DENISE CERQUEIRA PARANAGUA VEZOZZO
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
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- Liver elastography can predict degree of advanced fibrosis for autoimmune hepatitis in biochemical remission(2023) PARANAGUA-VEZOZZO, Denise Cerqueira; TERRABUIO, Debora Raquel Benedita; REINOSO-PEREIRA, Gleicy Luz; MOUTINHO, Renata; ONO, Suzane Kioko; SALAS, Veronica Walwyn; FRANCA, Joao Italo Dias; ALVES, Venancio Avancini Ferreira; CANCADO, Eduardo Luiz Rachid; CARRILHO, Flair JoseBackground and AimThe aim was to analyze the concordance of liver stiffness measurement (LSM) either by transient elastography (TE) or ARFI with liver biopsy in autoimmune hepatitis (AIH) patients with biochemical remission and to identify those with histological remission. Liver biopsy is still the golden standard for AIH diagnosis. However, it is an invasive procedure and these patients, most of the time, require many biopsies, so it would be valuable to search for noninvasive method that could select all these patients and keep under observation. MethodsThirty-three patients with AIH were submitted for liver biopsy to evaluate histological remission after at least 18 months of normal aminotransferases. The efficiency of LSM and fibrosis stages was tested by a receiver operating characteristic curve analysis (AUROC). ResultsOne patient (3%) was F0, 6 (18.2%) were F1, 8 (24.2%) were F2, 10 (30.3%) were F3, and 8 (24.2%) were F4, according to METAVIR. Thirteen of thirty-three (39.4%) patients did not achieve histological remission. AUROC for F4 stage was 0.83 (IC: 0.76-0.99) for TE and 0.78 (IC: 0.65-0.95) for ARFI. Optimal LSM cutoff values were 12.3 kPa (Se = 87.5%, Sp = 88%) for TE and 1.65 m/s (Se = 87.5%, Sp = 76%) for ARFI. The tests were unable to differentiate patients with histological activity from those in histological remission (P < 0.05). ConclusionTE and ARFI accurately identify liver fibrosis by METAVIR score in AIH patients with biochemical remission. No cutoff value was detected to indicate whether the patient achieved histological remission.
- BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA(2020) CHAGAS, Aline Lopes; MATTOS, Angelo Alves de; CARRILHO, Flair José; BITTENCOURT, Paulo Lisboa; VEZOZZO, Denise Cerqueira Paranaguá; HORVAT, Natally; ROCHA, Manoel de Souza; ALVES, Venâncio Avancini Ferreira; CORAL, Gabriela Perdomo; ALVARES-DA-SILVA, Mario Reis; BARROS, Fabio Marinho do Rego; MENEZES, Marcos Roberto; MONSIGNORE, Lucas Moretti; COELHO, Fabricio Ferreira; SILVA, Renato Ferreira da; SILVA, Rita de Cássia Martins Alves; BOIN, Ilka de Fatima Santana Ferreira; D`ALBUQUERQUE, Luiz Augusto Carneiro; GARCIA, José Huygens Parente; FELGA, Guilherme Eduardo Gonçalves; MOREIRA, Airton Mota; BRAGHIROLI, Maria Ignez Freitas Melro; HOFF, Paulo Marcelo Gehm; MELLO, Vivianne Barretto de; DOTTORI, Mariana Fonseca; BRANCO, Tiago Pugliese; SCHIAVON, Leonardo de Lucca; COSTA, Thaisa de Fátima AlmeidaABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.
- Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma(2015) CARRILHO, Flair J; MATTOS, Angelo Alves de; VIANEY, Alex F; VEZOZZO, Denise Cerqueira P; MARINHO, Fábio; SOUTO, Francisco J; COTRIM, Helma P; COELHO, Henrique Sergio M; SILVA, Ivonete; GARCIA, José Huygens P; KIKUCHI, Luciana; LOFEGO, Patricia; ANDRAUS, Wellington; STRAUSS, Edna; SILVA, Giovanni; ALTIKES, Isaac; MEDEIROS, Jose Eymard; BITTENCOURT, Paulo L; PARISE, Edison RABSTRACT Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.
- Accuracy of transient elastography-FibroScan (R), acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C(2017) RAGAZZO, Taisa Grotta; PARANAGUA-VEZOZZO, Denise; LIMA, Fabiana Roberto; MAZO, Daniel Ferraz de Campos; PESSOA, Mario Guimaraes; OLIVEIRA, Claudia Pinto; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JoseOBJECTIVES: Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan (R), acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. METHODS: We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clinicas, Department of Gastroenterology of University of Sao Paulo School of Medicine, Sao Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (>= F2), advanced fibrosis (>= F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan (R), 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. RESULTS: A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (>= F2): FibroScan (R) : 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (>= F3): FibroScan (R) : 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan (R) : 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION: Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.
- Significance of CT scan and color Doppler duplex ultrasound in the assessment of Abernethy malformation(2015) NACIF, Lucas Souto; PARANAGUA-VEZOZZO, Denise Cerqueira; GALVAO, Flavio Henrique Ferreira; ROCHA, Manoel S.; ANDRAUS, Wellington; CARRILHO, Flair Jose; D'ALBUQUERQUE, Luiz CarneiroBackground: Abernethy malformation is a rare congenital vascular abnormality in which the portal vein bypasses the liver and drains directly into the inferior vena cava. Diagnosis is complex and requires good quality imaging methods to identify details in systemic and portal circulation in order to establish diagnostic confirmation and treatment strategy. In this study we highlight the significance of the use of CT scans and Color Doppler Duplex Ultrasound for the diagnosis, treatment and evolution assessment in two adults with Abernethy malformation. Case presentation: The diagnosis and the treatment of two patients with Abernethy malformation by CT scan and Color Doppler Duplex Ultrasound is described. One patient was submitted to liver transplantation due to chronic liver disease and multiple nodules diagnosed as adenoma. The other patient had normal liver function and a mild neurological and psychomotor dysfunction, therefore we adopted clinical treatment and close liver parenchyma evaluation and nodule surveillance, using an imaging approach involving intercalating CT scan and Color Doppler Duplex Ultrasound every 6 months. We highlight some important direct and indirect findings of non-invasive imaging methods. Conclusion: Abernethy malformation requires meticulous image diagnosis to improve treatment and avoid iatrogenic procedures. CT scans and Color Doppler Duplex Ultrasound are both efficient methods for diagnosis, treatment planning and evolution assessment of patients with Abernethy malformation.
- HIGHER VALUES IN LIVER ELASTOGRAPHY AND MELD SCORE ARE MORTALITY PREDICTORS ON LIVER TRANSPLANT WAITING LIST(2018) NACIF, Lucas Souto; PARANAGUA-VEZOZZO, Denise C.; MATSUDA, Alina; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair J.; FARIAS, Alberto Queiroz; D'ALBUQUERQUE, Luiz Carneiro; ANDRAUS, WellingtonBackground: Liver elastography have been reported in hepatocellular carcinoma (HCC) with higher values; however, it is unclear to identify morbimortality risk on liver transplantation waiting list. Aim: To assess liver stiffness, ultrasound and clinical findings in cirrhotic patients with and without HCC on screening for liver transplant and compare the morbimortality risk with elastography and MELD score. Method: Patients with cirrhosis and HCC on screening for liver transplant were enrolled with clinical, radiological and laboratory assessments, and transient elastography. Results: 103 patients were included (without HCC n=58 (66%); HCC n=45 (44%). The mean MELD score was 14.7 +/- 6.4, the portal hypertension present on 83.9% and the mean transient elastography value was 32.73 +/- 22.5 kPa. The median acoustic radiation force impulse value of liver parenchyma was 1.98 (0.65-3.2) m/s and 2.16 (0.59-2.8) m/s in HCC group. The HCC group was significantly associated with HCV infection (OR 26.84; p<0.0001), higher levels of serum alpha-fetoprotein (OR 5.51; p=0.015), clinical portal hypertension (OR 0.25; p=0.032) and similar MELD score (p=0.693). The area under the receiver operating characteristics (AUROC) showed sensitivity and specificity for serum alpha-fetoprotein (cutoff 9.1 ng/ml), transient elastography value (cutoff value 9 kPa), and acoustic radiation force impulse value (cutoff value 2.56 m/s) of 50% and 86%, 92% and 17% and 21% and 92%, respectively. The survival group had a mean transient elastography value of 31.65 +/- 22.2 kPa vs. 50.87 +/- 20.9 kPa (p=0.098) and higher MELD scores (p=0.035). Conclusion: Elastography, ultrasound and clinical findings are important non-invasive tools for cirrhosis and HCC on screening for liver transplant. Higher values in liver elastography and MELD scores predict mortality.
- NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features(2022) RECUERO, Amanda Medeiros; GOMES, Larissa Garcia; MACIEL, Gustavo Arantes Rosa; MALTA, Fernanda de Mello; SALLES, Ana Paula Moreira; VEZOZZO, Denise Cerqueira Paranagua; BARACAT, Edmund Chada; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; STEFANO, Jose Tadeu; OLIVEIRA, Claudia P.Background: The aim of this study was to determine the frequency of the rs738409 polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) gene in patients with polycystic ovary syndrome (PCOS) and its impact on nonalcoholic fatty liver disease (NAFLD) risk and severity. We also evaluated other risk factors associated with NAFLD and advanced fibrosis. Methods: This was a cross-sectional study involving 163 patients with PCOS at a tertiary center. Genotyping for the PNPLA3 polymorphism was undertaken using a TaqMan assay. The degree of fibrosis was defined by transient elastography. Results: The prevalence of NAFLD was 72.4%, and the polymorphism was heterozygous in 41.7% and homozygous in 8% of patients. Homeostasis model assessment of insulin resistance >= 2.5 was the main factor associated with the risk of developing NAFLD (OR = 4.313, p = 0.022), and its effect was amplified by the polymorphism (OR = 12.198, p = 0.017). Age > 32 years also conferred a higher risk for NAFLD. HDL values >= 50 mg/dL conferred protection against the outcome. Metabolic syndrome (OR = 13.030, p = 0.020) and AST > 32 U/L (OR = 9.039, p = 0.009) were independent risk factors for advanced fibrosis. Conclusions: In women with PCOS, metabolic characteristics are more relevant than PNPLA3 polymorphism regarding the risk for NAFLD and its advanced forms, but these factors can act synergistically, increasing disease risk.
- Strong correlation by ultrasonography of hepatomegaly and the presence of co-infection in HIV/HCV cirrhotic patients(2013) VEZOZZO, Denise Cerqueira Paranagua; MENDES-CORREA, Maria Cassia; CUNHA-SILVA, Marlone; ALVARADO-MORA, Monica Viviana; FRANCA, Joao Italo Dias; SEBBA, Jose Luiz; NICODEMO, Antonio Carlos; OLIVEIRA, Claudia P. M. S.; CARRILHO, Flair JoseObjectives: Progression of hepatic fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C virus compared to hepatitis C virus mono-infected patients. This study aimed to compare ultrasound features and selected clinical and biochemical variables between patients with human immunodeficiency virus/hepatitis C virus co-infection (n = 16) versus hepatitis C virus mono-infection (n = 16). Methods: Each patient underwent abdominal ultrasound, and a specific evaluation was performed in order to detect findings consistent with chronic liver disease. Characterization of spleen size, liver structural pattern, diameter of the portal, spleen, and mesenteric veins was based on classical ultrasound parameters. Propensity score was used for control of selection bias and performed using binary logistic regression to generate a score for each patient. The Fisher and Mann-Whitney tests were used to evaluate categorical variables and continuous variables, respectively. Results: On univariate analysis right hepatic lobe size was larger in human immunodeficiency virus/hepatitis C virus patients (157.06 +/- 17.56 mm) compared to hepatitis C virus mono-infected patients (134.94 +/- 16.95 mm) (p = 0.0011). The left hepatic lobe was also significantly larger in human immunodeficiency virus/hepatitis C virus patients (115.88 +/- 22.69 mm) versus hepatitis C virus mono-infected patients (95.06 +/- 24.18 mm) (p = 0.0177). Also, there was a strong correlation between hepatomegaly and co-infection (p = 0.005). Conclusion: Human immunodeficiency virus infection was the primary variable influencing liver enlargement in this population. Hepatomegaly on ultrasound was more common among cirrhotic human immunodeficiency virus/hepatitis C virus co-infected patients than among cirrhotic hepatitis C virus mono-infected patients. This aspect is very important in the management of human immunodeficiency virus/hepatitis C virus co-infected patients, because screening for hepatocellular carcinoma is necessary in this population.
- Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review(2015) TODA, Karla Sawada; KIKUCHI, Luciana; CHAGAS, Aline Lopes; TANIGAWA, Ryan Yukimatsu; PARANAGUA-VEZOZZO, Denise Cerqueira; PFIFFER, Tulio; ROCHA, Manoel de Souza; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JoseBackground and Aims: Schistosomiasis is a major chronic disease of humans in endemic regions, and infected individuals may develop a spectrumof pathology, including hepatic fibrosis, hepatosplenomegaly, and portal hypertension. Hepatocellular carcinoma (HCC) is considered the fifth most common cancer in the world, and there is limited and controversial evidence suggesting that Schistosoma mansoni infection may be a possible risk factor for HCC. The aim of this study was to report a case series of patients with HCC and S. mansoni infection and to conduct a literature review on the topic. Methods: From January 2002 to January 2015, an institutional database was screened retrospectively to identify patients with HCC and S. mansoni infection at a single center in the Department of Gastroenterology of University of Sao Paulo School of Medicine and Hospital das Clinicas, Brazil. Results: Seven cases were included. The mean age of patients was 62.1 +/- 10.3 years; six (85.7%) were male and one (14.3%) was female. All cases had positive epidemiology, coming from endemic areas of S. mansoni infection in Brazil, and four (57.1%) had previous complications (upper gastrointestinal bleeding) related toportal hypertension or surgery intervention (splenectomy) performed more than 10 years before the HCC diagnosis. Nontumoral portal vein thrombosis was identified in five (71.4%) patients. All patients had negative serology for HCV, and four (57.1%) had positivity of HBVcore antibodies without evidence of viral replication. According to BCLC staging, one (14.3%) patient was BCLC A and received TACE instead of RFA because HCC size was >30 mm; three (42.8%) BCLC B patients received sorafenib instead of local regional treatment due to the presence of nontumoral TPV. During follow-up, all patients developed tumoral progression and died. Conclusions: It remains unclear if S. mansoni infection alone has carcinogenic potential. The available literature indicates that S. Mansoni, in the presence of HBV and HCV infections, likely acts as a cofactor for the hepatic lesion and potentiates injury.
- HIGH VALUES OF LIVER STIFFNESS PLAY AN IMPORTANT ROLE IN STRATIFYING THE RISK OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC HEPATITIS C PATIENTS(2022) REINOSO-PEREIRA, Gleicy Luz; PARANAGUÁ-VEZOZZO, Denise Cerqueira; MAZO, Daniel F; FRANÇA, João Italo Dias; ONO, Suzane Kioko; CARRILHO, Flair JoséABSTRACT Background: Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. Methods: A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. Results: The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). Conclusion: A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.