Predictive factors for decompensating events in patients with cirrhosis with primary biliary cholangitis under different lines of therapy.

BACKGROUND AND AIMS: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients. APPROACH AND RESULTS: Multicenter study enrolling 388 patients with PBC-cirrhosis from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and PBC OCA international study of efficacy criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the propensity score-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, clinically significant portal hypertension, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin (OR 0.21 [95% CI: 0.06-0.73]) and AST (OR 0.97 [95% CI: 0.95-0.99]), while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95% CI: 0.95-0.98]). In patients treated with OCA, drug response (sHR 0.23 [95% CI: 0.08-0.64]), diabetes (sHR 5.62 [95% CI: 2.02-15.68]), albumin (sHR 0.34 [95% CI: 0.13-0.89]), and platelets (sHR 0.99 [95% CI: 0.98-1.00]) were related to decompensation. In patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (sHR 3.70 (95% CI: 1.17-11.70]) were associated with decompensated cirrhosis. CONCLUSIONS: Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.

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.

Clinical profile of Spanish hepatitisC virus-infected treatment-naïve patients with compensated cirrhosis in the CREST study. / Perfil clínico de los pacientes españoles con hepatitisC naïve con cirrosis compensada tratados en el estudio CREST.

BACKGROUND AND AIM OF THE STUDY: There are still patients with hepatitisC in Spain who have yet to be diagnosed, but their clinical profile is unclear. In 2021, 21.93% of patients diagnosed had cirrhosis and were mostly treatment-naïve. METHODS: This sub-analysis describes the clinical profile of the 60Spanish treatment-naïve patients with compensated cirrhosis who were included in the CREST study. MAJOR RESULTS: Sixty percent of patients were male, median age 56years, and 33% had a history of drug use. Almost three-quarters (71.3%) had more than one comorbidity and 78.3% took concomitant medication. At treatment initiation, median platelet count was 139×103/µL and FibroScan® 17kPa. No virological failure was observed and no patient discontinued treatment due to adverse events. No clinically significant changes were noted during or after treatment in the median platelet, albumin, bilirubin, and transaminase levels. CONCLUSIONS: Treatment with glecaprevir/pibrentasvir for 8weeks in this cohort of treatment-naïve patients with compensated cirrhosis in Spain was safe and effective. This information reinforces the use of this short antiviral regimen even when there is compensated cirrhosis, simplifying the approach to hepatitisC among those patients still to be diagnosed and treated in Spain.

The biochemical pattern defines MASLD phenotypes linked to distinct histology and prognosis.

BACKGROUND: MASLD can manifest as hepatocellular damage, which can result in mild elevation of aminotransferases. However, in some patients, MASLD presents with cholestatic pattern. OBJECTIVE: To assess the impact of the biochemical pattern on the natural course of MASLD, including liver damage in histology, the accuracy of non-invasive tests(NITs), and prognosis. METHODS: Multicenter study enrolling 2156 patients with biopsy-proven MASLD, who were classified based on their[ALT/ULN)]/[(ALP/ULN)] levels at the time of biopsy: (a) hepatocellular pattern(H), > 5; (b) mixed pattern(M),2-5; (c) cholestatic pattern(C), < 2. OUTCOMES: (a) histological evaluation of the single components of NAS, MASH, and fibrosis; (b) NITs and transient elastography assessing advanced fibrosis; (c) prognosis determined by the appearance of decompensated cirrhosis and death. RESULTS: Out of the 2156 patients, 22.9% exhibited the H-pattern, whilst 31.7% exhibited the C-pattern. Severe steatosis, ballooning, lobular inflammation, and MASH (56.4% H vs. 41.9% M vs. 31.9% C) were more common in H-pattern (p = 0.0001),whilst C-pattern was linked to cirrhosis (5.8% H vs. 5.6% M vs. 10.9% C; p = 0.0001). FIB-4(0.74(95% CI 0.69-0.79) vs. 0.83 (95% CI 0.80-0.85); p = 0.005) and Hepamet Fibrosis Score(0.77 (95% CI 0.69-0.85) vs. 0.84 (95% CI 0.80-0.87); p = 0.044)exhibited lower AUROCs in the H-pattern. The C-pattern[HR 2.37 (95% CI 1.12-5.02); p = 0.024], along with age, diabetes, and cirrhosis were independently associated with mortality. Most patients maintained their initial biochemical pattern during the second evaluation. CONCLUSIONS: The H-pattern exhibited greater necro-inflammation in the histology than the C-pattern, whereas the latter showed more cirrhosis. The accuracy of NITs in detecting fibrosis was decreased in H-pattern. The occurrence of decompensated events and mortality was predominant in C-pattern. Therefore, identifying MASLD phenotypes based on the biochemical presentation could be relevant for clinical practice.

Resultados al aplicar el sistema de clasificación de pacientes RUG-T18 en ancianos ingresados a un hospital universitario / Application of RUG-T18 classification to elderly patients admitted to an university hospital

Background: Among case mix classifications, the best for hospitalized elders is the Resource Utilization Groups (RUG) system, which allows a better location of patients, resource administration and the design of health care strategies for elderly people. Aim: To report the results of RUG-T18 classification of elderly patients admitted to an university hospital. Patients and methods: RUG-T18 classification was applied to 210 patients aged 75.2 ñ 7.2 years old, 108 male, admitted to the Clinical Hospital of the Catholic University of Chile. Results: The clinical classification of assessed patients was rehabilitation in 50.9 per cent of cases, special care in 10.5 per cent, clinically complex in 37.1 per cent and reduced physical functions in 0.5 per cent. None had behavioral alterations. There were no differences between subjects older or younger than 75 years old. Daily life activities showed that help was required for sphincter control in 46 per cent of patients, for feeding in 44 per cent and for mobilization in 64 per cent (28 per cent of patients required help from two or more people). Geriatric assessment showed that, since 1993, the proportion of elders with greater functional derangement increased from 18 to 28 per cent, and the proportion of those with mental disturbances from 4 to 12 per cent, specially among those over 75 years old. Conclusions: Most elders admitted to the hospital are classified in the superior categories of the RUG-T18 system and have severe mental and functional limitations. These patients require a multidisciplinary approach with a great emphasis in rehabilitation

Aspecto ético clínico de la kinesiterapia en el paciente terminal / Ethical clinic aspects of the physical therapy in terminal patient

La variedad de situaciones a las que el kinesiológo se ve enfrentado y el carácter evolutivo de la enfermedad, han planteado desde siempre difíciles problemas técnicos y éticos relativos al cúando, cómo, con qué intensidad y hasta dónde el profesional kinesiológo debe llegar con su acción terapéutica. Estos problemas se han visto agravados por el aumento del poder de transformación que ha proporcionado la técnica en relación al diagnóstico, la terapéutica, la rehabilitación, la prevención, lo cual va inexorablemente acompañado del aumento en las posibilidades de causar daño y en el aumento de la magnitud de estas mismas. En consecuencia, salta la pregunta ¿por qué criterios se puede uno guiar para saber cuando es legítimo y bueno abstenerse de algunas acciones kinésicas?. Este problema relativo a la regulación y linitación de la acción tiene hoy particular relevancia en relación a la limitación de tratamiento y sobre él nos centraremos

Tropisetrón en la prevención de náuseas y vómitos por quimioterapia: estudio clínico multicéntrico / Tropisetron in the prevention of nausea and vomiting due to chemotherapy: multicentric clinical study

The antiemetic effect of tropisetron was studied in 97 cancer patients (67 men, 30 women) receiving cisplatin in doses of 75 mg/m² or higher. On 279 chemotherapy cycles studied (max 6 per patient) 5 mg of tropisetron was admonistered once a day i.v. on day 1 and p.o. on day 2 to 6. Efficacy preventing vomiting and nausea was measured in 24 hour period as: complete control 0 episodes, major control 1 to 2 episodes, minor control 3 to 4 episodes and no control 5 or more episodes. Satisfactory vomiting control (complete and major) was 69 percent, 63 percent, 82 percent,88 percent, 96 percent and 96 percent in days 1 to 6 of cycle 1. Satisfactory nausea control (complete and major) for the same day was 70, 66, 72, 85 92 and 97 percent. Similar data was obtained for the subsequeny cycles. Complete vomiting control was obtained in 47, 35, 56, 72, 81 and 84 percent and for nausea in 42, 39, 48, 64, 81 and 87 percent. 19 patients presented adverse effects (19,6 percent). Only 2 headache episodes had a definitive relation with antiemetic drug. 12 patients discontinued the medication; 6 due to drug inefficacy, 2 to illness unrelated to the drug, 1 to lack of collaboration, and 3 due to other reasons. We conclude that tropisetron allows satisfactory control of acute and delayed vomiting in a high percentage of patients treated with high doses of cisplatin. The drug does not have significant secondary effects. Tropisetron administration in only 1 daily dose implies an evident advantage and a treatment cost reduction