ABSTRACT Hepatitis E Virus (HEV) is an infection known worldwide for its asymptomatic and self-limited course in most cases. Some cases progressing to chronicity have been described in immunosuppressed patients, especially in recipients of solid organ transplants. We evaluated laboratory parameters of HEV infection (HEV RNA, anti-HEV IgM and anti-HEV IgG) through enzyme-linked immunosorbent assay (Elisa), confirmed by immunoblotting, in a cohort of 294 patients who received liver transplants at the HCFMUSP (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo). Laboratory and demographic data were collected from the entirety of the transplanted population. Hepatic biopsies of 122 patients transplanted due liver failure secondary to hepatitis C (HCV), with or without serological or molecular markers of HEV, were analyzed according to METAVIR score. Out of 24 (8.2%) patients tested positive for anti-HEV IgG, six (2%) were positive for anti-HEV IgM and 17 (5.8%) for HEV RNA. Of the patients transplanted because of HCV infection, 95 (77.8%) had received treatment including ribavirin for at least six months before blood sample collection. Among patients transplanted due to HCV cirrhosis who tested positive for anti-HEV IgG, only three (37.5%) showed fibrosis beyond stage 2, while five (41.7%) of the HEV RNA-positive patients had liver fibrosis beyond stage 2. Overall, the prevalence of HEV in the post-hepatic transplant scenario appears to be low, and, at least histologically, seemingly not harmful. We conclude that, although some studies reported a risk of HEV chronification, patients who had their livers transplanted due to HCV and showed serological or molecular markers of HEV did not have higher levels of fibrosis compared to patients who showed no indications of HEV infection at the time of the analysis.

OBJECTIVES: Co-infection with hepatitis A or B viruses may aggravate liver injury in patients infected with hepatitis C virus (HCV). However, few studies have assessed co-infection with hepatitis E virus (HEV) and HCV. Therefore, this study aimed to assess the prevalence and impact of HEV infection among Brazilian patients with chronic HCV infection. METHODS: This observational study included adult patients with chronic HCV infection who were naive to antiviral therapy from January 2013 to March 2016. A total of 181 patients were enrolled, and HEV serology and PCR were performed for all patients. RESULTS: Seropositivity for anti-HEV IgG was detected in 22 (12.0%) patients and anti-HEV immunoglobulin M in 3 (1.6%). HEV RNA showed inconclusive results in nine (4.9%) patients and was undetectable in the remaining patients. HEV serology positive patients had more severe liver disease, characterized by liver fibrosis ≥3 versus ≤2 (p<0.001), Aspartate Aminotransferase-to-Platelet Ratio Index of ≥1.45 (p=0.003), and Fibrosis-4 score of ≥3.25 (p=0.001). Additionally, the odds of HEV-positive patients developing diabetes mellitus were 3.65 (95% CI 1.40-9.52) times the corresponding odds of HEV-negative patients. A case-control-based histological analysis (n=11 HEV-HCV-positive patients and n=22 HCV-positive patients) showed no significant differences between the groups. CONCLUSIONS: This prevalence is higher than that reported in previous studies of the general population in Brazil. Thus, HEV infection may influence the severity of liver disease and may represent an additional risk of developing diabetes mellitus in patients with HCV infection.

OBJECTIVES: 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®, 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 Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São 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®, 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®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 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®: 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.

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Background: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective.Methods: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2).Results: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n= 325,900) and decompen- sated (n= 45,000) cirrhosis; hepatocellular carcinoma (n= 19,100); and liver-related deaths (n= 16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively.Conclusions: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.

RACIONAL: A recurrência da hepatite C no período pós-operatório do transplante hepático é um dos principais desafios atualmente enfrentados pela comunidade transplantadora. O tratamento com interferon peguilado e ribavirina tem sido associado à resposta virológica sustentada em 21% a 45% dos casos e constitui a única conduta eficaz, até o momento, para mudar o curso da progressão acelerada da doença no período pós-operatório do transplante hepático, que pode levar à perda do enxerto e à necessidade de retransplante. No entanto, a portaria n° 863 do Ministério da Saúde não disponibiliza esse tratamento para pacientes com recidiva da hepatite C após o transplante hepático. OBJETIVOS: Avaliar as condutas de acompanhamento e tratamento de pacientes com vírus C submetidos a transplante hepático em diferentes centros nacionais. MÉTODOS: Foram enviados questionários à maioria dos centros de transplante hepático nacionais de adultos sobre condutas acerca de acompanhamento e/ou tratamento de pacientes com hepatite C. RESULTADOS: Dezenove centros nacionais que congregam mais de 2 800 pacientes (51% com hepatite C) submetidos a transplante hepático responderam o questionário. A maioria (53%) usa tacrolimus e prednisona como esquema de indução e 32% usam esquemas diferenciados para hepatite C. Treze centros fazem biopsia protocolar para seguimento, sendo empregados diferentes critérios histológicos para diagnóstico de recurrência. Todos os centros indicam tratamento com interferon peguilado e ribavirina apenas na recurrência histológica da hepatite C e 46% empregam estádios de fibrose inferiores a F2 de acordo com a classificação METAVIR, mais leves do que aqueles preconizados para tratamento de pacientes não transplantados. A duração do tratamento é de 1 ano em 32% dos centros, baseada no genótipo em 21% e a la carte em 47%. A maioria dos centros (84%) não interrompe o tratamento na 12ª semana, na ausência de resposta virológica. CONCLUSÕES: A despeito da portaria nº. 863 do Ministério da Saúde, todos os centros estão viabilizando tratamento mediante acordo com secretarias regionais de saúde ou por intermédio de liminares concedidas aos pacientes pela justiça comum.

BACKGROUND: Recurrence of hepatitis C after orthotopic liver transplantation is one of the major clinical challenges faced by the liver transplantation community. Treatment of hepatitis C recurrence with peguilated interferon and ribavirin has been associated with sustained virological response in 21% to 45% of treated patients. Furthermore, it has been shown to halt disease progression after orthotopic liver transplantation and to prevent graft failure and the need for retransplantation at least in those subjects with sustained virological response. However, treatment of hepatitis C recurrence after orthotopic liver transplantation in Brazil was not recommended according to ministerial Law number 863. AIMS: To assess the management and treatment options of hepatitis C recurrence after orthotopic liver transplantation in different liver transplantation centers in Brazil. METHODS: Inquiries were sent to active liver transplantation centers throughout the country. RESULTS: Nineteen centers accepted to participate and answered the questionnaire. Altogether they transplanted around 2,800 subjects, half of them with hepatitis C. Immunosuppressive regimen is comprised by tacrolimus and short-term prednisone in 53% of the centers. One third of them claim to use different schedules for hepatitis C patients. Protocol biopsies for diagnosis of recurrence are employed by 13 centers. Different histological criteria are used for the either diagnosis or decision for treatment in most of the centers. Approximately half of them (42%) indicate treatment in subjects with less severe stages of fibrosis (less than F2 according to METAVIR classification). All centers are referring patients for treatment with peguilated interferon and ribavirin, for 1 year, for 6 months or 1 year based on the genotype, or a la carte based on response, respectively, in 32%, 21% and 47% of the centers. Most of them (84%) do not stop treatment in early non-responders at the 12th week. CONCLUSIONS: Even in the absence of national guidelines and federal support, most of the liver transplantation centers in Brazil are treating patients with hepatitis C recurrence after orthotopic liver transplantation.