Hepatitis mortality in Brazil and regions, 2001-2020: temporal trend and spatial analysis / Mortalidade por hepatites no Brasil e regiões, 2001-2020: tendência temporal e análise espacial

ABSTRACT Objective: To analyze the spatial distribution and the temporal trend of the hepatitis mortality rate in Brazil from 2001 to 2020. Methods: Ecological, temporal, and spatial study on mortality from hepatitis in Brazil with data from the Mortality Information System (Sistema de Informações sobre Mortalidade - SIM/DATASUS). Information was stratified by year of diagnosis, region of the country, municipalities (of residence). Standardized mortality rates (SMR) were calculated. The temporal trend was estimated by Prais-Winsten regression and the spatial distribution by the Global Moran Index (GMI). Results: The highest SMR means in Brazil were for Chronic viral hepatitis with 0.88 deaths per 100,000 inhabitants (SD=0.16), followed by Other viral hepatitis with 0.22/100,000 (SD=0.11). In Brazil, the temporal trend of mortality from Hepatitis A was −8.11% per year (95%CI −9.38; −6.82), while for Hepatitis B it was −4.13% (95%CI −6.03; −2.20), of Other viral hepatitis of −7.84% (95%CI −14.11; −1.11) and of Unspecified Hepatitis −5.67% per year (95%CI −6.22; −5.10). Mortality due to chronic viral hepatitis increased by 5.74% (95%CI 3.47; 8.06) in the North and 4.95% in the Northeast (95%CI 0.27; 9.85). The Moran Index (I) for Hepatitis A was 0.470 (p<0.001), for Hepatitis B 0.846 (p<0.001), Chronic viral hepatitis=0.666 (p<0.001), other viral hepatitis=0.713 (p<0.001), and Unspecified Hepatitis=0.712 (p<0.001). Conclusion: The temporal trend of hepatitis A, B, other viral, and unspecified hepatitis was decreasing in Brazil, while mortality from chronic hepatitis was increasing in the North and Northeast.

RESUMO Objetivo: Analisar a distribuição espacial e a tendência temporal da taxa de mortalidade por hepatites no Brasil no período de 2001 a 2020. Métodos: Estudo ecológico, temporal e espacial sobre a mortalidade por hepatites no Brasil com dados do Sistema de Informações sobre Mortalidade (SIM/Datasus). As informações foram estratificadas por ano do diagnóstico, região do país, municípios (de residência). Foram calculadas as taxas padronizadas de mortalidade (TPM). A tendência temporal foi estimada pela regressão de Prais-Winsten e a distribuição espacial pelo Índice Global de Moran (IGM). Resultados: As maiores médias da TPM no Brasil foram para hepatite viral crônica, com 0,88 mortes para cada 100 mil habitantes (desvio padrão — DP=0,16), seguida de outras hepatites virais, com 0,22/100 mil (DP=0,11). No Brasil, a tendência temporal da mortalidade por hepatite A foi de −8,11% ao ano (intervalo de confiança de 95% — IC95% −9,38; −6,82), enquanto por hepatite B foi de −4,13% (IC95% −6,03; −2,20); de outras hepatites virais, foi de −7,84% (IC95% −14,11; −1,11) e de hepatite não especificada, de −5,67% ao ano (IC95% −6,22; −5,10). A mortalidade por hepatite viral crônica cresceu 5,74% (IC95%3,47; 8,06) no norte e 4,95% no nordeste (IC95% 0,27; 9,85). O Índice de Moran (I) para hepatite A foi de 0,470 (p<0,001), para hepatite B de 0,846 (p<0,001), hepatite viral crônica=0,666 (p<0,001), outras hepatites virais=0,713 (p<0,001) e hepatites não especificadas=0,712 (p<0,001). Conclusão: A tendência temporal das hepatites A, B, de outras hepatites virais e das não especificadas foi de diminuição no Brasil, enquanto a mortalidade por hepatites crônicas foi de crescimento nas Regiões Norte e Nordeste.

Efficacy and safety of ledipasvir/sofosbuvir versus elbasvir/grazoprevir in treatment of genotype 1b chronic hepatitis C / 中华临床感染病杂志

Objective:To compare the clinical efficacy and safety of ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) in treatment of patients with chronic hepatitis C (CHC).Methods:The clinical data of 143 patients with genotype 1b CHC treated in Huzhou Central Hospital from January 2020 to December 2021 were retrospectively analyzed, including 74 cases treated with LDV/SOF and 69 cases treated with EBR/GZR. The virological response after 4 and 12 weeks of treatment and 12wk after drug withdrawal was determined; and the serological and liver inflammation indexes before and after treatment in two groups were compared. SPSS 25.0 software was used for statistical analysis of the data.Results:The virological response rates of the LDV/SOF group and EBR/GZR group were 97.30% and 98.55%, 98.65% and 100.00%, 97.30% and 98.55% after 4 and 12 weeks of treatment and 12 weeks after the end of treatment, respectively (all P > 0.05). At the end of treatment, the liver inflammation indexes ALT, AST and GGT in the two groups were significantly lower than the baseline levels ( Z=-7.470 and -6.974, -9.757 and -6.832, -3.578 and -4.054, P<0.01). Adverse reactions in both groups were mild, and no serious adverse events occurred. Conclusion:Both LDV/SOF and EBR/GZR have good clinical efficacy in the treatment of genotype 1b CHC patients. And the patients are well tolerated.

[Diagnosis and treatment of new-onset or uncontrolled hyperthyroidism-induced liver injury].

The thyroid gland is the largest endocrine gland in the human body, which mainly secretes thyroid hormones. Thyroid hormone acts on almost all tissues and cells at different level regulating growth and development, metabolism and other functional activities of the body. Therefore, abnormal thyroid function can affect the multiple organs throughout the body. Liver, as the largest biochemical plant in the whole body, is widely regulated by thyroid hormones, and is one of the important target organs of the thyroid gland. Hyperthyroidism (HT for short) is a common disease of the endocrine system, which can cause liver injury, such as hepatomegaly, abnormal liver function, jaundice, cirrhosis, and liver failure. This phenomenon is also known as hyperthyroidism-induced liver injury, and it is more common in new or untreated or improperly treated patients with hyperthyroidism. The basic liver function test at the beginning of antithyroid drugs (ATD) treatment can clarify the degree of liver injury caused by hyperthyroidism itself, and further predict the additional liver injury with ATD therapy initiation. The core of treating hyperthyroidism-induced liver injury is to rapidly control hyperthyroidism, and restore normal liver function. This review briefly summarizes the incidence rate, possible mechanisms, pathological changes, clinical manifestations, laboratory, imaging and pathologic findings, and the recent advances in diagnosis and treatment of the hyperthyroidism-induced liver injury.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis.

BACKGROUND/AIMS: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. METHODS: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. RESULTS: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). CONCLUSION: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

[Viral hepatitis A-E]. / Virushepatitis A­E.

Hepatitis viruses A-E cause acute and chronic liver inflammation and thus lead to significant morbidity and mortality worldwide. They differ significantly in their biology, course of disease and therapy options. While hepatitis A virus only causes acute infection, hepatitis B can become chronic, even reactivate or occur as coinfection with hepatitis D virus. Whereas these infections are preventable through vaccination, a vaccine does not exist against HCV. However, new direct antiviral agents reliably lead to cure of chronic hepatitis C. Hepatitis E virus frequently causes acute or-in case of immunosuppression-even chronic hepatitis. Continual screening of patients with elevated liver enzymes or risk groups using simple serological markers can enable virus-specific therapy of mostly asymptomatic chronic virus hepatitis, preventing the development of liver cirrhosis and hepatocellular carcinoma.

Autoimmune hepatitis in practice, from diagnosis to complications: What is the role of imaging? A clinicoradiological review.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown origin that can lead to liver cirrhosis, hepatocellular carcinoma (HCC), liver transplantation or death. The diagnosis is performed upon a multifactorial score. Treatment is based on the combination of immunosuppressants and aims at clinical, laboratory and histological remission, the latter being the most difficult to be achieved and proven. The absence of liver inflammation, defined by biopsy, is the main determinant in remission or therapeutic modification. Imaging exams have a limited role in this clinical management and the main findings are those related to chronic liver disease. Imaging's relevance, therefore, lies mainly in helping to exclude overlapping syndromes and in assessing complications related to cirrhosis, such as in screening for HCC. In recent years, however, the radiological literature has been witnessing increasing advances with regard to imaging biomarkers in liver disease, leading some authors to consider a future of virtual liver biopsy performed by magnetic resonance imaging. The present study aims to review the role of imaging in the management of AIH in the light of recent advances in the current literature and to provide an illustrated guide with the main findings described in the disease.

Research advances in T helper 17 cells in chronic inflammatory liver diseases / 临床肝胆病杂志

T helper 17 (Th17) cells, differentiated from nave CD4+T cells, can secrete a series of cytokines including interleukin-17, interleukin-21, and interleukin-22 and are meanwhile regulated by a variety of cytokines and genes, playing an important role in various inflammatory diseases. Th17 cells are widely distributed in vivo and are associated with diseases in many systems. They are involved in the regulation of chronic inflammatory/autoimmune diseases by secreting pro-inflammatory factors and antagonizing the immunosuppressive effect of regulatory T cells. This article reviews the recent studies on the association between Th17 cells and the pathogenesis of various chronic inflammatory liver diseases, so as to provide a reference for scientific research and clinical treatment.

Hypovitaminosis D in Hepatitis C patients and its relation with demographic and laboratory data.

OBJECTIVE: To determine the frequency of vitamin-D deficiency in hepatitis C patients and its relation with demographic and baseline laboratory data. METHODS: The cross-sectional study was conducted at the University Institute of Medical Laboratory Technology, Faculty of Allied Health Sciences, The University of Lahore, Pakistan, from April 3 to July 24, 2017, and comprised diagnosed hepatitis C genotype 3 patients aged 18-60 years. Demographic data was collected on a predesigned proforma. Tests included complete blood counts, liver function test, hepatitis C viral load and 25-hydroxy Vitamin-D level. Data was analysed using SPSS 24. RESULTS: Of the 115 patients, 54(47%) were male and 61(53%) were females. Mean vitamin-D level was 22.3±11.3. Total 25(21.7%) patients showed normal level of vitamin-D while the level was low in 90(78.3%) patients; 41(35.6%) showed vitamin-D insufficiency and 49(42.6%) vitamin-D deficiency. Significant effect of sun exposure was recorded on patient's vitamin-D level (p=0.00). Significantly low hepatitis C viral load was seen in patients with normal vitamin-D (p= 0. 02 6 ). CONCLUSIONS: Patients with hepatitis C virus infection had high incidence of hypo-vitaminosis D.

[Effect of chronic hepatitis B virus DNA negative transformation and HBsAg clearance on the occurrence of hepatocellular carcinoma].

Achieving HBV DNA negative transformation and HBsAg clearance with effective antiviral therapy can reduce the incidence of HCC, but some patients are still at risk of developing HCC. Therefore, screening high-risk patients for close monitoring is essential to reduce the incidence of HCC. This paper reviews the occurrence of HCC, risk factors and risk prediction models of HBV DNA negative transformation and HBsAg clearance, and provides a basis for screening and follow-up management of high-risk group of HCC with chronic hepatitis B.

Histological assessment of reversal of liver fibrosis and cirrhosis / 临床肝胆病杂志

Liver fibrogenesis is a common pathway of pathological progression of chronic liver injuries. The diagnosis of liver fibrosis provides an important basis for treatment decision-making and prognostic evaluation of chronic liver diseases. With the rapid development of therapeutics, many new clinical issues have emerged, which requires new techniques for the diagnosis of liver fibrosis. At present, histological assessment remains the most reliable method for a definite diagnosis of liver fibrosis and cirrhosis. With reference to related clinical articles and data, this article analyzes the clinical value and research directions of histological assessment in chronic liver disease management and diagnosis of liver fibrosis/cirrhosis and its reversal.

Effect of chronic hepatitis B virus DNA negative transformation and HBsAg clearance on the occurrence of hepatocellular carcinoma / 中华肝脏病杂志

Achieving HBV DNA negative transformation and HBsAg clearance with effective antiviral therapy can reduce the incidence of HCC, but some patients are still at risk of developing HCC. Therefore, screening high-risk patients for close monitoring is essential to reduce the incidence of HCC. This paper reviews the occurrence of HCC, risk factors and risk prediction models of HBV DNA negative transformation and HBsAg clearance, and provides a basis for screening and follow-up management of high-risk group of HCC with chronic hepatitis B.

The clinical application of laboratory tests and diagnosis for common chronic liver diseases / 中华检验医学杂志

Chronic liver disease has a high incidence and prevalence in China, which had done great harm to people's health. Laboratory detection is an effective way to diagnose and evaluate therapeutic effect of chronic liver disease. However, the selection and interpretation of laboratory tests are difficult for the various causes of liver diseases. According to etiology of the chronic liver diseases, application of common laboratory tests for liver diseases based on the clinical guidelines were interpreted in this article .

A comparative analysis of pathological grading and staging systems for chronic hepatitis / 临床肝胆病杂志

Liver biopsy plays an important role in the diagnosis and treatment of liver diseases and can give a comprehensive and detailed description of the morphology of lesions and objective grading and staging scores. There are several pathological grading and staging systems for chronic viral hepatitis and chronic hepatitis due to other causes. This article describes the application and advantages/disadvantages of each scoring system and summarizes related precautions.

Development and prospects of pathological classification systems for chronic hepatitis / 临床肝胆病杂志

Liver pathology is the gold standard for the diagnosis of chronic hepatitis.Although there are many effective noninvasive diagnostic methods,liver pathology is still the most direct and reliable method for evaluating inflammation and fibrosis in patients with chronic hepatitis.The classification system for liver pathology has been also constantly changing,so as to provide more accurate information of grading and staging and to guide clinical and scientific research.This article reviews the development of classification systems for liver pathology,the basic criteria and disadvantages of each major classification system,and the prospects of pathological classification systems for chronic hepatitis.

[Quantitative comparison of diffusion weighted image in liver at two field strengths for chronic hepatitis B].

Objective: To evaluate whether there were differences between apparent diffusion coefficient (ADC) values derived from 3.0 T and 1.5 T MR diffusion-weighted imaging (DWI) in liver of patients with chronic hepatitis B. Methods: From January 2016 to November 2016, a total of 40 chronic hepatitis B prospectively underwent both 1.5 T and 3.0 T DWI before liver biopsy, the interval between two scans was within 15 minutes, the protocol was respiratory-triggered DWI(RT-DWI). The ADC values were measured at both field strengths using ROI method. Bland-Altman tests and paired t-tests were used to compare ADC values obtained at 1.5 T and 3.0 T. Results: The ADC values of different b values for patients with mild inflammation at 1.5 T were(1.22-1.48(1.35±0.08)×10(-3) mm(2)/s), the ADC values of different b values for patients with mild inflammation at 3.0 T were(1.18-1.45(1.30±0.08)×10(-3) mm(2)/s); the ADC values of different b values for patients with moderate to severe inflammation at 1.5 T were(1.11-1.37(1.25±0.06)×10(-3) mm(2)/s), the ADC values of different b values for patients with moderate to severe inflammation at 3.0 T were(1.08-1.31(1.20±0.06)×10(-3) mm(2)/s). There were significantly differences between the ADC values of different b values for patients with chronic hepatitis B obtained at two field strengths (P<0.01). Conclusions: Different field strengths have influence on ADC values in liver, the ADC values derived from 3.0 T are lower than the ADC values derived from 1.5 T.

Changes of peripheral blood during the antiviral treatment with Peg-IFNα-2 a for patients with chronic hepatitis B and the relationship between the changes and effect / 中华实验和临床病毒学杂志

Objective@#To observe the changes of peripheral blood picture of CHB with Peg-IFN, and explored the relationship between the changes and decline of HBV DNA, clearance of HBsAg.@*Methods@#Patients with CHB treated with Peg-IFN α-2 a in the Second Division of Liver Disease in Beijing Ditan Hospital were monitored for blood routine examination and Liver function, kidney function, thyroid function of baseline and weeks 2, 4, 8, 12, 24, 36, 48, and weeks 12, 24, and 48 after the end of treatment for chronic hepatitis B, and HBV DNA, HBsAg.@*Results@#The decrease of peripheral blood cells began to occur at week 2 of treatment. For CHB with HBeAg negative patients, white blood cells, lymphocyte, neutrophils, hemoglobin and platelets significantly decreased at 2 weeks, while a minimum value occurred at 48 weeks. The recovery was obvious at the end of treatment (48 weeks), and reached pre-treatment levels at 48 weeks after the end of treatment. For CHB with HBeAg positive patients, white blood cells, neutrophils, hemoglobin and platelets significantly decreased at 2 weeks, while a minimum value was found at 36-48 weeks. The recovery was obvious at the end of treatment (48 weeks), and reached pre-treatment levels at 48weeks after the end of treatment. For patients with CHB, hemoglobin declined by more than13.64% at 36th week, which means that the patient would have a predictive significance for decrease of HBV DNA, and drops of more than 0.33% at 2nd week means that the patient would have a predictive significance for clearance of HBsAg.@*Conclusions@#During the treatment with interferon, the variation regularity of blood picture for predicting result have a certain effect, which may help predict and monitor the change of blood picture in clinical work.

Association of programmed cell death-1 gene polymorphisms with chronic hepatitis C virus infection and antiviral effect / 临床肝胆病杂志

ObjectiveTo investigate the association of single nucleotide polymorphisms (SNPs) of programmed cell death-1 (PD-1) gene with chronic hepatitis C virus (HCV) infection and the effect of antiviral therapy with interferon combined with ribavirin. MethodsA total of 228 patients with chronic hepatitis C (CHC) who were hospitalized in seven hospitals in Hebei Province, China from October 2010 to October 2012 were enrolled and treated with interferon combined with ribavirin as the individualized antiviral therapy. Eighty-one persons who underwent physical examination were enrolled as control group. The TaqMan probe method was used to detect PD-1 gene polymorphisms. The distribution of alleles and genotypes at PD-1.1 and PD-1.3 were compared between the two groups, and the association between the SNPs of PD-1.1 and PD-1.3 and anti-HCV effect was analyzed. The chi-square test was used for the comparison of categorical data between groups. ResultsThe CHC group showed significantly higher frequencies of T allele and TT genotype at PD-1.1 than the control group (52.41% vs 43.21%, χ2=4.059, P=0.044; 28.51% vs 14.81%, χ2=6.469, P=0.039). The SNPs of PD-1.1 gene were not significantly associated with complete early virologic response or sustained virologic response (both P＞0.05). Both groups had CC genotype at PD-1.3. ConclusionPD-1.1 T allele might be associated with chronic HCV infection, and patients carrying TT genotype have a high risk of chronic HCV infection. PD-1.1 polymorphism is not associated with virologic response to anti-HCV therapy.

Clinical observation of interferon-induced mental disorder in patients with chronic hepatitis / 中国基层医药

Objective To explore clinical haracteristics, diagnosis, treatment, prognosis and prevention of mental disorder induced by interferon.Methods Thirty cases of interferon treatment for chronic hepatitis were select-ed as research subjects.The psychotic symptoms of these patients induced by interferon were analysized by clinical statistics.Results The Self-Rating Depression Scale( SDS) and the Self-Rating Anxiety Scale( SAS) scores after treatment were (47.10 ±9.47) points and (43.00 ±10.34) points,these were higher than before treatment and the difference was statistically significant (t=8.39,7.66,all P<0.01).The incidence rates of the psychotic symptoms in this group of interferon-induced were 66.7%(20/30).The occurrence rates of headaches,insomnias,depres-sions,anxieties and personality changes were respectively 36.7%,30.0%,16.7%,10.0%,10.0%.Before and after treatment,the difference was statistically significant (χ2 =15.43,P<0.01).Conclusion The symptoms of mental disorder induced by interferon have high incidence rate and serious consequences,so early detection and early treat-mentcan contribute a better prognosis.

Curative effect of interferon in the treatment of chronic hepatitis / 中国基层医药

Objective To investigate the effect of recombinant interferon in the treatment of chronic hepatitis and the influence of neutralizing antibody (NA) on its clinical efficacy.Methods 80 cases with chronic hepatitis were randomly divided into the treatment group(n=40) and control group(n=40).The content of HBV DNA was determined by fluorescence quantitative polymerase chain reaction ( PCR) assay.The neutralizing antibodies against interferon were measured by antiviral-neutralizing assay(AVA).Results After the treatment,the content of HBV DNA in the observation group was significantly lower than before treatment (F=12.55,P0.05).The contents of HBV DNA in NA positive group had no significant difference before and after treatment (F=0.88,P>0.05);The contents of HBV DNA in NA negative group had significant difference before and after the treatment ( F=11.55,P<0.05).In 80 cases,degree of cell lesions in 0 grade(10 cases),1 grade(25 cases),2 grade (25 cases),3 grade (12 cases) and 4 grade(8 cases).Conclusion The recombinant interferon in the treatment of chronic hepatitis has certain effect,but NA can affect its treatment effect .

Rare hepatic metastases of colorectal cancer in livers with symptomatic HBV and HCV hepatitis.

AIM: The liver is the most common site of metastases in colorectal cancer but metastases seem to be less common in patients with a chronically liver damage. The aim of our study was to assess the development of metachronous liver metastases in patients affected by HBV or HCV related liver diseases. MATERIAL OF STUDY: We retrospectively evaluated above all the development of liver metastases and the 5-year disease free in 457 patients radically treated for colorectal cancer with healthy liver and in 31 patients radically treated for colorectal cancer affected by liver damage (HBV or HCV related). RESULTS: Overall incidence of liver metastases was 9% (44/488), in particular 3.2% in infected patients and 9.4% in non-infected patients (p= 0.34). Our results revealed that there is no statistically significant difference between the number of positive lymph nodes of primary colorectal cancer and the number of indifferentiated cancers in infected compared with non-infected patients (29% vs 34.1% and 9.7% vs 13.6% respectively), and the 5-year disease free is better for infected patients (93% and 80%, p = 0.17). DISCUSSION: In infected patients we registered a better crude 5-year disease free interval and a fewer incidence of metachronous liver metastases. This difference is in agreement with other results mentioned in literature. CONCLUSION: In the light of the reported data, the authors consider that the recent pathogenetic theory of the "metalloproteinase inhibitor" should be taken in account.