Suzane K Ono - Academia.edu (original) (raw)

Papers by Suzane K Ono

Research paper thumbnail of UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients: Outcomes from a case-control study

Medicine, 2017

Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugate... more Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1*28 (UGT1A1*28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions' to the liver disease scenario. Our aim was to assess UGT1A1 genotypes' frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case-control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)-polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients....

Research paper thumbnail of A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin

Brazilian Journal of Medical and Biological Research, 2005

The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) marker... more The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and nongenetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectivelly. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.

Research paper thumbnail of Development of Hepatitis C Virus Genotyping by Real-Time PCR Based on the NS5B Region

PLOS One, 2010

Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response ... more Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response to antiviral therapy. The aim of this study was to develop and evaluate a novel real-time PCR method for HCV genotyping based on the NS5B region. Methodology/Principal Findings: Two triplex reaction sets were designed, one to detect genotypes 1a, 1b and 3a; and another to detect genotypes 2a, 2b, and 2c. This approach had an overall sensitivity of 97.0%, detecting 295 of the 304 tested samples. All samples genotyped by real-time PCR had the same type that was assigned using LiPA version 1 (Line in Probe Assay). Although LiPA v. 1 was not able to subtype 68 of the 295 samples (23.0%) and rendered different subtype results from those assigned by real-time PCR for 12/295 samples (4.0%), NS5B sequencing and real-time PCR results agreed in all 146 tested cases. Analytical sensitivity of the real-time PCR assay was determined by end-point dilution of the 5000 IU/ ml member of the OptiQuant HCV RNA panel. The lower limit of detection was estimated to be 125 IU/ml for genotype 3a, 250 IU/ml for genotypes 1b and 2b, and 500 IU/ml for genotype 1a. Conclusions/Significance: The total time required for performing this assay was two hours, compared to four hours required for LiPA v. 1 after PCR-amplification. Furthermore, the estimated reaction cost was nine times lower than that of available commercial methods in Brazil. Thus, we have developed an efficient, feasible, and affordable method for HCV genotype identification.

Research paper thumbnail of Development of Hepatitis C Virus Genotyping by Real-Time PCR Based on the NS5B Region

PLOS One, 2010

Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response ... more Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response to antiviral therapy. The aim of this study was to develop and evaluate a novel real-time PCR method for HCV genotyping based on the NS5B region. Methodology/Principal Findings: Two triplex reaction sets were designed, one to detect genotypes 1a, 1b and 3a; and another to detect genotypes 2a, 2b, and 2c. This approach had an overall sensitivity of 97.0%, detecting 295 of the 304 tested samples. All samples genotyped by real-time PCR had the same type that was assigned using LiPA version 1 (Line in Probe Assay). Although LiPA v. 1 was not able to subtype 68 of the 295 samples (23.0%) and rendered different subtype results from those assigned by real-time PCR for 12/295 samples (4.0%), NS5B sequencing and real-time PCR results agreed in all 146 tested cases. Analytical sensitivity of the real-time PCR assay was determined by end-point dilution of the 5000 IU/ ml member of the OptiQuant HCV RNA panel. The lower limit of detection was estimated to be 125 IU/ml for genotype 3a, 250 IU/ml for genotypes 1b and 2b, and 500 IU/ml for genotype 1a. Conclusions/Significance: The total time required for performing this assay was two hours, compared to four hours required for LiPA v. 1 after PCR-amplification. Furthermore, the estimated reaction cost was nine times lower than that of available commercial methods in Brazil. Thus, we have developed an efficient, feasible, and affordable method for HCV genotype identification.

Research paper thumbnail of A randomized crossover trial to assess therapeutic efficacy and cost reduction of acid ursodeoxycholic manufactured by the university hospital for the treatment of primary biliary cholangitis

BMC Gastroenterology

Background: Health care costs are growing faster than the rest of the global economy, according t... more Background: Health care costs are growing faster than the rest of the global economy, according to the World Health Organization (WHO). Countries' health expenditures include paying for general medicine, diagnostic procedures, hospitalizations and surgeries, as well as medications and prescribed treatment. Primary biliary cholangitis (PBC) is a rare autoimmune liver disease and the first line available treatment is ursodeoxycholic acid (UDCA), however, direct and indirect treatment costs are expensive. Main aim of this trial was to assess if the therapeutic efficacy of UDCA manufactured by the university hospital is equivalent to that of standard UDCA and treatment cost reduction in patients with PBC. Methods: It is a prospective, interventional, randomized, and crossover study in patients diagnosed with PBC. UDCA 300 mg tablets and capsules were developed and manufactured by the university hospital. Thirty patients under treatment with standard UDCA, in stable doses were randomized in sequence A and B, 15 patients in each arm. The groups were treated for 12 weeks and after, the UDCA formulation was changed, following for another 12 weeks of continuous therapy (tablets and capsules / capsules and tablets). Laboratory tests were performed at time T0 (beginning of treatment), T1 (at the 12 week-therapy, before the crossing-over) and T2 (end of treatment). The evaluation was done by comparing the hepatic parameters ALP, GGT, ALT, AST and total bilirubin, also considering the adverse events. The comparison of costs was based on price of the manufactured UDCA and standard UDCA price of the hospital. Results: Hospital reduced 66.1% the PBC treatment costs using manufactured UDCA. There were no differences in the biochemical parameters between sequence (A and B) and tablets or capsules of UDCA formulations applied in the treatment of PBC.

Research paper thumbnail of Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV study

Research paper thumbnail of Alcohol-related Liver Disease is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide

Clinical Gastroenterology and Hepatology

Research paper thumbnail of Acute acalculous cholecystitis during zika virus infection in an immunocompromised patient

Hepatology (Baltimore, Md.), 2018

Research paper thumbnail of Clinical pharmacology profile of care in Hepatology clinic

Revista da Associação Médica Brasileira

Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institut... more Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institute of Hospital das Clínicas of the University of São Paulo Medical School (HC-FMUSP, in the Portuguese acronym) has been developing specialized electives assistance activities in the Outpatient Specialty Clinic, Secondary Level, in São Paulo NGA-63 Várzea do Carmo. The objective of this study was to analyze the pharmacotherapeutic profile of patients. This is a cross-sectional and retrospective study in which patients were seen at the Hepatology sector and the results were submitted to descriptive statistics. During the study period, 492 patients were treated at the clinic, with a mean age of 58.9 years and frequency of 61.2% female and 74.8% living in São Paulo. This population was served by various other medical specialties (cardiology and endocrine among others) and the major liver diagnoses were: chronic hepatitis B and C and fatty liver. Comorbidities were also identified, such as di...

Research paper thumbnail of Concordance of non-invasive mechanical and serum tests for liver fibrosis evaluation in chronic hepatitis C

World journal of hepatology, Jan 18, 2017

To determine the sensitivity and specificity of liver stiffness measurement (LSM) and serum marke... more To determine the sensitivity and specificity of liver stiffness measurement (LSM) and serum markers (SM) for liver fibrosis evaluation in chronic hepatitis C. Between 2012 and 2014, 81 consecutive hepatitis C virus (HCV) patients had METAVIR score from liver biopsy compared with concurrent results from LSM [transient elastography (TE) [FibroScan(®)/ARFI technology (Virtual Touch(®))] and SM [FIB-4/aspartate aminotransferase-to-platelet ratio index (APRI)]. The diagnostic performance of these tests was assessed using receiver operating characteristic curves. The optimal cut-off levels of each test were chosen to define fibrosis stages F ≥ 2, F ≥ 3 and F = 4. The Kappa index set the concordance analysis. Fifty point six percent were female and the median age was 51 years (30-78). Fifty-six patients (70%) were treatment-naïve. The optimal cut-off values for predicting F ≥ 2 stage fibrosis assessed by TE were 6.6 kPa, for acoustic radiation force impulse (ARFI) 1.22 m/s, for APRI 0.75 a...

Research paper thumbnail of English

Research paper thumbnail of Interferon in viral liver diseases: pharmacological aspects

Revista do Hospital das Clínicas

In 1957, two English investigators, Alick Isaacs and Jean Lindenmann made a very important discov... more In 1957, two English investigators, Alick Isaacs and Jean Lindenmann made a very important discovery. They observed that when a virus species colonized cells in animals, this invasion interfered with the ability of other viruses, without any association with the former, to produce simultaneous infection. Both investigators observed that the substance responsible for the inhibition was secreted by the infected cells and called it interferon. They also observed that this protein did not directly interact with the virus, but induced the infected cells and surrounding cells to produce other proteins, which were in turn able to block the multiplication of the invading virus.

Research paper thumbnail of Pegylated interferon alfa for chronic hepatitis B: systematic review and meta-analysis

Journal of Viral Hepatitis, 2015

Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used... more Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNa) treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB. We searched electronic databases-PubMed, EMBASE, Cochrane Library and LILACSfor randomized controlled trials evaluating PEG-IFNa therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG-IFNa + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNa monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment. PEG-IFNa + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNa in HBeAg-positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG-IFNa combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies.

Research paper thumbnail of Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator

Journal of virology, 1997

The hepatitis C virus (HCV) nonstructural region 5A (NS5A) protein, without its 146 amino-termina... more The hepatitis C virus (HCV) nonstructural region 5A (NS5A) protein, without its 146 amino-terminal amino acids and fused to the DNA-binding domain of GAL4, strongly activates transcription in yeast and human hepatoma cells. Transcriptional activation by the HCV NS5A protein may play a role in viral replication and hepatocarcinogenesis.

Research paper thumbnail of Clearance of hepatitis C viral RNA in cirrhotic patients with antiviral therapy

Revista do Hospital das Clínicas

Interferon is indicated in chronic infection by hepatitis C virus (HCV), however, cirrhosis has b... more Interferon is indicated in chronic infection by hepatitis C virus (HCV), however, cirrhosis has been reported as a bad response factor to the therapy. Fifteen cirrhotic patients with HCV, undergoing treatment with recombinant interferon-alpha, ribavirin and/or ursodeoxycholic acid were studied. They were followed-up and evaluated with dosages of alanine aminotransferase and HCV RNA investigation by PCR technique. Of the 15 cirrhotic patients, seven were negative for HCV RNA after antiviral treatment, however ALT was normal in only three of them. Of the eight patients who were not negative, two had normal ALT. Biochemical-virological discrepancy in the follow-up of the patients after antiviral treatment observed in this study has also been reported by other authors. These reports show that the criteria for response to the treatment is to be established.

Research paper thumbnail of m-RECIST at 1 month and Child A are survival predictors after percutaneous ethanol injection of hepatocellular carcinoma

Annals of hepatology

Percutaneous ethanol injection (PEI) is a well-established therapeutic option in patients with ci... more Percutaneous ethanol injection (PEI) is a well-established therapeutic option in patients with cirrhosis and hepatocellular carcinoma (HCC). The modified-Response Evaluation Criteria in Solid Tumors (m-RECIST) are an important tool for the assessment of HCC response to therapy. The aim was to evaluate whether HCC response according to the m-RECIST criteria could be an effective predictor of long-term survival in Barcelona Clinic Liver Cancer (BCLC) stage 0 and A HCC patients undergoing PEI. 79 patients were followed-up for median time of 26.8 months. HCC diagnosis was based on the current guidelines of the American Association for Study of the Liver Diseases (AASLD) and European Association for Study of the Liver (EASL). Patient survival was calculated from the first PEI session to the end of the follow-up. The 1-, 3-, and 5-year overall survival rates were 79, 48 and 37%, respectively. In the multivariate analysis, Child-Pugh-Turcotte (CPT) (p = 0.022) and the response to m-RECIST ...

Research paper thumbnail of Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort

Annals of hepatology

The lack of information about hepatocellular carcinoma (HCC) in Brazil weakens health policy in p... more The lack of information about hepatocellular carcinoma (HCC) in Brazil weakens health policy in preventing deaths from the illness. The aim of this study was to establish the cumulative incidence and the risk factors for hepatocellular carcinoma development in patients under a surveillance program. 884 patients with compensated cirrhosis were prospectively followed up for at least five years, from August 1998 until August 2008, with at least one annual ultrasonography liver examination and serum alpha fetoprotein (AFP) measurement. Among 884 patients, 72 (8.1%) developed a tumor with a median follow up of 21.4 months. In the hepatocellular carcinoma group, hepatitis C virus infection was the major etiological factor (65.3%), 56.9% (41/72) were male and the mean average age was 57 ± 10 years. The annual incidence of hepatocellular carcinoma was 2.9%. 79.2% (57/72) of HCCs were detected within Milan Criteria, and the mean survival time was 52.3 months, significantly higher than for th...

Research paper thumbnail of Long term follow-up and patterns of response of ALT in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha

Revista do Instituto de Medicina Tropical de São Paulo, 1995

The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as c... more The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as complete, partial or absent, according to the behavior of serum alanine aminotransferase (ALT). However, a more detailed observation of the enzymatic activity has shown that the patterns may be more complex. The aim of this study was to describe the long term follow-up and patterns of ALT response in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha. A follow-up of 6 months or more after interferon-a was achieved in 44 patients. We have classified the serum ALT responses into six patterns and the observed frequencies were as follows: I. Long term response = 9 (20.5%); II. Normalization followed by persistent relapse after IFN = 7 (15.9%); III. Normalization with transient relapse = 5 (11.9%); IV. Temporary normalization and relapse during IFN = 4 (9.1%); V. Partial response (more than 50% of ALT decrease) = 7 (15.9%); VI. No response = 12 (27.3%). In conclus...

Research paper thumbnail of Hepatocellular Carcinoma: The Final Moments of Life

Journal of Cancer Therapy, 2013

Hepatocellular carcinoma (HCC) is a wide world prevalent hepatic disease, being the third greater... more Hepatocellular carcinoma (HCC) is a wide world prevalent hepatic disease, being the third greater cancer related death cause and most of the patients are not eligible for liver transplant. Palliative care is an option for, in average, half of hepatocellular carcinoma diagnosed patients and only recently the molecular targeted drug, Sorafenib, has been introduced among the therapeutic options for these patients. The physical pain comes frequently associated with progression disease (metastasis). Patients may be very fragile, with immobility, loss of interest in food and beverage intake, as well as weakness and drowsiness. Therefore, it is important that health professionals start planning care with patients and their relatives, before the end-stage disease. Informing the patient about therapeutic options guarantee a doctor patient relationship improvement and more belief on the health team.

Research paper thumbnail of Simultaneous quantitation of serum HBV DNA and HBeAg can distinguish between slow and fast viral responses to antiviral therapy in patients with chronic hepatitis B

Revista do Instituto de Medicina Tropical de São Paulo

The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chro... more The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chronic hepatitis B. In this study, 21 patients receiving varying therapies were followed and their viral response monitored by concomitant viral load and HBeAg quantitation in order to study the meaning and the kinetics of both parameters. It was possible to distinguish between three different patterns of viral response. The first was characterized by a simultaneous decrease in serum HBV DNA and HBeAg. The second pattern was characterized by a decrease in serum HBeAg but persistent detection of HBV DNA. The third pattern was characterized by undetectable HBV DNA with persistent HBeAg positivity, which points to a non-response (Pattern III-B) except when HBeAg levels showed a slow but steady drop, characterizing a 'slow responder' patient (Pattern III-A). The first pattern is compatible with a viral response. A long-term HBeAg seropositivity with a slow and persistent decrease (Patte...

Research paper thumbnail of UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients: Outcomes from a case-control study

Medicine, 2017

Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugate... more Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1*28 (UGT1A1*28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions' to the liver disease scenario. Our aim was to assess UGT1A1 genotypes' frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case-control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)-polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients....

Research paper thumbnail of A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin

Brazilian Journal of Medical and Biological Research, 2005

The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) marker... more The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and nongenetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectivelly. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.

Research paper thumbnail of Development of Hepatitis C Virus Genotyping by Real-Time PCR Based on the NS5B Region

PLOS One, 2010

Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response ... more Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response to antiviral therapy. The aim of this study was to develop and evaluate a novel real-time PCR method for HCV genotyping based on the NS5B region. Methodology/Principal Findings: Two triplex reaction sets were designed, one to detect genotypes 1a, 1b and 3a; and another to detect genotypes 2a, 2b, and 2c. This approach had an overall sensitivity of 97.0%, detecting 295 of the 304 tested samples. All samples genotyped by real-time PCR had the same type that was assigned using LiPA version 1 (Line in Probe Assay). Although LiPA v. 1 was not able to subtype 68 of the 295 samples (23.0%) and rendered different subtype results from those assigned by real-time PCR for 12/295 samples (4.0%), NS5B sequencing and real-time PCR results agreed in all 146 tested cases. Analytical sensitivity of the real-time PCR assay was determined by end-point dilution of the 5000 IU/ ml member of the OptiQuant HCV RNA panel. The lower limit of detection was estimated to be 125 IU/ml for genotype 3a, 250 IU/ml for genotypes 1b and 2b, and 500 IU/ml for genotype 1a. Conclusions/Significance: The total time required for performing this assay was two hours, compared to four hours required for LiPA v. 1 after PCR-amplification. Furthermore, the estimated reaction cost was nine times lower than that of available commercial methods in Brazil. Thus, we have developed an efficient, feasible, and affordable method for HCV genotype identification.

Research paper thumbnail of Development of Hepatitis C Virus Genotyping by Real-Time PCR Based on the NS5B Region

PLOS One, 2010

Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response ... more Background: Hepatitis C virus (HCV) genotyping is the most significant predictor of the response to antiviral therapy. The aim of this study was to develop and evaluate a novel real-time PCR method for HCV genotyping based on the NS5B region. Methodology/Principal Findings: Two triplex reaction sets were designed, one to detect genotypes 1a, 1b and 3a; and another to detect genotypes 2a, 2b, and 2c. This approach had an overall sensitivity of 97.0%, detecting 295 of the 304 tested samples. All samples genotyped by real-time PCR had the same type that was assigned using LiPA version 1 (Line in Probe Assay). Although LiPA v. 1 was not able to subtype 68 of the 295 samples (23.0%) and rendered different subtype results from those assigned by real-time PCR for 12/295 samples (4.0%), NS5B sequencing and real-time PCR results agreed in all 146 tested cases. Analytical sensitivity of the real-time PCR assay was determined by end-point dilution of the 5000 IU/ ml member of the OptiQuant HCV RNA panel. The lower limit of detection was estimated to be 125 IU/ml for genotype 3a, 250 IU/ml for genotypes 1b and 2b, and 500 IU/ml for genotype 1a. Conclusions/Significance: The total time required for performing this assay was two hours, compared to four hours required for LiPA v. 1 after PCR-amplification. Furthermore, the estimated reaction cost was nine times lower than that of available commercial methods in Brazil. Thus, we have developed an efficient, feasible, and affordable method for HCV genotype identification.

Research paper thumbnail of A randomized crossover trial to assess therapeutic efficacy and cost reduction of acid ursodeoxycholic manufactured by the university hospital for the treatment of primary biliary cholangitis

BMC Gastroenterology

Background: Health care costs are growing faster than the rest of the global economy, according t... more Background: Health care costs are growing faster than the rest of the global economy, according to the World Health Organization (WHO). Countries' health expenditures include paying for general medicine, diagnostic procedures, hospitalizations and surgeries, as well as medications and prescribed treatment. Primary biliary cholangitis (PBC) is a rare autoimmune liver disease and the first line available treatment is ursodeoxycholic acid (UDCA), however, direct and indirect treatment costs are expensive. Main aim of this trial was to assess if the therapeutic efficacy of UDCA manufactured by the university hospital is equivalent to that of standard UDCA and treatment cost reduction in patients with PBC. Methods: It is a prospective, interventional, randomized, and crossover study in patients diagnosed with PBC. UDCA 300 mg tablets and capsules were developed and manufactured by the university hospital. Thirty patients under treatment with standard UDCA, in stable doses were randomized in sequence A and B, 15 patients in each arm. The groups were treated for 12 weeks and after, the UDCA formulation was changed, following for another 12 weeks of continuous therapy (tablets and capsules / capsules and tablets). Laboratory tests were performed at time T0 (beginning of treatment), T1 (at the 12 week-therapy, before the crossing-over) and T2 (end of treatment). The evaluation was done by comparing the hepatic parameters ALP, GGT, ALT, AST and total bilirubin, also considering the adverse events. The comparison of costs was based on price of the manufactured UDCA and standard UDCA price of the hospital. Results: Hospital reduced 66.1% the PBC treatment costs using manufactured UDCA. There were no differences in the biochemical parameters between sequence (A and B) and tablets or capsules of UDCA formulations applied in the treatment of PBC.

Research paper thumbnail of Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV study

Research paper thumbnail of Alcohol-related Liver Disease is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide

Clinical Gastroenterology and Hepatology

Research paper thumbnail of Acute acalculous cholecystitis during zika virus infection in an immunocompromised patient

Hepatology (Baltimore, Md.), 2018

Research paper thumbnail of Clinical pharmacology profile of care in Hepatology clinic

Revista da Associação Médica Brasileira

Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institut... more Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institute of Hospital das Clínicas of the University of São Paulo Medical School (HC-FMUSP, in the Portuguese acronym) has been developing specialized electives assistance activities in the Outpatient Specialty Clinic, Secondary Level, in São Paulo NGA-63 Várzea do Carmo. The objective of this study was to analyze the pharmacotherapeutic profile of patients. This is a cross-sectional and retrospective study in which patients were seen at the Hepatology sector and the results were submitted to descriptive statistics. During the study period, 492 patients were treated at the clinic, with a mean age of 58.9 years and frequency of 61.2% female and 74.8% living in São Paulo. This population was served by various other medical specialties (cardiology and endocrine among others) and the major liver diagnoses were: chronic hepatitis B and C and fatty liver. Comorbidities were also identified, such as di...

Research paper thumbnail of Concordance of non-invasive mechanical and serum tests for liver fibrosis evaluation in chronic hepatitis C

World journal of hepatology, Jan 18, 2017

To determine the sensitivity and specificity of liver stiffness measurement (LSM) and serum marke... more To determine the sensitivity and specificity of liver stiffness measurement (LSM) and serum markers (SM) for liver fibrosis evaluation in chronic hepatitis C. Between 2012 and 2014, 81 consecutive hepatitis C virus (HCV) patients had METAVIR score from liver biopsy compared with concurrent results from LSM [transient elastography (TE) [FibroScan(®)/ARFI technology (Virtual Touch(®))] and SM [FIB-4/aspartate aminotransferase-to-platelet ratio index (APRI)]. The diagnostic performance of these tests was assessed using receiver operating characteristic curves. The optimal cut-off levels of each test were chosen to define fibrosis stages F ≥ 2, F ≥ 3 and F = 4. The Kappa index set the concordance analysis. Fifty point six percent were female and the median age was 51 years (30-78). Fifty-six patients (70%) were treatment-naïve. The optimal cut-off values for predicting F ≥ 2 stage fibrosis assessed by TE were 6.6 kPa, for acoustic radiation force impulse (ARFI) 1.22 m/s, for APRI 0.75 a...

Research paper thumbnail of English

Research paper thumbnail of Interferon in viral liver diseases: pharmacological aspects

Revista do Hospital das Clínicas

In 1957, two English investigators, Alick Isaacs and Jean Lindenmann made a very important discov... more In 1957, two English investigators, Alick Isaacs and Jean Lindenmann made a very important discovery. They observed that when a virus species colonized cells in animals, this invasion interfered with the ability of other viruses, without any association with the former, to produce simultaneous infection. Both investigators observed that the substance responsible for the inhibition was secreted by the infected cells and called it interferon. They also observed that this protein did not directly interact with the virus, but induced the infected cells and surrounding cells to produce other proteins, which were in turn able to block the multiplication of the invading virus.

Research paper thumbnail of Pegylated interferon alfa for chronic hepatitis B: systematic review and meta-analysis

Journal of Viral Hepatitis, 2015

Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used... more Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are frequently used for chronic hepatitis B (CHB) treatment, but are associated with adverse effects and viral resistance. Here we performed a systematic review and meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNa) treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB. We searched electronic databases-PubMed, EMBASE, Cochrane Library and LILACSfor randomized controlled trials evaluating PEG-IFNa therapy between 1999 and September 2014. Virological response was the primary outcome. We identified 14 studies involving 2829 patients. Our analysis revealed that PEG-IFNa + lamivudine combination therapy produced better virological and biochemical responses than PEG-IFNa monotherapy in HBeAg-positive and HBeAg-negative patients at the end of treatment. PEG-IFNa + adefovir dipivoxil achieved better seroconversion rate than PEG-IFNa in HBeAg-positive patients at the end of treatment. The present findings demonstrated a beneficial response rate following PEG-IFNa combination therapy with nucelos(t)ides among HBeAg-positive and HBeAg-negative patients with CHB. Further trials are needed to investigate simultaneous and sequential therapy strategies.

Research paper thumbnail of Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator

Journal of virology, 1997

The hepatitis C virus (HCV) nonstructural region 5A (NS5A) protein, without its 146 amino-termina... more The hepatitis C virus (HCV) nonstructural region 5A (NS5A) protein, without its 146 amino-terminal amino acids and fused to the DNA-binding domain of GAL4, strongly activates transcription in yeast and human hepatoma cells. Transcriptional activation by the HCV NS5A protein may play a role in viral replication and hepatocarcinogenesis.

Research paper thumbnail of Clearance of hepatitis C viral RNA in cirrhotic patients with antiviral therapy

Revista do Hospital das Clínicas

Interferon is indicated in chronic infection by hepatitis C virus (HCV), however, cirrhosis has b... more Interferon is indicated in chronic infection by hepatitis C virus (HCV), however, cirrhosis has been reported as a bad response factor to the therapy. Fifteen cirrhotic patients with HCV, undergoing treatment with recombinant interferon-alpha, ribavirin and/or ursodeoxycholic acid were studied. They were followed-up and evaluated with dosages of alanine aminotransferase and HCV RNA investigation by PCR technique. Of the 15 cirrhotic patients, seven were negative for HCV RNA after antiviral treatment, however ALT was normal in only three of them. Of the eight patients who were not negative, two had normal ALT. Biochemical-virological discrepancy in the follow-up of the patients after antiviral treatment observed in this study has also been reported by other authors. These reports show that the criteria for response to the treatment is to be established.

Research paper thumbnail of m-RECIST at 1 month and Child A are survival predictors after percutaneous ethanol injection of hepatocellular carcinoma

Annals of hepatology

Percutaneous ethanol injection (PEI) is a well-established therapeutic option in patients with ci... more Percutaneous ethanol injection (PEI) is a well-established therapeutic option in patients with cirrhosis and hepatocellular carcinoma (HCC). The modified-Response Evaluation Criteria in Solid Tumors (m-RECIST) are an important tool for the assessment of HCC response to therapy. The aim was to evaluate whether HCC response according to the m-RECIST criteria could be an effective predictor of long-term survival in Barcelona Clinic Liver Cancer (BCLC) stage 0 and A HCC patients undergoing PEI. 79 patients were followed-up for median time of 26.8 months. HCC diagnosis was based on the current guidelines of the American Association for Study of the Liver Diseases (AASLD) and European Association for Study of the Liver (EASL). Patient survival was calculated from the first PEI session to the end of the follow-up. The 1-, 3-, and 5-year overall survival rates were 79, 48 and 37%, respectively. In the multivariate analysis, Child-Pugh-Turcotte (CPT) (p = 0.022) and the response to m-RECIST ...

Research paper thumbnail of Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort

Annals of hepatology

The lack of information about hepatocellular carcinoma (HCC) in Brazil weakens health policy in p... more The lack of information about hepatocellular carcinoma (HCC) in Brazil weakens health policy in preventing deaths from the illness. The aim of this study was to establish the cumulative incidence and the risk factors for hepatocellular carcinoma development in patients under a surveillance program. 884 patients with compensated cirrhosis were prospectively followed up for at least five years, from August 1998 until August 2008, with at least one annual ultrasonography liver examination and serum alpha fetoprotein (AFP) measurement. Among 884 patients, 72 (8.1%) developed a tumor with a median follow up of 21.4 months. In the hepatocellular carcinoma group, hepatitis C virus infection was the major etiological factor (65.3%), 56.9% (41/72) were male and the mean average age was 57 ± 10 years. The annual incidence of hepatocellular carcinoma was 2.9%. 79.2% (57/72) of HCCs were detected within Milan Criteria, and the mean survival time was 52.3 months, significantly higher than for th...

Research paper thumbnail of Long term follow-up and patterns of response of ALT in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha

Revista do Instituto de Medicina Tropical de São Paulo, 1995

The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as c... more The response to interferon treatment in chronic hepatitis NANB/C has usually been classified as complete, partial or absent, according to the behavior of serum alanine aminotransferase (ALT). However, a more detailed observation of the enzymatic activity has shown that the patterns may be more complex. The aim of this study was to describe the long term follow-up and patterns of ALT response in patients with chronic hepatitis NANB/C treated with recombinant interferon-alpha. A follow-up of 6 months or more after interferon-a was achieved in 44 patients. We have classified the serum ALT responses into six patterns and the observed frequencies were as follows: I. Long term response = 9 (20.5%); II. Normalization followed by persistent relapse after IFN = 7 (15.9%); III. Normalization with transient relapse = 5 (11.9%); IV. Temporary normalization and relapse during IFN = 4 (9.1%); V. Partial response (more than 50% of ALT decrease) = 7 (15.9%); VI. No response = 12 (27.3%). In conclus...

Research paper thumbnail of Hepatocellular Carcinoma: The Final Moments of Life

Journal of Cancer Therapy, 2013

Hepatocellular carcinoma (HCC) is a wide world prevalent hepatic disease, being the third greater... more Hepatocellular carcinoma (HCC) is a wide world prevalent hepatic disease, being the third greater cancer related death cause and most of the patients are not eligible for liver transplant. Palliative care is an option for, in average, half of hepatocellular carcinoma diagnosed patients and only recently the molecular targeted drug, Sorafenib, has been introduced among the therapeutic options for these patients. The physical pain comes frequently associated with progression disease (metastasis). Patients may be very fragile, with immobility, loss of interest in food and beverage intake, as well as weakness and drowsiness. Therefore, it is important that health professionals start planning care with patients and their relatives, before the end-stage disease. Informing the patient about therapeutic options guarantee a doctor patient relationship improvement and more belief on the health team.

Research paper thumbnail of Simultaneous quantitation of serum HBV DNA and HBeAg can distinguish between slow and fast viral responses to antiviral therapy in patients with chronic hepatitis B

Revista do Instituto de Medicina Tropical de São Paulo

The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chro... more The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chronic hepatitis B. In this study, 21 patients receiving varying therapies were followed and their viral response monitored by concomitant viral load and HBeAg quantitation in order to study the meaning and the kinetics of both parameters. It was possible to distinguish between three different patterns of viral response. The first was characterized by a simultaneous decrease in serum HBV DNA and HBeAg. The second pattern was characterized by a decrease in serum HBeAg but persistent detection of HBV DNA. The third pattern was characterized by undetectable HBV DNA with persistent HBeAg positivity, which points to a non-response (Pattern III-B) except when HBeAg levels showed a slow but steady drop, characterizing a 'slow responder' patient (Pattern III-A). The first pattern is compatible with a viral response. A long-term HBeAg seropositivity with a slow and persistent decrease (Patte...