FibroScan compared to liver biopsy for accurately staging recurrent hepatic steatosis and fibrosis after transplantation for MASH.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) recurrence after liver transplantation (LT) seems unavoidable and gradual. We aimed to evaluate the diagnostic accuracy in the post-LT setting of patients transplanted for metabolic dysfunction-associated steatohepatitis (MASH) of recurrent hepatic steatosis and fibrosis identified with FibroScan, compared to biopsy findings. METHODS: This prospective cohort study included adults transplanted for MASH between 2010 and 2022 in three LT centres in Spain who underwent FibroScan and biopsy at least 1-year after LT. RESULTS: In total, 44 patients transplanted for MASH after LT were included. The median time from LT to biopsy and FibroScan was 24.5 (interquartile range [IQR]:16-46) and 26.0 (IQR: 16.8-41.5) months, respectively. The median time between biopsy and FibroScan was 2.0 (IQR: 0-5) months. On FibroScan, significant steatosis was diagnosed in about half of the patients (n = 21, 47.7%), yet advanced fibrosis in only two cases (4.6%). On biopsy, a quarter of biopsied patients (n = 11, 25%) had a MASH diagnosis, two (4.6%) with significant fibrosis and one (2.3%) with cirrhosis. All patients with liver stiffness measurement (LSM) values <8 kPa (n = 35, 79.5%) had a fibrosis stage ≤F1 (negative predictive value = 100%). The combination of post-LT hypertension (odds ratio [OR]: 12.0, 95% confidence interval [CI]: 1.8-80.4, p = .010) and post-LT dyslipidaemia (OR: 7.9, 95% CI: 1.3-47.1, p = .024) with LSM (OR: 1.7, 95% CI: 1.1-2.8, p = .030) was independently associated with MASLD. CONCLUSIONS: Although biopsy remains the gold standard for detecting fibrosis, our results suggest that LSM values <8 kPa after LT for MASH are strongly correlated with absence of significant/advanced fibrosis.

Impact on neonatal morbidity of moderate to severe early foetal growth restriction defined by doppler criteria: multicentre study.

INTRODUCTION: In recent years, there has been a change in the conceptualization of foetal growth restriction (FGR), which has gone from being defined solely based on weight criteria to being defined and staged based on Doppler criteria. The aim of our study was to evaluate neonatal risk in a cohort of neonates with moderate to severe early-onset FGR defined by Doppler criteria. POPULATION AND METHODS: We conducted a multicentre prospective cohort study in a cohort of neonates with early-onset foetal growth restriction and abnormal Doppler findings and a control cohort without Doppler abnormalities matched for sex and gestational age. RESULTS: A total of 105 patients (50 cases, 55 controls) were included. We found a higher frequency of respiratory morbidity in the FGR group, with an increased need of surfactant (30% vs. 27.3%; OR, 5.3 [95% CI, 1.1-26.7]), an increased need for supplemental oxygen (66% vs. 49.1%; OR, 5.6 [95% CI, 1.5-20.5]), and a decreased survival without bronchopulmonary dysplasia (70 vs. 87.3%; OR, 0.16 [95% CI, 0.03-0.99]). Patients with FGR required a longer length of stay and more days of parenteral nutrition and had a higher incidence of haematological abnormalities such as neutropenia and thrombopenia. The lactate level at birth was higher in the severe FGR subgroup (6.12 vs. 2.4 mg/dL; P = .02). CONCLUSION: The diagnosis of early-onset moderate to severe FGR defined by Doppler criteria carries a greater risk of respiratory, nutritional and haematological morbidity, independently of weight and gestational age. These patients, therefore, should be considered at increased risk compared to constitutionally small for gestational age preterm infants or preterm infants without FGR.

Internal Audit to Monitor the Injected Activity in PET/CT Using Control Charts.

BACKGROUND AND OBJECTIVE: In an effort to limit the risks associated with medical radiation exposure, the last century witnessed the development of dose control mechanisms, recommended by the International Commission on Radiological Protection. This organization recommends the optimization of radiation protection to provide the highest level of safety that may reasonably be achievable. Adhering to the "as low as reasonably achievable" principle, the purpose of this study was to monitor the 18F-FDG injected activity in PET and optimize the radiation protection through an internal audit process. This monitoring allows the identification of opportunities for improvement in patient care and safety, as well as to establish a periodic review of the medical unit reference levels. METHODS: The methodology is based on short run Quesenberry (Q) statistics and normalized nonconstant sample size (Z-chart) control charts. Anonymized data from 512 patients were selected from a set of 18F-FDG PET/CT (Siemens, Biograph 6) examinations performed during 10 months. The analyzed variable was the ratio between the 18F-FDG injected activity (MBq) and patient weight (kg). RESULTS: Mean injected 18F-FDG activity was 347.811 ± 64.967 MBq corresponding to a mean effective dose of 6.608 ± 1.234 mSv. The ratio between the 18F-FDG injected activity and the body mass of patients was reduced from 5.243 ± 0.716 to 5.171 ± 0.672 MBq/kg during the statistical data analysis. The study demonstrates that control charts can be a useful tool to signal situations where patients receive an activity significantly different from the standard practice in a medical unit. CONCLUSION: The use of joint control charts is a suitable tool for detecting nonoptimized radiopharmaceutical administration. This analysis provides opportunities to evaluate and improve the quality of practice in nuclear medicine. This methodology constitutes an internal audit that may help health care professionals to make appropriate decisions to ensure all patients receive the safest and most appropriate care.

Unveiling the value of C-reactive protein as a severity biomarker and the IL4/IL13 pathway as a therapeutic target in recessive dystrophic epidermolysis bullosa: A multiparametric cross-sectional study.

Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience numerous complications, which are exacerbated by inflammatory dysregulation and infection. Understanding the immunological mechanisms is crucial for selecting medications that balance inflammation control and immunocompetence. In this cross-sectional study, aiming to identify potential immunotherapeutic targets and inflammatory biomarkers, we delved into the interrelationship between clinical severity and systemic inflammatory parameters in a representative RDEB cohort. Encompassing 84 patients aged 1-67 and spanning all three Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) severity categories, we analysed the interrelationship of infection history, standard inflammatory markers, systemic cytokines and Ig levels to elucidate their roles in RDEB pathophysiology. Our findings identify C-reactive protein as an excellent biomarker for disease severity in RDEB. A type 2 inflammatory profile prevails among moderate and severe RDEB patients, correlating with dysregulated circulating IgA and IgG. These results underscore the IL4/IL13 pathways as potential evidence-based therapeutic targets. Moreover, the complete inflammatory scenario aligns with Staphylococcus aureus virulence mechanisms. Concurrently, abnormalities in IgG, IgE and IgM levels suggest an immunodeficiency state in a substantial number of the cohort's patients. Our results provide new insights into the interplay of infection and immunological factors in the pathogenesis of RDEB.

Development and Validation of a Scoring System to Predict Response to Obeticholic Acid in Primary Biliary Cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA. METHODS: We used data from the Italian RECAPITULATE (N = 441) and the IBER-PBC (N = 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS) or also after 6 months of treatment (ORS+). Multivariable Cox regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [ULN]<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or normal range criteria (NR: normal ALP, alanine aminotransferase [ALT], and bilirubin) up to 24 months. RESULTS: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN, and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 0.78 for ORS+. Results were consistent across groups with mild/severe disease. CONCLUSIONS: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC.

Primary Sclerosing Cholangitis: Gender Effects in Valencia's Low-Prevalence Region.

BACKGROUND AND AIMS: Recent studies point out to epidemiological changes in primary sclerosing cholangitis (PSC). Our aims were to determine in PSC patients followed in several centers in a Mediterranean geographic area: (i) changes in baseline features and (ii) effect of gender on clinical course. METHODS: Retrospective multicenter study of PSC patients treated in 8 hospitals in a Mediterranean area between 2000 and 2021. Charts were reviewed compiling demographic, clinical, radiological, and histological variables. RESULTS: Cohort of 112 PSC patients included, 42% women, 70% diagnosed after 2010. Women were increasingly diagnosed in recent cohorts. The median time from diagnosis to the combined endpoint liver transplantation (Lt) and/or death was 6.9 years. Asthenia at diagnosis (p = 0.009) was associated with lower transplant-free survival, while diagnosis before 2005 was associated with greater LT-free survival (p < 0.001). By Cox regression, LT-free survival was not influenced by age, sex, or cirrhosis at the time of diagnosis. Women were found to have less jaundice at diagnosis (2 vs 14%; p = 0.013), higher prevalence of ANA antibodies (43.9 vs 15.7%; p = 0.003), and lower GGT levels at diagnosis (GGT 123 vs 209U/L; p = 0.014) than men. CONCLUSION: In an area traditionally considered to have low prevalence, the prevalence of affected women surpasses expectations based on existing literature. There appear to be gender-related variations in the presentation of the condition, highlighting the need for confirmation through larger-scale studies.

Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries.

Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (DILI-DRESS). We identified 53 DILI-DRESS cases from the Spanish DILI Registry and the Latin American DILI Network. For comparison purposes, we defined a group of DILI patients (n = 881). DILI-DRESS cases were younger (47 vs. 53 years, respectively; p = 0.042) and presented more frequently with cholestatic/mixed damage (p = 0.018). Most DILI-DRESS patients showed moderate liver injury, 13% developed severe damage, and only one patient (with hepatocellular injury due to anti-tuberculosis drugs) progressed to acute liver failure and died. DILI-DRESS cases showed a distinctive causative drug pattern compared to DILI cases. The most frequent drugs were carbamazepine (13%), anti-tuberculosis drugs (13%), amoxicillin-clavulanate (11%), and allopurinol and lamotrigine (7.6% each). Among all cases of DILI due to allopurinol and lamotrigine, 67% presented with a DILI-DRESS phenotype, respectively. Higher total bilirubin (TBL) levels at DILI recognition (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04-1.45) and absence of eosinophilia (OR 8.77; 95% CI 1.11-69.20) increased the risk for developing a severe-fatal injury in DILI-DRESS patients. DILI-DRESS patients have a more frequent cholestasis/mixed pattern of injury at presentation, with antiepileptics as distinctive causative drug class. Most of the lamotrigine and allopurinol cases present with this phenotype. Higher TBL levels and absence of eosinophilia at DILI recognition are markers of poor outcomes.

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries.

BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury (DILI) with autoimmune features is a liver condition with laboratory and histological characteristics similar to those of idiopathic autoimmune hepatitis (AIH), which despite being increasingly reported, remains largely undefined. We aimed to describe in-depth the features of this entity in a large series of patients from two prospective DILI registries. METHODS: DILI cases with autoimmune features collected in the Spanish DILI Registry and the Latin American DILI Network were compared with DILI patients without autoimmune features and with an independent cohort of patients with AIH. RESULTS: Out of 1,426 patients with DILI, 33 cases with autoimmune features were identified. Female sex was more frequent in AIH patients than in the other groups (p = .001). DILI cases with autoimmune features had significantly longer time to onset (p < .001) and resolution time (p = .004) than those without autoimmune features. Interestingly, DILI patients with autoimmune features who relapsed exhibited significantly higher total bilirubin and transaminases at onset and absence of peripheral eosinophilia than those who did not relapse. The likelihood of relapse increased over time, from 17% at 6 months to 50% 4 years after biochemical normalization. Statins, nitrofurantoin and minocycline were the drugs most frequently associated with this phenotype. CONCLUSIONS: DILI with autoimmune features shows different clinical features than DILI patients lacking characteristics of autoimmunity. Higher transaminases and total bilirubin values with no eosinophilia at presentation increase the likelihood of relapse in DILI with autoimmune features. As the tendency to relapse increases over time, these patients will require long-term follow-up.

[Usefulness of artery femoral ultrasound complementary to carotid exploration for the detection of subclinical atheromatosis in patients with human immunodeficiency virus infection]. / Utilidad de la ecografía de la arteria femoral complementaria a la exploración carotídea para la detección de ateromatosis subclínica en pacientes con infección por el virus de la inmunodeficiencia humana.

INTRODUCTION: Detection of subclinical atheromatosis disease (SAD) in patients with human immunodeficiency virus (HIV) infection is usually based on carotid ultrasound. However, studies in other pathologies have shown a probable underestimation of SAD when its detection is exclusively based on carotid exploration. This study evaluates the impact on detection of SAD in patients with HIV through combined carotid and femoral exploration. METHODS: Cross-sectional and prospective study of patients with HIV, diagnosed between 2008-2017. Carotid and femoral ultrasound examination was performed in all patients. EAS was defined according to Mannheim criteria. RESULTS: One hundred two patients were included (mean age: 40 years, 73.5% being male). The prevalence of carotid SAD in the total sample was 15.7% (n=16), and the prevalence of femoral SAD was 18.6% (n=19). The proportion of patients with global SAD criteria (carotid or femoral) was 23.5% (n=24), which implies an absolute increase in SAD detection of 7.84% (95% CI; 2.63-13.06%) at the total sample. CONCLUSIONS: Detection of SAD is significantly increased by the combined use of carotid and femoral arterial ultrasound in the population affected by HIV infection.

Bloodstream Infection in Children With Epidermolysis Bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is frequently complicated by skin infection, which can lead to bacteremia. However, bloodstream infections (BSI) in patients with EB have not been well described. METHODS: Retrospective study of BSI in children 0-18 years with EB from a national reference unit in Spain, in 2015-2020. RESULTS: Among 126 children with EB, we identified 37 BSI episodes in 15 patients (14 recessive dystrophic EB, 1 junctional EB). The most frequent microorganisms were Pseudomonas aeruginosa (n = 12) and Staphylococcus aureus (n = 11). Five P. aeruginosa isolates were ceftazidime-resistant (42%), 4 of which were also resistant to meropenem and quinolones (33%). As for S. aureus , 4 (36%) were methicillin-resistant and 3 (27%) clindamycin-resistant. In 25 (68%) BSI episodes skin cultures had been performed in the previous 2 months. The most frequent isolates were also P. aeruginosa (n = 15) and S. aureus (n = 11). In 13 cases (52%), smear and blood cultures grew the same microorganism, with the same antimicrobial resistance pattern in 9 isolates. Twelve patients (10%) died during follow-up (9 RDEB and 3 JEB). BSI was the cause of death in 1 case. In patients with severe RDEB, a history of BSI was associated with higher mortality (OR 6.1, 95% CI: 1.33-27.83, P = 0.0197). CONCLUSIONS: BSI is an important cause of morbidity in children with severe forms of EB. The most frequent microorganisms are P. aeruginosa and S. aureus , with high rates of antimicrobial resistance. Skin cultures can help guide treatment decisions in patients with EB and sepsis.

Budesonide as first-line treatment in patients with autoimmune hepatitis seems inferior to standard predniso(lo)ne administration.

BACKGROUND AND AIMS: In patients with non-severe acute or chronic autoimmune hepatitis (AIH) without cirrhosis, clinical practice guidelines recommend indistinct use of prednisone or budesonide. However, budesonide is infrequently used in clinical practice. We aimed to describe its use and compare its efficacy and safety with prednisone as first-line options. APPROACH AND RESULTS: This was a retrospective, multicenter study of 105 naive AIH patients treated with budesonide as the first-line drug. The control group included 276 patients treated with prednisone. Efficacy was assessed using logistic regression and validated using inverse probability of treatment weighting propensity score. The median time to biochemical response (BR) was 3.1 months in patients treated with budesonide and 4.9 months in those with prednisone. The BR rate was significantly higher in patients treated with prednisone (87% vs. 49% of patients with budesonide, p < 0.001). The probability of achieving BR, assessed using the inverse probability of treatment weighting propensity score, was significantly lower in the budesonide group (OR = 0.20; 95% CI: 0.11-0.38) at any time during follow-up, and at 6 (OR = 0.51; 95% CI: 0.29-0.89) and 12 months after starting treatment (0.41; 95% CI: 0.23-0.73). In patients with transaminases <2 × upper limit of normal, BR was similar in both treatment groups. Prednisone treatment was significantly associated with a higher risk of adverse events (24.2% vs. 15.9%, p = 0.047). CONCLUSIONS: In the real-life setting, the use of budesonide as first-line treatment is low, and it is generally prescribed to patients with perceived less disease activity. Budesonide was inferior to prednisone as a first-line drug but was associated with fewer side effects.

[Capillaroscopy, microangiopathy, and HIV. Descriptive study of capillaroscopy findings in HIV positive patients].

BACKGROUND: In this study, we aim to evaluate microangiopathy in HIV positive patients by using capillaroscopy. To date, few studies have been published on the topic. Capillaroscopy may be a tool for early diagnosis of cardiovascular involvement in this patient population. METHODOLOGY: Cross-sectional study with HIV positive patients >18 years. The enrolment period was set from January to June 2018. The following data were collected: demographic (sex, age), laboratory tests (duration of infection, CD4 cell count, CD4:CD8 ratio, coinfection with other viruses), antiretroviral treatment, dyslipidemia, and comorbidities (active smoking, alcoholism, high blood pressure, dyslipidaemia, diabetes, cardiopathy). The capillaroscopy and blood tests were performed simultaneously. The following alterations were evaluated in the capillaroscopy: congestion, tortuosity, haemorrhage, dilations, capillary loss, and presence of megacapillaries. RESULTS: One hundred and two patients were included; 73.5% were male, mean age was 40 years (SD: 10), and mean duration of infection 4.5 years (SD: 3.1). At diagnosis, mean CD4 cell count was 408/mm3 and CD4/CD8 ratio 0.4. A number of patients (14.7%) were coinfected with the hepatitis B virus; 31.3% were active smokers and 13.7% alcoholics. Capillaroscopy alterations were found in most study patients (93.1%): congestion (78.5%), tortuosity (77.5%), haemorrhage (13.8%), dilations (11.8%), capillary loss (5%), and megacapillaries (1%). Capillary tortuosity was associated with age and smoking; and haemorrhage with age, CD4, antiretroviral treatment, and hypertension. CONCLUSION: Prevalence of capillaroscopy alterations is high in HIV positive patients, particularly tortuosity and congestion. To the best of our knowledge, the later alteration has not been previously reported in this group of patients.

Interlaboratory Analytical Validation of a Next-Generation Sequencing Strategy for Clonotypic Assessment and Minimal Residual Disease Monitoring in Multiple Myeloma.

CONTEXT.­: Minimal residual disease (MRD) is a major prognostic factor in multiple myeloma, although validated technologies are limited. OBJECTIVE.­: To standardize the performance of the LymphoTrack next-generation sequencing (NGS) assays (Invivoscribe), targeting clonal immunoglobulin rearrangements, in order to reproduce the detection of tumor clonotypes and MRD quantitation in myeloma. DESIGN.­: The quantification ability of the assay was evaluated through serial dilution experiments. Paired samples from 101 patients were tested by LymphoTrack, using Sanger sequencing and EuroFlow's next-generation flow (NGF) assay as validated references for diagnostic and follow-up evaluation, respectively. MRD studies using LymphoTrack were performed in parallel at 2 laboratories to evaluate reproducibility. RESULTS.­: Sensitivity was set as 1.3 tumor cells per total number of input cells. Clonality was confirmed in 99% and 100% of cases with Sanger and NGS, respectively, showing great concordance (97.9%), although several samples had minor discordances in the nucleotide sequence of rearrangements. Parallel NGS was performed in 82 follow-up cases, achieving a median sensitivity of 0.001%, while for NGF, median sensitivity was 0.0002%. Reproducibility of LymphoTrack-based MRD studies (85.4%) and correlation with NGF (R2 > 0.800) were high. Bland-Altman tests showed highly significant levels of agreement between flow and sequencing. CONCLUSIONS.­: Taken together, we have shown that LymphoTrack is a suitable strategy for clonality detection and MRD evaluation, with results comparable to gold standard procedures.

Ertapenem neurotoxicity in liver transplantation.

Carbapenems are antibiotics of the cephalosporin family with a good penetrance into the central nervous system. Neurotoxicity is a rare adverse effect, most often associated with imipenem (0.4-10 %) and unusual with ertapenem. It usually presents as seizures, although encephalopathy or hallucinations may develop. However, a recent large study (n = 544) found neurotoxicity associated to the use of ertapenem with an incidence of 4.6 %. There were associated factors such as advanced age or renal dysfunction (ertapenem has a renal metabolism level of 80 %).

Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes.

Drug-induced liver injury (DILI) is an adverse toxic hepatic clinical reaction associated to the administration of a drug that can occur both at early clinical stages of drug development, as well after normal clinical usage of approved drugs. Because of its unpredictability and clinical relevance, it is of medical concern. Three DILI phenotypes (hepatocellular, cholestatic, and mixed) are currently recognized, based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values. However, this classification lacks accuracy to distinguish among the many intermediate mixed types, or even to estimate the magnitude and progression of the injury. It was found desirable to have additional elements for better evaluation criteria of DILI. With this aim, we have examined the serum metabolomic changes occurring in 79 DILI patients recruited and monitored using established clinical criteria, along the course of the disease and until recovery. Results revealed that free and conjugated bile acids, and glycerophospholipids were among the most relevant metabolite classes for DILI phenotype characterization. Using an ensemble of PLS-DA models, metabolomic information was integrated into a ternary diagram to display the disease phenotype, the severity of the liver damage, and its progression. The modeling implemented and the use of such compiled information in an easily understandable and visual manner facilitates a straightforward DILI phenotyping and allow to monitor its progression and recovery prediction, usefully complementing the concise information drawn out by the ALT and ALP classification.

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry.

BACKGROUND & AIMS: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. METHODS: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. RESULTS: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). CONCLUSIONS: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. LAY SUMMARY: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes.

Potentially inappropriate prescriptions and therapeutic complexity in older HIV patients with comorbidities.

BACKGROUND: The prolonged current survival of human immunodeficiency virus (HIV) patients exposes them to new problems arising from the comorbidities they face. OBJECTIVES: To describe the situation of comorbidities, polypharmacy, therapeutic complexity and adherence in people living with HIV over 65 years of age and to assess the presence of potentially inappropriate prescriptions (PIP) by applying deprescription criteria. METHODS: Observational study including HIV people (> 65 years) from a university tertiary level hospital. Demographic, clinical and pharmacotherapeutic characteristics of the patients and their treatments were studied. The prevalence of polypharmacy (> 5 medications) and the pharmacotherapy complexity, quantified by the Medication Regimen Complexity Index (MRCI), were calculated. Therapeutic adherence was assessed by the Simplified Medication Adherence Questionnaire (SMAQ) and the medication possession ratio, according to prescription dispensing records. The Screening Tool of Older People's Prescriptions (STOPP) and List of Evidence-baSed depreScribing for CHRONic patients (LESS-CHRON) criteria were applied to identify PIP. MAIN OUTCOME MEASURE: PIP in elderly people living with HIV. RESULTS: Thirty patients were included, 73% of whom were men, with a median age of 71 years (IQR 67 - 76) and a median duration of infection of 17 years (IQR, 9 - 21). Seventy percent of the patients suffered from dyslipemia, 66.7% from hypertension, 43.3% from diabetes and 26.7% from mental health disorders. Seventy percent of the patients took more than 5 medications and 30% more than 10. The MRCI of concomitant medications was higher (18.3 points) than the MRCI of antiretroviral therapy (5.1 points), 66.7% of the studied population was classified as adherent. Finally, 70% of the patients present some PIP according to the STOPP or LESS-CHRON criteria. The polypharmacy was significantly associated (p = 0.008) with meeting deprescription criteria. CONCLUSION: The elderly people living with HIV present numerous comorbidities and met the criteria for polypharmacy. Their pharmacotherapy complexity is mainly determined by the concomitant treatments. There is a high prevalence of meeting deprescription criteria in people living with HIV over the age of 65 and a clear relationship between polypharmacy and deprescription. The optimization of pharmacotherapy is necessary in this population.

Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid.

BACKGROUND: Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. AIM: To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. METHODS: Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). RESULTS: One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). CONCLUSIONS: This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability.