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Relationship between phase angle,steatosis,and liver fibrosis in patients coinfected with human immunodeficiency virus/hepatitis C virus

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World Journal of Hepatology 2022年第6期14卷 1173-1181页

作者： Sabrina Alves Fernandes cristiane valle tovo AndréLuiz Machado da Silva Letícia Pereira Pinto Randhall B Carteri Angelo A Mattos Postgraduate Program in Hepatology Universidade Federal de Ciências da Saúde de Porto Alegre(UFCSPA)Porto Alegre 90050-170Brazil Department of Infectology Service Hospital Nossa Senhora da ConceiçãoPorto Alegre 91350-200Brazil Department of Nutrition Centro Universitário Metodista-IPAPorto Alegre 90420-060Brazil Department of Nutrition Centro Universitário CESUCACachoeirinha 94935-630Brazil

BACKGROUND Malnutrition,lipodystrophy,and dyslipidemia are prevalent characteristics in patients with human immunodeficiency virus(HIV)infection with or without previous treatment.Such a clinical condition can lead to the hypothesis of the presence of hepatic steatosis with possible progression to fibrosis and the risk of hepatocellular carcinoma.Notably,a low phase angle(PA),evaluated by bioelectrical impedance analysis(BIA),is an independent prognostic marker of clinical progression and survival in HIV-infected patients.AIM To evaluate the relationship between PA and body composition with steatosis and hepatic fibrosis in HIV/hepatitis C virus(HCV)-coinfected patients.METHODS A retrospective observational study by convenience sampling of coinfected HIV/HCV patients,in which all patients underwent transient elastography(Fibroscan)and BIA evaluation.Student’s t test was used for group comparisons,and Spearman’s or Pearson’s correlation test was used when appropriate.The significance level was set at 5%,and analyses were performed using SPSS version 21.0.RESULTS Forty-three patients who received antiretroviral therapy met the inclusion criteria,and 23(53.5%)were under treatment with protease inhibitors(PIs).There was no difference in PA between those who used PIs and those who did not(P=0.635).There was no correlation between fibrosis grade and PA(P=0.355)or lean mass(P=0.378).There was a significant inverse correlation between the controlled attenuation parameter(CAP)and lean mass(P=0.378),positive correlation between PA and lean mass(P=0.378),and negative correlation between PA and fatty mass(P=0.378),although the CAP and PA were not correlated.When evaluated by sex,no significant correlations were found.CONCLUSION PA determines the muscle function of HIV/HCV-coinfected patients,and the CAP values reinforce the association with lean mass,suggesting that patients require early nutritional interventions.

关键词： Phase angle Bioelectrical impedance Coinfection Human immunodeficiency virus Hepatitis C virus Nutrition

Chronic liver failure-consortium acute-on-chronic liver failure and acute decompensation scores predict mortality in Brazilian cirrhotic patients

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World Journal of Gastroenterology 2017年第28期23卷 5237-5245页

作者： Rafael Veiga Picon Franciele Sabadin Bertol cristiane valle tovo Angelo Zambam de Mattos Gastroenterology and Hepatology Unit Nossa Senhora da Conceicao Hospital Gastro-enterology and Hepatology Unit Federal University of Health Sciences of Porto Alegre Gastroenterology and Hepatology Unit Pontifical Catholic University of Rio Grande do Sul

AIM To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients.METHODS This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium(CLIF-C) acute decompensation score(CLIF-C AD) and CLIF-C acute-on-chronic liver failure score(CLIF-C ACLF),regarding 28-d and 90-d mortality,as well as to compare them to other prognostic models,such as Model for End-Stage Liver Disease(MELD),MELD Sodium(MELD-Na),ChildPugh(CP) score,and the CLIF-C Organ Failure score(CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic(ROC) curves,area under the curves(AUC) and 95%CI.RESULTS One hundred and thirteen cirrhotic patients were included. At admission,18 patients had acute-onchronic liver failure(ACLF) and 95 individuals had acute decompensation(AD) without ACLF,of which 24 eventually developed ACLF during the course of hospitalization(AD evolving to ACLF group). The AD group had significantly lower 28-d(9.0%) and 90-d(18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group(both P < 0.001). On the other hand,28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group(P = 0.542 and P = 0.708,respectively). Among patients with ACLF,at 28 d from the diagnosis,CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line,with an AUC(95%CI) of 0.71(95%CI: 0.54-0.88,P = 0.021). Among patients with AD,all prognostic scores performed significantly better than the reference line regarding 28-d mortality,presenting with similar AUCs: CLIF-C AD score 0.75(95%CI: 0.63-0.88),CP score 0.72(95%CI: 0.59-0.85),MELD score 0.75(95%CI: 0.61-0.90),MELD-Na score 0.76(95%CI: 0.61-0.90),and CLIF-C OF score 0.74(95%CI: 0.60-0.88). The

关键词： Cirrhosis Acute-on-chronic liver failure Mortality Prediction Prognosis Acute decompensation of cirrhosis

Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database

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World Journal of Gastroenterology 2016年第40期22卷 8910-8917页

作者： Dimas Alexandre Kliemann cristiane valle tovo Ana Beatriz Gorini da Veiga Angelo Alves de Mattos Charles Wood Graduate Program in Medicine: Hepatology-Universidade Federal de Ciências da Saúde de Porto Alegre Porto Alegre RS 90050-170 Brazil Hospital Nossa Senhora da Conceicāo Portto Alegre RS 90050-170 Brazil Department of Basic Health Sciences Laboratory of Molecular Biology Graduate Program in Pathology-Universidade Federal de Ciências da Saúde de Porto Alegre RS 90050-170 Brazil School of Biological Sciences Nebraska Center for Virology University of Nebraska Lincoln NE 68511 United States

AIM To evaluate the occurrence of resistant mutations in treatment-na?ve hepatitis C virus(HCV) sequences deposited in the European hepatitis C virus database(euH CVdb). METHODS The sequences were downloaded from the eu HCVdb(https://euhcvdb.***.fr/eu HCVdb/). The search was performed for full-length NS3 protease, NS5 A and NS5 B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5 A and 535 NS5 B sequences from HCV genotypes1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents(DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioE dit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis.RESULTS The Q80 K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V(3.21%) in genotype 1a, and Y56F(15.93%), V132I(23.28%) and I170V(65.20%) in genotype 1b. For the NS5 A, 2.21% of the genotype 1a sequences have the P58 S mutation, 5.95% of genotype 1b sequences have the R30 Q mutation, 15.79% of subtypes 2a sequences have the Q30 R mutation, 23.08% of subtype 2b sequences have a L31 M mutation, and in subtype 3a sequences, 23.08% have the M31 L resistant variants. For the NS5 B, the V321 L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142 T variant was observed in 0.32% of subtype 1b sequences. The C316 Y, S556 G, D559 N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and

关键词：丙肝病毒抵抗 Quasispecies 指导抗病毒的代理人多型性药抵抗

Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus:a retrospective cohort study

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World Journal of Gastroenterology 2018年第5期24卷 613-622页

作者： Patrícia dos Santos Marcon cristiane valle tovo Dimas Alexandre Kliemann Patrícia Fisch Angelo Alves de Mattos Hepatology Post-Graduate Program Universidade Federal de Ciências da Saúde de Porto Alegre(UFCSPA)Porto Alegre 90020-090RSBrazil Infectology Department at Hospital Nossa Senhora da Conceicao Porto Alegre 91350-200RSBrazil Epidemiology Department at Hospital Nossa Senhora da Conceicao Porto Alegre 91350-200RSBrazil

AIM To assess the incidence of hepatocellular carcinoma(HCC) in chronic liver disease due to hepatitis B virus(HBV) or hepatitis C virus(HCV) coinfected with human immunodeficiency virus(HIV).METHODS A retrospective cohort study was performed, including patients with chronic liver disease due to HBV or HCV, with and without HIV coinfection. Patients were selected in the largest tertiary public hospital complex in southern Brazil between January 2007 and June 2014. We assessed demographic and clinical data, including lifestyle habits such as illicit drug use or alcohol abuse, in addition to frequency and reasons for hospital admissions via medical records review.RESULTS Of 804 patients were included(399 with HIV coinfection and 405 monoinfected with HBV or HCV). Coinfected patients were younger(36.7 ± 10 vs 46.3 ± 12.5, P < 0.001). Liver cirrhosis was observed in 31.3% of HIV-negative patients and in 16.5% of coinfected(P < 0.001). HCC was diagnosed in 36 patients(10 HIV coinfected and 26 monoinfected). The incidence density of HCC in coinfected and monoinfected patients was 0.25 and 0.72 cases per 100 patient-years(95%CI: 0.12-0.46 vs 0.47-1.05)(long-rank P = 0.002), respectively. The ratio for the HCC incidence rate was 2.98 for HIV-negative. However, when adjusting for age or when only cirrhotic are analyzed, the absence of HIV lost statistical significance for the development of HCC. CONCLUSION In this study, the presence of HIV coinfection in chronic liver disease due to HBV or HCV showed no relation to the increase of HCC incidence.

关键词： Hepatocellular carcinoma Chronic hepatitis human immunodeficiency virus Coinfection Cirrhosis

Role of micronutrients in staging of nonalcoholic fatty liver disease:A retrospective cross-sectional study

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World Journal of Gastrointestinal Surgery 2020年第6期12卷 269-276页

作者： Franciele Sabadin Bertol Bruna Araujo Brunno Brochado Jorge Natalino Rinaldi Luiz Alberto De Carli cristiane valle tovo Graduate Program of Medicine HepatologyUniversidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreRS 90430080Brazil

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) presents high incidence throughout the world and has been progressively increasing in prevalence. This disease has a heterogeneous natural history, including simple steatosis, nonalcoholic steatohepatitis(NASH), and cirrhosis. The factors that determine its evolution to more severe forms of the disease are still poorly understood, and micronutrients with antioxidant potential may be involved in the pathophysiology of the disease.AIM To evaluate the relationship between serum levels of micronutrients and the severity of NAFLD.METHODS A retrospective, observational and cross-sectional study was conducted. This study included all patients undergoing bariatric surgery who experienced liver biopsy during the procedure, and had serum levels of micronutrients(vitamin D,vitamin B12, zinc, iron, and magnesium), which was assessed in a preoperative evaluation conducted at a reference center in southern Brazil.RESULTS A total of 614 patients were analyzed, of which 93% had steatosis, 70.7% had NASH, and 49.3% had some degree of fibrosis. Serum levels of vitamin D were negatively correlated with the severity of steatosis and NASH, and serum levels of vitamin B12 were positively correlated with the severity of steatosis and fibrosis. The other micronutrients showed no association with NAFLD staging.CONCLUSION Serum levels of vitamin D are inversely related to the severity of steatosis and NASH, and serum levels of vitamin B12 are higher in more advanced stages of simple steatosis and liver fibrosis. Serum levels of zinc, iron, and magnesium were not associated with NAFLD severity.

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Liver cirrhosis Micronutrients Vitamin D Vitamin B12 Zinc Iron Magnesium

Drug-induced liver injury and COVID-19:A review for clinical practice

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World Journal of Hepatology 2021年第9期13卷 1143-1153页

作者： Gabriela Xavier Ortiz Gabriele Lenhart Matheus William Becker Karin Hepp Schwambach cristiane valle tovo Carine Raquel Blatt Graduate Program in Medicine Hepatology Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Rio Grande do SulBrazil Multiprofessional Residency Integrated in Health Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Rio Grande do SulBrazil Internal Medicine Department Graduate Program in Medicine-HepatologyFederal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Rio Grande do SulBrazil Pharmacoscience Department Graduate Program in Medicine-HepatologyFederal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Rio Grande do SulBrazil

Coronavirus disease 2019(COVID-19)consists of a systemic disease that can present many complications.The infection presents broad clinical symptoms and a high rate of transmissibility.In addition to severe acute respiratory syndrome,the patients manifest complications beyond the respiratory system.The frequency of liver damage in COVID-19 patients ranges from 14.8% to 53% of patients.One should pay attention to drug-induced liver injury(DILI)in patients with COVID-19,especially considering the off-label use of drugs in prophylactic and therapeutic regimens applied on large scales.This review aims to present relevant information on the medication used so far in COVID-19 patients and its possible hepatotoxicity.We reviewed liver damage in patients with COVID-19 on PubMed and Virtual Health Library to investigate DILI cases.Four studies were selected,involving the medicines remdesivir,tocilizumab and a pharmacovigilance analysis study.The hepatotoxicity profile of drugs presented in the literature considers use in accordance to usual posology standards for treatment.However,drugs currently used in the management of COVID-19 follow different dosages and posology than those tested by the pharmaceutical industry.The deficiency of uniformity and standardization in the assessment of hepatotoxicity cases hinders the publication of information and the possibility of comparing information among healthcare professionals.It is suggested that severe liver injury in COVID-19 patients should be reported in pharmacovigilance institutions,and physicians should pay attention to any considerable abnormal liver test elevation as it can demonstrate unknown drug hepatotoxicity.Liver disorders in COVID-19 patients and the use of several concomitant off-label medications—with a potential risk of further damaging the liver-should at least be a warning sign for rapid identification and early intervention,thus preventing liver damage from contributing to severe impairment in patients.

关键词： Liver injury Chemical and drug-induced liver injury COVID-19 SARSCoV-2 Pharmacovigilance

Incidence of hepatocellular carcinoma in outpatients with cirrhosis in Brazil: A 10-year retrospective cohort study

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World Journal of Gastroenterology 2016年第46期22卷 10219-10225页

作者： Marcelo Campos Appel-da-Silva Suelen Aparecida da Silva Miozzo Isabella de Azevedo Dossin cristiane valle tovo Fernanda Branco Angelo Alves de Mattos Graduate Program:Hepatology Universidade Federal de Ciências da Saúde de Porto Alegre(UFCSPA)Porto AlegreRS 900150-170Brazil Ultrasound Imaging Servince Hospital Santa Casa de Porto AlegrePorto AlegreRS 90050-170Brazil

AIM To determine the incidence of hepatocellular carcinoma(HCC) and the impact of HCC surveillance on early diagnosis and survival of cirrhotic outpatients. METHODS In this retrospective cohort study, cirrhotic outpatients undergoing HCC surveillance between March 2005 and March 2014 were analyzed. Exclusion criteria were HIV coinfection; previous organ transplantation; diagnosis of HCC at first consultation; missing data in the medical chart; and less than 1 year of follow-up. Surveillance was carried out every six months using ultrasound and serum alpha-fetoprotein determination. Ten-year cumulative incidence and survival were estimated through Kaplan-Meier analysis. RESULTS Four hundred and fifty-three patients were enrolled, of which 57.6% were male. Mean age was 55 years. Hepatitis C virus and heavy use of alcohol were the main etiologic agents of cirrhosis. HCC was diagnosed in 75 patients(16.6%), with an estimated cumulative incidence of 2.6% in the 1st year, 15.4% in the 5th year, and 28.8% in the 10 th year. Median survival was estimated at 17.6 mo in HCC patients compared to 234 mo in non-HCC patients(P < 0.001). Early-stage HCC was more often detected in patients who underwent surveillance every 6 mo or less(P = 0.05). However, survival was not different between patients with early stage vs non-early stage tumors [HR = 0.54(0.15-1.89), P = 0.33].CONCLUSION HCC is a frequent complication in patients with cirrhosis and adherence to surveillance programs favors early diagnosis.

关键词：肝肝硬化 Hepatocellular 癌传染病学监视幸存

Nutritional evaluation in cirrhosis: Emphasis on the phase angle

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World Journal of Hepatology 2016年第29期8卷 1205-1211页

作者： Sabrina Alves Fernandes Angelo Alves de Mattos cristiane valle tovo Claudio Augusto Marroni Postgraduate Program at Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) Post Graduation Program in Bioscience and Rehabilitation and the Post Graduation Program in Rehabilitation and Inclusion Methodist University-IPA

Protein-calorie malnutrition(PCM) is a common condition in cirrhotic patients, leading to a worse prognosis, complications, poor quality of life and lower survival rates. Among ways of assessing nutritional status, there are anthropometric methods such as the evaluation of the triceps skinfold, the arm circumference, the arm muscle circumference and the body mass index, and nonanthropometric methods such as the subjective global assessment, the handgrip strength of non-dominant hand, and the bioelectrical impedance analysis(BIA). PCM is frequently under-diagnosed in clinical settings in patients with cirrhosis due to the limitations of nutritional evaluation methods in this population. BIA is a useful method, but cannot be indicated in patients with abnormal body composition. In these situations, the phase angle(PA) has been used, and can become an important tool in assessing nutritional status in any situation. The PA is superior to anthropometric methods and might be considered as a nutritional indicator in cirrhosis. The early characterization of the nutritional status in patients with cirrhosis means an early nutritional intervention, with a positive impact on patients' overall prognosis. Among the usually accepted methods for nutritional diagnosis, the PA provides information in a quick and objective manner.

关键词：营养不良 Bioelectrical 阻抗阶段角度 Sarcopenia 营养

Chronic hepatitis C genotype 1 virus:Who should wait for treatment?

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World Journal of Gastroenterology 2014年第11期20卷 2867-2875页

作者： cristiane valle tovo Angelo Alves de Mattos Paulo Roberto Lerias de Almeida Department of Gastroenterology Universidade Federal de Ciências da Saúde de Porto AlegrePorto Alegre 90430-080Brasil Department of Gastroenterology Hospital Nossa Senhora da Concei??oPorto Alegre 91350-200Brasil

Elucidation of the natural history of chronic hepatitis C(CHC)and the identification of risk factors for its progression to advanced liver disease have allowed many physicians to recommend deferral treatment(triple therapy)in favour of waiting for new drug availability for patients who are at low risk of progression to significant liver disease.Newer generation drugs are currently under development,and are expected to feature improved efficacy and safety profiles,as well as less complex and shorter duration delivery regimens,compared to the current standards of care.In addition,patients with cirrhosis and prior null responders have a low rate(around 15%)of achieving sustained virological response(SVR)with triple therapy,and physicians must also consider the decision to wait for new treatments in the future for these patients as well.Naive patients are the most likely to achieve a close to 100%SVR rate;therefore,it may be advisable to recommend that patients with mild to moderate CHC should wait for the newer therapy options.In contrast,patients with advanced fibrosis and cirrhosis will be those with the greatest need for expedited therapeutic intervention.There remains a need,however,for establishing definitive clinical management guidelines to maximize the benefit of waiting for new drugs and minimize risk of side effects and non-response to the current triple therapy.

关键词： Hepatitis C virus Chronic hepatitis C Treatment of