Serious liver injury induced by Nimesulide: an international collaborative study.

Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and Latin American DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a twofold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was ≤ 15 days in 12 patients (21%) and one patient developed ALF within 7 days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (≤ 15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable.

Moving Fast Toward Hepatitis B Virus Elimination.

Currently, there are two safe and effective therapeutic strategies for chronic hepatitis B treatment, namely, nucleoside analogs and interferon alpha (pegylated or non-pegylated). These treatments can control viral replication and improve survival; however, they do not eliminate the virus and therefore require long-term continued therapy. In addition, there are significant concerns about virus rebound on discontinuation of therapy and the development of fibrosis and hepatocellular carcinoma despite therapy. Therefore, the search for new, more effective, and safer antiviral agents that can cure hepatitis B virus (HBV) continues. Anti-HBV drug discovery and development is fundamentally impacted by our current understanding of HBV replication, disease physiopathology, and persistence of HBV covalently closed circular DNA (cccDNA). Several HBV replication targets are the basis for novel anti-HBV drug development strategies. Many of them are already in clinical trial phase 1 or 2, while others with promising results are still in preclinical stages. As research intensifies, potential HBV curative therapies and modalities in the pipeline are now on the horizon.

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.

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. CONCLUSIONS: The study showed that there was no significant difference between manufactured UDCA (capsule and tablet) and standard UDCA. Hospital reduced the PBC treatment costs using the manufactured UDCA by the university hospital. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03489889 retrospectively registered on January 12th, 2018; Ethics Committee approved the study (ID: 1.790.088) on October 25th, 2016.

Access to antiviral therapy for chronic hepatitis B during COVID-19.

OBJECTIVE: Hepatitis B is an important public health concern. Currently, the COVID-19 pandemic is a major challenge for health systems, and the access to pharmacologic and non-pharmacologic treatment of chronic diseases, such as hepatitis B, may have been affected due to the contingency measures. This study aimed to evaluate the access to antiviral therapy during the ongoing pandemic. METHODS: This was a descriptive analysis of the access to treatment for chronic hepatitis B at a tertiary-level university hospital in São Paulo, integrated with the Brazilian health system. The study was conducted from April to December 2020. RESULTS: Access to antiviral therapy for 225 patients was assessed. The majority of the population was male (59%). The main type of service was the Programa Medicamento em Casa (Home Medication Delivery Program), which was availed by 144 (64%) patients. Women had poorer access to antiviral therapy (56%, p<0.05), and patients registered in the HMDP (68%, p<0.05) had better access. The age group of >48 years represented 70% of the group without access to antiviral therapy. Twenty-two pharmaceutical appointments were conducted through phone calls with patients without access to antiviral therapy. CONCLUSION: This study contributes to the rationalization of efforts in a public health crisis through the identification of groups with the highest risk of poor access to antiviral therapy and the demonstration of the benefits of a medication delivery system.

HIGH VALUES OF LIVER STIFFNESS PLAY AN IMPORTANT ROLE IN STRATIFYING THE RISK OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC HEPATITIS C PATIENTS.

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.

The Impact of Artificial Intelligence on Waiting Time for Medical Care in an Urgent Care Service for COVID-19: Single-Center Prospective Study.

BACKGROUND: To demonstrate the value of implementation of an artificial intelligence solution in health care service, a winning project of the Massachusetts Institute of Technology Hacking Medicine Brazil competition was implemented in an urgent care service for health care professionals at Hospital das Clínicas of the Faculdade de Medicina da Universidade de São Paulo during the COVID-19 pandemic. OBJECTIVE: The aim of this study was to determine the impact of implementation of the digital solution in the urgent care service, assessing the reduction of nonvalue-added activities and its effect on the nurses' time required for screening and the waiting time for patients to receive medical care. METHODS: This was a single-center, comparative, prospective study designed according to the Public Health England guide "Evaluating Digital Products for Health." A total of 38,042 visits were analyzed over 18 months to determine the impact of implementing the digital solution. Medical care registration, health screening, and waiting time for medical care were compared before and after implementation of the digital solution. RESULTS: The digital solution automated 92% of medical care registrations. The time for health screening increased by approximately 16% during the implementation and in the first 3 months after the implementation. The waiting time for medical care after automation with the digital solution was reduced by approximately 12 minutes compared with that required for visits without automation. The total time savings in the 12 months after implementation was estimated to be 2508 hours. CONCLUSIONS: The digital solution was able to reduce nonvalue-added activities, without a substantial impact on health screening, and further saved waiting time for medical care in an urgent care service in Brazil during the COVID-19 pandemic.

Contrast phase recognition in liver computer tomography using deep learning.

Hepatocellular carcinoma (HCC) has become the 4th leading cause of cancer-related deaths, with high social, economical and health implications. Imaging techniques such as multiphase computed tomography (CT) have been successfully used for diagnosis of liver tumors such as HCC in a feasible and accurate way and its interpretation relies mainly on comparing the appearance of the lesions in the different contrast phases of the exam. Recently, some researchers have been dedicated to the development of tools based on machine learning (ML) algorithms, especially by deep learning techniques, to improve the diagnosis of liver lesions in imaging exams. However, the lack of standardization in the naming of the CT contrast phases in the DICOM metadata is a problem for real-life deployment of machine learning tools. Therefore, it is important to correctly identify the exam phase based only on the image and not on the exam metadata, which is unreliable. Motivated by this problem, we successfully created an annotation platform and implemented a convolutional neural network (CNN) to automatically identify the CT scan phases in the HCFMUSP database in the city of São Paulo, Brazil. We improved this algorithm with hyperparameter tuning and evaluated it with cross validation methods. Comparing its predictions with the radiologists annotation, it achieved an accuracy of 94.6%, 98% and 100% in the testing dataset for the slice, volume and exam evaluation, respectively.

Building an outpatient telemedicine care pilot using Scrum-like framework within a medical residency program.

OBJECTIVES: A good health care does not only depend on good medical practice, but also needs great management of its resources, which are generally short. In this sense, PROAHSA has been training new health managers since 1972. With the arrival of the COVID-19 pandemic, it was clear that medicine will go through a new phase, where telehealth will be present in this "Improved Normal". This report is about how a pilot teleconsultation study was carried out for HCFMUSP patients through the Scrum-like framework. It is to deploy a pilot of remote assistance involving a doctor and a patient in the Ambulatory of Hepatology and Liver Transplantation of HCFMUSP. METHODS: We applied the Scrum-like framework to carry out this work with an interdisciplinary multifunctionality team. RESULTS: A full telemedicine service flow was implemented within eight weeks using existing infrastructure and resources implementing the Scrum methodology. Twenty-three teleconsultations were scheduled and eight guides built. CONCLUSION: Scrum framework has a great potential to improve the training of students and to conclude pilot projects.

Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters.

Background & aim: Genetic variability in drug absorption, distribution, metabolism and excretion (ADME) genes contributes to the high heterogeneity of drug responses. The present study investigated polymorphisms of ADME genes frequencies and compared the findings with populations from other continents, available in the 1000 Genome Project (1 KGP) and the Exome Aggregation Consortium (ExAC) databases. Methodology & results: We conducted a study of 100 patients in Brazil and a total of 2003 SNPs were evaluated by targeted next-generation sequencing in 148 genes, including Phase I enzymes (n = 50), Phase II enzymes (n = 38) and drug transporters (n = 60). Overall, the distribution of minor allele frequency (MAF) suggests that the distribution of 2003 SNPs is similar between Brazilian cohort, 1 KGP and ExAC; however, we found moderate SNP allele-frequency divergence between Brazilian cohort and both 1000 KGP and ExAC. These differences were observed in several relevant genes including CYP3A4, NAT2 and SLCO1B1. Conclusion: We concluded that the Brazilian population needs clinical assessment of drug treatment based on individual genotype rather than ethnicity.

Adverse events of nucleos(t)ide analogues for chronic hepatitis B: a systematic review.

Nucleos(t)ide analogues (NAs) are the main drug category used in chronic hepatitis B (CHB) treatment. Despite the fact that NAs have a favourable safety profile, undesired adverse events (AEs) may occur during the treatment of CHB. Given the eminent number of patients currently receiving NAs, even a small risk of any of these toxicities can represent a major medical issue. The main objective of this review was to analyse information available on AEs associated with the use of NAs in published studies. We choose the following MesH terms for this systematic review: chronic hepatitis B, side effects and treatment. All articles published from 1 January 1990 up to 19 February 2018 in MEDLINE of PubMed, EMBASE, the Cochrane Library and LILACS databases were searched. A total of 120 articles were selected for analysis, comprising 6419 patients treated with lamivudine (LAM), 5947 with entecavir (ETV), 3566 with tenofovir disoproxil fumarate (TDF), 3096 with telbivudine (LdT), 1178 with adefovir dipivoxil (ADV) and 876 with tenofovir alafenamide (TAF). The most common AEs in all NAs assessed were abdominal pain/discomfort, nasopharyngitis/upper respiratory tract infections, fatigue, and headache. TAF displays the highest density of AEs per patient treated among NAs (1.14 AE/treated patient). In conclusion, treatment of CHB with NAs is safe, with a low incidence of AEs. Despite the general understanding TAF being safer than TDF, the number of patients treated with TAF still is too small in comparison to other NAs to consolidate an accurate safety profile. PROSPERO Registration No. CRD42018086471.

Translational medical research and liver transplantation: systematic review.

Translational medicine has become a priority, but there is still a big difference between the arrival of new treatments and investment. Basic science should not be neglected because the translation from basic research is not sustained in the absence of basic research. The purpose of this literature review was to analyze the translational medicine in the liver transplant field: liver ischemia-reperfusion injury (IRI), immunosuppression, clinical and surgical complications, small-for-size syndrome (SFSS), rejection, and ongoing innovations (liver machine, liver preservation, artificial livers, and regenerative medicine). We performed a systematic literature review that were updated in October 2016. The searches were performed in the Cochrane Central Register of Controlled Trials and Review, PubMed/Medline, Embase, and LILACS databases. All the selected studies on the management of translational medical research in liver transplantation (LT) were analyzed. Initially the search found 773 articles. Methodological viewing and analysis of the articles, followed by the application of scientific models, including translational medicine in the liver transplant field. In conclusions, this review demonstrates the application of scientific research with translation medical benefits regarding the LT. The literature has a great tendency, improvements and investments in the study of translational medicine in LT. Innovative studies and technologies from basic science help to clarify clinical doubts. Moreover, evidence increases the importance of scientific research in quality of clinical practice care.

Assessment of the prevalence of vertical hepatitis B transmission in two consecutive generations.

INTRODUCTION: Hepatitis B is an important public health problem in the world and one of the forms of contagion would be through vertical transmission. Precose diagnosis allows the adoption of prophylaxis measures, which results in prevention in more than 90% of cases. OBJECTIVE: To describe the prevalences of vertical transmission and compare two generations (mother/patient and patient/child). METHOD: This was a cross-sectional study, which included 101 patients. The interviews were performed through the application of the instrument of data collection and information of the physical file before the medical consultation. RESULTS: The mean ± SD of age was 50.9 ± 13.1 years, the male gender predominated, with 56.4% of the patients, and the predominance was white, with 43.6%. Vertical transmission between mother and patient occurred in 17.8% and between patient and child, in 7.9%. In all of the eight cases of vertical transmission, the diagnosis was after the birth of children infected with HBV, and in 3/8 (37.5%), there was more than one case of infection by this mechanism per patient, totaling 13 children with the disease. CONCLUSION: There was a reduction in vertical transmission, showing that preventive measures were effective.

Clinical pharmacology profile of care in Hepatology clinic.

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 diabetes, hypertension and dyslipidemia. Most patients took their medication in the Basic Health Units. We found that 30% of patients use of more than five medications and the most prescribed were omeprazole 208 (42.3%), metformin 132 (26.8%) and losartan 80 (16.3%). Because it is an adult/elderly population, with several comorbidities and polymedication, it is important to be aware of the rational use of medication. The multidisciplinary team is important in applying correct conducts for the safe use of medicines, to reduce the burden on health spending and improving the quality of life of patients.

Clinical Features of Refractory Ascites in Outpatients.

OBJECTIVES:: To present the clinical features and outcomes of outpatients who suffer from refractory ascites. METHODS:: This prospective observational study consecutively enrolled patients with cirrhotic ascites who submitted to a clinical evaluation, a sodium restriction diet, biochemical blood tests, 24 hour urine tests and an ascitic fluid analysis. All patients received a multidisciplinary evaluation and diuretic treatment. Patients who did not respond to the diuretic treatment were controlled by therapeutic serial paracentesis, and a transjugular intrahepatic portosystemic shunt was indicated for patients who required therapeutic serial paracentesis up to twice a month. RESULTS:: The most common etiology of cirrhosis in both groups was alcoholism [49 refractory (R) and 11 non-refractory ascites (NR)]. The majority of patients in the refractory group had Child-Pugh class B cirrhosis (p=0.034). The nutritional assessment showed protein-energy malnutrition in 81.6% of the patients in the R group and 35.5% of the patients in the NR group, while hepatic encephalopathy, hernia, spontaneous bacterial peritonitis, upper digestive hemorrhage and type 2 hepatorenal syndrome were present in 51%, 44.9%, 38.8%, 38.8% and 26.5% of the patients in the R group and 9.1%, 18.2%, 0%, 0% and 0% of the patients in the NR group, respectively (p=0.016, p=0.173, p=0.012, p=0.012, and p=0.100, respectively). Mortality occurred in 28.6% of the patients in the R group and in 9.1% of the patients in the NR group (p=0.262). CONCLUSION:: Patients with refractory ascites were malnourished, suffered from hernias, had a high prevalence of complications and had a high postoperative death frequency, which was mostly due to infectious processes.

Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction.

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient's 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profile.

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

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. Genotypes and alleles frequencies were similar in case (n = 585; P = 0.101) and control groups (n = 313; P = 0.795). Total bilirubin increase was noticed according to thymine-adenine repeats in genotypes (P < 0.001), and the TB greater than 1 mg/dL group had more UGT1A1*28 subjects than in the group with TB values <1 mg/dL (18.3 vs 5.3; P < 0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A1*28 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism.

Altos valores de rigidez hepática desempenham um papel importante na estratificação do risco de carcinoma hepatocelular em pacientes cirróticos com vírus C / High values of liver stiffness play an important role in stratifying the risk of hepatocellular carcinoma in cirrhotic hepatitis c patients

ABSTRACT 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.

RESUMO Contexto: O carcinoma hepatocelular (CHC) é o tumor maligno hepático mais comum, e a cirrose é o principal fator de risco para o seu desenvolvimento. Objetivo: Avaliar o papel da medição da rigidez hepática por elastografia transitória (ET) como fator de risco para ocorrência de CHC em uma coorte prospectiva de pacientes brasileiros com cirrose por vírus da hepatite C (VHC). Métodos: Um total de 99 pacientes com VHC e medida de rigidez hepática ≥12 kilopascals (kPa) foram incluídos consecutivamente, entre 2011 e 2016. As variáveis do baseline foram avaliadas e a ocorrência de CHC foi documentada. Os testes de Kaplan-Meier e log-rank, além das análises uni e multivariadas de Cox avaliaram a associação entre as variáveis e os resultados clínicos. Resultados: A média de idade foi de 57,8±10,6 anos. Vinte (20,2%) pacientes desenvolveram CHC, num período médio de seguimento de 3,3 anos. Na análise de regressão logística univariada, as variáveis associadas à ocorrência de CHC foram: contagem de plaquetas mais baixa (P=0,0446), valores séricos mais elevados de alfa-fetoproteína (P=0,0041) e de bilirrubina (P=0,0008), maior pontuação do escore MELD (P=0,0068) e valores mais altos de rigidez hepática por ET (P=0,0354). A medição da rigidez hepática por ET foi independentemente associada ao desenvolvimento de CHC, e o melhor valor de corte para maior risco de CHC foi >21,1kPa (HR: 5,548; IC95%: 1,244-24,766; P=0,025). Conclusão: Um alto valor de rigidez hepática está relacionado substancialmente a um risco aumentado de ocorrência de CHC em pacientes brasileiros com cirrose por HCV.

Assessment of Adherence to Prescribed Therapy in Patients with Chronic Hepatitis B.

INTRODUCTION: Evidence shows that treatment for hepatitis B virus (HBV) can suppress viral load. Among the factors directly linked to therapeutic success is adherence to the treatment. Several instruments to assess adherence are available, but they are not validated for use in chronic hepatitis B. The purpose of this paper was to adapt and validate the "Assessment of Adherence to Antiretroviral Therapy Questionnaire-HIV" (CEAT-VIH) for patients with chronic hepatitis B (referred to herein as CEAT-HBV). METHODS: The validity of the adapted questionnaire evidence was established through concurrent, criterion, and construct validities. RESULTS: We found negative and significant correlation between the domain "degree of compliance to antiviral therapy" assessed by CEAT-HBV and the Morisky test (r = -0.62, P < 0.001) and between the domain "barriers to adherence" and HBV viral load (r = -0.42, P < 0.001). In terms of the construct's discriminative capacity, scores greater than or equal to 80 detected antiviral therapy success, which are necessary for the prediction of an undetectable HBV viral load. Thus, a cutoff value of 80.5 was set with a value of 81% for sensitivity and 67% for specificity. CONCLUSION: The CEAT-HBV identified 43% (n = 79) non-adherent patients and was shown to be a useful tool in clinical practice.

Frequency of Tabagism and N34S and P55S Mutations of Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) and R254W Mutation of Chymotrypsin C (CTRC) in Patients With Chronic Pancreatitis and Controls.

OBJECTIVE: This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. METHODS: The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. RESULTS: Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73.3% in alcoholic subjects without pancreatitis (P < 0.01). The difference in smoking frequency was not significant between the patients with idiopathic pancreatitis and blood donors. The N34S mutation of serine peptidase inhibitor, Kazal type 1 (SPINK1) was found in 2.7% of patients with chronic alcoholic pancreatitis, in 5.3% of patients with idiopathic pancreatitis, and in 0.4% of blood donors (P = 0.02). The P55S mutation of SPINK1 was found in 2.7% of patients with alcoholic pancreatitis and in 0.7% of blood donors (P = 0.12). The R254W mutation of chymotrypsin C was found in 0.9% of patients with alcoholic pancreatitis, in 0.9% of chronic alcoholic subjects without pancreatitis, and in 0.4% of blood donors (P = 0.75). In all cases, the mutations were heterozygous. CONCLUSIONS: Smoking and the N34S mutation of SPINK1 were positively correlated with chronic pancreatitis.