Pharmacological prophylaxis with lactulose and rifaximin shows promise, but current evidence is inconclusive. Procedural preventive measures, such as shunt embolization and monitoring portal pressure gradients, are explored. Treatment involves pharmacological options like lactulose and rifaximin, and procedural interventions like stent diameter reduction. Ongoing studies on novel predictive markers and emerging treatments, such as faecal microbiota transplant, reflect the evolving landscape in post-TIPS HE management. This concise review provides clinicians with insights into the multifaceted nature of post-TIPS HE, aiding in improved risk assessment, prophylaxis, and management for patients undergoing TIPS procedures.

Advance care planning in chronic liver disease.

The Danish Health Authority recommends that all patients with life threatening disease, regardless of the diagnosis, are offered palliative care with respect for individual goals of care. Only few studies have investigated the evidence of ACP in patients with decompensated liver cirrhosis. This review defines ways to identify patients with decompensated liver cirrhosis in need of palliative care and how to analyse the goals of care. We present a strategy for ACP-conversations and how to implement these in the daily clinical work.

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.

Gender and age effects on the continuous reaction times method in volunteers and patients with cirrhosis.

Minimal hepatic encephalopathy (MHE) is a metabolic brain disorder occurring in patients with liver cirrhosis. MHE lessens a patient's quality of life, but is treatable when identified. The continuous reaction times (CRT) method is used in screening for MHE. Gender and age effects on the CRT method are unknown and may confound the results. The aim of this study was to standardise the CRT method outcomes for age and gender effects. We studied 121 volunteers without known disease and 181 patients with cirrhosis by a CRT test. Reaction time to an auditory signal was measured 100 times, the 10th, 50th, and 90th reaction time percentiles were recorded, and the CRT index was calculated as the 50th percentile/(90th percentile-10th percentile), as a measure of intra-individual stability in reaction times. In volunteers, men reacted faster than women and their reaction times slowed with age. However, neither the gender nor the age effect was present regarding the CRT index. The patients with cirrhosis reacted slower and with a higher degree of instability than volunteers. Male patients reacted faster than female patients, and reaction times tended to slow with age. As among the volunteers, there was no gender or age effect on CRT index for the patients with cirrhosis. Age and gender influenced reaction times of both volunteers and patients with cirrhosis. The CRT index, however, was independent of age and gender in both groups. Screening of patients with cirrhosis using the CRT index, therefore, identifies brain dysfunction rather than effects of gender and age.

Critical flicker frequency and continuous reaction times for the diagnosis of minimal hepatic encephalopathy: a comparative study of 154 patients with liver disease.

Minimal hepatic encephalopathy (MHE) is intermittently present in up to 2/3 of patients with chronic liver disease. It impairs their daily living and can be treated. However, there is no consensus on diagnostic criteria except that psychometric methods are required. We compared two easy-to-perform reproducible bedside methods: the critical flicker frequency (CFF) and continuous reaction times (CRT) tests. A CFF <39 Hz and CRT-index <1.9 (index: the ratio 50/(90 minus 10) percentiles of reaction times) indicates cerebral dysfunction. 154 patients with acute or chronic liver disease with out overt hepatic encephalopathy (HE) underwent both tests at the same occasion. Both tests were abnormal in 20% of the patients and both tests were normal in 40% of the patients. In more than 1/3 the two tests were not in agreement as CFF classified 32% and CRT-index classified 48% of the patients as having MHE (p < 0.005). The two tests were weakly linearly correlated (r(2) = 0.14, p < 0.001) and neither test correlated with the metabolic liver function measured by the Galactose Elimination Capacity (GEC), nor with the blood ammonia concentration. Both tests identified a large fraction of the patients as having MHE and cleared only 40%. The two tests did not show concordant results, likely because they describe different aspects of MHE: the CFF gives a measure of astrocytic metabolic state and hence pathogenic aspects of MHE, whereas the CRT measures a composite key performance, viz. the ability of reacting appropriately to a sensory stimulus. The choice of test depends on the information needed in the clinical and scientific care and study of the patients.

Impact of liver disease on patients' quality of life: a mixed methods systematic review protocol.

OBJECTIVE: The objective of this systematic review is to explore the impact of liver disease on patients' quality of life in an attempt to develop effective evidence-based recommendations and strategies useful for clinical practice and health care professionals. INTRODUCTION: Liver diseases are common worldwide and a major cause of illness and death due to health problems and serious complications, which not only cause hospitalization and death, but also emotional distress, depression, and impaired quality of life. INCLUSION CRITERIA: This review will consider qualitative and quantitative studies on patients with liver disease of different severity and type. The qualitative component of this review will consider all studies that describe patients' lived experience and perception of having liver disease. The quantitative component will include studies that explore the quality of life in patients with liver disease. METHODS: CINAHL (EBSCO), Embase (Ovid), MEDLINE (Ovid), PsycINFO (Ovid), Scopus (Elsevier), and Web of Science (Ovid) will be searched for articles published in Danish and English without any restriction in terms of year of publication. Articles describing both qualitative and quantitative studies will be screened for inclusion, critically appraised for methodological quality, and have data extracted using JBI instruments for mixed methods systematic reviews. A convergent integrated approach to synthesis and integration will be used. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020173501.

Quality of life and unmet needs in patients with chronic liver disease: A mixed-method systematic review.

BACKGROUND & AIMS: In an attempt to uncover unmet patient needs, this review aims to synthesise quantitative and qualitative studies on patients' quality of life and their experience of having liver disease. METHODS: Three databases (CINAHL, Embase, and PubMed) were searched from January 2000 to October 2020. The methodological quality and data extraction of both quantitative and qualitative studies were screened and appraised using Joanna Briggs Institute instruments for mixed-method systematic reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A convergent, integrated approach to synthesis and integration was used. Studies including patients with autoimmune and cholestatic liver disease, chronic hepatitis B and C, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma were considered. RESULTS: The searches produced 5,601 articles, of which 95 (79 quantitative and 16 qualitative) were included in the review. These represented studies from 26 countries and a sample of 37,283 patients. The studies showed that patients´ quality of life was reduced. Unmet needs for information and support and perceived stigmatisation severely affected patients' quality of life. CONCLUSIONS: Our study suggests changes to improve quality of life. According to patients, this could be achieved by providing better education and information, being aware of patients' need for support, and raising awareness of liver disease among the general population to reduce misconceptions and stigmatisation. REGISTRATION NUMBER: PROSPERO CRD42020173501. LAY SUMMARY: Regardless of aetiology, patients with liver diseases have impaired quality of life. This is associated with disease progression, the presence of symptoms, treatment response, and mental, physical, and social factors such as anxiety, confusion, comorbidities, and fatigue, as well as limitations in daily living, including loneliness, low income, stigmatisation, and treatment costs. Patients highlighted the need for information to understand and manage liver disease, and awareness and support from healthcare professionals to better cope with the disease. In addition, there is a need to raise awareness of liver diseases in the general population to reduce negative preconceptions and stigmatisation.