Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study / 中华肝脏病杂志

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome / 中华肝脏病杂志

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.

A conceptual framework for dynamics of cccDNA in hepatitis B virus / 中华肝脏病杂志

The resolution of the hepatitis C issue has raised expectations for a chronic hepatitis B cure, driving the industry to expand investment in research and development efforts to strengthen functional cure strategies. These strategies have a wide variety of types, and the published research findings are heterogeneous. The theoretical analysis of these strategies is of great significance for determining prioritized research orientations as well as sensibly allocating research and development resources. However, due to a paucity of necessary conceptual models, current theoretical analysis has not been able to unify various therapeutic strategies into a proper theoretical framework. In view of the fact that the decrease in the quantity of cccDNA is an inevitable core event accompanied by the process of functional cure, this paper intends to analyze several chronic hepatitis B cure strategies using cccDNA dynamics as a framework. Furthermore, there are currently few studies on the dynamics of the cccDNA field, hoping that this article can promote recognition and research in this field.

Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection / 中华肝脏病杂志

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

Intrahepatic and extrahepatic clinical manifestations and treatment progress for hepatitis type E / 中华肝脏病杂志

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.

Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022) / 中华肝脏病杂志

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients / 中华预防医学杂志

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

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.

Study on the related factors of antiviral treatment in previously reported hepatitis C patients based on the Andersen model / 中华肝脏病杂志

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.

Demographic characteristics and associated influencing factors in treated patients with chronic hepatitis B with hypoviremia : a single-center retrospective cross-sectional study / 中华肝脏病杂志

Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.

Research progress on drug resistance of anti-varicella-zoster virus drugs / 中华预防医学杂志

Varicella-zoster virus (VZV) causes chickenpox when it first infects humans, and the virus may reactivate in adulthood and cause herpes zoster (HZ). Broad-spectrum antiviral drugs are one of the treatments for varicella and herpes zoster, but the emergence of drug resistance poses many challenges to this treatment and increases the burden of disease on patients. This paper discusses the resistance mechanisms, resistance sites and resistance detection methods of anti-VZV drugs in order to help further research on new anti-VZV targets, new drugs and monitoring of resistance to existing drugs.

Deciphering suppressive effects of Lianhua Qingwen Capsule on COVID-19 and synergistic effects of its major botanical drug pairs / 中国天然药物

The COVID-19 pandemic has resulted in excess deaths worldwide. Conventional antiviral medicines have been used to relieve the symptoms, with limited therapeutic effect. In contrast, Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect. The current review aims to: 1) uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19; 2) verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis; 3) investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule; and 4) clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs. Numerous bioactive ingredients in Lianhu Qingwen, such as quercetin, naringenin, β-sitosterol, luteolin, and stigmasterol, were identified to target host cytokines, and to regulate the immune defence in response to COVID-19. Genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR) were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19. Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19. Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19. In conclusion, the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed. Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B / 中南大学学报(医学版)

OBJECTIVES@#Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).@*METHODS@#This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.@*RESULTS@#Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).@*CONCLUSIONS@#The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

Expert consensus on the clinical application of the markers of hepatitis B virus / 中华肝脏病杂志

Hepatitis B virus biomarkers are mainly used in clinical practice to diagnose infection, monitor disease progression, evaluate response to chronic hepatitis B treatment, and evaluate the efficacy of novel antiviral drugs in clinical trials. In combination with the recent research progress of antiviral therapy for chronic hepatitis B and the actual needs of clinical diagnosis and treatment, the expert consensus was formulated by the Cooperative Group of Basic Research and Experimental Diagnosis of Liver Diseases, Chinese Society of Hepatology, Chinese Medical Association. It summarized the evidence and recommended the key points for the clinical application of classic and novel hepatitis B virus related biomarkers in order to guide the standardized and reasonable clinical application for these biomarkers.

Tratamientos y bioterapias para COVID-19 / Therapeutics and biotherapies for covid-19

INTRODUCCIÓN: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19.El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas. (AU)

INTRODUCTION: A new coronavirus outbreak emerged in 2019 in Wuhan, China, causing a shock to the healthcare system around the world; the International Committee on Taxonomy of Viruses named it SARS-CoV- 2, the infectious agent of the COVID-19 disease. The spectrum of severity of the disease is very wide, most patients are not serious, but others can develop pneumonia, with acute respiratory failure being the most frequent cause of mortality. Objective: to analyze and develop the different therapeutic alternatives provided by Biotechnology dedicated to Health, to treat the symptoms of those COVID-19 patients who require it, and thus reduce mortality.Methodology: a review of the available literature from January 2020 in PubMed of the treatments that are still in clinical trials and those that have been approved under emergency use for the disease COVID-19 was performed. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to health policies established for therapeutics during the mentioned pandemic. Results: this work addresses the new therapeutic alternatives derived from Biotechnology, which are both in use and in stages of clinical trials, to treat patients who developed COVID-19 included within the segment of biopharmaceuticals and biotherapies. A brief summary of the regulatory status of health entities, the mechanism of action of said therapies and general characteristics of each one is included. Innovative biotherapies that began to be implemented to face the pandemic are included. Conclusions: The coronavirus pandemic has driven the international health system to the test, to provide solutions both from the diagnosis, prevention and treatment of the population to reduce the mortality of patients. This obviously also included the area of Biotechnology applied to health, which has contributed in the three aspects mentioned. The present work focuses on the therapeutic responses that it has provided and that are commercialized or in clinical phases. (AU)

Review Covid-19 (sars-cov-2) and medicinal plants ­ literature / Revisão Covid-19 (sars-cov-2) e plantas medicinais - literatura / Revisión Covid-19 (sars-cov-2) y plantas medicinales - bibliografía

In December 2019, a new coronavirus originating from the city of Wuhan in China started an epidemic that brought many countries into chaos and despair. SARS-CoV-2, as identified, gave rise to the severe acute respiratory syndrome called COVID-19. Its transmission happens through droplets of saliva, hand or contaminated surfaces. Since its discovery, COVID-19 has led many to death, therefore, researchers from around the world have joined efforts to develop strategies to contain the virus. In this race, drugs such as Chloroquine and Hydroxychloroquine have become possible options for showing an antiviral effect, however, studies contest their efficiency, generating uncertainties. Therefore, other alternatives have been investigated in this context, and the study of medicinal plants has been the target of research for the treatment of COVID-19 in search of bioactive natural products that can exert an antiviral action. The study aimed to analyze the published literature on COVID-19 (SARS-CoV-2) and its relationship with medicinal plants. Bibliographical survey. So far, no specific treatment against the disease has been found, only supportive, with drugs that aim to improve the individual's immune system and ensure that the virus does not replicate, for example, there are options such as chloroquine, hydroxychloroquine, remdesivir and convalescent plasma. On the other hand, studies have revealed that medicinal plants such as garlic, among others, showed efficiency in modulating proteins with a view to preventing viral replication and improving immunity against COVID-19. So far, there are no drugs that are completely safe and have been shown to have activity against the new coronavirus (SARS-CoV-2). However, medicinal plants can contribute to the development of specific therapies against SARS-CoV-2 in a safe and effective way.

Em dezembro de 2019, um novo coronavírus originário da cidade de Wuhan, na China, iniciou uma epidemia que levou muitos países ao caos e ao desespero. O SARS-CoV-2, conforme identificado, deu origem à síndrome respiratória aguda grave chamada COVID-19. Sua transmissão acontece através de gotículas de saliva, mãos ou superfícies contaminadas. Desde sua descoberta, o COVID-19 levou muitos à morte, por isso, pesquisadores de todo o mundo uniram esforços para desenvolver estratégias para conter o vírus. Nesta corrida, medicamentos como Cloroquina e Hidroxicloroquina tornaram-se opções possíveis por apresentarem efeito antiviral, porém, estudos contestam sua eficiência, gerando incertezas. Portanto, outras alternativas têm sido investigadas nesse contexto, e o estudo de plantas medicinais tem sido alvo de pesquisas para o tratamento da COVID- 19 em busca de produtos naturais bioativos que possam exercer ação antiviral. O estudo teve como objetivo analisar a literatura publicada sobre COVID-19 (SARS-CoV-2) e sua relação com plantas medicinais. Levantamento bibliográfico. Até o momento, não foi encontrado nenhum tratamento específico contra a doença, apenas de suporte, com medicamentos que visam melhorar o sistema imunológico do indivíduo e garantir que o vírus não se replique, por exemplo, há opções como cloroquina, hidroxicloroquina, remdesivir e convalescença plasma. Por outro lado, estudos revelaram que plantas medicinais como o alho, entre outras, mostraram eficiência na modulação de proteínas visando prevenir a replicação viral e melhorar a imunidade contra a COVID-19. Até o momento, não existem medicamentos completamente seguros e que tenham demonstrado atividade contra o novo coronavírus (SARS-CoV-2). No entanto, as plantas medicinais podem contribuir para o desenvolvimento de terapias específicas contra o SARS-CoV-2 de forma segura e eficaz.

En diciembre de 2019, un nuevo coronavirus originario de la ciudad de Wuhan, en China, inició una epidemia que sumió a muchos países en el caos y la desesperación. El SARS-CoV- 2, tal y como fue identificado, dio lugar al síndrome respiratorio agudo severo denominado COVID-19. Su transmisión se produce a través de gotitas de saliva, de las manos o de superficies contaminadas. Desde su descubrimiento, el COVID-19 ha llevado a muchos a la muerte, por lo que investigadores de todo el mundo han aunado esfuerzos para desarrollar estrategias de contención del virus. En esta carrera, fármacos como la Cloroquina y la Hidroxicloroquina se han convertido en posibles opciones por mostrar un efecto antiviral, sin embargo, los estudios refutan su eficacia, generando incertidumbres. Por lo tanto, otras alternativas han sido investigadas en este contexto, y el estudio de las plantas medicinales ha sido el objetivo de la investigación para el tratamiento de COVID-19 en busca de productos naturales bioactivos que puedan ejercer una acción antiviral. El estudio tuvo como objetivo analizar la literatura publicada sobre el COVID-19 (SARS-CoV-2) y su relación con las plantas medicinales. Estudio bibliográfico. Hasta el momento, no se ha encontrado un tratamiento específico contra la enfermedad, sólo de soporte, con fármacos que buscan mejorar el sistema inmunológico del individuo y asegurar que el virus no se replique, por ejemplo, existen opciones como la cloroquina, hidroxicloroquina, remdesivir y plasma convaleciente. Por otro lado, estudios han revelado que plantas medicinales como el ajo, entre otras, mostraron eficacia en la modulación de proteínas con vistas a impedir la replicación viral y mejorar la inmunidad contra el COVID-19. Hasta el momento, no existen medicamentos que sean completamente seguros y que hayan demostrado tener actividad contra el nuevo coronavirus (SARS-CoV-2). Sin embargo, las plantas medicinales pueden contribuir al desarrollo de terapias específicas contra el SARS-CoV-2 de forma segura y eficaz.

Therapeutics and COVID-19: living guideline - 16 September 2022

The WHO Therapeutics and COVID-19: living guideline contains the Organization's most up-to-date recommendations for the use of therapeutics in the treatment of COVID-19. The latest version of this living guideline is available in pdf format (via the 'Download' button) and via an online platform, and is updated regularly as new evidence emerges. This twelfth version of the WHO living guideline now contains 19 recommendations. This latest update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers and Janus kinase (JAK) inhibitors in patients with severe or critical COVID-19, and modifies previous recommendations for the neutralizing monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe COVID-19.

Experiencia en cirugía de condilomas anales en mayores de 15 años / Experience in anal condyloma surgery in patients older than 15 years

Resumen Objetivo: Describir la experiencia en cirugía electiva de condilomas anales en pacientes mayores de 15 años en un hospital terciario de la Región Metropolitana. Material y Método: Estudio observacional retrospectivo y descriptivo, en el cual se analizan las intervenciones quirúrgicas electivas realizadas entre 2008 a 2021. Resultados: Dentro del período analizado se obtuvo 165 cirugías de condilomas anales, lo que corresponde a 137 pacientes en total. El 85% de los pacientes son de sexo masculino, el 68% de los pacientes son VIH positivo, un 87% de los pacientes MSM (hombres que tienen sexo con otros hombres) son VIH positivo, el 34% de los pacientes tiene antecedente de ETS, el 46% de los pacientes recibió terapia tópica como tratamiento preoperatorio o posoperatorio. Un 25% de los pacientes presenta recidiva en su historia personal, un 21% de los pacientes presenta lesiones anales intraepiteliales de alto grado, un 6% presenta carcinoma escamoso infiltrante. No hubo mortalidad descrita. Discusión: El presente estudio, describe la experiencia en cirugía de condilomas de un hospital terciario de la Región Metropolitana de Chile, cuya población corresponde a un estrato socioeconómico medio y bajo. Se logra describir a la población que es intervenida de condilomas acuminados, además de sus resultados quirúrgicos precoces y a largo plazo. Conclusión: El presente estudio, presenta una población de 137 pacientes operados de condilomas anales, a partir de los hallazgos de la cirugía. Se cumple el objetivo del estudio de caracterizar en un período de 12 años los resultados quirúrgicos de dicha serie, algo no reportado previamente en la literatura chilena.

Objective: To describe the experience in elective surgery for anal condylomas in patients over 15 years of age in a tertiary hospital in the Metropolitan Region. Materials and Method: Retrospective and descriptive observational study about elective surgical interventions performed between 2008 to 2021. Results: Within the analyzed period, 165 anal warts surgeries were obtained, corresponding to 137 patients. 85% of the patients are male, 68% are HIV positive, 87% of the MSM patients are HIV positive, 34% of the patients have a history of STDs, 46% of the patients received topical therapy as preoperative or postoperative treatment. 25% present recurrence in their personal history, 21% present high-grade anal intraepithelial lesions, 6% present infiltrating squamous carcinoma. There was no reported mortality. Discussion: The present study describes the experience in condyloma surgery in a tertiary hospital in the Metropolitan Region of Chile, whose population corresponds to a medium and low socioeconomic stratum. It is possible to describe the population that undergoes surgery for this reason, in addition to its early and long-term surgical results. Conclusion: The present study presents a population of 137 patients operated on for anal condylomas, based on the findings of the surgery. The objective of the study to characterize the surgical results of this series over a 12-year period is fulfilled, something not previously reported in the Chilean literature.

Remdesivir para el tratamiento de pacientes con COVID-19: (3 de junio de 2022) / Remdesivir for the treatment of patients with COVID-19: (June 3, 2022)

INTRODUCCIÓN: El remdesivir fue evaluado originalmente en ensayos clínicos para abordar el brote de virus del ébola en 2014.(13) Con la demostración de que remdesivir poseía una amplia actividad contra otros virus de ARN, incluidos los coronavirus, múltiples grupos evaluaron su actividad antiviral in vitro como in vivo en otras indicaciones. Posteriormente, se confirmó su actividad antiviral contra los coronavirus zoonóticos MERS, así como los coronavirus humanos circulantes HCoV-OC43 y HCoV-229E, agentes causantes del resfriado común.(14) Recientemente, también ha demostrado su actividad in vitro frente al SARS-CoV-2.(15) En un modelo de macaco Rhesus con infección por SARS-CoV-2 donde el tratamiento con remdesivir se inició poco después de la inoculación, los animales tratados con este fármaco presentaron niveles de virus más bajos en los pulmones y menos daño pulmonar respecto a los animales de control. Aunque este modelo animal no representa la enfermedad grave observada en algunos pacientes con COVID-19, se tomaron estos hallazgos como una posibilidad biológica para iniciar estudios clínicos con este fármaco antiviral en pacientes con COVID-19. OBJETIVO: El objetivo del presente informe es evaluar parámetros de eficacia, seguridad, conveniencia y recomendaciones disponibles acerca del empleo de remdesivir para el tratamiento de pacientes con COVID-19 en Argentina. MÉTODOS: Efectos en la Salud: Teniendo en cuenta la velocidad con la que la información relacionada a la pandemia aparece y se modifica, se desarrolló un protocolo sustentado en proyectos que resume activamente la evidencia científica a medida que la misma se hace disponible. Con este fin se utilizó la plataforma L- ove de Epistemonikos https://app.iloveevidence.com/topics para identificar revisiones sistemáticas "vivas". Se seleccionaron aquellas con una calidad metodológica apropiada evaluada a través de la herramienta AMSTAR-2, y que a su vez llevaran un proceso de actualización frecuente. De cada una de las revisiones sistemáticas identificadas se extractaron los efectos de la intervención sobre los desenlaces priorizados como importantes o críticos y la certeza en dichos efectos. Para la priorización de los desenlaces se adoptó una perspectiva desde el paciente considerando sus potenciales preferencias. La selección se realizó por consenso entre los autores y supervisores del informe considerando los resultados de múltiples ejercicios de priorización publicados, realizados en el marco del desarrollo de distintas guías de práctica clínica. Implementación: Este dominio contempla dos subdominios: la existencia de barreras y facilitadores en nuestro contexto para la implementación de la tecnología evaluada no consideradas en los otros dominios analizados, y los costos comparativos en relación con otras intervenciones similares. Con el objetivo de emitir un juicio de valor sobre la magnitud de dichos costos, en pacientes hospitalizados se utilizó como comparador al tratamiento con dexametasona, que ha demostrado ser una intervención accesible y de beneficios importantes en el contexto analizado. Recomendaciones: Para la identificación de recomendaciones sustentadas en evidencia y actualizadas, se utilizó la plataforma COVID recmap. Se seleccionaron aquellas guías con rigor metodológico apropiado según la herramienta AGREE II (> 70%) y se incorporaron sus recomendaciones al informe. RESULTADOS: Se identificaron tres revisiones sistemáticas que cumplieron con los criterios de inclusión del presente informe y reportaron resultados: Las revisiones sistemáticas identificadas incluyeron 12 estudios aleatorizados para remdesivir en COVID19 que aleatorizaron un total de 9869 pacientes. Los resultados de 12 ECCA, incluyendo los resultados finales del ensayo SOLIDARITY, muestran que, en pacientes hospitalizados con COVID-19 y enfermedad de moderada a crítica, el remdesivir probablemente reduce la mortalidad y la necesidad de ventilación mecánica invasiva, y podría mejorar el tiempo de resolución de los síntomas. La certeza de la evidencia fue clasificada como moderada debido a la imprecisión. En pacientes con enfermedad leve de comienzo reciente, el remdesivir podría reducir las hospitalizaciones, pero la certeza de la evidencia es baja también por imprecisión. Adicionalmente, existe información sobre la efectividad in vitro de remdesivir frente a las diferentes variantes de SARS-CoV-2. Esta información se encuentra disponible en OpenData Portal, que condensa lo reportado por conjunto priorizado de publicaciones (preprints y artículos revisados por pares). resultados muestran que remdesivir podría tener una efectividad similar frente a las nuevas variantes del SARS-CoV-2, incluida Omicrón y subvariantes (B.1.1.529; BA.1.1; BA.1; BA.1 [+Q493K]; BA.2; B.1.1.529 [+F694Y] en comparación de las variantes predominantes al momento de realizarse los estudios. CONCLUSIONES: El cuerpo de la evidencia disponible, muestra que en pacientes con enfermedad leve o de reciente comienzo y factores de riesgo para progresión a enfermedad severa, remdesivir podría disminuir las hospitalizaciones y podría aumentar la velocidad para la mejoría clínica y resolución de los sintomas. Sin embargo, la magnitud de la reducción solo resulta importante (mayor a 1%) para pacientes sin esquema de vacunación completo o con riesgo de respuesta inmune inapropriada. En pacientes hospitalizados con enfermedad severa en cambio, el remdesivir probablemente reduce la mortalidad y la necesidad de ventilación mecánica invasiva y podría mejorar el tiempo de resolución de los síntomas, sin aumentar los eventos adversos sérios. A pesar que remdesivir se encuentra autorizado para su comercialización en Argentina, existen algunas situaciones que podrían constituir barreras para el acceso. La vía de administración endovenosa podría no ser aceptada en personas con enfermedad leve. Además, el costo del tratamiento es muy elevado y existe una extensa población objetivo para la aplicación de este tratamiento, que podrían constituir también barreras de acceso. Las guías sugieren el tratamiento con remdesivir condicionado a aquellos pacientes no graves con mayor riesgo de hospitalización. También sugieren en forma condicional utilizar remdesivir en pacientes hospitalizados que requieren oxígeno y recomiendan fuertemente no utilizar en adultos hospitalizados con COVID-19 que requieran ventilación no invasiva o invasiva. En el contexto de América Latina y el Caribe, se sugirió que cada país debe evaluar la decisión de su uso con base en los recursos disponibles, la factibilidad de su implementación, el acceso, los factores específicos del paciente (p. ej., la duración de los síntomas, el funcionamiento renal, las interacciones farmacológicas), la cobertura de vacunación y la forma de administración. También, es importante que se determine la capacidad de los servicios para poder administrar los medicamentos y considerar el tiempo adecuado para su uso.