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.

Research progress on antiviral therapy in hepatitis C-negative recipients receiving kidney transplantation from infected donors / 中华临床感染病杂志

Kidney transplantation is the best option for end stage renal disease. Currently, shortage of donor kidneys become a global problem for kidney transplants, partly due to the abandonment of kidneys from donors infected with hepatitis C virus (HCV). With the advent of direct-acting antiviral drugs, the use of HCV infected donor kidneys has become an important measure to expand the donor pool. This article reviews the research progress on the safety, efficacy and timing of antiviral therapy for HCV-negative recipients receiving kidney transplantation from HCV-positive donors.

Recomendaciones en el tratamiento actual de la infección crónica por el virus de la hepatitis B / Current recommendations for the treatment of chronic hepatitis B infection

La infección crónica por el virus de la hepatitis B (VHB) se considera un problema de salud pública mundial. Se estima que al menos dos mil millones de personas han estado expuestas al VHB, y a pesar de una vacuna efectiva, 300 millones de personas están infectadas crónicamente a nivel mundial. Aunque el virus no es directamente citopático, la infección puede desencadenar cirrosis hepática y aun, carcinoma hepatocelular (CHC). El ADN circular cerrado covalentemente (ADNccc) en el núcleo de los hepatocitos y la incapacidad del sistema inmunitario para eliminar la infección crónica por el virus son los mecanismos más importantes de la infección por VHB. Las diferentes entidades, como la Asociación Europea para el Estudio del Hígado (EASL) y la Asociación Americana para el Estudio de las Enfermedades Hepáticas (AASLD), ponen a disposición las pautas para el manejo de esta enfermedad. A pesar de los avances en el tratamiento de la infección crónica por el VHB, en particular con el desarrollo de los análogos de los nucleótidos/ nucleósidos, quedan aún muchos interrogantes. Las investigaciones continúan para el desarrollo de nuevas opciones de tratamiento enfocadas principalmente en evitar que la suspensión de la terapia conlleve a un incremento de la carga viral, con el consecuente aumento del riesgo de progresión de la enfermedad hepática, y un eventual CHC.

Chronic hepatitis B virus (HBV) infection is considered a global public health problem. It is estimated that at least two billion people have been exposed to HBV, and despite an effective vaccine, 300 million people are chronically infected worldwide. Although the virus is not directly cytopathic, the infection can trigger liver cirrhosis and even hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) in the nucleus of hepatocytes and the inability of the immune system to eliminate chronic virus infection are the most important mechanisms of chronic HBV infection. Different entities, such as the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), provide guidelines for the management of this disease. Despite advances in the treatment of chronic HBV infection, including the development of nucleotide and nucleoside analogs, many questions remain. Research continues for the development of new treatment options focused mainly on avoiding a relapse on viral load after therapy discontinuation, with an increased risk of liver disease progression, and an eventual CHC.

New advances in drug therapy of chronic hepatitis B infection / 中华临床感染病杂志

Nucleos( t) ide analogs and interferon are currently the main drugs for the treatment of chronic hepatitis B; they can induce sustained virologic suppression of HBV DNA , but still can’t clear HBsAg effectively.With the further understanding of the biology and life cycle of HBV and the breakthrough of direct antiviral agent for HCV treatment , multiple new drugs aiming at ＂cure HBV＂and clear HBsAg are undergoing preclinical development and ／or clinical trials.This article reviews the latest advances in drug therapy of chronic hepatitis B infection.

Hepatitis C: una aproximación clínica y epidemiológica en Cali, Colombia / Clinical and epidemiological approach to Hepatitis C in Cali, Colombia

Resumen Introducción: en Colombia, la infección por el virus de la hepatitis C (VHC) representa alta morbilidad y elevados costos. Con la llegada de nuevos tratamientos más efectivos, se hace necesario conocer las características propias de esta población para su adecuado uso. Objetivos: describir las características epidemiológicas y clínicas de los pacientes con VHC manejados en un centro de referencia en enfermedades hepáticas. Materiales y métodos: se realizó un estudio descriptivo de corte transversal en una población de adultos con diagnóstico serológico de VHC entre el 2011 y el 2016. Resultados: se evaluaron 214 historias clínicas de pacientes con diagnóstico serológico confirmado de VHC. La mediana de edad fue de 59 años y el 62 % fue de sexo femenino. El genotipo se reportó en 114 pacientes, el 75 % presentó genotipo 1B. El 36,9 % de los pacientes había recibido algún hemoderivado y el 5 % tenía tatuajes. La prevalencia de cirrosis fue del 29,4 % y de hepatocarcinoma fue del 3,3 %. El 1,8 % y el 5,1 % de los pacientes presentó coinfección con el virus de la hepatitis B (VHB) y virus de la inmunodeficiencia humana (VIH), respectivamente. Conclusión: los factores determinantes de la infección por el VHC en Cali presentan un comportamiento clínico similar al que reporta la literatura científica a nivel mundial, lo que obliga a enfatizar en la prevención de la población en riesgo. El genotipo 1B continúa siendo el más frecuente en nuestro medio, lo que hace a esta población susceptible a los nuevos tratamientos.

Abstract Introduction: In Colombia, Hepatitis C virus infections have high rates of morbidity and high costs. The advent of new more effective treatments has produced a need for better knowledge of this population's characteristics to allow their proper use. Objectives: The objective of this study is to describe the epidemiological and clinical characteristics of patients with hepatitis C at a referral center for liver diseases. Materials and methods: We conducted a cross-sectional descriptive study of a population of adults with serological diagnoses of hepatitis C between 2011 and 2016. Results: We evaluated 214 clinical records of patients with confirmed serological diagnoses of hepatitis C. Their median age was 59 years, and 62 % were women. The HCV genotypes of 114 patients were reported: 75 % had genotype 1B. Transfusions of one or another type of blood product had been administered to 36.9 % of the patients, and 5% had tattoos. The prevalence of cirrhosis was 29.4 % while that of hepatocellular carcinoma was 3.3 %. Hepatitis B virus coinfections were found in 1.8 % of these patients, and 5.1 % of the patients had human immunodeficiency virus coinfections. Conclusion: The determinants of hepatitis C virus infection in Cali are similar to those reported in scientific literature worldwide and requires emphasis on prevention in the at-risk population. Genotype 1b continues to be the most frequent in our environment which makes this population susceptible to new treatments.

Clinical timing and benefit of antiviral treatment for hepatitis C / 中华肝脏病杂志

Current treatments for hepatitis C include pegylated interferon-α (Peg-IFNα) and ribavirin (RBV) combination therapy and direct antiviral agents (DAAs). Antiviral treatment can be initiated after 4 to 6 months of clinical observations for patients with acute infections, but should be started as early as possible for those with chronic infections. However, for patients who are ineligible for Peg-IFN and RBV combination therapy and have no unrestricted access to DAAs, it is advised that they wait for the approval of DAAs in China if their medical condition is under control. Though, antiviral therapy should be started immediately if the disease progresses. It has been reported that there are numerous clinical benefits of antiviral treatment for hepatitis C. However, the long-term impact of DAAs treatment including efficacy and safety is limited and remains to be explored.

Direct anti-HCV agents

Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the "cure HCV" goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.

The challenges to hepatitis C research in era of direct antiviral agents / 临床肝胆病杂志

Hepatitis C virus (HCV)is an important human pathogen that causes chronic viral hepatitis worldwide.HCV infection,often persistent and asymptomatic,could lead to liver fibrosis/cirrhosis and hepatocellular carcinoma.The interferon/ribavirin therapy has been widely used for treating chronic hepatitis C,but it is not always effective and has strong side effects.The development of small-molecule di-rect antiviral agents (DAA)has greatly improved the curing efficiency of chronic hepatitis C therapeutics and will likely replace the interfer-on-based therapy in the future.However,these developments do not necessarily suggest that the problems of chronic hepatitis C have been completely solved.The HCV research is still facing many challenges in this new DAA era.