[Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy].

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

[Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection].

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

[Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study].

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.

[Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022)].

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.

[Analysis of change in esophageal varices and clinical characteristics in hepatitis B virus-related cirrhosis after antiviral therapy].

Objective: To clarify the effect and related factors of antiviral therapy on the change of esophageal varices in patients with hepatitis B virus-related cirrhosis. Methods: Fifty-two cases with hepatitis B virus-related cirrhosis who underwent endoscopy before and after antiviral therapy were selected from prospective cohorts. Patients were divided into three groups: no, mild, and moderate-severe based on the degree of esophageal varices. The changes in the severity of esophageal varices in each group were compared after antiviral therapy. Clinical characteristics (platelet, liver and kidney function, liver stiffness, and virological response) of patients with different regressions were analyzed. Measurement data were analyzed by independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test, and Chi-Square test was used for count data. Results: All patients received entecavir-based antiviral therapy. The median treatment time was 3.1 (2.5-4.4) years. The proportion of patients without esophageal varices increased from 30.8% to 51.9%, the proportion of mild esophageal varices decreased from 40.4% to 30.8%, and the proportion of patients with moderate-to-severe esophageal varices decreased from 28.8% to 17.3% (χ2=14.067, P=0.001). A total of 40.4% of patients had esophageal varices regression, and 13.5% had esophageal varices progression. The progression rate was significantly higher in patients with moderate-severe esophageal varices than patients with mild and no esophageal varices (χ2=28.126, P<0.001), and 60.0% of patients with moderate-severe esophageal varices still remained in moderate-severe state after antiviral treatment. Baseline platelet count and 5-year mean change rates were significantly lower in patients with progressive moderate-to-severe esophageal varices than in those without progression (+3.3% vs. +34.1%, Z=7.00, P=0.027). Conclusion: After effective antiviral treatment, 40.4% of patients with hepatitis B virus-related cirrhosis combined with esophageal varices has obtained esophageal varices regression, but those with moderate to severe esophageal varices still have a considerable risk of progression while receiving mono antiviral treatment only. Thrombocytopenia and without significant improving are the clinical signs of progression risk after receiving antiviral treatment.

[Histological regression and clinical benefits in patients with liver cirrhosis after long-term anti-HBV treatment].

Objective: Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients. Methods: Treatment-naïve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis. Results: Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably (P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression (OR=0.887, 95%CI: 0.802-0.981, P=0.020). Conclusions: After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

[The relationship between adenovirus infection and severe acute hepatitis of unknown etiology].

Adenovirus infection can occur in all regions or countries of the world, with no obvious seasonality, but pandemics mostly occur in winter or early spring. Adenovirus infection is self-limited among immunocompetent host with supportive care, however fatal infection can occur among immunocompromised patients, mainly affecting respiratory, gastrointestinal tract and adjunctiva and very rarely causing hepatitis, cholecystitis, pancreatitis, hemorrhagic cystitis, myocarditis, meningitis or encephalitis. Adenovirus hepatitis mainly occur in malignant tumors or organ transplantation patients, but acute severe hepatitis can occur even in immunocompetent children or adults. On 5 April 2022, WHO was notified of 10 cases of severe acute hepatitis of unknown etiology in children. As of 21 April 2022, at least 169 cases of acute hepatitis of unknown origin have been reported from 12 countries (including 11 WHO European Region countries and the United States). Adenovirus has been detected in at least 74 cases; SARS-CoV-2 was identified in 20 cases of those that were tested. Furthermore, 19 were detected with a SARS-CoV-2 and adenovirus co-infection. At present, the etiology has not been fully elucidated. The leading hypotheses center around adenovirus, and the relationship with SARS-CoV-2 needs to be further ruled out.

[Self-awareness rate and its influencing factors of their infection status among hepatitis B surface antigen-positive persons aged 15-69 years in China].

Objectives: To understand the awareness rate and its influencing factors of their HBV infection status among HBsAg-positive persons aged 15-69 years in China. Methods: A cross-sectional design was used to conduct a questionnaire survey on the awareness of their infection status among HBsAg-positive persons aged 15-69 years who were identified in the 2020 national hepatitis B seroepidemiology survey. The awareness rate of the whole respondent and respondents with different characteristics were described, and the differences were compared with the χ2 test. The logistic regression model was used to analyze the factors influencing the awareness rate. Results: The overall awareness rate among the respondents was 43.10% (1 828/4 241). The awareness rate was lower in males than in females (41.30% vs. 44.65%). The awareness rate was lower in the 60-69-years-old age group than in other age groups (30.38% vs. 36.77%-57.58%). The awareness rate was lower in rural areas than in urban areas (39.43% vs. 47.32%). The awareness rate was lower in regions with a per capita gross domestic product (GDP) below RMB 54 000 than in regions with a per capita GDP of RMB 54 000 and above (36.81% vs. 41.61%-50.30%). The awareness rate was lower in respondents without other liver diseases than with other liver diseases (41.52% vs. 60.68%). The awareness rate was lower in respondents without a family history of hepatitis B-related disease or unknown family history than with a family history (43.58% vs. 68.26%; 24.71% vs. 68.26%). Multivariate logistic regression analysis showed that male [odds ratio (OR)=0.841, 95% confidence interval (CI): 0.734-0.964], high school and below [primary school and below, junior middle school, high school/technical secondary school, OR (95%CI): 0.247 (0.190-0.321), 0.451 (0.352-0.577), 0.634 (0.486-0.827)], rural areas (OR=0.822, 95%CI: 0.715-0.945) and regions with a per capita GDP below RMB 80 000 [54 000-80 000, OR (95%CI): 0.810 (0.688-0.954), below RMB 54 000, OR (95%CI): 0.793 (0.669-0.941)] were the negative factors influencing the awareness rate. While 30-39-years-old (OR=2.089, 95%CI: 1.626-2.683) and 40-49-years-old (OR=1.590, 95%CI: 1.250-2.023) age groups, with other liver diseases (OR=2.244, 95%CI: 1.754-2.871) and family history related to hepatitis B (OR=2.688, 95%CI: 2.242-3.223) were the positive factors influencing the awareness rate. Conclusion: The overall awareness rate of their infection status among HBsAg-positive persons aged 15-69 years is 43.10% in China. Health promotion and coverage expansion on HBV screening should be further strengthened to achieve the proposed World Health Organization's target of 90% HBV infection diagnosis rate by 2030.

[Paying attention to other systemic diseases of hepatic manifestations: a return to common sense in clinical practice].

Liver have complex functions with a high workload. Various liver diseases are the result of the interaction of diverse genetic and environmental factors. Moreover, other systemic diseases may also affect liver, producing corresponding manifestations, such as abnormal liver function tests, portal vein or hepatic vein thrombosis, portal hypertension, hepatosplenomegaly and liver space-occupying lesions. Therefore, it is extremely important for hepatologists to have an in-depth understanding of other systemic diseases of hepatic manifestations, especially hematologic, connective tissue, endocrine, and circulatory, in order to improve the level of clinical diagnosis and treatment.

[Liver involvement in endocrine diseases].

As a secondary endocrine organ, the liver is closely related to the endocrine system. Liver involvement is not uncommon in endocrine diseases, such as hyper/hypothyroidism, diabetes, dysfunction of adrenal and gonadal. It can be manifested in a variety of forms, including hepatocyte injury (elevated transaminase), bile duct injury (cholestasis), hepatocyte steatosis, vascular injury and liver tumor. Direct and indirect liver injury caused by abnormal hormone levels and side effects of drugs for the treatment of endocrine diseases are common pathogenesis. In addition, endocrine diseases can be concomitant with liver diseases, such as autoimmune thyroiditis and autoimmune hepatitis. Systemic diseases can also involve the endocrine system and liver at the same time, such as systemic lupus erythematosus and IgG4 related diseases. For patients with unexplained liver injury, endocrine system diseases should be considered as the differential diagnosis.

[Hepatic manifestations of hematological diseases].

Liver involvement is often observed in hematological disorders, resulting in liver abnormality, including unconjugated hyperbilirubinemia, monoclonal hyperglobulinemia, portal vein, or hepatic vein thrombosis or portal hypertension, hepatosplenomegaly, or iron accumulation in the liver. Here we summarize the major hematological diseases that often affect the liver: hemolytic anemia, defect in coagulation or anti-coagulation factors, myeloproliferative neoplasm, hemophagocytic lymphohistiocytosis, multiple myeloma, leukemia, and lymphoma. We hope this review will help clinicians diagnose and manage the patients with liver involvement by hematological disorders.

[Connective tissue diseases and the liver injury].

Connective tissue disease (CTD) are closely related to liver abnormality. CTD can affect the liver causing various degrees of liver injury, coexist with other liver diseases, especially autoimmune liver disease (ALD). Medications for CTD can also lead to liver injury or reactivate the hepatitis B virus. CTD patients can also be positive for ALD-related autoantibodies without corresponding manifestation; and vis versa. The diagnosis and differential diagnosis should be made on integrating clinical presentation, laboratory, imaging, and histological studies, not solely relying on autoantibody positivity.

[Liver manifestation of circulatory disorders].

The liver is abundant in blood supply and receives 25% of the cardiac output via the hepatic artery and portal vein. Circulatory disorders may cause hepatic injury, resulting in congestive hepatopathy(CH) and ischemic hepatitis(IH). Hepatic congestion arising from increased hepatic venous pressure and decreased cardiac output is the common pathophysiological basis of both CH and IH. In addition, extensive arteriovenous shunts affect portal pressure and cardiac function, leading to alterations of hepatic blood supply. The current review summarizes the pathophysiology, clinical manifestations and therapeutic interventions of the above diseases, in order to provide reference for clinical practice.

[Truth-seeking and innovation for the academic excellence].

The Chinese Journal of Hepatology has a 2020 core impact factor of 1.807, which position it first among the periodicals of gastroenterology. The China Association for Science and Technology classified it as T1 grade and included in the catalogue of high-level scientific and technological periodicals. Since 2021, it has received the special publishing fund of the Chongqing Municipal Bureau of Press and Publications, the High-quality Scientific and Technological Periodicals Funding Project of Chongqing Association for Science and Technology, and the Industry-university-research Cooperation and Collaborative Education Project of the Ministry of Education of the People's Republic of China and won many awards such as "Sichuan-Chongqing First-class Scientific and Technological Periodical" and "Chongqing High-quality Scientific and Technological Periodical", thereby ensuring the development of both qualitative and quantitative effects. Therefore, in 2022, we will work on attracting high-impact research reports, disseminate the academic results timely, efficiently and accurately, highlight the role of digital communication, and pave the way for the establishment of it as a first-class academic journal.

[Noninvasive assessment of the risk of esophageal variceal bleeding from noncirrhotic portal hypertension].

Objective: To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH). Methods: 111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results: Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively (P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 (P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups (P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively (P<0.05). Conclusion: Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.