Confidence in treatment is contributing to quality of life in autoimmune liver diseases. The results of ERN RARE-LIVER online survey.

BACKGROUND AND AIMS: Autoimmune liver diseases (AILDs) are associated with impaired health-related quality of life (HrQoL). The aim of this project was to identify potentially modifiable factors related to HrQoL in a large transnational cohort of patients with AILDs. METHODS: A cross-sectional online survey was conducted on patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or primary sclerosing cholangitis from 15 European countries. HrQoL was measured with EQ-5D-5L and EQ visual analogue scale (EQ-VAS) and analysed in relation to demographic, psychosocial, disease- and treatment-related factors. A Patient Health Questionnaire-2 score >3 indicated relevant depression. Multivariable linear regression analyses were used to identify potentially modifiable factors associated with HrQoL and confidence in treatment whilst adjusting for known confounders. RESULTS: A group of 1178 European patients (79% female, mean age 48 ± 14 years) participated in the study. HrQoL was impaired in all three diseases (mean EQ-5D-5L = 0.75, mean EQ VAS = 68.9), most markedly in PBC (mean EQ-5D-5L = 0.73, mean EQ-VAS = 66.2). Relevant depression, which was detected in 17% of patients, was prominently associated with impaired HrQoL. In the regression analysis, treatment confidence was identified as an important modifiable factor positively contributing to HrQoL. This influence was observable even after adjusting for other covariates including depression. Management in a transplant centre, treatment with azathioprine in AIH, and with ursodeoxycholic acid in PBC, was associated with increased treatment confidence. Finally, improved patient-physician relationships contributed to treatment confidence. CONCLUSION: Treatment confidence is a relevant modifiable determinant of HrQoL and should be further investigated to improve the standards of care for patients with AILDs.

Impact on follow-up strategies in patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival. METHODS: We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality. RESULTS: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed. CONCLUSIONS: Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

Chronic Fatigue Persists in a Significant Proportion of Female Patients After Transplantation for Primary Sclerosing Cholangitis.

Chronic fatigue and an impairment of general health-related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC-40 and Short Form 36 (SF-36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well-being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one-third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF-36 and PBC-40 domains. Recurrent PSC and unemployment negatively affected the well-being of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.

5-Lipooxygenase Derivatives as Serum Biomarkers of a Successful Dietary Intervention in Patients with NonAlcoholic Fatty Liver Disease.

Background: It was previously shown that a bodyweight reduction among patients with nonalcoholic fatty liver (NAFLD) was connected to the lower concentration of arachidonic and linoleic acid derivatives in their blood. We hypothesized that the concentration of these lipids was correlated with the extent of their body mass reduction and, thus, liver steatosis. Methods: We analyzed 68 individuals who completed the dietary intervention. Patients were divided into two groups depending on their body mass reduction (more or less than 7%). Before and after the dietary intervention, all patients had the following measurements recorded: body mass, waist circumference, stage of steatosis, fatty liver index, liver enzymes, lipid parameters, insulin and glucose. Concentrations of lipoxins A4 (LTX A4), hydroxyeicosatetraenoic fatty acids (5(S)-HETE, 12(S)-HETE and 16(S)-HETE), hydroxyoctadecaenoic acids (9(S)-HODE and 13(S)-HODE) and 5-oxo-eicosatetraenoic acid (5-oxo-ETE) were measured in serum samples collected before and after the dietetic intervention using high-performance liquid chromatography (HPLC). Results: Patients who reduced their body mass by more than 7% revealed a significant improvement in their steatosis stage, waist circumference, fatty liver index, triglycerides and cholesterol. Conclusion: A reduction in body mass by more than 7% but not by less than 7% revealed a significant improvement in steatosis stage; waist circumference; fatty liver index; and levels of triglycerides, cholesterol, 5-oxo-ETE and LTXA-4.

Autoimmune hepatitis exerts a profound, negative effect on health-related quality of life: A prospective, single-centre study.

BACKGROUND AND AIMS: Autoimmune hepatitis is a progressive chronic liver disease. Health-related quality of life in autoimmune hepatitis has not attracted much attention so far. We prospectively assessed various aspects of health-related quality of life in a well characterized group of patients with autoimmune hepatitis. METHODS: In total, 140 patients with autoimmune hepatitis (mean age 40 ± 17 years) and 170 controls (mean age 36 ± 14 years) were included. Health-related quality of life was evaluated with following questionnaires: The Short Form (36) Health Survey, Modified Fatigue Impact Score, State-Trait Anxiety Inventory and Patient Health Questionnaire-9 assessing depression. RESULTS: Patients with autoimmune hepatitis showed a significant impairment of health-related quality of life in all, but one, domains of The Short Form (36) Health Survey. Autoimmune hepatitis was associated with pronounced physical fatigue (P < 0.001), anxiety (P < 0.001) and depression (P < 0.001). As compared to males, female patients demonstrated greater impairment of physical aspects of The Short Form (36) Health Survey and Modified Fatigue Impact Score. Twenty-seven patients (19%) had moderate (Patient Health Questionnaire-9 >10) and 14 (10%) moderately severe depression (Patient Health Questionnaire-9 >15). Depression showed a very strong correlation with chronic fatigue (R = 0.68; P < 0.001); physical and mental components of The Short Form (36) Health Survey (R = 0.52/0.68 respectively; P < 0.001) and anxiety (R = 0.47; P < 0.001). There was a trend towards better life's quality in patients treated with budesonide in some aspects of their health-related quality of life. Duration of the disease, age at diagnosis, liver fibrosis and the presence of cirrhosis were not associated with health-related quality of life. CONCLUSIONS: Health-related quality of life is significantly impaired in patients with autoimmune hepatitis. Depression seems to be a dominant symptom affecting their well-being, not associated with clinical and biochemical features of the disease.

Plasmapheresis exerts a long-lasting antipruritic effect in severe cholestatic itch.

BACKGROUND & AIMS: The amelioration of refractory cholestatic pruritus after plasmapheresis has been reported in single patients. Here, we analyse the efficacy of plasmapheresis in a cohort of patients with primary biliary cholangitis (PBC). METHODS: Seventeen consecutive patients with PBC (age range 39-85 years, 16 females, 9 with cirrhosis) and refractory pruritus underwent 129 plasmapheresis procedures during 40 admissions. Pruritus was quantified by the 10-point numeric rating scale (NRS) before and after plasmapheresis, as well as ~30 and ~90 days later. RESULTS: The mean pruritus before plasmapheresis did not differ between patients with and without cirrhosis (P>.05). Cirrhotics presented, however, with significantly higher serum alanine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and bilirubin before plasmapheresis. Plasmapheresis decreased itching to NRS≤5 in all but five admissions: Mean pruritus decreased from 8.3±1.4 to 3.1±2.2 (P<.0001) in the entire cohort. It also led to a significant decrease in serum ALT, ALP, AST, GGT (all P<.001) and bilirubin (P=.002). Antipruritic effect persisted throughout the 90-days follow-up (P<.0001). The amelioration of pruritus was not affected by the presence of cirrhosis. CONCLUSIONS: Plasmapheresis is a promising method for reducing intractable itch in a significant proportion of PBC patients regardless of liver fibrosis. Long-lasting improvement of symptoms requires repeated procedures.

Enhanced liver fibrosis test predicts transplant-free survival in primary sclerosing cholangitis, a multi-centre study.

BACKGROUND & AIMS: Biomarkers reflecting disease activity and prognosis in primary sclerosing cholangitis (PSC) have not been firmly established. Enhanced liver fibrosis (ELF) test was previously reported to predict outcome in PSC. We aimed to validate the prognostic utility of ELF test in an independent, multi-centre, retrospective PSC study population. METHODS: We collected serum samples from PSC patients from seven countries. We estimated rates of transplant-free survival by the Kaplan-Meier method, used Cox proportional hazards regression to explore the association between ELF test and clinical outcome and determined prognostic performance of ELF test by computing the area under the receiver operating characteristic (AUC-ROC) curve. RESULTS: The final analysis included 534 PSC patients (61% males). Features of autoimmune hepatitis or concomitant inflammatory bowel disease affected 44 (8%) and 379 (71%) patients respectively. ELF test levels were higher in patients reaching the combined endpoint liver transplantation or death (median 10.9 [Interquartile range (IQR): 9.8-12.1]; n=24 deaths, 79 liver transplantations) compared to those censored (8.8 [IQR: 8.0-9.8]); P<.001. ELF test expressed as mild, moderate and severe fibrosis was significantly associated with the risk of reaching the endpoint (P<.001). ELF test independently predicted clinical outcome (Hazard ratio 1.31; 95% confidence interval [1.05-1.65]; P=.018), and enabled good discrimination between PSC patients with and without endpoint (AUC-ROC: 0.79). CONCLUSION: Our retrospective data validates the predictive utility of ELF test for clinical outcomes in PSC. The clinical utility of biomarkers for fibrosis in patients with PSC should be assessed in prospective patient cohorts.

Selective and sensitive quantification of the cytochrome P450 3A4 protein in human liver homogenates through multiple reaction monitoring mass spectrometry.

This study aimed at establishing a sensitive multiple reaction monitoring-mass spectrometry (MRM-MS) method for the quantification of the drug metabolizing cytochrome P450 (CYP)3A4 enzyme in human liver homogenates. Liver samples were subjected to trypsin digestion. MRM-MS analyses were performed using three transitions optimized on one purified synthetic peptide unique to CYP3A4 and the standardizing protein, calnexin. Coefficient of variations for the precision and reproducibility of the MRM-MS measurement were also determined. The method was applied to liver samples from ten non-cholestatic donors and 34 cholestatic patients with primary biliary cholangitis (n = 12; PBC), primary sclerosing cholangitis (n = 10; PSC) or alcoholic liver disease (n = 12; ALD). The established method presented high sensitivity with limit of detection lower than 5 fmol, and was successfully applied for the absolute and relative quantification of CYP3A4 in both whole liver homogenate and microsomal fractions. When all groups were analyzed together, a significant correlation was observed for the MRM-based CYP3A4 protein quantification in homogenates and microsomes (r = 0.49, p < 0.001). No statistically significant difference was detected between CYP3A4 levels in PSC, PBC, ALD and control samples. Finally, the MRM-MS quantification of CYP3A4 in homogenates also correlated (r = 0.44; p < 0.05) with the level of enzyme activity in the same samples, as determined by measuring the chenodeoxycholic to hyocholic acid conversion. The established method provides a sensitive tool to evaluate the CYP3A4 protein in human liver homogenates from patients with normal or chronic/severe hepatic injury.

Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis.

UNLABELLED: Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P<0.0001; gamma-glutamyl transpeptidase of 117.9%, P<0.0001; bilirubin of 50.0%, P<0.001; alanine aminotransferase of 63.9%, P<0.005; and aspartate aminotransferase of 45.0%, P<0.005) and increase of Mayo Risk Score for PSC (change from baseline of +0.5 point; P<0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. CONCLUSION: At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short-term markers of quality of life are unaffected.

Prospective evaluation of PBC-specific health-related quality of life questionnaires in patients with primary sclerosing cholangitis.

BACKGROUND & AIMS: Primary biliary cirrhosis and Primary sclerosing cholangitis are autoimmune cholestatic liver diseases sharing a lot in common, including a significant impairment of patients' health-related quality of life HRQoL HRQoL in PBC is assessed with disease-specific PBC-40 and PBC-27 questionnaires. A PSC-specific questionnaire has not been developed. Neither PBC-40 nor PBC-27s applicability for PSC has been evaluated. We applied these three questionnaires for HRQoL assessment in a large homogenous cohort of PSC patients. PATIENTS AND METHODS: This cross-sectional study enrolled 102 Caucasian PSCs and 53 matched healthy controls and measured HRQoL using generic SF-36, and disease-specific (PBC-40/PBC-27) questionnaires. RESULTS: (i) SF-36. Most SF-36 domains were significantly lower in PSCs than controls. Physical Functioning and Mental Component Summary scores were significantly lower in female patients and correlated negatively with age but not with concurrent inflammatory bowel disease. Cirrhosis was associated with lower Physical Functioning, Role Physical, General Health, Vitality and Physical Component Summary. (ii) PBC-40 and PBC-27. Both tools showed similar HRQoL impairment scoring. Fatigue and Cognitive were impaired in female patients. Several correlations existed between HRQoL and laboratory parameters, including cholestatic tests and Itch. Cirrhosis correlated with Other symptoms and Fatigue PBC-40. (iii) PBC-40 vs PBC-27. Strong correlations among most domains of both questionnaires were seen, as well as between (iv) SF-36 vs PBC-40 or SF-36 vs PBC-27. CONCLUSION: This is the first study directly comparing PBC-40, PBC-27 and SF-36 in PSC. PSC patients, especially females, show HRQoL impairment. PBC-40 and PBC-27 questionnaires could be of potential use for HRQoL assessment in PSC.

Normalization of the psychometric hepatic encephalopathy score in Polish population. A prospective, quantified electroencephalography study.

BACKGROUND: The psychometric hepatic encephalopathy score (PHES) is recommended as a gold standard in evaluation of minimal hepatic encephalopathy (HE). Normative databases have been collected in few countries, clearly showing differences among studied groups. Thus, the standardization of PHES for selected populations remains necessary. AIMS: To standardize PHES in a large cohort of Polish healthy subjects and to evaluate the normograms in patients with cirrhosis with quantified electroencephalography (EEG). METHODS: Three hundred and sixteen (142 males/174 females, aged 44.5 ± 12.1) normal individuals and 50 (31 males/19 females, aged 52.8 ± 12.4) patients with cirrhosis without overt HE were included. Key correction variables of psychometric tests were performed. The multivariate linear regression was used to calculate PHES normograms. RESULTS: Age and education levels were identified as predictors of all tests, therefore age- and education-adjusted normograms were developed. A weighted time-errors regression model for line tracing test (LTT) scoring was used. The PHES ranged between +5 and -15 points and the cut-off between normal and pathological PHES was set on ≤-5 points. By this cut-off level, PHES had a sensitivity of 57% and specificity of 97% to diagnose minimal HE (AUC = 0.866 ± 0.028). In patients with cirrhosis, PHES correlated with severity of liver disease (MELD, r = -0.475, P < 0.001 and Child-Pugh classification, r = -0.452, P < 0.002) and EEG (r = 0.547, P < 0.002). In patients with impaired EEG, PHES was lower than in individuals with unaltered EEG (P < 0.02); however, agreement between these two modalities was limited. CONCLUSIONS: Valid Polish PHES normograms, which incorporates w-LTT scoring system have been developed. Future multi-centre international studies are needed to validate widely applicable norms.

Mini-Mental State Examination in patients with hepatic encephalopathy and liver cirrhosis: a prospective, quantified electroencephalography study.

BACKGROUND: Mini-Mental State Examination (MMSE) is one of the most commonly used methods in the assessment of cognitive mental status. MMSE has been used in hepatology but its usefulness in the evaluation of hepatic encephalopathy (HE) has never been properly assessed. The aim of the study was to investigate the value of MMSE in detection of HE in patients with cirrhosis. METHODS: One hundred and one consecutive patients with liver cirrhosis underwent neurological examination, MMSE and electroencephalography (EEG). Spectral analysis of EEG was done with calculation of mean dominant frequency (MDF) and relative power of delta, theta, alpha and beta rhythms. Minimal HE was diagnosed in patients with normal neurological status and alterations in spectral EEG. Statistical analysis included Fisher's exact and Anova analysis. Categorical data were compared using Levene's test for equality of variances. Correlation-coefficient analysis was performed by the Pearson's r or Z-test, as needed. Tests performance was assessed by the calculating the area under the ROC curve (AUC) and evaluating its difference from reference area (AUC=0.5). A p value <0.05 was considered statistically significant. RESULTS: Overt HE was identified in 49 (48.5%) and minimal HE in 22 (21.8%) patients. Although there were significant correlations between both severity of liver disease (Child-Pugh classification), overt HE (West-Haven criteria) and various MMSE items, MDF showed no correlation with any of MMSE items as well as MMSE summary score. MMSE (score and items) did not discriminate patients without HE and minimal HE. The only significant differences between patients without HE and with overt HE were seen in respect of MMSE score (p<0.02), orientation to place (p<0.003), repetition (p<0.01) and complex commands-understanding (p<0.02). Test performance analysis has shown that MMSE has no value as a prediction method in determining minimal HE and in respect of overt HE has a sensitivity of 63% and specificity of 52% by a cut-off level at 27.5 points to diagnose overt HE. CONCLUSIONS: In conclusion, although MMSE score and single items are altered in patients with overt HE, MMSE has no value in the assessment of minimal HE. Because MMSE could be impaired in several cognitive dysfunctions, more specific test should be used for measuring HE.

TRAF1-C5 affects quality of life in patients with primary biliary cirrhosis.

BACKGROUND: Previous studies reported associations between specific alleles of non-HLA immunoregulatory genes and higher fatigue scores in patients with primary biliary cirrhosis (PBC). AIM: To study the relationship between variables of health-related quality of life (HRQoL) and single nucleotide polymorphisms of TRAF1-C5, a member of the tumor necrosis factor receptor family. PATIENTS AND METHODS: TRAF1-C5 gene polymorphisms, rs2900180 and rs3761847, were analysed in 120 Caucasian PBCs. The HRQoL was assessed with SF-36, PBC-40, and PBC-27 questionnaires. RESULTS: We found a negative association between TT genotype of rs2900180 and SF-36's domains vitality (P < 0.05), mental health (P < 0.05), and mental component summary score (P < 0.05). GG homozygotes of rs3761847 had lower vitality (P < 0.05), mental health (P < 0.05), mental component summary score (P < 0.05) and impairment of social functioning (P < 0.01). Allelic analysis has shown that T allele of rs2900180 and G allele of rs3761847 related to SF-36's vitality (P < 0.05 and P < 0.01), social functioning (P < 0.05 and P < 0.05), mental health (P < 0.01 and P < 0.05), and mental component summary score (P < 0.01 and P < 0.05), respectively. Genotyping and allelic analysis did not reveal correlation with PBC-40 and PBC-27 domains. CONCLUSION: The association between rs2900180 and rs3761847 polymorphisms and HRQoL variables indicates that TRAF1 is involved in the induction of impaired QoL in PBC.

Serum natremia affects health-related quality of life in patients with liver cirrhosis: a prospective, single centre study.

INTRODUCTION: Hyponatremia is associated with high mortality and predicts hepatic encephalopathy but its effect on health-related quality of life remains to be established. MATERIAL AND METHODS: In this study we prospectively analyzed the relationship between hyponatremia, clinical features and quality of life in a cohort of 116 patients with cirrhosis. Chronic Liver Disease Questionnaire and Medical Outcomes Study 36- Item Short Form Health Survey were performed to assess quality of life. Evaluation of hepatic encephalopathy included West-Haven criteria, Psychometric Hepatic Encephalopathy Score and Critical Flicker Frequency analysis. Severity of liver disease was assessed with Child-Pugh score and MELD. Univariate and multivariate analysis were implemented to evaluate the influence of analyzed factors on quality of life. RESULTS: Multivariate analysis has identified serum natremia, Psychometric Hepatic Encephalopathy Score, Critical Flicker Frequency and severity of liver disease measured with MELD and Child-Pugh score as independent factors affecting quality of life in patients with cirrhosis. West Heaven criteria failed to show the relationship with quality of life in analyzed subjects. Serum kalemia showed correlation with neither quality of life, hepatic encephalopathy nor severity of the disease. CONCLUSION: In patients with cirrhosis serum natremia along with severity of liver disease and hepatic encephalopathy exerts a significant effect on patients' quality of life.

Variants of autoimmune liver diseases: how to diagnose and treat them?

Autoimmune liver diseases (AILDs), such as autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC), are classified as rare diseases, but their incidence is increasing. In this review, we present the characteristics of AILDs in adults, and mainly focus on their variants in terms of diagnosis and management. The classic AILDs have been well defined in clinical guidelines, but a proportion of patients with a single AILD tend to show features of other AILDs. In these cases, AIH­PSC or AIH­PBC variants should be suspected, prompting evaluation in experienced centers. These variants are more representative of clinical categories rather than pathological diagnoses, and the leading component of the disease determines its treatment. However, treating these patients is challenging, even for experienced clinicians. Progression to end­stage liver disease is, unfortunately, not a rare course, despite combined and second­line therapies, particularly for AIH­PSC variants. Thus, studies based on prospective registers are necessary to elaborate upon widely accepted guidelines, to offer better care to these patients, and to improve their prognosis.

Health-related quality of life and symptoms in autoimmune liver diseases.

Assessment of Health-Related Quality of Life (HRQoL) has emerged as an important tool in the evaluation of both the well-being of patients and the results of their clinical management. Over the years, a large number of questionnaires focusing on various aspects of quality of life have been developed. They are frequently divided into generic questionnaires, which can be used under various conditions, disease-specific and symptom-specific questionnaires. Autoimmune liver diseases, such as autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cirrhosis, comprise a group of rare liver conditions (i.e. affecting fewer than 5 in 10,000 people in the general population). Unfortunately, HRQoL has not been well-studied in this group of patients. In this review, we comprehensively summarize the data available in the literature on HRQoL in these conditions, emphasizing the important role that quality of life plays in the successful management of such patients.

Small Intestinal Bacterial Overgrowth and Non-Alcoholic Fatty Liver Disease: What Do We Know in 2023?

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with the pathological accumulation of lipids inside hepatocytes. Untreated NAFL can progress to non-alcoholic hepatitis (NASH), followed by fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The common denominator of the above-mentioned metabolic disorders seems to be insulin resistance, which occurs in NAFLD patients. Obesity is the greatest risk factor for lipid accumulation inside hepatocytes, but a part of the NAFLD patient population has a normal body weight according to the BMI index. Obese people with or without NAFLD have a higher incidence of small intestinal bacterial overgrowth (SIBO), and those suffering from NAFLD show increased intestinal permeability, including a more frequent presence of bacterial overgrowth in the small intestine (SIBO). The health consequences of SIBO are primarily malabsorption disorders (vitamin B12, iron, choline, fats, carbohydrates and proteins) and bile salt deconjugation. Undetected and untreated SIBO may lead to nutrient and/or energy malnutrition, thus directly impairing liver function (e.g., folic acid and choline deficiency). However, whether SIBO contributes to liver dysfunction, decreased intestinal barrier integrity, increased inflammation, endotoxemia and bacterial translocation is not yet clear. In this review, we focus on gut-liver axis and discuss critical points, novel insights and the role of nutrition, lifestyle, pre- and probiotics, medication and supplements in the therapy and prevention of both SIBO and NAFLD.

TRAF1 gene polymorphism correlates with the titre of Gp210 antibody in patients with primary biliary cirrhosis.

BACKGROUND: Polymorphisms of TRAF1 (Tumor necrosis factor receptor-associated factor 1) are associated with rheumatoid arthritis (RA). Whether TRAF1 polymorphisms confer increased risk for primary biliary cirrhosis (PBC), an autoimmune liver disease which can co-exist with RA, is unknown. AIM OF THE STUDY: To assess the frequency of the RA-conferring susceptibility TRAF1 polymorphisms rs3761847 and rs2900180 in a cohort of PBC patients. The association of TRAF1 polymorphisms with clinical features and autoantibody markers was also analyzed. METHODS: We studied 179 PBC patients and 300 controls. Samples were genotyped for TRAF1 gene polymorphisms by real-time PCR. Autoantibodies were tested by ELISA. RESULTS: The frequency of rs3761847 and rs2900180 polymorphisms did not differ between patients and controls. Laboratory or clinical features were not associated with specific polymorphisms. Gp210 autoantibody titres were conspicuously higher among GG homozygotes of rs3761847 as compared with AA homozygotes (P = 0.02). In contrast, antichromatin titers were higher in AA compared to GG rs3761847 homozygotes (P = 0.04). Rheumatoid factor IgG titres were significantly higher in rs2900180 TT homozygotes than CC homozygotes (P = 0.02). CONCLUSIONS: TRAF1 polymorphisms occur with the similar frequency in PBC patients and in the general population, but their presence is probably involved in the regulation of specific PBC-related autoantibodies.