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1.
J Viral Hepat ; 30(1): 56-63, 2023 01.
Article in English | MEDLINE | ID: mdl-36197907

ABSTRACT

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Humans , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Latin America/epidemiology , Lost to Follow-Up , Hepacivirus/genetics , World Health Organization
2.
Int J Mol Sci ; 23(18)2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36142716

ABSTRACT

Adversity is particularly pernicious in early life, increasing the likelihood of developing psychiatric disorders in adulthood. Juvenile and adult rats exposed to social isolation show differences in anxiety-like behaviors and significant changes in dopamine (DA) neurotransmission in the nucleus accumbens (NAc). Brain response to stress is partly mediated by the corticotropin-releasing factor (CRF) system, composed of CRF and its two main receptors, CRF-R1 and CRF-R2. In the NAc shell of adult rats, CRF induces anxiety-like behavior and changes local DA balance. However, the role of CRF receptors in the control of neurotransmission in the NAc is not fully understood, nor is it known whether there are differences between life stages. Our previous data showed that infusion of a CRF-R1 antagonist into the NAc of juvenile rats increased DA levels in response to a depolarizing stimulus and decreased basal glutamate levels. To extend this analysis, we now evaluated the effect of a CRF-R1 antagonist infusion in the NAc of adult rats. Here, we describe that the opposite occurred in the NAc of adult compared to juvenile rats. Infusion of a CRF-R1 antagonist decreased DA and increased glutamate levels in response to a depolarizing stimulus. Furthermore, basal levels of DA, glutamate, and γ-Aminobutyric acid (GABA) were similar in juvenile animals compared to adults. CRF-R1 protein levels and localization were not different in juvenile compared to adult rats. Interestingly, we observed differences in the signaling pathways of CRF-R1 in the NAc of juveniles compared to adult rats. We propose that the function of CRF-R1 receptors is differentially modulated in the NAc according to life stage.


Subject(s)
Nucleus Accumbens , Receptors, Corticotropin-Releasing Hormone , Animals , Corticotropin-Releasing Hormone/metabolism , Dopamine/metabolism , Glutamates/metabolism , Humans , Microdialysis , Neurotransmitter Agents/metabolism , Nucleus Accumbens/metabolism , Rats , Receptors, Corticotropin-Releasing Hormone/metabolism , gamma-Aminobutyric Acid/metabolism
3.
Ann Hepatol ; 27(1): 100555, 2022.
Article in English | MEDLINE | ID: mdl-34626827

ABSTRACT

HCV infection is associated with an increased incidence of cardiovascular (CV) events. Mechanisms underlying this association remain unknown. In our study, twenty HCV patients (median age 60.5 years, 65% male and 80% with cirrhosis) were evaluated prior, during and after direct-acting antiviral treatment. Ninety percent of patients achieved sustained virological response (SVR). Significant changes were observed in LDL particle size index, measured by LDL-C/apoB ratio, which increased after treatment (p = 0.023). In addition, HDL antioxidant capacity improved gradually from 34.4% at baseline to 42.4% at 4 weeks (p = 0.011), 65.9% at end of treatment EOT (p = 0.002) and remained elevated at 12-week (p = 0.001) after EOT compared to baseline values. Our findings suggest that a shift to a less atherogenic lipid profile may be a possible mechanism associated with CV risk reduction in patients with HCV infection achieving SVR.


Subject(s)
Antioxidants/therapeutic use , Antiviral Agents/therapeutic use , Hepacivirus/isolation & purification , Hepatitis C, Chronic/blood , Lipoproteins, HDL/metabolism , Lipoproteins, LDL/blood , Sustained Virologic Response , Aged , Female , Follow-Up Studies , Hepatitis C, Chronic/drug therapy , Humans , Male , Middle Aged , Particle Size , Prospective Studies , Treatment Outcome
4.
JAMA Netw Open ; 4(8): e2120929, 2021 08 02.
Article in English | MEDLINE | ID: mdl-34424307

ABSTRACT

Importance: Active immunization for hepatitis B virus (HBV) infection is recommended in patients living with HIV. Limited evidence is available about the most appropriate regimen of HBV vaccination among those who have not responded to an initial schedule. Objective: To determine the efficacy of a high-dose schedule compared with a standard dose of HBV vaccination. Design, Setting, and Participants: This double-masked, parallel-group, randomized controlled trial included patients living with HIV at a single outpatient HIV and hepatology clinic in Chile for whom previous HBV vaccination had failed. Patients with hepatitis B surface antibody (anti-HBs) titers less than 10 IU/L after an initial HBV vaccination regimen were included. Consecutive patients were recruited between December 2013 and March 2018. Data were analyzed in June 2018 using intention-to-treat analysis. Intervention: The high-dose HBV vaccination group consisted of 3 doses of 40 µg recombinant hepatitis B vaccine at 0, 1, and 2 months. The standard-dose group received 3 doses 20 µg each at 0, 1, and 2 months. Main Outcomes and Measures: Primary outcome was the serologic response to HBV vaccination (anti-HBs greater than 10 IU/L) 4 to 8 weeks after completion of the schedule. Secondary outcomes were anti-HBs greater than 100 IU/L and seroprotective anti-HBs at 1 year follow up. Results: A total of 107 patients underwent randomization (55 to the standard-dose group, 52 to the high-dose group); 81 (75.7%) were men, and the mean (SD) patient age was 47.0 (13.3) years. Nearly all patients were receiving antiretroviral therapy (105 patients [98%]) and 92 patients (86%) had an undetectable HIV viral load. Mean (SD) CD4 count was 418 (205) cells/mm3. There were no differences in baseline characteristics between groups. Serological response in the high-dose group was found in 36 of 50 patients (72%; 95% CI, 56.9%-82.9%) compared with 28 of 55 patients in the standard-dose group (51%; 95% CI, 37.1%-64.6%) (odds ratio, 2.48; 95% CI, 1.02-6.10; P = .03). Mean (SD) anti-HB levels were 398.0 (433.4) IU/L in the high-dose group and 158.5 (301.4) IU/L in the standard-dose group (P < .001). Of patients with a serological response in the high-dose group, 29 of 36 (80.6%) had anti-HBs titers greater than 100 IU/L compared with 14 of 28 responders (50.0%) in the standard-dose group (P = .02). At 1-year follow-up, 20 of 25 patients (80.0%) with a serological response in the high-dose group had protective anti-HBs vs 9 of 23 patients (39.1%) in the standard-dose group (P = .01). Conclusions and Relevance: The results of this randomized clinical trial suggest that use of a high-dose regimen for HBV revaccination for patients with HIV achieves a higher and longer-lasting serological response as compared with a standard-dose regimen. Trial Registration: ClinicalTrials.gov Identifier: NCT02003703.


Subject(s)
HIV Infections/complications , Hepatitis B Vaccines/administration & dosage , Hepatitis B/prevention & control , Immunization, Secondary/methods , Chile , Double-Blind Method , Female , Hepatitis B/immunology , Humans , Immunization Schedule , Intention to Treat Analysis , Male , Middle Aged
5.
Transpl Int ; 34(1): 97-109, 2021 01.
Article in English | MEDLINE | ID: mdl-33040420

ABSTRACT

This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Carcinoma, Hepatocellular/surgery , Cohort Studies , Humans , Liver Neoplasms/surgery , Neoplasm Recurrence, Local , Patient Selection , Prospective Studies , Retrospective Studies
6.
Liver Int ; 41(4): 851-862, 2021 04.
Article in English | MEDLINE | ID: mdl-33217193

ABSTRACT

BACKGROUND & AIM: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Liver Transplantation , Carcinoma, Hepatocellular/surgery , Cohort Studies , Humans , Latin America/epidemiology , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/epidemiology , Prognosis , Retrospective Studies , Treatment Outcome
8.
Sci Rep ; 10(1): 22275, 2020 12 17.
Article in English | MEDLINE | ID: mdl-33335156

ABSTRACT

Chile has become a popular destination for migrants from South America and the Caribbean (low- and middle-income countries migration). Close to 200.000 Haitian migrants have arrived in Chile. Infectious and non-infectious disease burden among the Haitian adult population living in Chile is unknown. This study aimed to acquire the basic health information (selected transmissible and non-transmissible conditions) of the Haitian adult population living in Chile. A cross-sectional survey was performed, inviting Haitian-born residents in Chile older than 18 years old. Common conditions and risk factors for disease were assessed, as well as selected transmissible conditions (HIV, HBV, and HCV). 498 participants (60.4% female) from 10 communities in two regions of Chile were surveyed. Most subjects had never smoked (91.5%), and 80% drank less than one alcohol unit per month. The mean BMI was 25.6, with 45% of participants having a normal BMI (20-25). Hypertension was present in 31.5% (33% in the 25-44 age group). Prevalence of HIV was 2.4% (95 CI 1.3-4.2%), hepatitis B (HBsAg positive) was 3.4% (95 CI 2.1-5.5%), and hepatitis C was 0% (95 CI 0.0-0.9%). Quality of life showed a significant prevalence of depression and anxiety markers, particularly in those arriving in Chile less than 1 year ago. Low prevalence of obesity, diabetes, smoking, and drinking and estimated cardiovascular risk were found. Nonetheless, hypertension at a younger age, disproportionately higher prevalence of HIV and HBV infection and frequent markers of anxiety and depression were also found. Public policies for detecting and treating hypertension, HIV, and HBV screening, offering HBV vaccination, and organizing mental health programs for Haitian immigrants, are urgently needed.


Subject(s)
HIV Infections/enzymology , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Infections/epidemiology , Adolescent , Adult , Caribbean Region/epidemiology , Chile/epidemiology , Female , Global Burden of Disease , HIV Infections/genetics , HIV Infections/virology , Hepacivirus/pathogenicity , Hepatitis B/virology , Hepatitis B virus/pathogenicity , Hepatitis C/virology , Humans , Infections/virology , Male , Middle Aged , Noncommunicable Diseases/epidemiology , Quality of Life , Risk Factors , Young Adult
9.
J Med Virol ; 92(12): 3545-3555, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32749710

ABSTRACT

INTRODUCTION: Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. METHODS: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). RESULTS: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01). CONCLUSION: In this real-life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time-point of DAA treatment (NCT03775798; www. CLINICALTRIALS: gov).

10.
Ann Hepatol ; 19(4): 353-358, 2020.
Article in English | MEDLINE | ID: mdl-32425991

ABSTRACT

The ongoing pandemic of coronavirus disease 2019 (COVID-19) pandemic poses a serious threat to healthcare systems globally. Information regarding how the infection affects the liver and relevance of pre-existing liver disease as a risk factor for acquiring the infection or having a severe disease are still scarce. Also, considerations in liver transplant patients, those having hepatocellular carcinoma or under immunosuppressive therapy are being matter of analysis as information is being generated. Different treatments for COVID-19 are currently under study, some of which may be associated to hepatotoxicity. In the present review we discuss current data on the COVID-19 and liver, aiming to provide hepatologists with updated information to face this pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/therapy , Liver Diseases/therapy , Liver Diseases/virology , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , COVID-19 , Humans , Liver Diseases/pathology , Pandemics , Risk Factors , SARS-CoV-2
11.
Clin Gastroenterol Hepatol ; 18(11): 2554-2563.e3, 2020 10.
Article in English | MEDLINE | ID: mdl-32113892

ABSTRACT

BACKGROUND & AIMS: Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. METHODS: We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. RESULTS: During a median follow-up period of 26.2 months (interquartile range, 15.3-37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%-4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P = .02) in the overall cohort. CONCLUSIONS: Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Liver Neoplasms , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/epidemiology , Cohort Studies , Disease Progression , Hepacivirus , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Liver Cirrhosis/drug therapy , Liver Cirrhosis/epidemiology , Liver Neoplasms/drug therapy , Liver Neoplasms/epidemiology , Prospective Studies , Risk Factors , Sustained Virologic Response
12.
Liver Int ; 40(6): 1427-1434, 2020 06.
Article in English | MEDLINE | ID: mdl-31916360

ABSTRACT

BACKGROUND: Baveno VI and expanded Baveno VI criteria have been recommended to circumvent the need for endoscopy screening in patients with a very low probability of varices needing treatment (VNT). AIM: To validate these criteria in a Latin American population. METHODS: The ability of Baveno VI criteria (liver stiffness measurement (LSM) <20 kPa and platelet count >150 × 103/µL) and expanded Baveno VI criteria (LSM < 25kPa and platelet count >110 × 103/µL) to exclude the presence of VNT was tested in a prospectively recruited cohort of patients with Child-Pugh A liver cirrhosis and with no previous variceal haemorrhage who attended the liver clinics of three major hospitals in Chile. RESULTS: Three hundred patients were included. The median (IQR) age was 61 [18-86] years, median MELD was 8.0 (6-17), median LSM was 17.2 (10.2-77) kPa and median platelet count was 137 (23-464) × 103 /µL. The main aetiology was non-alcoholic fatty liver disease (67.3%). VNT were present in 18% of patients. The Baveno VI criteria had a sensitivity of 98.1% and a specificity of 38.2%, potentially sparing 31.3% of upper endoscopies with a very low risk of missing VNT (1.1%). The expanded Baveno VI criteria had a sensitivity of 90.7% and a specificity of 61%, potentially sparing 51.3% of upper endoscopies with a risk of missing VNT of 3.6%. Both criteria were independently associated with the absence of VNT. CONCLUSION: We validated the Baveno VI and expanded Baveno VI criteria in Chilean population, potentially sparing 31.3% and 51.3% of endoscopies, respectively, with a very low risk of missing VNT. Fondecyt 1191183.


Subject(s)
Elasticity Imaging Techniques , Esophageal and Gastric Varices , Adolescent , Adult , Aged , Aged, 80 and over , Chile , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/etiology , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Humans , Liver Cirrhosis/complications , Middle Aged , Young Adult
13.
World J Gastroenterol ; 26(48): 7693-7706, 2020 Dec 28.
Article in English | MEDLINE | ID: mdl-33505145

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) disease can frequently affect the liver. Data on hepatic histopathological findings in COVID-19 is scarce. AIM: To characterize hepatic pathological findings in patients with COVID-19. METHODS: We conducted a systematic review with meta-analysis registered on PROSPERO (CRD42020192813), following PRISMA guidelines. Eligible trials were those including patients of any age and COVID-19 diagnosis based on a molecular test. Histopathological reports from deceased COVID-19 patients undergoing autopsy or liver biopsy were reviewed. Articles including less than ten patients were excluded. Proportions were pooled using random-effects models. Q statistic and I 2 were used to assess heterogeneity and levels of evidence, respectively. RESULTS: We identified 18 studies from 7 countries; all were case reports and case series from autopsies. All the patients were over 15 years old, and 67.2% were male. We performed a meta-analysis of 5 studies, including 116 patients. Pooled prevalence estimates of liver histopathological findings were hepatic steatosis 55.1% [95% confidence interval (CI): 46.2-63.8], congestion of hepatic sinuses 34.7% (95%CI: 7.9-68.4), vascular thrombosis 29.4% (95%CI: 0.4-87.2), fibrosis 20.5% (95%CI: 0.6-57.9), Kupffer cell hyperplasia 13.5% (95%CI: 0.6-54.3), portal inflammation 13.2% (95%CI: 0.1-48.8), and lobular inflammation 11.6% (95%CI: 0.3-35.7). We also identified the presence of venous outflow obstruction, phlebosclerosis of the portal vein, herniated portal vein, periportal abnormal vessels, hemophagocytosis, and necrosis. CONCLUSION: We found a high prevalence of hepatic steatosis and vascular thrombosis as major histological liver features. Other frequent findings included portal and lobular inflammation and Kupffer cell hyperplasia or proliferation. Further studies are needed to establish the mechanisms and implications of these findings.


Subject(s)
COVID-19/complications , Fatty Liver/epidemiology , Hepatic Veins/pathology , Liver/pathology , Venous Thrombosis/epidemiology , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Fatty Liver/etiology , Fatty Liver/pathology , Humans , Kupffer Cells/pathology , Liver/blood supply , Liver/cytology , Prevalence , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Venous Thrombosis/etiology , Venous Thrombosis/pathology
15.
Liver Int ; 39(6): 1033-1043, 2019 06.
Article in English | MEDLINE | ID: mdl-30636361

ABSTRACT

BACKGROUND & AIMS: Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. METHODS: This was a prospective multicentre cohort study from Latin America including 1400 F1-F4-treated patients with DAAs (F3-F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. RESULTS: During a median follow-up of 16 months (IQR 8.9-23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02-0.05) at 12 months and 0.06 (CI 0.04-0.08) at 24 months of follow-up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non-responder, Child-Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%-91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. CONCLUSIONS: Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/complications , Liver Neoplasms/epidemiology , Aged , Carcinoma, Hepatocellular/virology , Female , Hepacivirus/drug effects , Hepatitis C, Chronic/complications , Humans , Incidence , Latin America/epidemiology , Liver Cirrhosis/virology , Liver Neoplasms/virology , Male , Middle Aged , Propensity Score , Proportional Hazards Models , Prospective Studies , Risk Factors , Sustained Virologic Response
16.
Rev. méd. Chile ; 146(10): 1215-1219, dic. 2018. graf
Article in Spanish | LILACS | ID: biblio-978759

ABSTRACT

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.


Subject(s)
Humans , Male , Adult , Acquired Immunodeficiency Syndrome/drug therapy , Liver Transplantation/methods , Antiretroviral Therapy, Highly Active/adverse effects , Chemical and Drug Induced Liver Injury/surgery , Treatment Outcome , Chemical and Drug Induced Liver Injury/pathology , Immunocompetence
17.
Clin Res Hepatol Gastroenterol ; 42(5): 443-452, 2018 10.
Article in English | MEDLINE | ID: mdl-29773419

ABSTRACT

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trends of liver related HCC etiologies during the last years in Latin America. METHODS: From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005-2006, 2007-2008, 2009-2010 and 2011-2012 were considered. Etiology of liver disease was confirmed in the explant. RESULTS: Participating LT centers per country included 2 from Brazil (n=191), 5 transplant programs from Argentina (n=98), 2 from Colombia (n=65), 4 from Chile (n=49), 2 from Mexico (n=12), and 1 from Peru (n=11) and Uruguay (n=9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis accounted for 6% and 7%, respectively. While HCV decreased from 48% in 2005-06 to 26% in 2011-12, NAFLD increased from 1.8% to 12.8% during the same period, accounting for the third cause of HCC. This represented a 6-fold increase in NAFLD-HCC, whereas HCV had a 2-fold decrease. Patients with NAFLD were older, had lower pre-LT serum AFP values and similar 5-year survival and recurrence rates than non-NAFLD. CONCLUSION: There might be a global changing figure regarding etiologies of HCC in Latin America. This epidemiological change on the incidence of HCC in the world, although it has been reported, should still be confirmed in prospective studies.


Subject(s)
Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/etiology , Liver Neoplasms/surgery , Liver Transplantation , Cohort Studies , Female , Humans , Latin America , Male , Middle Aged
18.
Euro Surveill ; 23(9)2018 03.
Article in English | MEDLINE | ID: mdl-29510780

ABSTRACT

A hepatitis A outbreak has occurred in Chile since November 2016. Men are predominantly affected, with a large proportion of men who have sex with men (MSM). We describe 12 consecutive unrelated confirmed cases who presented at our healthcare institution in Santiago Metropolitan Area. Nine were men, all reporting having had sex with men. Ten viral sequences, genotyped as IA, clustered with the V16-25801 strain causing outbreaks mostly in MSM in Europe since mid-2016.


Subject(s)
Disease Outbreaks , Hepatitis A virus/genetics , Hepatitis A virus/isolation & purification , Hepatitis A/epidemiology , Homosexuality, Male , Sequence Analysis, DNA , Adult , Chile/epidemiology , Europe/epidemiology , Genotype , Hepatitis A/diagnosis , Hepatitis A/virology , Hepatitis A virus/classification , Humans , Male , Middle Aged , Polymerase Chain Reaction , RNA, Viral/blood , RNA, Viral/genetics , Young Adult
19.
Ann Hepatol ; 17(2): 256-267, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29469048

ABSTRACT

BACKGROUND AND AIMS: Heterogeneous data has been reported regarding liver transplantation (LT) for hepatocellular carcinoma (HCC) in Latin America. We aimed to describe treatment during waiting list, survival and recurrence of HCC after LT in a multicenter study from Latin America. MATERIAL AND METHODS: Patients with HCC diagnosed prior to transplant (cHCC) and incidentally found in the explanted liver (iHCC) were included. Imaging-explanted features were compared in cHCC (non-discordant if pre and post-LT were within Milan, discordant if pre-LT was within and post-LT exceeding Milan). RESULTS: Overall, 435 patients with cHCC and 92 with iHCC were included. At listing, 81% and 91% of cHCC patients were within Milan and San Francisco criteria (UCSF), respectively. Five-year survival and recurrence rates for cHCC within Milan, exceeding Milan/within UCSF and beyond UCSF were 71% and 16%; 66% and 26%; 46% and 55%, respectively. Locoregional treatment prior to LT was performed in 39% of cHCC within Milan, in 53% beyond Milan/within UCSF and in 83% exceeding UCSF (p < 0.0001). This treatment difference was not observed according to AFP values (≤100, 44%; 101-1,000, 39%, and > 1,000 ng/mL 64%; p = 0.12). Discordant imaging-explanted data was observed in 29% of cHCC, showing lower survival HR 2.02 (CI 1.29; 3.15) and higher recurrence rates HR 2.34 when compared to AFP <100 ng/mL. Serum AFP > 1,000 ng/mL at listing was independently associated with a higher 5-year recurrence rate and a HR of 3.24 when compared to AFP <100 ng/mL. CONCLUSION: Although overall results are comparable to other regions worldwide, pre-LT treatment not only considering imaging data but also AFP values should be contemplated during the next years.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Liver Transplantation , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/mortality , Female , Humans , Latin America/epidemiology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/mortality , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Neoplasm Recurrence, Local , Risk Factors , Time Factors , Treatment Outcome , Waiting Lists
20.
Rev Med Chil ; 146(10): 1215-1219, 2018 Dec.
Article in Spanish | MEDLINE | ID: mdl-30724988

ABSTRACT

Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Antiretroviral Therapy, Highly Active/adverse effects , Chemical and Drug Induced Liver Injury/surgery , Liver Transplantation/methods , Adult , Chemical and Drug Induced Liver Injury/pathology , Humans , Immunocompetence , Male , Treatment Outcome
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