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.

Strengthening the study of chronic hepatitis E / 中华肝脏病杂志

This paper summarizes the incidence, modes of transmission, diagnosis, treatment and prevention of chronic hepatitis E.

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.

Expanding the treatment of chronic hepatitis B / 临床肝胆病杂志

Among chronic hepatitis B patients eligible for treatment, only 5% have received antiviral therapy worldwide. The strictness of treatment criteria in current guidelines is one of the contributing factors for the low treatment rate of patients with chronic hepatitis B, and expanding the treatment criteria for chronic hepatitis B established in current guidelines may reduce disease burden. Universal hepatitis B vaccination, universal screening, and treatment of all HBV DNA-positive patients will help to achieve the goal of HBV elimination by 2030 proposed by the World Health Organization.

Debates on the natural history of chronic hepatitis B virus infection during the update of Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version) / 临床肝胆病杂志

This article introduces the debates on the natural history of chronic hepatitis B virus (HBV) infection during the update of Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version), including nomenclature and definition, HBV infection, HBV DNA threshold for patients in the immune-tolerant phase, indeterminate phase and natural history, clinical diagnosis and natural history, and HBV DNA threshold for patients in the inactive phase.

Further discussion on the antiviral treatment of chronic hepatitis B patients with indeterminate phase / 临床肝胆病杂志

This paper discusses further on the antiviral treatment of chronic hepatitis B patients with indeterminate phase. These patients have a high proportion of significant necroinflammation and fibrosis in the liver， and a higher risk of disease progression compared with those with true HBeAg－positive chronic hepatitis B virus （HBV） infection （formerly called the immune tolerance phase） or HBeAg－negative chronic HBV infection （formerly called the immune control phase）. Antiviral therapy may reduce the risk of HBV－related hepatocellular carcinoma in chronic hepatitis B patients with indeterminate phase.

Comprehensive treatment of acute Stanford type A aortic dissection with limb malperfusion / 中华胸心血管外科杂志

Objective:To explore different strategies of central repair first or malperfusion first to treat type A aortic dissection complicated with limb malperfusion.Methods:From January 2020 to December 2021, 302 patients were diagnosed with acute type A aortic dissection, and 17 consecutive patients were diagnosed as type A acute aortic dissection complicated with limb malperfusion and underwent Sun’s procedure. There were 16 males and 1 female with an average of(52.6±4.2)years. Surgical strategies were as follows: immediate central repair-Sun’s procedure in 14 patients, endovascular stenting followed by central repair in 3 patients, endovascular stenting after central repair in 1 patient.Results:The incidence rate of limb malperfusion of acute Stanford A aortic dissection was 5.6%(17/302). Average extracorporeal circulation time was(271.8±38.9)min, average aortic cross-clamp time was (186.3±31.8)min, and the average circulatory arrest time was (48.75±11.3)min. Early mortality rate was 17.6%(3/17). Two patients were left hospital voluntarily because of cerebral infarction. One patient underwent leg incision osteofascial compartment syndrome and discharged unevently. Five patients underwent continuous renal replacement therapy and hemoperfusion. Follow-up results showed that patients with serious limb malperfusion have symptoms of nerve dysfunction including amyosthenia and sensory disturbance, but recovered gradually with rehabilitation.Conclusion:Sun’s procedure is safe and feasible for type A acute aortic dissection complicated with mild limb malperfusion. For serious limb malperfusion, endovascular stent followed by Sun’s procedure is a good choice with CRRT and hemoperfusion.

An investigation of hepatitis D virus infection among patients with chronic hepatitis B virus infection in some regions of China / 临床肝胆病杂志

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

The research on hepatitis D should be taken seriously / 临床肝胆病杂志

Hepatitis D virus (HDV) infection is an important health problem around the world. The epidemiology of HDV infection has been changed significantly over the past 10 years due to widespread hepatitis B vaccination and human migration. HDV infection can manifest as co-infection or superinfection. Patients with HBV/HDV co-infection have a significantly higher risk of liver cirrhosis and hepatocellular carcinoma than those with HBV infection alone. Research and development are being conducted for new therapeutic drugs for hepatitis D, some of which have entered phase Ⅲ clinical trials. These drugs will replace the current therapies with lower efficacy.

Clinical symptoms and imaging findings of cervical instability in young adult / 中国骨伤

OBJECTIVE@#To explore clinical symptoms and X-ray imaging features of cervical instability in young adult represented by postgraduates with a master's degree in medicine.@*METHODS@#Totally 91 postgraduates with a master's degree in medicine were investigated from September to December 2021, including 45 males and 46 females;aged from 22 to 30 years old with an average of (25.30±2.18) years old. The cervical spondylosis-related discomfort symptoms of the subjects were collected and examined by the examiner for neck and shoulder tenderness point examination and cervical vertebra positive and lateral and functional X-ray radiography. According to the results of X-ray examination, the subjects were divided into stable cervical group and unstable cervical group.@*RESULTS@#Among 91 subjects, there were 50 patients with cervical instability, accounting for 54.90% of total number of subjects. The cervical curvature was abnormal in 78 patients, accounting for 85.70% of total number of subjects. Among 50 patients with cervical instability, 50 patients were diagnosed as cervical instability on the basis of angular displaxement(AD)≥ 11 °, including 13 cases of C3,4 instability, 30 cases of C4,5 instability and 7 cases of C5,6 instability;and 5 cases were diagnosed as cervical instability based on horizontal displacement(HD)≥ 3.5 mm, including 1 case of C3,4 instability and 4 cases of C4,5 instability. Compared with stable cervical group, the number of discomfort symptoms of neck pain, headache and shoulder pain in instability group was significantly higher than that of in stable cervical group(P<0.05);and the number of tenderness in spinous process space of C4,5 and C5,6, 2 cm adjacent to the spinous process of C2-C5 and the superior angle of the scapula (the stop point of levator scapulae) in the instability group was significantly higher than that in the stable cervical group (P<0.05);and the cervical curvature in the instability group was significantly lower than that in stable cervical group(P<0.05).@*CONCLUSION@#The incidence of cervical instability in young adult represented by postgraduates with a master's degree in medicine is high, they are mainly diagnosed as cervical instability on the basis of vertebral angular displacement ≥ 11°, and the instability segments are concentrated on C3,4, C4,5 and C5,6 segments, the occurrence of cervical instability is often accompanied by abnormalities of cervical curvature. Most of clinical manifestations are head, neck and shoulder pain, especially neck pain in unstable segment.

Clinical application of serum Golgi protein 73 in patients with chronic liver diseases / 中华肝脏病杂志

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.

Urgent scientific issues to be solved in clinical trials of capsid assembly modulator combined with nucleos(t)ide analogues for the treatment of chronic hepatitis B / 临床肝胆病杂志

Chronic hepatitis B virus (HBV) infection is the main cause of viral hepatitis, liver cirrhosis, and primary liver cancer. At present, nucleos(t)ide analogues (NUC) and pegylated interferon α used in clinical practice cannot directly target covalently closed circular DNA, and it is difficult to achieve clinical cure of chronic hepatitis B patients; therefore, it is urgently needed to develop direct-acting antiviral agents targeting all stages of the HBV replication cycle. Capsid assembly modulator (CpAM) targets the assembly of viral capsids through various mechanisms, thereby exerting a direct-acting antiviral effect. Its combination with NUC should have a good synergistic antiviral effect, but the results of existing clinical trials have shown that chronic hepatitis B patients who received a limited course of antiviral therapy with CpAM and NUC all experienced off-therapy viral rebound. Based on the mechanism of action of these two types of drugs, this article provides a reasonable explanation for the above clinical trial results and points out that a longer course of antiviral therapy with CpAM and NUC may be needed in the future clinical trials with safe drug withdrawal as the end point of observation, so as to deplete or silence the pool of covalently closed circular DNA and increase the possibility of safe drug withdrawal in CHB patients. In addition, further studies are needed to explore antiviral therapeutic strategies with a combination of multiple targets.

Effect of the change in antiviral therapy indication in increasing the treatment rate of chronic hepatitis B / 临床肝胆病杂志

Objective To investigate the impact of the change in anti-hepatitis B virus (HBV) therapy indication on treatment rate and the features of the population requiring treatment. Methods The treatment-naïve patients with chronic hepatitis B (CHB) in the China Registry of Hepatitis B (CR-HepB) database were selected as subjects, and related demographic, virological, hematological, and biochemical data were collected. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results A total of 3640 treatment-naïve CHB patients were included in this study, among whom 64.4% were male, 68.7% had an age of 30-59 years, and 46.8% had an indeterminate clinical stage. According to the 2015 and 2019 editions of Guidelines for the prevention and treatment of chronic hepatitis B and the 2022 edition of expert consensus, the number of patients who had the indication for antiviral therapy was 625(17.2%), 1333(36.6%), and 2890(79.4%), respectively. The number of patients requiring treatment was increased by 1557 according to the 2022 edition of expert consensus, among whom 1424(91.5%) met the treatment threshold of alanine aminotransferase (ALT) > 30 U/L for male patients or ALT > 19 U/L for female patients. The additional patients requiring treatment according to the 2022 edition of expert consensus had significantly higher levels of ALT and HBV DNA and significantly lower scores of APRI and FIB-4 than the additional patients requiring treatment according to the 2019 edition of Guidelines (all P < 0.05). Conclusion The expansion of antiviral therapy indications for CHB may significantly increase the proportion of CHB patients receiving antiviral treatment and help mild CHB patients at the risk of disease progression to receive timely treatment and achieve the improvement in long-term prognosis.

Clinical significance of determining the serum levels of large, middle, and small hepatitis B virus surface proteins / 临床肝胆病杂志

This article reviews the research advances in large, middle, and small hepatitis B virus (HBV) surface proteins, including their gene structures, characteristics, detection methods, and clinical significance. Up to now, the clinical significance of large, middle, and small HBV surface proteins remains unclear and requires further studies.

Are there only a few steps away from the prime time for hepatitis B virus RNA as a routine marker to guide decision making in treatment of chronic hepatitis B? / 临床肝胆病杂志

This paper discusses HBsAg and HBV RNA as routine markers to guide treatment decisions of chronic hepatitis B.

Why do patients with chronic hepatitis B virus infection develop hepatocellular carcinoma after HBsAg seroclearance? / 临床肝胆病杂志

This article summarizes the risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection after HBsAg seroclearance, as well as its mechanism and implications.

Clinical observation of chiropractic manipulation in the treatment of degenerative scoliosis / 中国骨伤

OBJECTIVE@#To observe clinical efficacy of chiropractic manipulation in the treatment of degenerative scoliosis (DS).@*METHODS@#From June 2017 to September 2019, 120 patients with degenerative scoliosis were randomly divided into treatment group (60 cases) and control group(60 cases). The patients in treatment group were treated with chiropractic manipulation once every other day for 4 weeks. The patients in control group were treated with eperisone hydrochloride tablets combined with thoracolumbar orthopedic(TSLO)brace, oral eperisone hydrochloride tablets 50 mg three times a day, wearing TSLO brace for not less than 8 hours a day. The course of treatment was 4 weeks. After the patients were selected into the group, visual analogue scale (VAS) and Oswestry Disability Index (ODI) were recorded before treatment, 1, 2, 3, 4 weeks after treatment and 1 month after treatment. The full length X-ray of the spine was taken before and 4 weeks after treatment, and the scoliosis Cobb angle, sagittal vertical axis (SVA) and lumbar lordosis (LL) were measured and compared. The adverse reactions during the treatment were recorded.@*RESULTS@#There were significant differences in VAS and ODI between two groups at each time point after treatment (P<0.001), VAS and ODI at 2 weeks after treatment (PVAS=0.025, PODI=0.032) and 3 weeks after treatment(PVAS=0.040, PODI=0.044) in treatment group were significantly different from those in control group, but there was no significant difference in VAS and ODI at other time points between treatment group and control group (P>0.05). There was significant difference in Cobb angle between treatment group(P=0.010) and control group(P=0.017) after treatment, but there was no significant difference in LL and SVA between treatment group and control group. There was no significant difference in Cobb angle, LL and SVA between two groups before and after treatment. During the treatment, there were 4 mild adverse reactions in the control group and no adverse reactions in the treatment group.@*CONCLUSION@#Chiropractic manipulation can effectively relieve pain and improve lumbar function in patients with degenerative scoliosis. The onset of action is faster than that oral eperisone hydrochloride tablets combined with TSLO brace, and it has better safety and can improve Cobb angle of patients with degenerative scoliosis.

Should chronic hepatitis B in the indeterminate phase be treated？ / 临床肝胆病杂志

This article discusses the definition of the indeterminate phase of chronic hepatitis B and summarizes the proportion of patients in the indeterminate phase of chronic hepatitis B among patients with chronic HBV infection, as well as their risk of hepatocellular carcinoma and related treatment recommendations.

Association between the alteration of serum N-glycan profile and the change of glycosyltransferase expression in liver tissue in patients with hepatitis B virus-related hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the potential mechanism of serum N-glycan alterations in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by measuring serum N-glycan profile and comparing glycosyltransferase gene expression between HCC tissue and adjacent tissue. MethodsThe samples of HCC tissue, adjacent tissue, and normal liver tissue were collected from 34 patients with HBV-related HCC who were admitted to Chinese PLA General Hospital, and serum samples were also collected. Among these 34 patients, 8 were randomly selected and their serum samples were established as HCC experimental group, and the serum samples of 20 healthy adults were established as control group. DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis was used to analyze serum N-glycan profile in the HCC experimental group and the control group. Quantitative real-time PCR was used to measure the mRNA expression of 8 glycosyltransferase genes (FUT3, FUT4, FUT6, FUT7, FUT8, Gn-TIII, Gn-TIVa, and Gn-TV) in the HCC tissue and adjacent tissue of 34 patients with HBV-related HCC, and Western blot was used to measure the expression of corresponding proteins. The independent samples t-test was used for comparison of continuous data between two groups. ResultsCompared with the control group, the HCC experimental group had a significant increase in the abundance of N-glycan peak9 (NA3Fb) in serum(t=-2.514,P＜0.05). There were significant differences in the mRNA expression of FUT8, Gn-TIVa, and Gn-TV between HCC tissue and adjacent tissue, and the mRNA and protein expression levels of FUT8 and Gn-TV in HCC tissue were significantly higher than those in adjacent tissue (FUT8 mRNA: 1.50±0.34 vs 0.65±0.11, t=-2.354，P=0.022; Gn-TV mRNA: 3.57±0.64 vs 1.33±016, t=-3.384,P=0001; FUT8 protein: 0.70±0.11 vs 0.083±0.017, t=9.555,P=0.001; Gn-TV protein: 1.33±0.19 vs 0.60±0.15, t=5.097,P=0.007). The mRNA expression level of Gn-TIVa in HCC tissue was significantly higher than that in adjacent tissue (2.90±0.47 vs 1.68±0.19, t=-2.403,P=0.019), but there was no significant difference in the protein expression level of Gn-TIVa between HCC tissue and adjacent tissue (052±0.24 vs 0.24±0.11,t=1.833, P=0.141). The changes of glycosyltransferase gene expression in HCC tissue were consistent with the alteration of serum N-glycan profile. ConclusionSerum N-glycan alterations in patients with HBV-related HCC may be closely associated with the upregulated expression of the glycosyltransferase genes FUT8, Gn-TIVa, and Gn-TV in HCC tissue.

Should patients in the immune tolerance stage of chronic hepatitis B virus infection be treated? / 临床肝胆病杂志

Major international guidelines have not yet reached a consensus on the definition of the immune tolerance stage of chronic hepatitis B virus infection; however, almost all guidelines do not recommend starting treatment for patients in the immune tolerance stage of chronic hepatitis B. This article discusses the latest evidence for the treatment of such patients to prevent liver cirrhosis and hepatocellular carcinoma.