Exploring relief for Behçet's disease refractory oral ulcers: a comparison of TNF inhibitors versus apremilast.

OBJECTIVES: Oral and genital ulcers are the hallmark manifestation of Behçet's disease (BD), significantly impacting patients' quality of life. Our study focuses on comparing the effectiveness and safety of TNF inhibitors (TNFis) and apremilast in controlling oral ulcers of BD, aiming to provide evidence-based guidance for physicians in selecting appropriate treatment modalities. METHODS: A retrospective analysis was performed on BD patients treated between December 2016 and December 2021 with TNFis or apremilast for refractory oral ulcers. The study assessed treatment response by the absence of oral ulcers at 3 and 6 months, with additional evaluations for genital ulcers and articular involvement. RESULTS: The study included 78 patients, equally allocated between TNFis and apremilast treatments. Both groups showed significant oral ulcer reduction at 3 (p< 0.001) and 6 months (p= 0.01) with no significant difference between the treatments. Apremilast had a notable corticosteroid-sparing effect by the 3-month follow-up, persisting through 6 months. Both treatments were equally effective in reducing genital ulcers, with TNFis showing greater effectiveness in addressing articular involvement. Apremilast had a higher discontinuation rate due to gastrointestinal side effects. CONCLUSION: TNFis and apremilast are both effective for treating BD refractory oral ulcers. While TNFis may offer broader benefits for other disease manifestations, apremilast is distinguished by its corticosteroid-sparing effect, especially for patients with a milder disease phenotype. Treatment selection should consider individual disease severity and clinical features to ensure a personalized and effective management strategy.

From systemic lupus erythematosus to lupus nephritis: The evolving road to targeted therapies.

Systemic lupus erythematosus is a chronic autoimmune disease characterized by loss of tolerance against nuclear and cytoplasmic self-antigens, induction of immunity and tissue inflammation. Lupus nephritis (LN), the most important predictor of morbidity in SLE, develops in almost 30% of SLE patients at disease onset and in up to 50-60% within the first 10 years. Firstly, in this review, we put the pathogenic mechanisms of the disease into a conceptual frame, giving emphasis to the role of the innate immune system in this loss of self-tolerance and the induction of the adaptive immune response. In this aspect, many mechanisms have been described such as dysregulation and acceleration of cell-death pathways, an aberrant clearance and overload of immunogenic acid-nucleic-containing debris and IC, and the involvement of antigen-presenting cells and other innate immune cells in the induction of this adaptive immune response. This result in a clonal expansion of autoreactive lymphocytes with generation of effector T-cells, memory B-cells and plasma cells that produce autoantibodies that will cause kidney damage. Secondly, we review the immunological pathways of damage in the kidney parenchyma, initiated by autoantibody binding and immune complex deposition, and followed by complement-mediated microvascular injury, activation of kidney stromal cells and the recruitment of leukocytes. Finally, we summarize the rationale for the treatment of LN, from conventional to new targeted therapies, focusing on their systemic immunologic effects and the minimization of podocytary damage.

Persistence of a SARS-CoV-2 T-cell response in patients with long COVID and lung sequelae after COVID-19.

1 year after an acute COVID-19 episode, patients with either lung sequelae or long COVID show a stronger SARS-CoV-2-specific T-cell response than fully recovered individuals, suggesting persistent cell stimulation by residual viral reservoirs https://bit.ly/40bPZm7.

External clinical validation of automated software to identify structural abnormalities and microhaemorrhages in nailfold videocapillaroscopy images.

OBJECTIVES: Automated systems to analyse nailfold videocapillaroscopy (NVC) images are needed to promptly and comprehensively characterise patients with systemic sclerosis (SSc) or Raynaud's phenomenon (RP). We previously developed, and validated in-house, a deep convolutional neural network-based algorithm to classify NVC-captured images according to the presence/absence of structural abnormalities and/or microhaemorrhages. We present its external clinical validation. METHODS: A total of 1,164 NVC images of RP patients were annotated by 5 trained capillaroscopists according to the following categories: normal capillary; dilation; giant capillary; abnormal shape; tortuosity; microhaemorrhage. The images were also presented to the algorithm. Matches and discrepancies between algorithm predictions and those annotations obtained by consensus of ≥3 or ≥4 interobservers were analysed. RESULTS: Consensus among ≥3 capillaroscopists was achieved in 86.9% of images, 75.8% of which were correctly predicted by the algorithm. Consensus among ≥4 experts occurred in 52.0% of cases, in which 87.1% of the algorithm's results matched with those of the expert panel. The algorithm's positive predictive value was >80% for microhaemorrhages and unaltered, giant or abnormal capillaries. Sensitivity was >75% for dilations and tortuosities. Negative predictive value and specificity were >89% for all categories. CONCLUSIONS: This external clinical validation suggests that this algorithm is useful to assist in the diagnosis and follow-up of SSc or RP patients in a timely manner. It may also be helpful in the management of patients with any pathology presenting with microvascular changes, as the algorithm has been designed to also be useful for research aiming at extending the usage of nailfold capillaroscopy to more conditions.

Anti-dsDNA B-Cell ELISpot as a Monitoring and Flare Prediction Tool in SLE Patients.

Anti-dsDNA autoantibodies quantification and complement levels are widely used to monitor disease activity in systemic lupus erythematosus (SLE). However, better biomarkers are still needed. We hypothesised whether the dsDNA antibody-secreting B-cells could be a complementary biomarker in disease activity and prognosis of SLE patients. Fifty-two SLE patients were enrolled and followed for up to 12 months. Additionally, 39 controls were included. An activity cut-off (comparing active and non-active patients according to clinical SLEDAI-2K) was established for SLE-ELISpot, chemiluminescence and Crithidia luciliae indirect immunofluorescence tests (≥11.24, ≥374.1 and ≥1, respectively). Assays performances together with complement status were compared regarding major organ involvement at the inclusion and flare-up risk prediction after follow-up. SLE-ELISpot showed the best performance in identifying active patients. High SLE-ELISpot results were associated with haematological involvement and, after follow-up, with an increased hazard ratio for disease flare-up (3.4) and especially renal flare (6.5). Additionally, the combination of hypocomplementemia and high SLE-ELISpot results increased those risks up to 5.2 and 32.9, respectively. SLE-ELISpot offers complementary information to anti-dsDNA autoantibodies to evaluate the risk of a flare-up in the following year. In some cases, adding SLE-ELISpot to the current follow-up protocol for SLE patients can improve clinicians' personalised care decisions.

Patient Care Pathways for Pregnancy in Rare and Complex Rheumatic Diseases: Results From an International Survey.

OBJECTIVE: To map existing organizational care pathways in clinical centers of expertise that care for pregnant women affected by rare and complex connective tissue diseases (rcCTDs). METHODS: An international working group composed of experts in the field of pregnancy in rcCTDs co-designed a survey focused on organizational aspects related to the patient's pathway before, during, and after pregnancy. The survey was distributed to subject experts through referral sampling. RESULTS: Answers were collected from 69 centers in 21 countries. Patients with systemic lupus erythematosus and/or antiphospholipid syndrome were followed by more than 90% of centers, whereas those with disorders such as IgG4-related diseases were rarely covered. In the majority of centers, a multidisciplinary team was involved, including an obstetrician/gynecologist in 91.3% of cases and other healthcare professionals less frequently. Respondents indicated that 96% of the centers provided routine pre-pregnancy care, whereas the number of patient visits during pregnancy varied across centers. A formalized care pathway was described in 49.2% of centers, and 20.3% of centers had a predefined protocol for the monitoring of pregnant patients. Access to therapies during pregnancy also was heterogeneous among different centers. CONCLUSION: In international referral centers, a high level of care is provided to patients with rcCTDs before, during, and after pregnancy. No significant discrepancies were found between European and non-European countries. However, this work highlights a potential benefit to streamlining the care approaches across countries to optimize pregnancy and perinatal outcomes among patients with rcCTDs.

Structural brain changes in post-acute COVID-19 patients with persistent olfactory dysfunction.

OBJECTIVE: This research aims to study structural brain changes in patients with persistent olfactory dysfunctions after coronavirus disease 2019 (COVID-19). METHODS: COVID-19 patients were evaluated using T1-weighted and diffusion tensor imaging (DTI) on a 3T MRI scanner, 9.94 ± 3.83 months after COVID-19 diagnosis. Gray matter (GM) voxel-based morphometry was performed using FSL-VBM. Voxelwise statistical analysis of the fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was carried out with the tract-based spatial statistics in the olfactory system. The smell identification test (UPSIT) was used to classify patients as normal olfaction or olfactory dysfunction groups. Intergroup comparisons between GM and DTI measures were computed, as well as correlations with the UPSIT scores. RESULTS: Forty-eight COVID-19 patients were included in the study. Twenty-three were classified as olfactory dysfunction, and 25 as normal olfaction. The olfactory dysfunction group had lower GM volume in a cluster involving the left amygdala, insular cortex, parahippocampal gyrus, frontal superior and inferior orbital gyri, gyrus rectus, olfactory cortex, caudate, and putamen. This group also showed higher MD values in the genu of the corpus callosum, the orbitofrontal area, the anterior thalamic radiation, and the forceps minor; and higher RD values in the anterior corona radiata, the genu of the corpus callosum, and uncinate fasciculus compared with the normal olfaction group. The UPSIT scores for the whole sample were negatively associated with both MD and RD values (p-value ≤0.05 FWE-corrected). INTERPRETATION: There is decreased GM volume and increased MD in olfactory-related regions explaining prolonged olfactory deficits in post-acute COVID-19 patients.

Early Prediction of Adverse Pregnancy Outcome in Women with Systemic Lupus Erythematosus, Antiphospholipid Syndrome, or Non-Criteria Obstetric Antiphospholipid Syndrome.

A prospectively study of pregnant women with systemic lupus erythematosus (SLE), antiphospholipid syndrome, or non-criteria obstetric antiphospholipid syndrome was conducted to describe the characteristics of women followed in a referral unit and to derive a predictive tool for adverse pregnancy outcome (APO). Demographic characteristics, treatments, SLE activity, and flares were recorded. Laboratory data included a complete blood cell count, protein-to-creatinine urinary ratio (Pr/Cr ratio), complement, anti dsDNA, anti-SSA/Ro, anti-SSB/La, and antiphospholipid antibodies status. A stepwise regression was used to identify baseline characteristics available before pregnancy and during the 1st trimester that were most predictive of APO and to create the predictive model. A total of 217 pregnancies were included. One or more APO occurred in 45 (20.7%) women. A baseline model including non-Caucasian ethnicity (OR 2.78; 95% CI [1.16-6.62]), smoking (OR 4.43; 95% CI [1.74-11.29]), pregestational hypertension (OR 16.13; 95% CI [4.06-64.02]), and pregestational corticosteroids treatment OR 2.98; 95% CI [1.30-6.87]) yielded an AUC of 0.78 (95% CI, [0.70-0.86]). Among first-trimester parameters, only Pr/Cr ratio improved the model fit, but the predictive performance was not significantly improved (AUC of 0.78 vs. 0.81; p = 0.16). Better biomarkers need to be developed to efficiently stratify pregnant women with the most common autoimmune diseases.

Standardized incidence ratios and risk factors for cancer in patients with systemic sclerosis: Data from the Spanish Scleroderma Registry (RESCLE).

AIM: Patients with systemic sclerosis (SSc) are at increased risk of cancer, a growing cause of non-SSc-related death among these patients. We analyzed the increased cancer risk among Spanish patients with SSc using standardized incidence ratios (SIRs) and identified independent cancer risk factors in this population. MATERIAL AND METHODS: Spanish Scleroderma Registry data were analyzed to determine the demographic characteristics of patients with SSc, and logistic regression was used to identify cancer risk factors. SIRs with 95% confidence intervals (CIs) relative to the general Spanish population were calculated. RESULTS: Of 1930 patients with SSc, 206 had cancer, most commonly breast, lung, hematological, and colorectal cancers. Patients with SSc had increased risks of overall cancer (SIR 1.48, 95% CI 1.36-1.60; P < 0.001), and of lung (SIR 2.22, 95% CI 1.77-2.73; P < 0.001), breast (SIR 1.31, 95% CI 1.10-1.54; P = 0.003), and hematological (SIR 2.03, 95% CI 1.52-2.62; P < 0.001) cancers. Cancer was associated with older age at SSc onset (odds ratio [OR] 1.22, 95% CI 1.01-1.03; P < 0.001), the presence of primary biliary cholangitis (OR 2.35, 95% CI 1.18-4.68; P = 0.015) and forced vital capacity <70% (OR 1.8, 95% CI 1.24-2.70; P = 0.002). The presence of anticentromere antibodies lowered the risk of cancer (OR 0.66, 95% CI 0.45-0.97; P = 0.036). CONCLUSIONS: Spanish patients with SSc had an increased cancer risk compared with the general population. Some characteristics, including specific autoantibodies, may be related to this increased risk.

Systemic sclerosis and pregnancy outcomes: a retrospective study from a single center.

BACKGROUND: Pregnancy in systemic sclerosis (SSc) patients is no more an infrequent event as it used to be, but literature data on pregnancy outcomes in women with SSc are scarce. The rate of preterm deliveries and intrauterine growth restriction (IUGR) seems to be increased, while the risk of miscarriages is controversial. Moreover, no study compared pregnancy outcomes in SSc with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We performed a retrospective study to compare the pregnancy and disease outcomes of women with SSc with a cohort of age-matched women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and healthy controls (HC). METHODS: A total of 154 pregnancies from SSc, SLE, APS patients, and HC were prospectively followed at the High-Risk Pregnancy Unit of our center from 2008 to 2019. The primary outcome was a composite endpoint of miscarriages, fetal deaths, intrauterine growth restriction (IUGR), preeclampsia, neonatal deaths, preterm birth, and small-for-gestational-age (SGA) newborns. Single adverse pregnancy outcomes (APO) represented secondary endpoints. SSc activity variations in relation to pregnancy were assessed. RESULTS: The risk of APO was significantly higher in SSc patients compared to HC (60.6% vs 10.0%; OR = 14.42; 95% CI 3.70-56.18, p = 0.001) and SLE patients (60.6% vs 37.5%; OR = 3.56; 95% CI 1.29-9.83, p = 0.014). Compared to HC, women with SSc had an increased frequency of first trimester miscarriage (15% vs 0 %; p = 0.016), preeclampsia (12% vs 0%, p = 0.038), and SGA newborns (21.2% vs 0%; p = 0.003). Preterm deliveries were more frequent in SSc pregnancies in comparison with HC (24.2% vs 5%; OR = 6.08; 95% CI 1.19-31.02, p = 0.036) and SLE patients (24.2% vs 7.5%, OR = 5.68; 95% CI 1.1-29.38, p = 0.038). Disease remained stable in all SSc patients during pregnancy and up to 1 year after delivery. CONCLUSIONS: We found an increased risk of APO in our SSc cohort in comparison with HC (with higher rates of miscarriages, preeclampsia, SGA newborns, and preterm deliveries) and SLE patients (presenting a higher rate of preterm deliveries). High-risk multidisciplinary management of SSc pregnant women is highly recommended.

Anti-Polymyositis/Scl Antibodies in Systemic Sclerosis: Clinical Associations in a Multicentric Spanish Cohort and Review of the Literature.

OBJECTIVES: To assess the clinical profile of patients with anti-polymyositis/Scl (PM/Scl) antibodies in a cohort of Spanish patients with systemic sclerosis. METHODS: From the Spanish Scleroderma Study Group database, we selected patients in whom PM/Scl antibodies had been tested. We compared demographic, clinical, laboratory, and survival data between patients with and without PM/Scl antibodies. RESULTS: Seventy-two of 947 patients (7.6%) tested positive for PM/Scl antibodies. Patients with PM/Scl antibodies presented initially with more puffy fingers and arthralgias but less Raynaud phenomenon. Regarding cumulative manifestations, myositis and arthritis were more prevalent in patients with PM/Scl antibodies, as well as pulmonary fibrosis. On the contrary, patients with PM/Scl antibodies had less pulmonary hypertension. No difference in terms of survival at 5 and 10 years was noticed between the 2 groups. CONCLUSIONS: In systemic sclerosis patients from Spain, PM/Scl antibodies are associated with a distinct clinical profile. However, PM/Scl antibodies did not influence survival.

Assessing and counteracting fibrosis is a cornerstone of the treatment of CKD secondary to systemic and renal limited autoimmune disorders.

Chronic kidney disease (CKD) is an increasing cause of morbidity and mortality worldwide. Besides the higher prevalence of diabetes, hypertension and aging worldwide, immune mediated disorders remain an important cause of kidney disease and are especially prevalent in young adults. Regardless of the initial insult, final pathway to CKD and kidney failure is always the loss of normal tissue and fibrosis development, in which the dynamic equilibrium between extracellular matrix synthesis and degradation is disturbed, leading to excessive production and accumulation. During fibrosis, a multitude of cell types intervene at different levels, but myofibroblasts and inflammatory cells are considered critical in the process. They exert their effects through different molecular pathways, of which transforming growth factor ß (TGF-ß) has demonstrated to be of particular importance. Additionally, CKD itself promotes fibrosis due to the accumulation of toxins and hormonal changes, and proteinuria is simultaneously a manifestation of CKD and a specific driver of renal fibrosis. Pathways involved in renal fibrosis and CKD are closely interrelated, and although important advances have been made in our knowledge of them, it is still necessary to translate them into clinical practice. Given the complexity of this process, it is highly likely that its treatment will require a multi-target strategy to control the origin of the damage but also the mechanisms that perpetuate it. Fortunately, rapid technology development over the last years and new available drugs in the nephrologist's armamentarium give reasons for optimism that more personalized assistance for CKD and renal fibrosis will appear in the future.

Understanding tubulointerstitial injury and repair mechanisms paves the way for renal outcome improvement in lupus nephritis / Entender la lesión tubulointersticial y los mecanismos de reparación será la vía para mejorar los desenlaces renales en nefritis lúpica

ABSTRACT Despite improvements in patient survival and quality of life, long-term renal survival has not changed significantly in the recent decades and nephritis relapses affect over 50% of patients with lupus nephritis. Renal fibrosis affecting the tubulointerstitial compartment is a central determinant of the prognosis of any kidney disease. Notwithstanding this evidence, the current 2003 ISN/RPS classification still focuses on glomerular pathology and does not include a mandatory score with clear subcategories of the tubulointerstitial injury in the biopsy. The pathogenesis, and the morphological and molecular characteristics of this process in patients with lupus nephritis will be considered, together with a discussion about the concepts the clinician needs to efficiently address in this injury during daily practice and in future clinical trials. Both tubulointerstitial inflammation and fibrosis are strongly correlated with poor renal outcomes in lupus nephritis, regardless of the extent of glomerular damage. Therefore, it is essential to develop reliable and noninvasive approaches to predict which patients are most likely to develop CKD so that appropriate interventions can be adopted before ESRD is established. Currently, no ideal method for monitoring kidney fibrosis exists, since repeated renal biopsies are invasive. Promising methods for assessing and monitoring fibrosis non-invasively include imaging techniques, such as magnetic resonance imaging or ex vivo confocal microscopy, integrated in computational and digital pathology techniques. Finally, beyond specific immunosuppressive treatment in Lupus Nephritis, identifying and treating cardiovascular risk factors should be a cornerstone of treatment in these patients.

RESUMEN A pesar de las mejoras en la sobrevida de los pacientes y su calidad de vida, la sobrevida renal en el largo plazo no ha cambiado significativamente durante las últimas décadas, y las recidivas nefríticas afectan a más del 50% de los pacientes con nefritis lúpica. La fibrosis renal, que afecta el compartimiento tubulointersticial, es un factor determinante central en el pronóstico de todas las patologías renales. A pesar de la evidencia, la actual clasificación ISN/RPS del 2003 todavía se concentra en la patología glomerular y no incluye un score obligatorio con claras subcategorías de la lesión tubulointersticial en la biopsia. Se hablará de la patogenia y las características morfológicas y moleculares de este proceso en pacientes con nefritis lúpica, así como de los conceptos que el clínico necesita para abordar esta lesión de manera eficiente en su práctica cotidiana y en los estudios clínicos a futuro. Tanto la inflamación tubulointersticial como la fibrosis se relacionan fuertemente con desenlaces renales pobres en la nefritis lúpica, con independencia de la extensión del dañío glomerular. Resulta por lo tanto esencial desarrollar sistemas confiables y no invasivos para predecir cuáles pacientes tendrán mayor probabilidad de desarrollar enfermedad renal crónica, a fin de realizar las intervenciones apropiadas antes de que se establezca la enfermedad renal terminal (ERT). En la actualidad, no existe un método ideal para monitorear la fibrosis renal, dado que las biopsias repetidas son procedimientos invasivos. Algunos de los métodos promisorios para evaluar y monitorear la fibrosis de manera no invasiva son las técnicas de imágenes, tales como la resonancia magnética o la microscopía confocal ex vivo, integradas en técnicas de patología computarizadas y digitales. Finalmente, más allá del tratamiento inmunosupresor específico para la nefritis lúpica, identificar y tratar los factores de riesgo cardiovascular deberá ser uno de los pilares de tratamiento en estos pacientes.

The incidence rate of pulmonary arterial hypertension and scleroderma renal crisis in systemic sclerosis patients with digital ulcers on endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i).

INTRODUCTION: Endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i) are beneficial in pulmonary arterial hypertension (PAH) and digital ulcers (DU) and prevent from DU recurrences. Our study aimed to determine the difference in the incidence rate of PAH and scleroderma renal crisis (SRC) in patients with SSc and DU (SSc-DU) under ERAs/PDE5i or without treatment. METHODS: We conducted a retrospective cohort study including SSc-DU patients from the Spanish Scleroderma Registry (RESCLE). The primary outcome was the incidence rate of PAH and SRC in patients under ERAs/PDE5i or not. RESULTS: Some 544 patients out of 1817 (29.9%) in the RESCLE database had DU, 221 (40.6%) under ERAs/PDE5i and 323 (59.4%) not. The incidence rate (95% CI) difference between patients under treatment or not under did not reach statistical significance in PAH [-0.1 (-4.8, 4.69), P = 0.988] or in SRC [0.7 (-2.2, 3.7), P = 0.620]. However, the time from the first DU to the diagnosis of SRC was delayed in treated patients [mean (s.d.) 7.6 (5.8) years vs 2.9 (5.3); P = 0.021]. The dcSSc subset was more prevalent in the treatment group (36 vs 26%; P = 0.018), along with anti-topoisomerase I antibodies (34 vs 18%; P < 0.001) and tendon friction rubs (12 vs 6%; P = 0.038), whereas the lcSSc subset was more prevalent in the no-treatment group (57 vs 66%; P = 0.031) along with ACA (37 vs 46%; P = 0.031). CONCLUSION: There was no difference in the incidence rate of PAH and SRC between groups. However, treatment with ERAs and/or PDE5i appeared to delay the occurrence of SRC.

Benefits of hepatitis C cure with antivirals: why test and treat?

Chronic hepatitis C virus (HCV) infection is one of the major causes of death worldwide due to infectious agents. The advent of direct-acting antivirals has dramatically improved the chance of HCV elimination, even for patients with decompensated cirrhosis. Along with HCV cure, benefits are recognized in terms of regression of liver fibrosis and risk of hepatocellular carcinoma. Furthermore, beyond hepatic outcomes, several extrahepatic benefits may result from sustained HCV eradication, including improvements in the neurocognitive function and reduced cardiovascular disease risk. Finally, there is no doubt that the individual success of direct-acting antivirals is largely contributing to halt HCV transmission globally, in the absence of an effective HCV prophylactic vaccine.

Regression of liver fibrosis after curing chronic hepatitis C with oral antivirals in patients with and without HIV coinfection.

BACKGROUND: Treatment with direct-acting antivirals (DAA) eradicates hepatitis C virus (HCV) from most chronic carriers. Information on regression of liver fibrosis and the influence of HIV is scarce in cured patients. METHODS: All consecutive HCV-infected individuals treated with DAA at our institution were examined. Hepatic elastography was performed at baseline and at the time of SVR12. Liver fibrosis regression was defined as a shift from advanced fibrosis (Metavir F3-F4) to null-mild fibrosis (F0-F2) and/or a reduction greater than 30% kPa. AST to platelet ratio index (APRI) and fibrosis 4 (FIB-4) scores were calculated in parallel. RESULTS: A total of 260 patients were treated with DAA. All but 14 achieved SVR12 and represented the study population. HIV confection was present in 42%. At baseline, 57.2% had advanced liver fibrosis with a median of 11 kPa, FIB-4 of 2.4, and APRI of 0.95. At the time of SVR12, a median reduction of 2.1 kPa (P < 0.001) was recognized using elastography. A significant fibrosis regression was seen in 40%, being more frequent in patients with baseline advanced fibrosis than in those with null-mild fibrosis (52.3 vs. 22.5%; P < 0.001). Even so, 41.2% of patients with baseline F3-F4 kept within cirrhotic scores. In multivariable analysis, only baseline stiffness was significantly associated with the extent of liver fibrosis regression. CONCLUSION: HCV cure with DAA is associated with regression of liver fibrosis in most patients treated with DAA, as measured using elastography, FIB-4 and APRI. This benefit is more pronounced in patients with baseline advanced fibrosis and cirrhosis. The dynamics of liver fibrosis regression are not influenced by HIV coinfection.