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Liver fibrosis is a key determinant of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Its increasing prevalence and a lack of effective treatments make it a major health problem worldwide, particularly in people living with HIV, among whom the prevalence of advanced fibrosis is higher. We have published preclinical data showing that Rilpivirine (RPV), a widely used anti-HIV drug, selectively triggers hepatic stellate cell (HSC) inactivation and apoptosis through signal transducer and activator of transcription (STAT)1-mediated pathways, effects that clearly attenuate liver fibrosis and promote regeneration. We performed a retrospective, cross-sectional study of RPV-induced effects on steatosis, inflammation, and fibrosis in liver biopsies from well-controlled HIV-infected subjects diagnosed with MASLD. Patients on RPV exhibited similar levels of HIV-related parameters to those not receiving this drug, while showing a tendency toward improved liver function and lipid profile, as well as an enhanced activation of STAT1 in hepatic non-parenchymal cells in those with identified liver injury. This protective effect, promoting STAT1-dependent HSC inactivation, was observed at different stages of MASLD. Our results suggest that RPV-based therapy is especially indicated in HIV-infected patients with MASLD-derived liver injury and highlight the potential of RPV as a new therapeutic strategy for liver diseases.
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BACKGROUND AND AIMS: The relationship between primary biliary cholangitis (PBC) and metabolic dysfunction-associated steatotic liver disease, and its impact on treatment response and prognosis, remains underexplored. METHODS: Patient cohort from two centres comprising long-term follow-up data. All patients had histologically confirmed PBC. Biopsies were classified according to Non-Alcoholic Steatohepatitis Clinical Research Network. Diagnosis of metabolic dysfunction-associated steatotic liver disease was established when steatosis exceeded 5%, along with at least one metabolic risk factor. Patients with specific aetiologies of steatosis, other liver diseases, incomplete results and inadequate treatment with ursodeoxycholic acid were excluded. Data from patients initiating second-line treatment were censored. Treatment response was assessed using the Toronto, Paris II and AST-to-platelet at 12-month criteria. The UK PBC and Globe scores, and liver events were utilized as outcome measures. RESULTS: The study included 129 patients, 36 showing histologically confirmed overlap between PBC and steatosis. Patients with overlap showed worse prognosis according to Paris II (61.1% vs. 33.3%, p = 0.004), Toronto (52.5% vs. 24.7%, p = 0.002), AST-to-platelet 12-month >0.54 (36.1% vs. 17.2%, p = 0.021), Globe >0.30 (49.2% vs. 29.2%, p = 0.033) and UK PBC at 5, 10 and 15 years (p ≤ 0.001). Liver-related mortality and liver transplant were more prevalent in the overlap group (p = 0.001). In the multivariate analysis, steatosis, dyslipidaemia and advanced fibrosis were independently associated to worse outcomes. CONCLUSIONS: Our findings suggest that metabolic dysfunction-associated steatotic liver disease worsens the prognosis of PBC.
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Cirrose Hepática Biliar , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Cirrose Hepática Biliar/complicações , Idoso , Prognóstico , Ácido Ursodesoxicólico/uso terapêutico , Fígado Gorduroso/complicações , Resultado do Tratamento , Fatores de Risco , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Estudos Retrospectivos , Estudos de CoortesRESUMO
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.
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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.
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Years ago, patients with hemophilia were often cared for because of liver issues. The use of hemoderivatives in the 1970s and 1980s, and the natural history of chronic hepatitis B and C, led to a surge of patients with cirrhosis and related complications after two or three decades. It was not until the approval of entecavir and tenofovir (2005-2008) against the B virus, and of direct-acting antiviral agents (2015) against the C virus, that a truly effective treatment became available for liver disease. Since then, patients with hemophilia disappeared from hepatology clinics and wards, apart from specific isolated problems.
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Gastroenterologia , Hemofilia A , Hepatite B Crônica , Hepatite C Crônica , Humanos , Antivirais/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia A/complicações , Hepatite C Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/complicações , Resultado do Tratamento , Cirrose Hepática/complicações , Vírus da Hepatite BRESUMO
Wilson disease (WD) is a rare copper metabolism disorder caused by mutations in the ATP7B gene. It usually affects young individuals and can produce hepatic and/or neurological involvement, potentially affecting health-related quality of life (HRQoL). We assessed HRQoL in a cohort of Spanish patients with WD and evaluated disease impact on several domains of patients' lives, treatment adherence, drug preference and satisfaction, and healthcare resource utilisation in a cross-sectional, retrospective, multicentric, observational study. A total of 102 patients were included: 81.4% presented isolated liver involvement (group H) and 18.6% presented neurological or mixed involvement (group EH). Up to 30% of patients reported a deteriorated emotional status with anxiety and depression, which was greater in the EH subgroup; the use of neuropsychiatric drugs was high. Over 70% of the patients were satisfied with their current treatment but complained about taking too many pills, stating they would consider switching to another more patient-friendly treatment if available. The Simplified Medication Adherence Questionnaire revealed only 22.5% of patients were fully adherent to therapy, suggesting that alternative therapies are needed. This real-world study, even though is highly enriched with hepatic patients and mild disease, shows that WD impacts patients' HRQoL, especially in the emotional domain.
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Interleukin 17 (IL-17) is an effector cytokine that plays a key role in the pathogenesis of both psoriasis and metabolic-associated fatty liver disease (MAFLD), a condition that is more prevalent and severe in patients with psoriasis. In liver inflammation, IL-17 is mainly produced by CD4+ T (TH17) and CD8+ T cells (Tc17), although numerous other cells (macrophages, natural killer cells, neutrophils and Tγδ cells) also contribute to the production of IL-17. In hepatocytes, IL-17 mediates systemic inflammation and the recruitment of inflammatory cells to the liver, and it is also implicated in the development of fibrosis and insulin resistance. IL-17 levels have been correlated with progression from MAFLD to steatohepatitis, cirrhosis, and even hepatocellular carcinoma. Clinical trials have shown that inhibiting IL-17A in patients with psoriasis could potentially contribute to the improvement of metabolic and liver parameters. A better understanding of the key factors involved in the pathogenesis of these chronic inflammatory processes could potentially lead to more efficient treatment for both psoriasis and MAFLD, and help to develop holistic strategies to improve the management of these patients.
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BACKGROUND: In patients with clinically severe obesity, metabolic associated fatty liver disease (MAFLD) and steatohepatitis are highly prevalent. There is a lack of prospective studies evaluating the impact of bariatric surgery (BS) on MAFLD using both noninvasive and histological criteria. The present study aims to assess the impact of BS on MAFLD using histological and biochemical criteria. METHODS: This is a prospective study of 52 patients subjected to BS. Noninvasive fibrosis risk scores (NIFRS) along with anthropometric, clinical, and biochemical parameters were recorded pre- and 12 months post-BS. Liver biopsy was obtained in all individuals at baseline (wedge biopsy) and was repeated at 12 months (percutaneous Tru-cut) in those diagnosed with steatohepatitis. The primary outcome was the change in the degree of steatohepatitis and fibrosis. The secondary outcome was the change in scores for hepatocellular ballooning, lobular inflammation, steatosis, and fibrosis. RESULTS: One year after BS, steatohepatitis resolved in core biopsies with no worsening of fibrosis in 95.7% of individuals (n = 21, 95% CI: 87.3-100), and 13 (56.5%) exhibited complete resolution. Of 15 patients with fibrosis at baseline, 13 (86.7%) showed improvement and 12 exhibited fibrosis resolution. The values of transaminases improved, but only gamma glutamyl transferase (GGT) showed statistical significance. Among the NIFRS, NAFLD fibrosis score (NFS) and Hepamet fibrosis score (HFS) showed significant improvement. CONCLUSIONS: In the setting it was studied, BS improved or resolved steatohepatitis and fibrosis in patients with obesity. NIFRS, especially NFS and HFS, and levels of GGT could be used as markers of recovery of liver function after BS.
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Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Biópsia , Fibrose , Humanos , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade Mórbida/cirurgia , Estudos Prospectivos , gama-GlutamiltransferaseRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in morbid obesity (MO). A considerable proportion of patients with MO have non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is the only procedure that reliably differentiates NASH from other stages of NAFLD, but its invasive nature prevents it from being generalisable. Hence, non-invasive assessment is critical in this group of patients. OBJECTIVES: To report NAFLD/NASH prevalence in a cohort of patients with MO and to identify predictors of NASH. METHODS: Fifty-two consecutive patients subjected to bariatric surgery in a University hospital in Spain underwent LB. Anthropometric, clinical and biochemical variables were registered. According of the results of the LB, individuals were classified by whether they had NASH or not. Multiple logistic regression analysis was performed to identify independent factors associated with NASH. RESULTS: NAFLD was reported in 94.2% of the patients, simple steatosis was present in 51.92% and NASH in 42.31%. Meanwhile, 17.3% of patients exhibited significant fibrosis (≥F2). HIGHT score for NASH risk was established using five independent predictors: systemic Hypertension, Insulin resistance, Gamma-glutamyl transferase, High density lipoprotein cholesterol and alanine Transaminase. This score ranges from 0 to 7 and was used to predict NASH in our cohort (area under the receiver operator characteristic curve 0.846). A score of 4 or greater implied high risk (sensitivity 77.3%, specificity 73.3%, positive predictive value 68%, negative predictive value 81.5%, accuracy 75%). CONCLUSIONS: NAFLD is practically a constant in MO with a considerable proportion of patients presenting NASH. The combination of five independent predictors in a scoring system may help the clinician optimise the selection of patients with MO for LB.
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Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Biópsia , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , PrevalênciaRESUMO
BACKGROUND AND AIMS: To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. METHODS: This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan-Meier and Cox regression methods were used for data analysis. RESULTS: Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4-67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2-0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8-0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0-75.8]; specificity 95.2% [95% CI: 89.9-97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3-2.1). CONCLUSION: Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided.
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Encefalopatias , Hepatite Autoimune , Doença Aguda , Adolescente , Corticosteroides/uso terapêutico , Ascite , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Humanos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: The current study aimed to assess the impact of HIV on the production of anti-HCV antibodies in HCV-infected individuals with advanced HCV-related cirrhosis before and 36 weeks after the sustained virological response (SVR) induced by direct-acting antivirals (DAAs) therapy. METHODS: Prospective study on 62 patients (50 HIV/HCV-coinfected and 12 HCV-monoinfected). Plasma anti-E2 and HCV-nAbs were determined respectively by ELISA and microneutralization assays. RESULTS: At baseline, the HCV-group had higher anti-E2 levels against Gt1a (p = 0.012), Gt1b (p = 0.023), and Gt4a (p = 0.005) than the HIV/HCV-group. After SVR, anti-E2 titers against Gt1a (p < 0.001), Gt1b (p = 0.001), and Gt4a (p = 0.042) were also higher in the HCV-group than HIV/HCV-group. At 36 weeks post-SVR, plasma anti-E2 titers decreased between 1.3 and 1.9-fold in the HIV/HCV-group (p < 0.001) and between 1.5 and 1.8-fold in the HCV-group (p ≤ 0.001). At baseline, the HCV-group had higher titers of HCV-nAbs against Gt1a (p = 0.022), Gt1b (p = 0.002), Gt2a (p < 0.001), and Gt4a (p < 0.001) than the HIV/HCV-group. After SVR, HCV-nAbs titers against Gt1a (p = 0.014), Gt1b (p < 0.001), Gt2a (p = 0.002), and Gt4a (p = 0.004) were also higher in the HCV-group. At 36 weeks post-SVR, HCV-nAbs decreased between 2.6 and 4.1-fold in the HIV/HCV-group (p < 0.001) and between 1.9 and 4.0-fold in the HCV-group (p ≤ 0.001). CONCLUSIONS: HIV/HCV-coinfected patients produced lower levels of broad-spectrum anti-HCV antibodies than HCV-monoinfected patients.
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Coinfecção , Infecções por HIV , Hepatite C Crônica , Anticorpos Neutralizantes/uso terapêutico , Antivirais/uso terapêutico , Anticorpos Amplamente Neutralizantes , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus , Anticorpos Anti-Hepatite C/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Estudos ProspectivosRESUMO
OBJECTIVE: The prevalence of subclinical liver abnormalities is high among people with HIV, but data regarding perinatally HIV-infected children and adolescents (PHIV) are scarce. Noninvasive image techniques offer an opportunity to address nonalcoholic fatty liver disease (NAFLD) in a population in which the scores validated for adults have not been tested. DESIGN: Prospective cross-sectional study including PHIV and uninfected controls. METHODS: Noninvasive imaging techniques for the diagnosis of NAFLD and/or fibrosis were performed, and four scores to predict NAFLD were evaluated. RESULTS: Seventy-six participants (59.2% women) with a median of 19âyears old (interquartile range: 15.5-25.6) were included, 38 were PHIV and 38 were age and sex-matched controls. All HIV participants were on ART at the moment of inclusion, and 86.8% were virologically suppressed. A total of 11 PHIV and three controls were diagnosed with NAFLD (28.9% vs. 7.9%; Pâ=â0.02) by noninvasive imaging techniques. The performance of scores based on clinical and analytical parameters was very poor. Although nonsignificant, overweight was more common among participants with NAFLD, who had a significantly higher BMI. Differences in HIV-related parameters between the groups were nonsignificant, except for the CD4+/CD8+ T-cells ratio, decreased among PHIV diagnosed with NAFLD (Pâ=â0.04). CONCLUSIONS: The prevalence of NAFLD was high (28.9%) among PHIV, and only partially explained by overweight and metabolic syndrome defining factors. The scores based on clinical and analytical parameters did not accurately identify participants at risk. Therefore, liver ultrasound assessment should be considered for the screening of NAFLD among PHIV in routine clinical practice.
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Infecções por HIV , Hepatopatia Gordurosa não Alcoólica , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Sobrepeso , Prevalência , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Patients with a significant decrease in hepatic venous pressure gradient (HVPG) have a considerable reduction of liver complications and higher survival after HCV eradication. OBJECTIVES: To evaluate the association between the baseline blood microbiome and the changes in HVPG after successful direct-acting antiviral (DAA) therapy in patients with HCV-related cirrhosis. METHODS: We performed a prospective study in 32 cirrhotic patients (21 HIV positive) with clinically significant portal hypertension (HVPG ≥10 mmHg). Patients were assessed at baseline and 48 weeks after HCV treatment completion. The clinical endpoint was a decrease in HVPG of ≥20% or HVPG <12 mmHg at the end of follow-up. Bacterial 16S ribosomal DNA was sequenced using MiSeq Illumina technology, inflammatory plasma biomarkers were investigated using ProcartaPlex immunoassays and the metabolome was investigated using GC-MS. RESULTS: During the follow-up, 47% of patients reached the clinical endpoint. At baseline, those patients had a higher relative abundance of Corynebacteriales and Diplorickettsiales order, Diplorickettsiaceae family, Corynebacterium and Aquicella genus and Undibacterium parvum species organisms and a lower relative abundance of Oceanospirillales and Rhodospirillales order, Halomonadaceae family and Massilia genus organisms compared with those who did not achieve the clinical endpoint according to the LEfSe algorithm. Corynebacteriales and Massilia were consistently found within the 10 bacterial taxa with the highest differential abundance between groups. Additionally, the relative abundance of the Corynebacteriales order was inversely correlated with IFN-γ, IL-17A and TNF-α levels and the Massilia genus with glycerol and lauric acid. CONCLUSIONS: Baseline-specific bacterial taxa are related to an HVPG decrease in patients with HCV-related cirrhosis after successful DAA therapy.
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Hepatite C Crônica , Hipertensão Portal , Microbiota , Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Hipertensão Portal/tratamento farmacológico , Hipertensão Portal/etiologia , Cirrose Hepática/complicações , Estudos ProspectivosRESUMO
BACKGROUND AND OBJECTIVE: The emergence of highly tolerable, effective, and shorter duration direct-acting antivirals (DAAs) regimens offers the opportunity to simplify hepatitis C virus management but medical costs are unknown. Thus, we aimed to determine the direct medical costs associated with a combo-simplified strategy (one-step diagnosis and low monitoring) to manage HCV infection within an 8-week glecaprevir/pibrentasvir (GLE/PIB) regimen in clinical practice in Spain. PATIENTS AND METHODS: Healthcare resources and clinical data were collected retrospectively from medical charts of 101 eligible patients at 11 hospitals. Participants were adult, treatment naïve subjects with HCV infection without cirrhosis in whom a combo-simplified strategy with GLE/PIB for 8 weeks were programmed between Apr-2018 and Nov-2018. RESULTS: The GLE/PIB effectiveness was 100% (CI95%: 96.2-100%) in the mITT population and 94.1% (CI95%: 87.5-97.8%) in the ITT population. Three subjects discontinued the combo-simplified strategy prematurely, none of them due to safety reasons. Five subjects reported 8 adverse events, all of mild-moderate intensity. Combo-simplified strategy mean direct costs were 754.35±103.60 compared to 1689.42 and 2007.89 of a theoretical 12-week treatment with 4 or 5 monitoring visits, respectively; and 1370.95 and 1689.42 of a theoretical 8-week with 3 or 4 monitoring visits, respectively. Only 4.9% of the subjects used unexpected health care resources. CONCLUSIONS: 8-week treatment with GLE/PIB combined with a combo simplified strategy in real-life offers substantial cost savings without affecting the effectiveness and safety compared to traditional approaches.
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Hepatite C Crônica , Hepatite C , Adulto , Ácidos Aminoisobutíricos , Antivirais/efeitos adversos , Benzimidazóis , Ciclopropanos , Genótipo , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Prolina/uso terapêutico , Pirrolidinas , Quinoxalinas , Estudos Retrospectivos , SulfonamidasRESUMO
We recently reported our experience searching for patients with primary biliary cholangitis (PBC) who were lost in the health system. Our search of databases in 4 hospitals, 3 of which were tertiary institutions, revealed that sufficient data were available to ensure a reliable diagnosis (i.e., cholestasis, positive antimitochondrial antibody titer, and no other liver disease) in 14.3 % (100/697) of PBC cases. However, patients remained undiagnosed, thus missing an opportunity to start early treatment and follow-up. Even more strikingly, of 30 rescued patients, 27 % had an elastography result indicating a poorer prognosis (> 9.5 kPa).
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Colangite , Colestase , Cirrose Hepática Biliar , Hepatopatias , Humanos , Cirrose Hepática Biliar/diagnóstico , Hepatopatias/diagnóstico por imagemRESUMO
BACKGROUND & AIMS: Patients with chronic hepatitis C and stage 3 fibrosis are thought to remain at risk of hepatocellular carcinoma after sustained virological response. We investigated this risk in a large cohort of patients with well-defined stage 3 fibrosis. METHODS: We performed a multicentre, ambispective, observational study of chronic hepatitis C patients with sustained virological response after treatment with direct-acting antivirals started between January and December 2015. Baseline stage 3 was defined in a two-step procedure: we selected patients with transient elastography values of 9.5-14.5 kPa and subsequently excluded those with nodular liver surface, splenomegaly, ascites or collaterals on imaging, thrombopenia or esophago-gastric varices. Patients were screened twice-yearly using ultrasound. RESULTS: The final sample comprised 506 patients (median age, 57.4 years; males, 59.9%; diabetes, 17.2%; overweight, 44.1%; genotype 3, 8.9%; HIV coinfection, 18.4%; altered liver values, 15.2%). Median follow-up was 33.7 (22.1-39.1) months. Five hepatocellular carcinomas and 1 cholangiocarcinoma were detected after a median of 29.4 months (95% CI: 26.8-39.3), with an incidence of 0.47/100 patients/year (95% CI: 0.17-1.01). In the multivariate analysis, only males older than 55 years had a significant higher risk (hazard ratio 7.2 [95% CI: 1.2-41.7; P = .029]) with an incidence of 1.1/100 patients/year (95% CI: 0.3-2.8). CONCLUSIONS: In a large, well-defined cohort of patients with baseline hepatitis C stage-3 fibrosis, the incidence of primary liver tumours was low after sustained virological response and far from the threshold for cost-effectiveness of screening, except in males older than 55 years.
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Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resposta Viral SustentadaRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in morbid obesity (MO). A considerable proportion of patients with MO have non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is the only procedure that reliably differentiates NASH from other stages of NAFLD, but its invasive nature prevents it from being generalisable. Hence, non-invasive assessment is critical in this group of patients. OBJECTIVES: To report NAFLD/NASH prevalence in a cohort of patients with MO and to identify predictors of NASH. METHODS: Fifty-two consecutive patients subjected to bariatric surgery in a University hospital in Spain underwent LB. Anthropometric, clinical and biochemical variables were registered. According of the results of the LB, individuals were classified by whether they had NASH or not. Multiple logistic regression analysis was performed to identify independent factors associated with NASH. RESULTS: NAFLD was reported in 94.2% of the patients, simple steatosis was present in 51.92% and NASH in 42.31%. Meanwhile, 17.3% of patients exhibited significant fibrosis (≥F2). HIGHT score for NASH risk was established using five independent predictors: systemic Hypertension, Insulin resistance, Gamma-glutamyl transferase, High density lipoprotein cholesterol and alanine Transaminase. This score ranges from 0 to 7 and was used to predict NASH in our cohort (area under the receiver operator characteristic curve 0.846). A score of 4 or greater implied high risk (sensitivity 77.3%, specificity 73.3%, positive predictive value 68%, negative predictive value 81.5%, accuracy 75%). CONCLUSIONS: NAFLD is practically a constant in MO with a considerable proportion of patients presenting NASH. The combination of five independent predictors in a scoring system may help the clinician optimise the selection of patients with MO for LB.
RESUMO
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.