Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Improvement of Mueller-Kauffman Tetrathionate-Novobiocin (MKTTn) enrichment medium for the detection of Salmonella enterica by the addition of ex situ-generated tetrathionate.

The detection of Salmonella in food is based on the use of a selective enrichment broth such as Muller-Kauffman Tetrathionate-Novobiocin (MKTTn), in which tetrathionate plays a key role by providing Salmonella with a growth advantage. As sodium tetrathionate is unstable, it is generated in situ by the addition of iodine (Lugol's solution) before seeding. This step is cumbersome as the solution is easily spilled, compromising the performance of the medium and hindering the work of technicians. The aim of this study was to optimize MKTTn broth by generating tetrathionate ex situ through an external reaction between iodine and thiosulphate followed by lyophilization. Quality control procedures were performed to compare the modified and original media, testing pure productivity (enrichment with 50-120 CFU of Salmonella Thyphimurium ATCC 14028 and Salmonella Enteritidis ATCC 13076 and plating on Xylose Lysine Deoxycholate agar, XLD), mixed productivity (50-120 CFU of Salmonella strains and Pseudomonas aeruginosa and Escherichia coli at ≥104 CFU and XLD plating) and selectivity (≥104 CFU of P. aeruginosa and Enterococcus faecalis and plating on Tryptone Casein Soy agar, TSA). The modified MKTTn medium (S/L) performed comparably with the original medium in terms of growth of both Salmonella strains (>300 colonies in XLD), alone or with P. aeruginosa and E. coli. Quantitative assays showed no statistically significant differences in the number of colonies grown on XLD after 10-5 dilution (p = 0.7015 with S. Thyphimurium ATCC 14028 and p = 0.2387 with S. Enteritidis ATCC 13076; ANOVA test). MKTTn medium (S/L) was also selective against E. coli (≤100 colonies) and E. faecalis (<10 colonies). These results suggest that adding tetrathionate as a lyophilisate (S/L) is a feasible alternative to the use of Lugol's solution for the preparation of MKTTn enrichment broth and does not affect the properties of the medium.

Clinical standards for the dosing and management of TB drugs.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Influence of media and testing methodology on susceptibility to tigecycline of Enterobacteriaceae with reported high tigecycline MIC.

The tigecycline susceptibility of six different Enterobacteriaceae strains with reported high tigecycline MICs was determined in quintuplicate by four methodologies using Mueller-Hinton agar and broth from six manufacturers. The MICs determined by Etest were a >or=1-fold dilution lower than those determined by broth microdilution and agar dilution, with the highest modal values given by agar dilution. The highest modal MICs were obtained using Oxoid medium, and the lowest inhibition zone values (disc diffusion) were obtained using Oxoid and bioMérieux media. The lowest MICs were obtained by Etest using Difco or Merck media.

Functional impact of sequelae in drug-susceptible and multidrug-resistant tuberculosis.

BACKGROUND: Evidence on the impact of tuberculosis (TB) treatment on lung function is scarce. The aim of this study was to evaluate post-treatment sequelae in drug-susceptible and drug-resistant-TB (DR-TB) cases in Mexico and Italy.METHODS: At the end of TB treatment the patients underwent complete clinical assessment, functional evaluation of respiratory mechanics, gas exchange and a 6-minute walking test. Treatment regimens (and definitions) recommended by the World Health Organization were used throughout.RESULTS: Of 61 patients, 65.6% had functional impairment, with obstruction in 24/61 patients (39.4%), and 78% with no bronchodilator response. These effects were more prevalent among DR-TB cases (forced expiratory volume in 1 s/forced vital capacity [FEV1/FVC] < lower limit of normality, 14/24 vs. 10/34; P = 0.075). DR-TB patients showed moderately severe (FEV1 < 60%) and severe obstruction (FEV1 < 50%) (P = 0.008). Pre- and post-bronchodilator FEV1 and FEV1/FVC (% of predicted) were significantly lower among DR-TB cases. Plethysmography abnormalities (restriction, hyperinflation and/or air trapping) were more frequent among DR-TB cases (P = 0.001), along with abnormal carbon monoxide diffusing capacity (DLCO) (P = 0.003).CONCLUSION: The majority of TB patients suffer the consequences of post-treatment sequelae (of differing levels), which compromise quality of life, exercise tolerance and long-term prognosis. It is therefore important that lung function is comprehensively evaluated post-treatment to identify patient needs for future medication and pulmonary rehabilitation.

Beta-lactam activity against penicillin-resistant Streptococcus pneumoniae strains exhibiting higher amoxicillin versus penicillin minimum inhibitory concentration values: an in vitro pharmacodynamic simulation.

BACKGROUND: Activity of simulated serum concentrations after oral therapy with 400 mg cefditoren pivoxil b.i.d., 500 mg cefuroxime axetil b.i.d. and 875/125 mg amoxicillin/clavulanic acid b.i.d. and t.i.d. regimens was explored over 24 h against Streptococcus pneumoniae. METHODS: Computerized pharmacodynamic simulations were performed against strains with penicillin/amoxicillin/cefuroxime/cefditoren minimum inhibitory concentrations (MICs, microg/ml) and serotypes: strain 1 (0.25/0.12/1/0.12; serotype 6A), strain 2 (2/4/ 2/0.25; serotype 6B), strain 3 (4/16/4/0.5; serotype 14), and strain 4 (4/16/8/1; serotype 14). RESULTS: Bactericidal activity (> or =3 log(10) reduction) at 12 and 24 h was obtained against all strains with cefditoren, against strains 1 and 2 with cefuroxime and amoxicillin/clavulanic acid t.i.d., but only against strain 1 with amoxicillin/clavulanic acid b.i.d.. Bactericidal activity at 24 h was related to T > MIC of >30% dosing interval, 1.7-2.0 log(10) reductions with T > MIC of 20-30%, and <1 log(10) reduction or regrowth with T > MIC of 0%. CONCLUSIONS: It is difficult to achieve pharmacodynamic coverage and bactericidal activity by physiological concentrations of oral beta-lactams against penicillin-resistant pneumococcal strains exhibiting higher amoxicillin versus penicillin MICs. Cefditoren may offer alternatives.

Tuberculosis, social determinants and co-morbidities (including HIV).

The risk of exposure, progression to active tuberculosis (TB) and then to cure is a process affected by several risk factors. Along with well known risk factors such as human immunodeficiency virus (HIV), use of immunosuppressive drugs and being of young age, emerging risk factors such socio-economic and behavioral aspects play a significant role in increasing the susceptibility to infection, and unsuccessful treatment outcomes. This paper summarizes the effects of these socio-economic determinants and co-morbidities (including HIV) on TB infection and disease.

New drugs and perspectives for new anti-tuberculosis regimens.

Tuberculosis (TB) is the ninth cause of global death, more than any other infectious disease. With growing drug resistance the epidemic remains and will require significant attention and investment for the elimination of this disease to occur. With susceptible TB treatment not changing over the last four decades and the advent of drug resistance, new drugs and regimens are required. Recently, through greater collaboration and research networks some progress with significant advances has taken place, not withstanding the comparatively low amount of resources invested. Of late the availability of the new drugs bedaquiline, delamanid and repurposed drugs linezolid, clofazimine and carbapenems are being used more frequently in drug-resistant TB regimens. The WHO shorter multidrug-resistant tuberculosis regimen promises to reach more patients and treat them more quickly and more cheaply. With this new enthusiasm and hope we this review gives an update on the new drugs and perspectives for the treatment of drug-susceptible and drug-resistant tuberculosis.

Team approach to manage difficult-to-treat TB cases: Experiences in Europe and beyond.

As recommended by the World Health Organization (WHO), optimal management of MDR-TB cases can be ensured by a multi-speciality consultation body known as 'TB Consilium'. This body usually includes different medical specialities, competences and perspectives (e.g., clinical expertise both for adults and children; surgical, radiological and public health expertise; psychological background and nursing experience, among others), thus lowering the risk of making mistakes - or managing the patients inappropriately, in order to improve their clinical outcomes. At present, several high MDR-TB burden countries in the different WHO regions (and beyond) have introduced TB Consilium-like bodies at the national or subnational level to reach consensus on the best treatment approach for their patients affected by TB. In addition, in countries/settings where a formal system of consultation does not exist, specialized staff from MDR-TB reference centres or international organizations usually spend a considerable amount of their working time responding to phone or e-mail clinical queries on how to manage M/XDR-TB cases. The aim of this manuscript is to describe the different experiences with the TB Consilia both at the international level (European Respiratory Society - ERS/WHO TB Consilium) and in some of the countries where this experience operates successfully in Europe and beyond. The Consilium experiences are described around the following topics: (1) history, aims and focus; (2) management and funding; (3) technical functioning and structure; (4) results achieved. In addition a comparative analysis of the TB Consilia in the different countries has been performed.

Rapid diagnostic testing to improve access to screening for syphilis in prison.

OBJECTIVES: To assess the accuracy of on-site rapid treponemal test for syphilis diagnosis in women deprived of liberty in Bolivia. MATERIAL AND METHODS: Serological tests for syphilis were performed on 219 women deprived of liberty from the San Sebastián prison in Cochabamba, Bolivia. Syphilis was diagnosed using RPR (bioMérieux) and TPPA (Fujirebio) serological tests, and the results were compared to on-site rapid treponemal test (Alere DetermineTM Syphilis TP) in whole blood. Diagnostic performance of two FTA tests were also compared (bioMérieux and Biocientífica). RESULTS: All participants (28) with RPR+/TPPA+ had the rapid syphilis test positive (sensitivity 100%). Eleven participants had rapid syphilis test positive without RPR and TPPA both positive; nevertheless 7 of them had RPR or TPPA positive. Of 33 participants with FTA-bioMérieux positive, 22 (66.6%) had FTA-Biocientífica positive. DISCUSSION: The rapid syphilis test Determine shows excellent performance as a screening tool among women deprived of liberty affected by high prevalence of syphilis. This test is particularly indicated when there are barriers for access to conventional serological tests. It is inexpensive, easy to use and does not require electricity and laboratory infrastructure. The FTA test performed with reagents from Biocientífica had a suboptimal sensitivity.

Syphilis, human immunodeficiency virus, herpes genital and hepatitis B in a women's prison in Cochabamba, Bolivia: prevalence and risk factors.

OBJECTIVE: To determine the prevalence and factors associated with syphilis, human immunodeficiency virus (HIV), hepatitis B (HBV) and herpes type 2 (HSV2) among women in the prison of San Sebastian in Cochabamba (Bolivia). MATERIAL AND METHODS: We carried out a cross-sectional study including a standardized questionnaire to assess socio-demographics characteristics and risk factors (sexual practices and exposure to blood); and serological tests for syphilis, HSV2, VIH, and HBV. We performed bivariate and multivariate analyses to test the associations between variables of interest and infections. RESULTS: A total of 219 out of 220 prisoners (99.5%) participated in the study. For syphilis, 12.8% of participants had both reactive tests (RPR+/TPPA+). The prevalence of HSV2 and VIH was 62.6% and 1.4%, respectively. Anti-HBc, indicating a resolved or chronic HBV, was positive in 11.9% of participants and 0.5% had active HBV (HBsAg positive). A low level of education was associated with syphilis, HSV2 and HBV. Having occasional sexual partners was associated with syphilis and HSV2. Being over 36 years old and having more than 3 children were associated with HBV. The number of sexual partners, history of prostitution and rape, having sexual intercourses in prison and detention time were not associated with any of these infections. DISCUSSION: The prevalence of syphilis, HIV, HSV2 and HBV was higher in this vulnerable female population than in the general population in Bolivia. Control measures in detention are needed to limit the spread of these infections both in prisons and in the community.

Levofloxacin vs. azithromycin pharmacodynamic activity against S. pneumoniae and H. influenzae with decreased susceptibility to amoxicillin/clavulanic acid.

Resistant clones/phenotypes are putting into question the activity of commonly used beta-lactams, thus prompting the need for alternative options. A 500 mg levofloxacin vs. azithromycin once daily pharmacodynamic simulation was performed against 10(8) cfu/ml of four Streptococcus pneumoniae strains (exhibiting higher amoxicillin than penicillin MIC) and four Haemophilus influenzae strains: beta-lactamase producing, BLNAR (beta-lactamase-negative ampicillin-resistant) and BLPACR (beta-lactamase-positive amoxicillin/clavulanate-resistant). High levofloxacin AUC/MIC values for H. influenzae, and values of 50-100 for S. pneumoniae produced a >5 log(10) reduction at 24h for all strains. Azithromycin AUC/MIC values of approximately 10 were needed to obtain a 2-3 log(10) reduction of S. pneumoniae initial inocula, but lower AUC/MIC values (of approximately 6) obtained > or =3 log(10) reduction against all strains of H. influenzae. While in vitro simulated serum concentrations of levofloxacin were bactericidal at the end of the dosing interval against all S. pneumoniae strains and azithromycin against the susceptible ones, both antimicrobials achieved this endpoint against the BLNAR and BLPACR strains.

Novel role for IL-22 in protection during chronic Mycobacterium tuberculosis HN878 infection.

Approximately 2 billion people are infected with Mycobacterium tuberculosis (Mtb), resulting in 1.4 million deaths every year. Among Mtb-infected individuals, clinical isolates belonging to the W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is exceedingly important to identify the immune mechanisms that mediate protection against rapidly emerging Mtb strains, such as W-Beijing lineage. IL-22 is a member of the IL-10 family of cytokines with both protective and pathological functions at mucosal surfaces. Thus far, collective data show that IL-22 deficient mice are not more susceptible to aerosolized infection with less virulent Mtb strains. Thus, in this study we addressed the functional role for the IL-22 pathway in immunity to emerging Mtb isolates, using W-Beijing lineage member, Mtb HN878 as a prototype. We show that Mtb HN878 stimulates IL-22 production in TLR2 dependent manner and IL-22 mediates protective immunity during chronic stages of Mtb HN878 infection in mice. Interestingly, IL-22-dependent pathways in both epithelial cells and macrophages mediate protective mechanisms for Mtb HN878 control. Thus, our results project a new protective role for IL-22 in emerging Mtb infections.

Comparison of bacteriological conversion and treatment outcomes among MDR-TB patients with and without diabetes in Mexico: Preliminary data.

Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). However, it is not known to what extent DM affects the outcome in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) treated with second-line anti-TB drugs. The objective of this study was to compare the microbiological evolution (sputum smear and culture conversion) and final outcomes of MDR/XDR-TB patients with and without DM, managed at the national TB reference centre in Mexico City. RESULTS: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (e.g. MDR-TB with additional resistance to one injectable drug or a fluoroquinolone, 12.2%) and 6 (6.7%) with XDR-TB. Out of these, 49 (54.4%) had DM and 42 (86%) were undergoing insulin treatment. No statistically significant differences were found in treatment outcomes comparing DM vs. non-DM MDR-TB cases: 18/32 (56.3%) of DM cases and 19/24 (79.2%) non DM patients achieved treatment success (p=0.07). The time to sputum smear and culture conversion was longer (although not statistically) in patients without DM, as follows: the mean (±SD) time to sputum smear conversion was 53.9 (±31.4) days in DM patients and 65.2 (±34.8) days in non-DM ones (p=0.15), while the time to culture conversion was 66.2 (±27.6) days for DM and 81.4 (±37.7) days for non-DM MDR-TB cases (p=0.06). CONCLUSIONS: The study results support the Mexican National TB programme to strengthen its collaboration with the DM programme, as an entry point for TB (and latent TB infection) screening and management.

[Influence of the displacement of protein binding by ibuprofen in the activity of a third-generation cephalosporin against Streptococcus pneumoniae]. / Influencia del desplazamiento de la unión a proteínas por ibuprofeno en la actividad de una cefalosporina de tercera generación frente a Streptococcus pneumoniae.

The clinical significance of protein binding remains to be fully elucidated. The aim of this study was to evaluate the effect in the in vitro bactericidal activity of cefditoren through killing curves at Cmax concentrations against three Streptococcus pneumoniae strains (cefditoren MICs of 0.12, 0.25 and 0.5 mg/l) with or without human albumin (4 g/dl) and ibuprofen at Cmax concentrations (32.3 mg/l) and 10 times the Cmax (323 mg/l). Cefditoren was rapidly bactericidal (3 log(10) CFU/ml reduction) against the three strains at 4.2 mg/l concentration in Mueller-Hinton broth plus 5% lysed horse blood. In presence of human albumin, this effect was maintained against the most susceptible strain (MIC = 0.12 mg/l). Regrowths were observed with higher MIC values. The presence of ibuprofen (32.3 mg/l) slightly delayed regrowth while the increase of ibuprofen concentration up to 10 x Cmax recovered the bactericidal activity against all strains. The activity of an antimicrobial with high protein binding should not be linked exclusively with the theoretical unbound fraction extrapolated from the plasma concentration. The role of protein binding antagonists merits analysis due to their frequent use associated with cephalosporins in respiratory tract infections.

Hepatitis Autoinmune y Colangitis Biliar Primaria en Paciente con Crioglobulinemia

Resumen Paciente mujer de 55 años con antecedente de crioglobulinemia mixta con compromiso renal glomerulonefritis membranoproliferativa, enfermedad renal crónica (ERC) en estadio G5, presenta cuadro de ictericia, coluria los exámenes complementarios muestran incremento de las pruebas hepáticas con hipertransaminasemia, hiperbilirrubinemia y colestasis, serologías hepáticas virales negativas, anticuerpo antimitocondrial (AMA) +, se realiza biopsia hepática identificando hepatitis de interfase y en el interior de los septos fibrosos, reacción ductal focal y leve proliferación de ramas de la vena porta que están distorsionadas entre gruesas fibras de colágeno, llegando al diagnóstico de síndrome de superposición, se inicia tratamiento con corticoides 1 mgr/Kgr/día y ácido ursodeoxicólico 13 mgr/kgr/día con buena evolución, logrando normalizar las enzimas hepáticas. Ambas patologías "crioglobulinemia mixta y hepatopatías autoinmunes", son entidades poco frecuentes que presentan buenas respuestas al tratamiento inmunosupresor e inmunomodulador.

Abstract A 55-year-old female patient with a history of mixed cryoglobulinemia with renal involvement, membranoproliferative glomerulonephritis, chronic kidney disease (CKD) stage G5, presented with jaundice, choluria, complementary examinations showed increased liver tests with hypertransaminasemia, hyperbilirubinemia and cholestasis, negative viral liver serologies, anti-mitochondrial antibody (AMA) +, a liver biopsy was performed identifying interphase hepatitis and in the interior of the fibrous septa, focal ductal reaction and slight proliferation of branches of the portal vein which are distorted between thick collagen fibres, leading to the diagnosis of overlap syndrome, treatment was started with corticosteroids 1 mg/Kg/day and ursodeoxycholic acid 13 mg/kg/day with good evolution, achieving normalization of liver enzymes. Both pathologies "mixed cryoglobulinemia and autoimmune hepatopathies" are rare entities that respond well to immunosuppressive and immunomodulatory treatment.