Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C / 中华肝脏病杂志

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.

A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China / 中华肝脏病杂志

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

Occurrence and recurrence of hepatitis C-related hepatocellular carcinoma after direct antiviral treatment / 中华肝脏病杂志

Hepatitis C virus (HCV) RNA can be cleared from the blood circulation by direct antiviral treatment to achieve sustained virologic response (SVR). Studies have shown that SVR after direct antiviral therapy can reduce the incidence of hepatocellular carcinoma; however, monitoring for hepatocellular carcinoma is still needed. This review briefly summarizes and discusses the existing studies on the possible causes of hepatitis C secondary to HCC after antiviral therapy, which is mainly divided into epigenetic alterations and abnormal DNA methylation, HCV-related cirrhosis and abnormal DNA amplification, HBV reactivation, several aspects of occult HCV infection, and the effect of direct antiviral treatment on hepatocellular carcinoma recurrence. In few cases, direct antiviral treatment cannot completely prevent the occurrence and recurrence of hepatitis C-related hepatocellular carcinoma. Therefore, its mechanism needs to be studied and explored, and clinicians should also approach it with caution.

Changes of serum uric acid levels in patients with chronic hepatitis C after using direct antiviral agents therapy / 中华肝脏病杂志

Objective: To observe the changes of serum uric acid levels and clinical characteristic in patients with chronic hepatitis C combined with hyperuricemia after direct antiviral agents (DAA) therapy. Methods: A prospective cohort study was used to investigate the risk of hyperuricemia in patients with chronic hepatitis C who received DAA treatment to obtain sustained virological response. The changes and factors influencing serum uric acid levels after 12 weeks of DAA treatment were observed. Comparisons between groups were performed using χ (2) test or Fisher's exact test, analysis of variance, Student's t test, or the non-parametric Mann-Whitney U test. Serum uric acid (SUA) changes, liver and kidney function indexes before and after treatment were compared by repeated measurement and paired t-test. Uric acid reduction was defined as a decrease in SUA from baseline at 12 weeks after treatment. Rates of change in eGFR, aspartate aminotransferase/platelet ratio, alanine aminotransferase and controlled attenuation parameter were defined from baseline (baseline to 12 weeks after treatment). Binary logistic regression analysis was used to compare the risk factors and factors influencing high and low uric acid level. Results: 161 cases with chronic hepatitis C who received DAA treatment were included, of which 19.3% patients were hyperuricemic. eGFR < 60 ml/(min·1.73 m(2)) and body mass index were independent risk factors for hyperuricemia in patients with chronic hepatitis C (eGFR: OR = 0.123, P = 0.002; body mass index: OR = 1.220, P = 0.002). SUA levels was changed significantly before treatment, at the end of treatment and at 12 weeks after treatment (327.96 vs. 320.76 vs. 314.92, F = 3.272, P = 0.042). At 12 weeks after treatment, SUA, liver stiffness, alanine aminotransferase and control attenuation parameters were all significantly lower than baseline (P < 0.05). The rate of increase in eGFR from baseline and the rate of decrease in controlled attenuation parameter during treatment were the factors influencing SUA reduction (eGFR: OR = 5124, P = 0.000; controlled attenuation index: OR = 0.010, P = 0.039). Conclusion: In chronic hepatitis C, reduced eGFR and body mass index are the risk factors for the development of hyperuricemia and a significant reduction in serum uric acid levels after DAA treatment can eradicate the virus.

Advances in new antivirals for chronic hepatitis B / 中华医学杂志(英文版)

Chronic hepatitis B virus (HBV) infection remains a global health burden. Timely and effective antiviral therapy is beneficial for patients with HBV infection. With existing antiviral drugs, including nucleos(t)ide analogs and interferon-alfa, patients can achieve viral suppression with improved prognosis. However, the rate of hepatitis B surface antigen loss is low. To achieve a functional cure and even complete cure in chronic hepatitis B patients, new antivirals need to be developed. In this review, we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.

PERFIL EPIDEMIOLÓGICO DE PACIENTES COM HEPATITE C CRÔNICA TRATADOS COM ANTIVIRAIS DE AÇÃO DIRETA EM UM CENTRO DE REFERÊNCIA NO ESTADO DO RIO DE JANEIRO / EPIDEMIOLOGICAL PROFILE OF PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH DIRECT ACTION ANTIVIRALS IN A REFERENCE CENTER IN THE STATE OF RIO DE JANEIRO

Segundo o Ministério da Saúde, o número de casos notificados e confirmados de hepatite C no período entre 1999 e 2020 foi de 262.815 casos no Brasil. Em 2016, a OMS estabeleceu como objetivo global que as hepatites não fossem mais um problema de saúde pública em 2030. A partir de 2015, os agentes antivirais de ação direta (DAA) começaram a ser utilizados nessa terapêutica. O tratamento atual da hepatite C com os novos DAA revolucionou o cenário mundial com taxas de cura de até 98%. O objetivo desse artigo é apresentar e discutir o tratamento realizado com DAA em pacientes com hepatite C crônica em um centro de referência no Estado do Rio de Janeiro no período entre novembro de 2015 e julho de 2019. Trata-se de um estudo observacional, prospectivo e descritivo de pacientes com hepatite C crônica tratados com DAA no ambulatório de hepatologia de um hospital de referência. No presente estudo pode ser concluído que a maioria dos pacientes evoluiu para a cura após o tratamento. Foi possível concluir também que os esforços idealizados pela OMS para que o vírus da hepatite C seja erradicado estão ocorrendo de forma positiva e que com as novas DAAs é possível ter um número satisfatoriamente alto de RVS, evitando, assim, desfechos desfavoráveis, como por exemplo, o surgimento de carcinoma hepatocelular.

According to the Ministry of Health, the number of notified and confirmed cases of hepatitis C in the period between 1999 and 2020 was 262,815 cases in Brazil. In 2016, the WHO established as a global goal that hepatitis was no longer a public health problem in 2030. As of 2015, direct action antiviral agents (DAA) began to be used in this therapy. The current treatment of hepatitis C with the new DAA has revolutionized the world scenario with cure rates of up to 98%. The aim of this article is to present and discuss the treatment performed with DAA in patients with chronic hepatitis C in a reference center in the state of Rio de Janeiro between November 2015 and July 2019. This is an observational, prospective and descriptive study of patients with chronic hepatitis C treated with DAA in the hepatology clinic of a reference hospital. In the present study, it can be concluded that most patients evolved to cure after treatment. It was also possible to conclude that the efforts idealized by the WHO to eradicate the hepatitis C virus are occurring in a positive way and that with the new DAAs it is possible to have a satisfactorily high number of SVR, thus avoiding unfavorable outcomes, such as the appearance of hepatocellular carcinoma.

Microeliminação da hepatite C na população carcerária: realmente possível? / Micro-elimination of hepatitis c in the incarcerated population: is it really possible?

ABSTRACT According to the World Health Organization, 71 million people live with chronic hepatitis C. The treatment of this disease requires assistance from specialized physicians and a highly complex health care system. The prison population has been recognized as being at a high risk of acquiring confinement-related infections, including viral hepatitis. Hepatitis C virus (HCV) infection is a primary cause of death owing to liver disease among liberty-deprived individuals. Generally, prisons do not have adequate isolation wards for persons with communicable diseases, and overcrowding is a risk factor for this population. Besides prison overcrowding, violence, poor sanitary conditions, low socioeconomic status, social isolation, and emotional instability are factors that can lead detainees to adopt unhealthy habits that make them more susceptible to infections, including HCV, and complicate effective treatment. The Criminal Execution Law 7, 210 of July 11, 1984, in Article 14, grants preventive and curative medical, dental, and pharmacological healthcare to detainees. However, adequate hepatitis C treatment is rarely provided at prisons owing to social stigma and lack of knowledge on the severity of this condition or because most detainees are unaware of their condition. Given the multiple limitations imposed by the prison system model, implementing measures to treat diseases effectively is challenging. However, it is possible to eliminate hepatitis C in prisons in the long term through the coordinated action of public health institutions and the prison system.

RESUMO De acordo com a Organização Mundial da Saúde, 71 milhões de pessoas vivem com hepatite C crônica. O tratamento dessa doença requer assistência de médicos especializados e um sistema de saúde de alta complexidade. A população carcerária tem sido reconhecida como sendo de alto risco de adquirir infecções relacionadas às condições de confinamento, incluindo hepatites virais. O vírus da hepatite C (VHC) é uma causa primária de morte por doença hepática em pessoas privadas de liberdade. Geralmente, as prisões não possuem locais adequados para isolamento de pessoas com doenças transmissíveis e a superlotação é um fator de risco para essa população. Além da superlotação das prisões, violência, más condições sanitárias, baixo nível socioeconômico, isolamento social e instabilidade emocional são motivos adicionais que induzem os detidos a praticar hábitos não saudáveis, que os tornam mais suscetíveis a certas infecções (incluindo VHC) e complicam o tratamento específico. A Lei de Execução Penal n. 7.210, de 11 de julho de 1984, em seu artigo 14, garante assistência preventiva e curativa à saúde, incluindo assistência médica, farmacêutica e odontológica aos detidos. No entanto, o tratamento adequado da hepatite C é raramente fornecido nas prisões devido estigma social ou falta de conhecimento de sua condição ou porque a maioria dos detidos não tem conhecimento de sua condição. Devido a múltiplas limitações impostas pelo modelo prisional, a implementação de medidas para o tratamento eficaz de doenças é desafiadora. No entanto, é possível eliminar a hepatite C em um ambiente prisional de longa permanência através de ações coordenadas de instituições de saúde pública e o sistema prisional.

Tratamiento de infección por virus hepatitis C con nuevos antivirales en pediatría: a propósito de un caso / Treatment of hepatitis C virus infection with new direct-acting antivirals agents in pediatrics. Case report

La infección por virus de la hepatitis C en pediatría se produce principalmente por transmisión vertical. La historia natural en niños consiste en alta tasa de eliminación espontánea, infección asintomática o cambios histológicos mínimos. Las complicaciones suelen observarse en la adolescencia o en la edad adulta. El tratamiento clásico con interferón pegilado y ribavirina presenta efectos adversos, es de duración prolongada y logra una respuesta virológica sostenida (RVS) en el 50 % de los pacientes con infección por genotipo 1. Los nuevos antivirales de acción directa se encuentran disponibles para su indicación a partir de los 12 años, con excelente tolerancia y alta tasa de RVS. Se sugiere conducta terapéutica expectante en pacientes asintomáticos hasta acceder a la medicación. Reportamos el caso de un adolescente con hepatitis C crónica sin cirrosis que recibió tratamiento durante 12 semanas con ledipasvir/sofosbuvir y se logró una RVS.

Hepatitis C virus infection in children occurs mainly through vertical transmission. The natural history at this age consists in a high rate of spontaneous clearance, asymptomatic infection, or minimal histological changes. Disease complications are commonly seen in adolescence or adulthood. The classic treatment with pegylated interferon and ribavirin presents adverse effects, prolonged duration and achieves sustained viral response (SVR) in 50 % of patients with genotype 1 infection (the most frequent). New direct-acting antiviral treatments have been available in recent years for their indication from 12 years of age with excellent tolerance and a high SVR rate. Expectant therapeutic behavior is suggested in asymptomatic patients until they can access to them. We report the case of an adolescent with chronic hepatitis C without cirrhosis who received 12 weeks treatment with ledipasvir/sofosbuvir, achieving SVR.

Simplified treatment of hepatitis C: another strategy to overcome the barriers to its elimination / Tratamiento simplificado de la hepatitis C: otra estrategia para superar las barreras hacia su eliminación

Abstract The clinical management of hepatitis C virus (HCV) infection presents several challenges today. WHO's goal is to eliminate it by 2030. It is an ambitious goal and difficult to meet given the barriers to care that arise. This is possible today thanks to the discovery of direct-acting antivirals (DAAs). This treatment achieves a high cure rate and is virtually free of adverse effects. To try to comply with this, in addition to the use of DAAs, it is necessary to reduce the rate of undiagnosed patients and facilitate the access of those diagnosed to care and treatment. For that, it is proposed to carry out a simplified treatment of HCV. This involves reducing controls during and after treatment. This simplification varies according to whether patients have cirrhosis or not. In this way, it seeks to increase significantly the number of patients treated and cured to reduce the burden on public health of this disease.

Resumen El manejo clínico de la infección por el virus la hepatitis C (HCV) presenta varios desafíos en la actualidad. El objetivo de la OMS es eliminarlo para el 2030. Es un objetivo ambicioso y muy difícil de cumplir dadas las barreras al cuidado que se presentan. Sin embargo, esto es posible hoy gracias al descubrimiento de los antivirales de acción directa (AAD). Este tratamiento logra una alta tasa de curación y prácticamente está libre de efectos adversos. Para tratar de cumplirlo, además del uso de los AAD, es nece sario reducir la tasa de pacientes no diagnosticados y facilitar el acceso de los diagnosticados al cuidado y el tratamiento. Para eso se propone llevar adelante el tratamiento simplificado del HCV. Esto implica reducir los controles durante y después del tratamiento. Esta simplificación varía según los pacientes tengan o no cirrosis. De esta manera se busca aumentar significativamente el número de pacientes tratados y curados para así poder reducir el impacto en la salud pública de esta enfermedad.

Remission of long-term hepatic and renal disease induced by HCV after direct-acting antivirals therapy / Remissão de doença hepática e renal a longo prazo induzida pelo HCV após terapia antiviral de ação direta

Abstract In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.

Resumo Além da doença hepática, o vírus da hepatite C (HCV) tem sido associado a fenômenos autoimunes, como crioglobulinemia mista (CM) e glomerulonefrite (GN). Até recentemente, a hepatite crônica e as manifestações extra-hepáticas do HCV eram tratadas com peg-interferon com ribavirina; no entanto, essas drogas apresentavam baixa eficácia e induziam efeitos colaterais graves. Atualmente, a hepatite crônica por HCV tem sido tratada com antivirais de ação direta (AAD), mas estudos sobre a terapia com AAD para glomerulonefrite associada ao HCV são escassos. Aqui, descrevemos dois casos de glomerulonefrite associada ao HCV que foram tratados com AAD. Nestes dois casos, previamente tratados com peg-interferon e ribavirina, a terapia com sofosbuvir com simeprevir foi eficaz, sem efeitos colaterais significativos, e interrompeu a evolução de pelo menos 20 anos de doenças hepáticas e renais. Esses casos se juntam aos sete casos descritos anteriormente que foram tratados com essa associação de AAD.

Tratamiento de la hepatitis C en el conurbano de Buenos Aires / Hepatitis C treatment in the surrounding area of Buenos Aires

Resumen La principal infección viral transmisible por sangre es actualmente la debida al virus de hepatitis C (VHC). Uno de los mayores obstáculos para el logro de su control en la Argentina se relaciona con las dificultades de acceso al diagnóstico y tratamiento oportuno de las personas infectadas. Este estudio se realizó con el objetivo de caracterizar a los pacientes infectados con VHC que iniciaron tratamiento con antivirales de acción directa (AAD) y describir la experiencia vinculada al tratamiento. Se seleccionaron las historias clínicas de 82 pacientes, 44 (53.7%) de sexo masculino, 37 (45.1%) de sexo femenino, y uno (1.2%) transgénero. La media de edad fue de 49 años. Se halló una frecuencia de cirrosis de 39%, 32 pacientes, coinfección con HIV en 48 (58.5%) y con VHB en 27 (32.9%). En 52 (63.4%) no se observó ningún factor de riesgo claramente asociado a infección. Todos completaron la terapia, de ellos 72 (87.8%) efectuaron el control para confirmar respuesta viral sostenida (RVS), que fue de 98.6%. Concluimos que el testeo universal debe implementarse por sobre el testeo con enfoque de riesgo, y que debe promoverse un criterio de atención simplificado y descentralizado, reservando la atención especializada para pacientes con cirrosis descompensada y cáncer de hígado.

Abstract Hepatitis C virus (HCV) infection is currently the main blood-borne viral infection. One of the main obstacles to achieving its control in Argentina is related to difficulties in accessing the diagnosis and timely treatment of infected people. We carried out this study with the aim of characterizing the HCV-infected patients who started treatment with direct-acting antivirals (DAAs) and to describe the experience related to treatment. The medical records of 82 patients, 44 (53.7%) male, 37 (45.1%) female, and one (1.2%) transgender, were selected. The mean age was 49 years. We report a frequency of cirrhosis, 39%, in 32 patients, coinfection with HIV in 48 (58.5%) and with HBV in 27 (32.9%). In 52 patients (63.4%), no risk factor clearly associated with infection was observed. All completed the therapy, of them 72 (87.8%) carried out the control to confirm sustained viral response (SVR), that attained 98.6%. We conclude that universal testing should be implemented over testing based on a risk approach, and that a simplified and decentralized care criterion should be promoted, reserving specialized care for patients with decompensated cirrhosis and liver cancer.

The Current Status and Research Progress of Antiviral Therapy in HCV-Associated Lymphoma --Review / 中国实验血液学杂志

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. HCV is not only related to hepatic malignancies but may also promote lymphoid neoplasms. Currently, research has confirmed HCV-related lymphoma, including marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma (BL). Many types of research have shown that antiviral therapy can improve or even remission several HCV-related lymphomas. The direct-acting antiviral agents (DAAs) (such as NS5A protease inhibitors, NS4/4A protease inhibitors and viral polymerase inhibitors) have shown clinical advantages of high efficacy and low side effects for both virus elimination and tumor regression in several HCV-related lymphomas, which may make the selected HCV-related lymphoma patients treated without chemotherapy. In this review the research progress and development direction of antiviral therapy in treating HCV-related lymphoma has summarized briefly.

Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study

OBJECTIVES: Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS: We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS: Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS: Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.

Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.

A real-life study of the positive response to DAA-based therapies for hepatitis C in Brazil

ABSTRACT A retrospective cohort of 11,308 chronic hepatitis C infected patients treated with regimens that included Sofosbuvir (SOF), Daclatasvir (DCV), Simeprevir (SMV), or an association of Ombitasvir, Veruprevir/Ritonavir and Dasabuvir (3D) with or without Ribavirin (RBV) were assessed for sustained virologic response (SVR) or viral cure after a 12-week treatment. Logistic regression analyses were used to identify factors independently associated with positive response to direct-acting antivirals (DAA)-based therapies.Overall 57.1% were male; 48.3% self-identified as white; 78.3% were over 50 years old; 44.1% were from the Southeast region; 47.7% had genotype 1b; and 84.5% were treated for 12 weeks. The SVR rates with DAAs ranged from 87% to 100%. Genotypes 1 and 4 had higher SVR rates (96.3-100%), and genotypes 2 and 3 had SVR of 90.6-92.2%, respectively. Treatment durations of 12 and 24 weeks were associated with an average SVR of 95.0% and 95.9%, respectively. Females were half as likely (OR 0.5; 95% CI 0.4−0.6) to have a negative response to therapy compared to males, and those with genotypes 2 and 3 were one and half fold more likely (OR 1.5-2.2; 95 CI% 0.7-2.9; 1.2-3.6 and OR 2.7-2.8; 95% CI 2.0-3.8, respectively) to not have SVR compared to genotype 1. Patients in the age-range of 50-69 years old were 1.2-fold (OR 1.2; 95% CI 0.7-1.9) more likely to not have SVR compared to other age groups, although not statistically significant.This study is the first of this magnitude to be held in a Latin-American country with high SVR results, supported by a free-of-charge universal and public health system. The high performance found in this study gives support to the Brazilian public health policy decision of adopting DAA-based therapies as a strategy to eliminate HCV by 2030.

Polimorfismos del gen de interleucina 10 y respuesta virológica sostenida en pacientes cubanos coinfectados con virus de hepatitis C y virus de inmunodeficiencia humana / Interleukin-10 gene polymorphisms and sustained virological response in Cuban patients coinfected with hepatitis C virus and human immunodeficiency virus

Introducción: En pacientes infectados con el virus de la hepatitis C se demostró que los polimorfismos de un simple nucleótido del gen de la interleucina 10 (IL10), influyen en la respuesta virológica sostenida al tratamiento con interferón y ribavirina, y en la inmunopatogénesis de la enfermedad. Objetivo: Determinar la frecuencia de los polimorfismos de un simple nucleótido de la región promotora del gen de la interleucina 10, según respuesta virológica sostenida y grado de lesión hepática. Métodos: Se realizó un estudio descriptivo, de corte transversal y se determinó la carga del virus de la hepatitis C por RT-PCR en tiempo real. Se estudiaron 25 pacientes cubanos con virus de inmunodeficiencia humana coinfectados con VHC, 24 semanas después del tratamiento con interferón y ribavirina. Para evaluar la variabilidad genética de la interleucina 10, los polimorfismos de un simple nucleótido se identificaron por secuenciación nucleotídica, -592 (A>C) y -819 (T>C). El grado de fibrosis hepática se calculó por el índice aspartato aminotransferasa/plaquetas. Resultados: El 44,0 por ciento (11/25) de los pacientes lograron respuesta virológica sostenida, y en el 56,0 por ciento (14/25) restante no se obtuvo esta. En los individuos en que se dio la respuesta predominaron los genotipos bajos productores de la interleucina 10, -592AA (36,3 por ciento vs. 21,4 por ciento) y -819TT (54,5 por ciento vs. 21,4 por ciento). En estos casos, el análisis de la frecuencia alélica mostró mayor frecuencia del alelo T para el SNP -819 (p= 0,0470). El índice aspartato aminotransferasa/plaquetas fue compatible con fibrosis hepática sin cirrosis en pacientes sin respuesta virológica sostenida, mientras que en los coinfectados que tuvieron respuesta indicó ausencia de lesión hepática. Conclusiones: Los resultados sugieren que las variantes de los polimorfismos de un simple nucleótido del gen de la interleucina 10 evaluados, podrían estar relacionados con la respuesta virológica sostenida y la patogénesis de la hepatitis C en los pacientes estudiados(AU)

Introduction: The study of patients infected with hepatitis C virus revealed that polymorphisms of a single nucleotide of the interleukin-10 (IL10) gene influence the sustained virological response to the treatment with interferon and ribavirin, and the immunopathogenesis of the disease. Objective: Determine the frequency of single-nucleotide polymorphisms from the interleukin-10 gene promoter region according to the sustained virological response and the degree of liver injury. Methods: A descriptive cross-sectional study was conducted and hepatitis C viral load was determined by RT-PCR. A sample of 25 Cuban HIV/HCV coinfected patients were studied 24 weeks after treatment with interferon and ribavirin. To evaluate the genetic variability of interleukin 10, the single-nucleotide polymorphisms were identified by nucleotide sequencing, -592 (A>C) and -819 (T>C). The degree of liver fibrosis was estimated by the aspartate aminotransferase / platelet index. Results: Of the patients studied, 44.0 percent (11/25) achieved a sustained virological response and 56.0 percent (14/25) did not. In individuals displaying the response, a predominance was found of low interleukin-10 producing genotypes, -592AA (36.3 percent vs. 21.4 percent) and -819TT (54.5 percent vs. 21.4 percent). In those cases, allele frequency analysis showed a greater allele T frequency for SNP -819 (p= 0.0470). The aspartate aminotransferase / platelet index was compatible with kidney fibrosis without cirrhosis in patients without a sustained virological response, and indicated an absence of liver injury in coinfected patients displaying a response. Conclusions: Results suggest that the variants evaluated of single-nucleotide polymorphisms of the interleukin-10 gene could be related to the sustained virological response and the pathogenesis of hepatitis C in the patients studied(AU)

Hepatitis aguda por virus C: reporte de siete casos en centro de referencia en Chile

Hepatitis C virus infection is a major global public health problem. Treatment with direct-acting antivirals is intended to eradicate the chronic form of this infection by 2030. Although uncommon, the acute form of presentation is increasingly recognized, especially in some high-risk populations, such as men who have sex with men without protection. Its virological and serological diagnosis is not standardized, so clinical suspicion is essential. Its early detection allows a timely treatment. We report seven cases of acute HCV hepatitis in a national reference center, its presentation, diagnosis and treatment. We discuss populations at risk and the change in therapeutics with the use of direct-acting antiviral drugs.

A cura da hepatite C crônica com os novos antivirais de ação direta não resultou em melhora da resistência insulínica a curto prazo / Curing hepatitis c with the new direct acting antivirals did not improve insulin resistance after one year

ABSTRACT BACKGROUND: Chronic hepatitis C still figures as an important cause of morbidity among the Brazilian population, and is closely associated with metabolic disturbances, including insulin resistance (IR), which can be evaluated by the Homeostatic Model Assessment (HOMA-IR). IR may entail lower sustained virologic response (SVR) on certain therapeutic regimens and faster progression to advanced hepatic fibrosis. With the arrival of the direct acting agents (DAA) in hepatitis C treatment, there is an increased need in observing the impact in patients' IR profile while using such therapies. OBJECTIVE: - 1) To compare the results of HOMA-IR in patients affected by chronic hepatitis C before treatment with DAA and 12 months after finishing it with SVR. 2) To evaluate the evolution of weight after curing chronic hepatitis C. METHODS: We included patients older than 18 from two tertiary care in Curitiba - PR, of both sexes, with chronic hepatitis C, treated with DAA, from July 2015 to September 2017. We also evaluated the patients' levels of fasting insulin, fasting glucose and glycated hemoglobin before starting treatment and 12 months after finishing it. We also used epidemiologic data, such as age, sex, hepatic fibrosis degree, body mass index, abdominal circumference, viral genotype and the presence of diabetes mellitus before and after treatment. IR was assessed before and after treatment and calculated by the HOMA-IR score. Insulin resistance was defined by a HOMA-IR greater than 2.5. We excluded patients who lost follow-up, those who did not achieve SRV and those who did not have a laboratory profile. The results of quantitative variables were described by means, medians, and standard deviations. P values <0.05 indicated statistical significance. RESULTS: We included 75 patients in this study, with a mean age of 55.2 years and 60% of males. Forty-three patients had advanced fibrosis. Twenty one (28%) had a previous diabetes mellitus diagnosis. We identified 31 (41.3%) patients with IR before antiviral treatment, and this number increased to 39 (52%) after 12 months of finishing treatment, according to HOMA-IR. There was no statistic difference between insulin, glucose and HOMA-IR measurements before and after curing hepatitis C. We observed a weight gain in patients shortly after curing hepatitis C, but this did not persist at the end of the study. We also had no significant difference in IR prevalence when viral genotype was concerned. CONCLUSION: In this study, there was no statistically significant difference between HOMA-IR results in patients before and 12 months after treatment for hepatitis C. Even though patients gained weight after the cure, this was not statistically significant after a year (P=0.131).

RESUMO CONTEXTO: A hepatite C crônica ainda figura como importante causa de morbimortalidade na população brasileira, e está associada a alterações metabólicas, incluindo a resistência insulínica (RI), que pode ser avaliada pelo índice HOMA-IR. A RI pode inclusive implicar em menores taxas de reposta virológica sustentada (RVS) em certos regimes terapêuticos e à uma mais rápida progressão para fibrose hepática avançada. Com o advento dos novos antivirais de ação direta (DAA) oferecidos para hepatite C, há crescente necessidade de observar o impacto dos mesmos no perfil de RI em pacientes submetidos à tais terapêuticas. OBJETIVO: - 1) Comparar os valores do HOMA-IR dos pacientes com hepatite C crônica antes do tratamento com os DAAS com os valores deste índice após 12 meses do término do tratamento com RVS. 2) Avaliar evolução do peso após obtenção da cura da hepatite C crônica. MÉTODOS: Foram incluídos pacientes maiores de 18 anos de dois serviços terciários de Curitiba - PR, de ambos os sexos, portadores de hepatite C crônica, com tratamento com os antivirais de ação direta, no período de julho de 2015 a setembro de 2017. Tais pacientes também foram submetidos a dosagem dos níveis de insulina de jejum, glicemia de jejum e hemoglobina glicada antes de iniciar o tratamento da hepatite C e até 12 meses após o término. Também foram utilizados dados como idade, sexo, grau de fibrose hepática, índice de massa corporal, circunferência abdominal, genótipo viral e presença de diabetes mellitus antes e depois do tratamento. A RI foi estimada antes e após 12 meses do término do tratamento e calculada pelo HOMA-IR. Os resultados de variáveis quantitativas foram descritos por médias, medianas, valores mínimos, valores máximos e desvios padrões. Valores de P<0,05 indicaram significância estatística. RESULTADOS: Foram incluídos 75 pacientes no estudo com média de idade de 55,2 anos, sendo 60% do sexo masculino. Destes pacientes, 43 tinham fibrose avançada. Vinte e um (28%) pacientes tinham o diagnóstico de diabetes mellitus. A RI foi observada em 31 (41,3%) pacientes antes do tratamento antiviral, sendo que este número aumentou para 39 (52%) de acordo com a dosagem do HOMA-IR 12 meses após o término do tratamento. Não houve diferença estatística entre os valores de insulina, glicemia e HOMA-IR antes e após a cura da hepatite. Houve um ganho de peso inicial após a obtenção da cura da hepatite C, mas que não se manteve ao final do estudo. CONCLUSÃO: Não foi vista diferença estatística significante entre os valores do HOMA-IR apresentados pelos pacientes portadores de hepatite C crônica antes do tratamento e 12 meses após a cura da doença. Embora tenha ocorrido ganho de peso após obtenção da cura da doença, este não se deu de forma estatisticamente significativa (P=0,131) ao final de um ano.

Tratamento da hepatite C em pacientes com doença renal crônica e pós-tranplante renal: eficácia e segurança dos esquemas de antivirais de ação direta contendo sofosbuvir / Hepatitis c treatment of renal transplant and chronic kidney disease patients: efficacy and safety of direct-acting antiviral regimens containing sofosbuvir

ABSTRACT BACKGROUND: Direct-acting antivirals have revolutionized hepatitis C treatment, also for patients with chronic kidney disease (CKD), but some controversy exists regarding the use of sofosbuvir (SOF) in patients with glomerular filtration rate (GFR) <30 mL/min. OBJECTIVE: To evaluate the efficacy and safety of these regimens for hepatitis C treatment of patients with CKD and after renal transplantation, as well as the impact of SOF on renal function in non-dialysis patients. METHODS: All patients with hepatitis C and CKD or renal transplant treated with direct-acting antivirals at a referral center in Brazil between January 2016 and August 2017 were included. Efficacy was evaluated based on viral load (HCV RNA) and a sustained virological response (SVR) consisting of undetectable RNA 12 and/or 24 weeks after the end of treatment (SVR12 and SVR24) was defined as cure. Safety was determined by adverse events and ribavirin, when combined, was administered in escalating doses to all patients with GFR <60 mL/min. The impact of SOF on renal function was determined by the measurement of baseline creatinine during and after the end of treatment and its increase was evaluated using the Acute Kidney Injury Network (AKIN) classification. RESULTS: A total of 241 patients (52.7% females) with a mean age of 60.72±10.47 years were included. The combination of SOF+daclatasvir was the predominant regimen in 75.6% of cases and anemia was present in 28% of patients who used ribavirin (P=0.04). The SVR12 and SVR24 rates were 99.3% and 97.1%, respectively. The treatment was well tolerated and there were no major clinically relevant adverse events, with the most prevalent being asthenia (57.7%), itching (41.1%), headache (40.7%), and irritability (40.2%). Among conservatively treated and renal transplant patients, oscillations of creatinine levels (AKIN I) were observed in 12.5% of cases during treatment and persisted in only 8.5% after the end of treatment. Of these, 2.0% had an initial GFR <30 mL/min and this percentage decreased to 1.1% after SOF use. Only 0.5% and 1.6% of the patients progressed to AKIN II and AKIN III elevation, respectively. CONCLUSION: The direct-acting antivirals were safe and efficacious in CKD patients treated with SOF-containing regimens, with the observation of high SVR rates, good tolerability and few severe adverse events. The combination with ribavirin increased the risk of anemia and the administration of escalating doses seems to be useful in patients with GFR <60 mL/min. In patients with GFR <30 mL/min, SOF had no significant renal impact, with serum creatinine returning to levels close to baseline after treatment.

RESUMO CONTEXTO: Os antivirais de ação direta revolucionaram o tratamento da hepatite C, inclusive para os pacientes com doença renal crônica (DRC), porém ainda há divergências no emprego do sofosbuvir (SOF) quando taxa de filtração glomerular (TFG) <30 mL/min. OBJETIVO: Avaliar a eficácia e segurança desses esquemas no tratamento da hepatite C em pacientes com DRC e pós-transplante renal, além de avaliar o impacto do SOF sobre a função renal dos não-dialíticos. MÉTODOS: Todos os pacientes com hepatite C e DRC ou transplante renal que realizaram tratamento com antivirais de ação direta em centro referenciado do Brasil no período de janeiro/2016 a agosto/2017 foram incluídos. A eficácia foi avaliada por meio da carga viral (HCV-RNA), considerando-se cura uma resposta virológica sustentada (RVS) com resultado indetectável após 12 e/ou 24 semanas do término do tratamento (RVS12 e RVS24). A segurança foi determinada pelos eventos adversos e a ribavirina, quando associada, foi introduzida de forma escalonada em todos os pacientes com TFG <60 mL/min. Para determinação do impacto do SOF sobre a função renal, foram observadas as dosagens de creatinina basal, durante e após término do tratamento com seu incremento avaliado por meio da classificação de AKIN (acute kidney injury network). RESULTADOS: Foram incluídos 241 pacientes, sendo 52,7% do sexo feminino, com média de idade de 60,72±10,47 anos. A associação de SOF+daclatasvir predominou em 75,6% dos casos e anemia esteve presente em 28% dos pacientes que utilizaram ribavirina (P=0,040). As taxas de RVS12 e RVS24 foram de 99,3% e 97,1%. O tratamento foi bem tolerado, com eventos adversos pouco relevantes, sendo os mais prevalentes: astenia (57,7%), prurido (41,1%), cefaleia (40,7%) e irritabilidade (40,2%). Entre os pacientes em tratamento conservador e transplantados renais, os valores de creatinina sofreram oscilações AKIN I em 12,5% dos casos, durante o tratamento, persistindo em apenas 8,5% da amostra após o término, dos quais 2,0% apresentavam TFG <30 mL/min inicialmente, com queda para 1,1% após uso do SOF. Apenas 0,5% e 1,6% evoluíram com elevação AKIN II e AKIN III. CONCLUSÃO: Os antivirais de ação direta foram seguros e eficazes em pacientes com DRC tratados com esquemas contendo SOF, apresentando altas taxas de RVS, boa tolerabilidade e poucos eventos adversos graves. A associação com ribavirina aumentou o risco de anemia, portanto sua introdução de forma escalonada parece ser útil nos pacientes com TFG <60 mL/min. Em pacientes com TFG <30 mL/min o SOF não apresentou impacto renal significativo, com creatinina sérica retornando a valores próximos ao basal após o tratamento.