Unmet needs in autoimmune hepatitis: Results of the prospective multicentre European Reference Network Registry (R-LIVER).

BACKGROUND AND AIMS: The European Reference Network on Hepatological Diseases (ERN RARE-LIVER) launched the prospective, multicentre, quality-controlled R-LIVER registry on rare liver diseases. The aim of this study was to assess the presentation and outcome of autoimmune hepatitis (AIH) after 1 year of treatment. METHODS: Data were prospectively collected at the time of diagnosis and after 6 and 12 months follow-up. Complete biochemical response (CBR) was defined as normalization of alanine aminotransferase (ALT) and immunoglobulin G (IgG) serum levels. RESULTS: A total of 231 patients from six European centres were included in the analysis. After 6 months of treatment 50% (106/212), and after 12 months 63% (131/210) of patients reached CBR with only 27% (56/211) achieving a steroid-free CBR within the first year. Overall, 16 different treatment regimens were administered. Change of treatment, mostly due to intolerance, occurred in 30.4% within the first 6 months. In multivariate analysis, younger age at diagnosis (odds ratio [OR] = 1.03 [95% confidence interval (CI) 1.01-1.05]; p = .007), severe fibrosis (OR .38 [95% .16-.89], p = .026) and change of treatment within the first 6 months (OR .40 [95% CI .2-.86]; p = .018) were associated with a lesser chance of ALT normalization at 12 months follow-up. CONCLUSION: The landscape of AIH treatment in Europe is highly heterogeneous, even between expert centres. The results from this first European multicentre prospective registry reveal several unmet needs, highlighted by the overall low rates of CBR and the frequent failure to withdraw corticosteroids.

Measurement of liver and spleen stiffness as complementary methods for assessment of liver fibrosis in autoimmune hepatitis.

BACKGROUND AND AIMS: Liver stiffness measurements (LSM), commonly performed by transient elastography (TE) or two-dimensional shear wave elastography (2D-SWE), are used to quantify liver fibrosis. Active hepatitis, a hallmark of autoimmune hepatitis (AIH), could bias LSM. This bias might be overcome by measurement spleen 2D-SWE. Here, we compare liver and spleen 2D-SWE to TE and liver biopsy (LB) in prospectively recruited patients with AIH. METHODS: We analysed liver and spleen 2D-SWE in relation to liver TE in 90 patients treated ≥ 6 months for AIH. Liver and spleen 2D-SWE were also compared to LB in 63 individuals with AIH. Finally, we evaluated these tools in 220 patients with AIH and during 18 months follow-up. RESULTS: Liver 2D-SWE correlated with surrogate markers of active hepatitis (ALT and IgG, both P < .001) but there was no link between spleen 2D-SWE and ALT. Liver 2D-SWE, but not spleen 2D-SWE, was associated with histopathological inflammatory score (P < .01). When compared to LB, the optimal cut-offs for detecting cirrhosis by liver and spleen 2D-SWE were 16.1 kPa (AUROC 0.93) and 29.8 kPa (AUROC 0.95), respectively. In patients with active hepatitis the combined diagnostic approach including liver and spleen 2D-SWE had significantly better AUROC for detecting cirrhosis than liver 2D-SWE alone. CONCLUSIONS: Liver and spleen 2D-SWE are reliable complementary methods for the diagnosis of advanced fibrosis in AIH. Spleen 2D-SWE seems to be less biased by inflammation and could facilitate fibrosis assessment in therapy-naïve patients or in the presence of active hepatitis.

Synergistic effects of extracellular vesicle phenotyping and AFP in hepatobiliary cancer differentiation.

BACKGROUND: Biliary cancer, comprising cholangio- and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation. METHODS: Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two-step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis. RESULTS: Two directly tumour-related antigen combinations (AnnV+ CD44v6+ and AnnV+ CD44v6+ CD133+ ) and two combinations related to progenitor cells from the tumour microenvironment (AnnV+ CD133+ gp38+ and AnnV+ EpCAM+ CD133+ gp38+ ) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV+ CD44v6+ EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively. CONCLUSIONS: EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.

Acute-On-Chronic Liver Failure: The Role of Prognostic Scores in a Single-Center Experience.

BACKGROUND Acute-on-chronic liver failure (ACLF) is associated with multi-organ failure and high short-term mortality. We evaluated the role of currently available prognostic scores for prediction of 90-day mortality in ACLF patients. MATERIAL AND METHODS Fifty-five (M/F=40/15, mean age 60.0±11.1years) consecutive cirrhotic patients with severe liver insufficiency (mean MELD 28.4±9.0, Child-Pugh score - C-12) were enrolled into the study. MELD variants and SOFA, CLIF-SOFA, and CLIF-C scores were calculated, mortality predicting factors were identified, and clinical comparisons between ACLF and AD patients were performed. RESULTS In total, 30 (55%) patients were transplanted (22 ACLF and 8 AD), and 20 (30%) died (19 ACLF and 1 AD). Five (9%) patients survived without liver transplantation (LT) (3 ACLF and 2 AD), and 3 transplant recipients died within 1 month. SOFA, CLIF-SOFA, CLIF-C OF, and INR were significantly associated with the incidence of 90-day mortality in competing risk regression analysis (all p<0.001). The model based on SOFA had the lowest BIC, with the optimal cut-off for 90-day mortality prediction ≥12, with the area under the receiver operating characteristic (AUROC) of 0.901 (95% CI 0.779-1.000; p<0.001), and corresponding incidence of transplantation rates of 85.5% and 11.8%, respectively (p<0.001). Of note, the important role of 24-h urine output is emphasized. CONCLUSIONS In this series of ACLF patients, SOFA score outperformed the CLIF-C scores in predicting 90-day mortality. Multi-organ failure scores performed better in predicting patient mortality than conventional liver function assessment. LT is possible and remains effective in selected ACLF patients.

Intermittent high-flux albumin dialysis with continuous venovenous hemodialysis for acute-on-chronic liver failure and acute kidney injury.

Acute-on-chronic liver failure (ACLF) requiring intensive medical care and associated with acute kidney injury (AKI) has a mortality rate as high as 90% due to the lack of effective therapies. In this study, we assessed the effects of intermittent high-flux single-pass albumin dialysis (SPAD) coupled with continuous venovenous hemodialysis (CVVHD) on 28-day and 90-day survival and an array of clinical and laboratory parameters in patients with severe ACLF and renal insufficiency. Sixteen patients were studied. The diagnosis of ACLF and AKI was made in accordance with current EASL Clinical Practice Guidelines, including the recommendations of the International Club of Ascites. All patients received SPAD/CVVHD treatments as the blood purification therapy to support liver, kidneys, and other organs. Five patients were transplanted and 11 were not listed for transplantation because of active alcoholism. Data at the initiation of SPAD/CVVHD were compared with early morning data after the termination of the extracorporeal treatment phase. All patients had ACLF and renal insufficiency with 13/16 additionally fulfilling the AKI criteria. A total of 37 SPAD/CVVHD treatments were performed [2.3 ± 1.4]. The baseline MELD-Na score was 37.6 ± 6.6 and decreased to 33.4 ± 8.7 after SPAD/CVVHD (P < 0.001). In parallel, the CLIF-C ACLF grade and OF score, estimated at 28- and 90-day mortality, AKI stage, hepatic encephalopathy grade, and liver function tests were lowered (P = 0.001-0.032). The 28- and 90-day survivals were 56.2% overall and 53.8% in AKI. Survival in patients not transplanted (n = 11) was 45.4%. In patients with severe ACLF and AKI, the renal replacement therapy coupled with high-performance albumin dialysis improved estimated 28- and 90-day survival and several key clinical and laboratory parameters. It is postulated that these results may be further improved with earlier intervention and more SPAD treatments per patient. High-performance albumin dialysis improves survival and key clinical and laboratory parameters in severe ACLF and AKI.

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.

Renaissance of Modified Charlson Comorbidity Index in Prediction of Short- and Long-Term Survival After Liver Transplantation?

BACKGROUND Orthotopic liver transplantation (OLT) is the standard of care for end-stage liver disease. The Charlson Comorbidity Index (CCI) was originally created to assess the survival rate of patients with chronic diseases, although it was modified and adopted in OLT recipients as CCI-OLT. MATERIAL AND METHODS In total of 248 consecutive liver transplant recipients with viral cirrhosis in 98 (39.5%) patients were included. CCI-OLT was calculated assigning a weight of 3 to chronic obstructive pulmonary disease; weight of 2 to coronary artery disease, connective tissue disease, and renal insufficiency; and a weight of 1 to diabetes mellitus. RESULTS CCI-OLT was significantly correlated with recipient age (p<0.001; R=0.333) and was a significant risk factor for early post-transplant mortality (p=0.004). The presence of diabetes mellitus significantly increased the odds of early mortality (p=0.010). The optimal cut-off for CCI-OLT in prediction of mortality during the first 90 days after transplantation was ≥1, with an AUROC of 0.780 (95% CI: 0.670-0.891; p<0.001). Increasing CCI-OLT was a significant risk factor for worse 5-year post-transplant survival (p=0.001), along with coronary artery disease (p=0.008) and diabetes mellitus (p=0.021). The optimal cut-off for prediction of 5-year mortality for CCI-OLT was ≥1, with the AUROC of 0.638 (95% CI: 0.544-0.733; p=0.004). CONCLUSIONS CCI-OLT is a useful tool for measuring the effect of pretransplant comorbidities and to stratify the effect of risk on both short- and long-term outcomes after OLT. Recipient age and diabetes strongly affected short-term survival after OLT, and metabolic and vascular complications were the leading causes of death at 5 years after OLT.

Acute liver injury, acute liver failure and acute on chronic liver failure: A clinical spectrum of poisoning due to Gyromitra esculenta.

Gyromitra esculenta, also known as "false morel" is one of the most poisonous mushrooms. This species is found all over the world, growing in coniferous forest in early spring time. Common manifestation of poisoning includes gastrointestinal symptoms which include varied degrees of liver impairment. We describe three cases: acute liver injury, acute liver failure and acute-on-chronic liver failure due to G. esculenta poisoning. At admission patients presented with encephalopathy and features of liver failure. Two of them recovered completely following supportive management while the remaining patient who also had preexisting liver disease developed multiorgan failure and subsequently died. Although a rare occurrence, G. esculenta poisoning should be considered in the differential diagnosis of acute liver failure.

Effects of liver transplantation on health-related quality of life in patients with primary biliary cholangitis.

BACKGROUND: Patients with primary biliary cholangitis (PBC) have decreased health-related quality of life (HRQoL). Here, we investigate HRQoL in two cohorts of transplanted patients with PBC and compare their results to healthy subjects. PATIENTS AND METHODS: We used generic SF-36 and disease-specific PBC-40 questionnaires to evaluate HRQoL in 26 patients with PBC (23 females, age 59.4 ± 5.7 years) before and after liver transplantation (LT), and in 107 patients with PBC (99 females, age 62.8 ± 6.7 years) who were previously transplanted. The control group was comprised of 60 healthy controls (55 females, age 54.6 ± 8.8 years). RESULTS: Health-related quality of life improved after LT in 85% of PBC patients. The SF-36 measure showed significant (all P < 0.05) improvements in the majority of domains after LT, and in the summary scores both physical and mental. We also documented significant improvements in pruritus and fatigue after LT (all P < 0.01). However, liver graft recipients had significantly worse physical functioning, physical role, and emotional role domains, and physical component score (all P < 0.001), as compared to healthy subjects. No differences in HRQoL were detected between patients evaluated after short and prolonged post-LT periods (P > 0.05). CONCLUSION: Liver transplantation substantially improves most aspects of life quality in PBC patients. Nevertheless, their HRQoL remains worse in comparison to healthy individuals, mainly in physical aspects.

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.

Does transient elastography correlate with liver fibrosis in patients with PSC? Laennec score-based analysis of explanted livers.

BACKGROUND AND AIMS: Previous studies demonstrated a close correlation between transient elastography (TE) and liver histology in chronic liver diseases. Data on the accuracy of TE in primary sclerosing cholangitis (PSC) remains scarce. Here, we investigated the association between TE, serum marker of liver injury and histology of explanted livers in PSC patients. METHODS: Thirty patients were prospectively recruited. TE (Fibroscan®) and blood sampling were performed during evaluation for liver transplantation (LT); the second blood sampling was performed on the day of LT. Fibrosis of explanted livers according to the seven-point Laennec staging system and liver collagen contents were measured. RESULTS: TE correlated with Laennec stages of fibrosis (p = .001), collagen contents (p < .001) and with diameter of thickest septa (p = .034) in explanted livers. It also correlated with serum indices of liver injury, namely AST, bilirubin as well as FIB-4 and APRI scores (all p < .05). In a multivariate model, only liver fibrosis, according to either Laennec score (p = .035) or collagen contents (p = .005), was significantly associated with TE. Finally, patients with cirrhosis had increased liver stiffness (p = .002) and the TE cut-off of 13.7 kPa showed the best predictive value (AUC = .90, 95% CI: 0.80-1.00, p < .001) for detecting cirrhosis. CONCLUSIONS: TE correlates with liver fibrosis and markers of liver injury in patients with PSC. However, liver fibrosis seems to be the strongest predictor of liver stiffness assessed with TE. Hence, we postulate that TE is a reliable tool for non-invasive monitoring of PSC.

Good outcome following liver transplantation using pericardial-peritoneum window for hepato-atrial anastomosis to overcome advanced hepatic alveolar echinococcosis and secondary Budd-Chiari Syndrome - a case report.

BACKGROUND: This report presents a case of a 57- year old female with advanced Hepatic Alveolar Echinococcosis causing a secondary Budd-Chiari Syndrome due to infiltration of the suprahepatic inferior vena cava treated successfully by liver transplantation. CASE PRESENTATION: A temporary veno-venous bypass was introduced, but a typical end to end cavo-caval anastomosis wasn't possible in this case. In order to access a disease free part of the inferior vena cava, an oval window of the diaphragm was excised, providing communication between the peritoneum and pericardium. A vascular clamp was placed onto the right atrium which allowed for an atrial-caval anastomosis. The remainder of hepatectomy was performed in a conventional manner. In the post-operative period and during the 18 month follow-up there were no complications. The patient remains in good general condition with optimal graft function. CONCLUSIONS: A hepato-atrial anastomosis with a pericardial-peritoneum window during liver transplantation is feasible and extends the curability potential for patients with advanced Hepatic Alveolar Echinococcosis considered for liver transplantation.

Hepatic abscess: a rare complication after liver transplant.

BACKGROUND: This study was conducted to evaluate the predisposing factors, microbiology, treatment, and outcomes associated with hepatic abscess, a rare but serious complication which may accur after an orthotopic liver transplant (OLT). METHODS: This was a retrospective study based on a prospectively maintained database of 1100 patients who underwent OLT at the Medical University of Warsaw. An abscess was defined on imaging as solitary or multiple localized parenchymal collections in patients with clinical signs of infection, with or without positive cultures from blood or abscess aspirate. RESULTS: Fifteen patients (1.4%) developed hepatic abscess, including 12 (80%) with multiple abscesses. Predisposing factors included biliary pathology (eight patients), hepaticojejunostomy (six patients), and hepatic artery stenosis or thrombosis (five patients). Ten patients were treated using multiple percutaneous and endoscopic interventional procedures in addition to antimicrobial treatment whereas five were treated solely with antibiotics. Five patients (33.3%) died due to multi-organ failure secondary to abscess treatment, including one unsuccessful case of re-OLT. Thirteen patients (87%) had bacterial growth and five (33.3%) had fungal growth in their blood or abscess aspirates. CONCLUSIONS: Hepatic abscess after liver transplantation may be treated successfully with percutaneous and endoscopic intervention, along with antibiotics according to the results of microbial cultures of blood and/or abscess aspirates.

Nutritional Strategies for the Individualized Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) Based on the Nutrient-Induced Insulin Output Ratio (NIOR).

Nutrients play a fundamental role as regulators of the activity of enzymes involved in liver metabolism. In the general population, the action of nutrients may be affected by gene polymorphisms. Therefore, individualization of a diet for individuals with fatty liver seems to be a fundamental step in nutritional strategies. In this study, we tested the nutrient-induced insulin output ratio (NIOR), which is used to identify the correlation between the variants of genes and insulin resistance. We enrolled 171 patients, Caucasian men (n = 104) and women (n = 67), diagnosed with non-alcoholic fatty liver disease (NAFLD). From the pool of genes sensitive to nutrient content, we selected genes characterized by a strong response to the NIOR. The polymorphisms included Adrenergic receptor (b3AR), Tumor necrosis factor (TNFα), Apolipoprotein C (Apo C III). Uncoupling Protein type I (UCP-1), Peroxisome proliferator activated receptor γ2 (PPAR-2) and Apolipoprotein E (APOEs). We performed three dietary interventions: a diet consistent with the results of genotyping (NIOR (+)); typical dietary recommendations for NAFLD (Cust (+)), and a diet opposite to the genotyping results (NIOR (-) and Cust (-)). We administered the diet for six months. The most beneficial changes were observed among fat-sensitive patients who were treated with the NIOR (+) diet. These changes included improvements in body mass and insulin sensitivity and normalization of blood lipids. In people sensitive to fat, the NIOR seems to be a useful tool for determining specific strategies for the treatment of NAFLD.

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.

Metabolites of arachidonic acid and linoleic acid in early stages of non-alcoholic fatty liver disease--A pilot study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions related to fat infiltration. The role of liver triacylglycerol accumulation in NAFLD is not fully understood. METHODS: Twenty-four patients, 12 in the first and 12 in the second stage of NAFLD, were prospectively enrolled in this study. Biochemical parameters and eicosanoids (HETE and HODE) were compared between the first and the second stage of hepatic steatosis and the effect of a 6-month dietary intervention on these parameters was evaluated. Eicosanoid profiles were extracted from 0.5 ml of plasma using solid-phase extraction RP-18 SPE columns. The HPLC separations were performed on a 1260 liquid chromatograph. RESULTS: Patients with stage I NAFLD had a significantly higher level of HDL cholesterol and a lower level of 5-HETE. Patients with grade II steatosis had higher concentrations of 9-HODE. Following the six-month dietary intervention, hepatic steatosis resolved completely in all patients. This resulted in a significant decrease in the concentrations of all eicosanoids (LX4, 16-HETE, 13-HODE, 9-HODE, 15-HETE, 12-HETE, 5-oxoETE, 5-HETE) and key biochemical parameters (BMI, insulin, HOMA-IR, liver enzymes). CONCLUSION: A significant reduction in the analyzed eicosanoids and a parallel reduction in fatty liver confirmed the usefulness of HETE and HODE in the assessment of NAFLD.