Objective:To investigate the pathological characteristics in chronic HBV infection patients with different upper limits of alanine aminotransferase (ALT) normal values and the influencing factors of liver tissue injury.Methods:The clinical data of 667 chronic HBV infection patients with ALT<40 U/L and HBV DNA loads >30 IU/mL who received liver biopsy in Zhenhai District Hospital of Traditional Chinese Medicine and Hwa Mei Hospital from January 2014 to December 2020 were retrospectively analyzed. The enrolled patients were divided into ALTⅠ group (<30 U/L for males, <19 U/L for females), ALTⅡ group (≥30 U/L and <35 U/L for males, ≥19 U/L and <25 U/L for females) and ALT Ⅲ group (≥35 U/L and <40 U/L for males, ≥25 U/L and <40 U/L for females). According to the degree of liver inflammation (G) and fibrosis stage (S), the enrolled patients were divided into non-significant damage group (G<2 and S<2) and significant damage group (≥G2 or/and ≥S2). Ridit analysis was used to compare the G/S composition ratio among three ALT groups, Logistic regression was used to analyze the risk factors of liver injury, the receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to analyze the optimal diagnostic threshold of ALT.Results:There were significant differences in the composition ratio of G and S among the three ALT groups( χ2=13.926 and 14.702, both P<0.001). The constituent ratios of significant liver pathological damage in the three groups of ALT levels were 26.05% (99/380), 32.03% (41/128) and 46.54% (74/159), respectively( χ2=21.596, P<0.001). Multivariate logistic regression analysis showed that high white/globulin ratio and PLT counts( OR=0.246 and 0.986, both P<0.001)were the protective factors for liver tissue injury; while negative HBcAg staining and elevated ALT and GGT levels ( OR=3.797, 1.053 and 1.013, P<0.001 or <0.05) were the risk factors of liver injury. ROC curve demonstrated the ALT threshold of liver tissue damage in male and female patients were 25.6 U/L and 25.5 U/L. Conclusions:In chronic HBV infection patients with normal ALT, with the increase of ALT level, the degree of liver tissue pathological damage may become more severe. The study demonstrates that it is necessary to lower the ALT threshold for protecting patients from liver tissue pathological damage.

Objective:To establish and evaluate a new diagnostic model for significant liver tissue damage in patients with chronic hepatitis B virus (HBV) infection in the immune tolerance phase.Methods:The clinical data of 275 chronic HBV infection patients in the immune tolerance phase who underwent liver biopsy from January 2015 to November 2020 in the Hwa Mei Hospital, University of Chinese Academy of Sciences were included. According to the liver pathological changes, patients were divided into

Objective:To compare and analyze the clinicopathological features and significance for indications of different types of antiviral therapy in chronic hepatitis B (CHB).Methods:Clinical data of 861 CHB cases who received liver biopsy, had hepatitis B virus (HBV) DNA-positive (> 30 IU/ml) and met the indications for antiviral therapy from January 2014 to December 2019 were included. Liver pathological changes and their correlation with clinical characteristics were compared and analyzed. According to different data, t-test, analysis of variance, nonparametric test, χ2 test, Ridit and logistic regression analysis were used for statistical analysis. Results:Most of the cases (72.24%) had remarkable pathological damage. The degree of liver fibrosis was higher in the normal than the abnormal group ( P<0.001). 17.54% cases had hepatic steatosis. The vast majority of cases (97.33%) had positive hepatitis B surface antigen (HBsAg), while only 50.87% had positive hepatitis B core antigen (HBcAg). The positive correlation factors affecting the severity of liver histopathology were alkaline phosphatase level, while the negative correlation factors were positive HBcAg staining, albumin and platelet level. The degree of liver inflammation and fibrosis had statistically significant differences with different HBcAg staining levels ( χ2=44.142 and 102.386, respectively; P<0.001), and the severity was more apparent in the negative group. Conclusion:There exist differences in clinicopathological features for indications of different types of antiviral therapy in patients with CHB. Liver function test range is inconsistent with degrees of hepatic histological severity. The positive and intensity of liver tissue HBcAg staining, and albumin and alanine aminotransferase levels have negative correlation with disease severity.

The pathogen of COVID-19 is 2019-nCoV, which belongs to the beta coronavirus. Angiotensin-converting enzyme 2 (ACE2) is the receptor of 2019-nCoV as the same of SARS-CoV. Most of the severe patients were the elderly with underlying diseases, which may be related to the decrease in the number of naive T cells. In addition to pulmonary symptoms, COVID-19 can also cause multiple organ dysfunction and even multiple organ failure (liver, nervous system, heart, kidney, etc.). Pathogenic mechanisms such as direct virus invasion, cytokine storm, endothelial cells damage, and down-regulation of ACE2 may play important roles in the severity of the disease.

Objective:To analyze the liver pathology, clinical characteristics and influence factors in patients with chronic hepatitis B virus (HBV) infection in immune tolerant phase (IT).Methods:The clinical data of 273 patients in IT phase who underwent liver biopsy from January 2015 to December 2019 were included in this study. The correlation between liver pathological changes and clinical features was analyzed.Results:There were 43 cases (15.75%) with liver histologic activity ≥ G2, 30 cases (10.99%) with liver fibrosis ≥ S2, and 55 cases (20.15%) with liver pathology ≥ G2 and/or ≥ S2. A total of 17.95% patients had liver steatosis. The majority (98.17%) of tissue samples were positive for HBsAg staining, while only 79.49% were positive for HBcAg. The characteristics of liver pathology were comparable in men from women patients. The differences of G and S were not statistically significant according to different HBsAg positivity, while those were statistically significant according to different HBcAg positivity. By univariate and multivariate analysis, the independent risk factors of pathological severity were HBcAg intensity, HBeAg level, and age. However, the differences of liver histologic activity and fibrosis were not statistically significant between those younger than 30 years old group from those older than 30 years old, neither between those younger or older than 40. Although the diagnostic value of liver inflammation and fibrosis 5 (LIF-5) was better than that of aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis 4 score (FIB-4), three diagnostic models for predicting the pathological severity were not strong enough (all area under the curves<0.8). Only the specificity of LIF-5 for predicting≥ G2, ≥ G2 and/or ≥ S2 was over 80%.Conclusions:Approximately 20% patients with chronic HBV infection in IT phase have progressive liver inflammation or fibrosis. The intensity of liver HBcAg and HBeAg level are negatively correlated with the severity of disease. The diagnostic models or most clinical indicators have low predictive effect for chronic HBV infections in IT phase.

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the outbreak of COVID-19 in Wuhan. It is a kind of enveloped positive-strand RNA virus, belonging to the subgenus Sarbecovirus of the genus Betacoronavirus. It is similar to other viruses of the subgenus Sarbecovirus in genomic structure and closely related to the bat coronavirus (RaTG13), indicating that its natural host is likely to be bat, but the intermediate host is still controversial. SARS-CoV-2 infects host cells with angiotensin-converting enzyme 2 (ACE2) as a receptor. At present, SARS-CoV-2 has undergone some mutations. This article reviewed the current research situation and progress in the etiology of COVID-19.

Objective To analyze the heterogeneities of hepatitis B virus ( HBV ) reverse transcriptase domain (RT) gene mutations related to nucleos (t)ide analogues (NAs) resistance.Methods Blood samples from 2765 chronic hepatitis B patients with virological breakthrough or poor drug response treated in Ningbo No .2 Hospital and Ningbo Fourth Hospital from April 2011 to March 2018 were collected . According to the medication status , it was divided into LAM monotherapy group ( n =603 ) , LdT monotherapy group (n=147), ADV monotherapy group (n=68), ETV monotherapy group (n=10) and the sequential or combined drug resistance of NAs group (n=365).The resistance mutation sites and drug resistance patterns (pathways) of each group were analyzed .The SPSS 19.0 software was used to analyze the data.Results Among 2765 serum samples, the NAs-related HBV-RT resistance mutations were detected in 1193 cases with an overall mutation rate of 43.15％.The mutation rate of LAM monoclonal resistance group was 62.62％ (603/963) with 19 mutation types, the most common single point mutation was rtM204I/V (40.30％, 243/603).The mutation rate of LdT monoclonal resistance group was 45.51％(147/323), and there were 3 mutation types, with the single point mutation rtM204I/V being the most common (59.86％, 88/147).The mutation rate of the ADV monoclonal resistance group was 17.80％(68/382), mainly rtA181T single point mutation (64.71％, 44/68).The mutation rate of the ETV monoclonal resistance group was 4.06％(10/246), and the single point mutation of rtT184A/G/S/I/L/F was the most common one (80.00％, 8/10).The mutation rate of the sequential or combination therapy group was 41.91％ (365/871), among which the mutation rate of the LAM/LdT poor response or the resistance with the sequential ADV group was 63.39％(142/224), and the most single mutation point was rtA181V/T ( 35.21％, 50/142 );the mutation rate of LAM/LdT poor response or drug-resistant with combined ADV group was 42.19％ (54/128), and the most common mutation point was rtA181V/T (46.30％, 25/54);the mutation rate of LAM/LdT with poor response or resistance after sequential ETV 1.0 mg was 44.66％(117/262), and the most common mutation point was rtL180M+M204I/V+S202G/I (31.62％, 37/117);the LAM/LdT poor response or the drug-resistant ETV combined with ADV group had a mutation rate of 7.14％(5/70), all of which were multi-site mutations;the mutation rate of poor response to ADV or resistant with sequential ETV 0.5 mg group was 28.14％(47/167), all of which were multi-site mutations.Secondary ( compensation ) sites such as rtV173L, rtL180M, and rtV214A, and single-point mutations such as rtV207I/L/G, rtS213Tand rtN238T, which were not fully defined , were detected.The resistance patterns ( pathways ) of NAs monotherapy were relatively simple , and the resistance patterns ( pathways ) of NAs experienced patients ( sequential or combined treatment group ) were complex and diverse, and multiple resistance patterns (pathways) existed, along with NAs increasing in species.Non-first-line NAs-related resistance patterns ( pathways ) showed an overall downward trend sand ETV-related drug-resistant mutation showed an overall upward trend .Conclusion The NAs-related HBV resistance mutation sites ( patterns ) are complex and diverse , especially multi-site mutations , refractory drug resistance mutations, multidrug resistance mutations and cross-resistance mutations.Therefore, the optimization of antiviral treatment strategies and drug resistance management concepts need to be continuously updated .

Objective To investigate the intensity of HBsAg and HBcAg expression in liver tissue of patients with chronic hepatitis B virus (HBV) infection and its clinical significance.Methods A total of 994 HBV infected patients underwent liver biopsy and histopathological examination.The expression of HBsAg and HBcAg in liver tissue was detected by histoimmunochemistry.Patients were divided into HBeAg (+)/HBVDNA(+), HBeAg(-)/HBV DNA(+) and HBeAg(-)/HBV DNA(-) groups according to HBeAg and HBV DNA levels;patients were divided into ＜2 × normal (ULN) group, 2-＜5 × ULN groupand ≥5 × ULN group according to the alanine aminotransferase (ALT) levels.The histologic activity (A), fibrosis (F), the expression of HBsAg and HBcAg in liver tissue and their correlations with clinical features were analyzed.Logistic regression analysis was used to study the factors affecting the expression of HBsAg and HBcAg in liver tissue.Results Among 994 HBV infected patients, 941 cases (94.67％) were intrahepatic HBsAg positive and 553 cases (55.63％) were intrahepatic HBcAg positive;403 cases (40.85％) were ≥A2 in histologic activity and 371 cases (36.09％) were ≥F2 in fibrosis.The degree of A and F was the highest in HBeAg (-) / HBV DNA (+) group, followed by HBeAg (-) / HBV DNA (-) group, and was the lowest in HBeAg (+) / HBV DNA (+) group.The intensity of intrahepatic HBsAg expression was significantly different among three groups (x2 =6.299, r =-0.760, P ＜ 0.05), however, the difference was not showed in pairwise comparisons.The difference of intrahepatic HBcAg intensity among three groups was statistically significant (x2 =282.995, r =-0.645, P ＜ 0.01), the intensity was the highest in HBeAg (+) / HBV DNA (+) group and the lowest in HBeAg (-) / HBV DNA (-) group.The constituent ratio of HBeAg positive and HBV DNA level were higher and the average age was lower in intrahepatic HBsAg positive group than those in HBsAg negative group.The constituent ratio of positive HBeAg, the levels of ALT, AST, PLT and HBV DNA were higher and the average age, the average FIB-4 level were lower in intrahepatic HBcAg positive group than those in HBcAg negative group.The HBV DNA level was an independent risk factor for intrahepatic HBsAg intensity, and the HBeAg positive and HBV DNA level were independent risk factors for intrahepatic HBcAg intensity.There were no significant differences in A and F among different groups of intrahepatic HBsAg intensity (x2 =1.943 and 2.630, both P ＞ 0.05).There was significant difference in F among different groups of intrahepatic HBcAg intensity (x2 =12.352, P ＜ 0.01), but not in A.The degree of F was the highest in intrahepatic HBcAg negative group.There was significant difference in intrahepatic HBcAg intensity among different groups of ALT level (x2 =16.349, P ＜ 0.01), but not in intrahepatic HBsAg intensity.The intrahepatic HBcAg intensity in ALT ＜ 2 × ULN group was lower than that in other two groups.Conclusions Most of patients with chronic HBV infection are intrahepatic HBsAg positive and more than half of them are intrahepatic HBcAg positive.The intrahepatic HBsAg intensity is not associated with A and F, but correlates with HBV DNA level.The intrahepatic HBcAg intensity is not associated with A, but it is negatively correlated with F and positively correlated with positive HBeAg expression, HBV DNA level and ALT level.

Objective To assess the liver biopsy and the clinical characteristics of inactive HBsAg carriers.Methods One hundred and ten inactive HBsAg carriers,including 76 males and 34 females aged (38.9 ± 9.4) years (21-66),underwent liver biopsy from January 2011 to September 2015,the histopathological findings and clinical features were analyzed.Among 110 cases the inflammation activity (A) was ＜ A2 in 73 cases and ≥A2 in 37 cases;the fibrosis (F) ＜ F2 in 63 cases and ≥F2 in 47 cases.The upper limits of normal (ULN) for ALT was defined as 30 U/L for men and 19 U/L for women according to World Health Organization (WHO) standard,and 50 U/L for men and 40 U/L for women according to Chinese national standard.There were 59 cases with ALT ＜ 1 × ULN of WHO standard and 110 cases with ALT ＜ 1 × ULN of Chinese standard.Results In 110 inactive HBsAg carriers,there were 100 cases (90.9％) ≥A1 and 37 cases (33.6％) ≥A2,84 cases (76.3％) ≥F1 and 47 cases (42.7％) ≥F2.The severity of A and F were both higher in males than that in females,especially that of F (U =2.162,P =0.032;x2 =5.315,P =0.021).But there were no statistical differences between WHO standard group and Chinese standard group (U =0.951,0.435;P =0.341,0.663).Along with the increase of age,the degrees of A and F aggravated (F =3.705,5.915;P =0.014,0.001).The average ages in ≥ A2 group and ≥F2 group were (41.7 ± 9.6) years and (38.7 ± 8.1) years,respectively.The independent risk factors for severity of A and F were age,gender (male) and age,respectively.Conclusion There may be histological damages of varying degree in liver tissues of most inactive HBsAg carriers,and for those aged 40 years and over,especially males screening of liver histological activity and fibrosis would be necessary.

Objective To analyze the correlation between liver pathology and clinical characteristics in a large series of patients with chronic HBV infections , so as to provide the data base for non-invasive medical diagnosis .Methods Liver pathology and clinical characteristics of 1 397 patients with chronic HBV infections were retrospectively analyzed . Ridit analysis and Spearman correlation analysis were performed to investigate the correlations of clinical characteristics with liver pathology of patients .Results In 1 397 patients, there were 604 patients (43.24%) with liver inflammation grading ≥G2 and 504 patients (36.08%) with fibrosis stage ≥S2.Inflammation grade and fibrosis stage of liver tissues were both higher in male patients than those in females (u=3.093 and 2.854, P<0.01).Inflammation grade and fibrosis stage of liver tissues in patients aged ≤30 years were lower than those in patients aged >30-40 years and >40 years (r=0.259 and 0.303, P<0.01;F=4.199 and 12.226,11.610 and 24.359, P<0.05 and <0.01).Patients with HBeAg( -) and HBV DNA≥103 copies/mL were of higher degrees in liver tissue inflammation compared with those with HBeAg ( +) and those with HBeAg ( -) but HBV DNA <103 copies/mL (F=8.788 and 5.635, all P<0.01);while the fibrosis stage in patients with HBeAg (-) and HBV DNA≥103 copies/mL was only higher than that in HBeAg ( +) patients (F=12.886, P<0.01). Liver tissue inflammation and liver fibrosis aggravated with the increase of ALT ( r=0.537 and 0.517, P<0.01).There was no significant difference in liver tissue inflammation among different age groups of patients with ALT (1-<2) ×ULN and HBV DNA≥103 copies/mL (χ2 =4.365, P >0.05),but there was significant difference in liver fibrosis in patients between aged >40 years and ≤30 years ( F=3.177,P<0.05).Conclusions Liver biopsy and antiviral therapy should be considered in chronic HBV infected patients with age of >30 years, lightly elevated ALT levels , HBeAg(-) and detectable HBV DNA levels , especially in male patients .Screening for liver fibrosis should be considered in patients with HBeAg ( -) and low HBV DNA levels .