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Introduction: The clinical significance of persistent positive in Hepatitis B Virus (HBV) DNA level in patients receiving antiviral therapy is not well known. We investigated factors associated with persistent viremia (PV) in patients with chronic hepatitis B (CHB) given 78-week entecavir., Methods: A total of 394 treatment-naïve CHB patients who had undergone liver biopsy at baseline and week 78 of treatment were analyzed in this prospective multicentre study. We identified patients with PV (above the lower limit of quantification, 20 IU/ml) after 78 weeks of entecavir therapy. Stepwise, forward, multivariate regression analyses of specified baseline parameters were apllied to identify factors associated with PV. Futhermore, we assessed the incidence of hepatocellular carcinoma (HCC) in all patients using models of the risk of HCC development., Results: Of the 394 patients, 90 (22.8%) still with PV after 78-week antiviral treatment. Factors associated significantly with PV (vs complete virological response, CVR) were HBV DNA level ≥8 log10 IU/mL (OR, 3.727; 95% CI, 1.851-7.505; P < 0.001), Anti-HBc level < 3 log10 IU/mL (OR, 2.384; 95% CI, 1.223-4.645; P=0.011), and HBeAg seropositivity (OR, 2.871; 95% CI, 1.563-5.272; P < 0.001). Patients with PV were less likely to have fibrosis progression and HCC development than those with the CVR. Of the 11 HBeAg-positive patients with HBV DNA level ≥8 log10 IU/mL and Anti-HBc level < 3 log10 IU/mL at baseline, 9 (81.8%) had persistent positivity in HBV DNA level and 0 had fibrosis progression at week 78 of treatment., Discussion: In conclusion, HBV DNA level ≥8 log10 IU/mL, Anti-HBc level < 3 log10 IU/mL and HBeAg seropositivity at baseline contribute to PV in patients with CHB receiving 78-week antiviral treatment. In addition, the rate of fibrosis progression and the risk of HCC development in patients with PV were kept low. The complete protocol for the clinical trial has been registered at clinicaltrials.gov (NCT01962155 and NCT03568578)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Dong, Cao, Zhang, Zhao, Shang, Zhang, Ma, Xie, Gui, Zhang, Liu, Shang, Xie, Liu, Zhang, Wang, Zhao and China HepB Related Fibrosis Assessment Research Group.)

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV)., Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment., Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p =0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p =0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p =0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p =0.031)., Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients., Competing Interests: The authors have no conflict of interests related to this publication., (© 2023 Authors.)

The ozone concentration characteristics of 13 cities in Beijing-Tianjin-Hebei regions from 2016 to 2020 were analyzed based on ecological environment monitoring and meteorological observation data. The influence of meteorological elements such as daily maximum temperature ( T max ), daily average ground pressure ( p ), daily average ground relative humidity (RH), and daily average ground wind speed ( v ) on ozone concentration[ ρ (O 3 -8h)] and the exceeding standard rate of O 3 -8h were discussed. The AQI, ozone concentration range, and ozone pollution level forecast accuracy rates were evaluated using the neural network statistical model. The results showed that the concentrations of O 3 -8h-90per[ ρ (O 3 -8h-90per)] of 13 cities in the Beijing-Tianjin-Hebei region from 2016 to 2020 were 157.4, 177.2, 177.3, 190.6, and 175.6 μg·m -3 , respectively. The regional ozone concentration increased by 11.6% over the five years from 2016 to 2019. From 2016 to 2019, there was an overall upward trend in volatility, followed by a decline in 2020. Compared with that in 2016, the concentration of O 3 -8h-90per in the other 10 cities increased by 6-45.5 μg·m -3 , except for in Beijing, Zhangjiakou, and Chengde, where it decreased slightly. The average value of ρ (O 3 -8h) from April to September was higher than 100 μg·m -3 , and the highest monthly average concentration of O 3 -8h was 158.10 μg·m -3 in June. The range of the over standard rate of O 3 -8h was 8.6%-19.2% in the 13 cities, and 97.8% of ozone concentrations exceeded the standard in the period from April to September. At the regional scale, the concentration of O 3 -8h had the strongest correlation with the daily maximum temperature. Furthermore, when T max was in the range of 25-28℃, the concentration of O 3 -8h in the 13 cities began to exceed the standard concentration of 160 μg·m -3 . Additionally, the concentration of O 3 -8h negatively correlated with p . When RH was below 60%, ozone concentration increased slowly with relative humidity in most cities. When RH was above 61%-70%, ozone concentration decreased with the increase in daily relative humidity in most cities. When ozone exceeded the standard concentration of 160 μg·m -3 , the dominant wind was mainly southerly wind, and the high ozone concentration in most cities tended to be concentrated in the low wind speed range of 2-3 m·s -1 and below. Moreover, the correlation coefficient range of the statistical model of OPAQ 1-9 days in advance was 0.72-0.86, the average accuracy of AQI level forecasts was 67%-86%, and the average accuracy of O 3 -8h concentration forecasts was 63%-84%. In April to September, when ozone exceeded the standard of 160 μg·m -3 , the accuracy rates of the model forecast of light ozone pollution and ozone exceeding the standard concentration of 160 μg·m -3 three days in advance were 69% and 66%, which can provide a reference for the management and control of ozone pollution.

Cardiovascular disease is one of the most common diseases in the elderly population, and its incidence has rapidly increased with the prolongation of life expectancy. Hyperhomocysteinemia is an independent risk factor for various cardiovascular diseases, including atherosclerosis, and damage to vascular function plays an initial role in its pathogenesis. This review presents the latest knowledge on the mechanisms of vascular injury caused by hyperhomocysteinemia, including oxidative stress, endoplasmic reticulum stress, protein N-homocysteinization, and epigenetic modification, and discusses the therapeutic targets of natural polyphenols. Studies have shown that natural polyphenols in plants can reduce homocysteine levels and regulate DNA methylation by acting on oxidative stress and endoplasmic reticulum stress-related signaling pathways, thus improving hyperhomocysteinemia-induced vascular injury. Natural polyphenols obtained via daily diet are safer and have more practical significance in the prevention and treatment of chronic diseases than traditional drugs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Whether to initiate antiviral therapy in chronic hepatitis B virus (HBV) infected population with normal alanine aminotransferase (ALT) is hot and difficult issue. Improvements in drug availability and affordability have paved the way for more data, which may become a medium for confirming whether this population needs antiviral treatment. Regardless of whether HBeAg is positive or negative, there are still a considerable number of patients with chronic HBV infection with normal ALT, who have obvious liver inflammation, fibrosis or cirrhosis and need to start antiviral therapy. Liver biopsy or non-invasive techniques can be used as diagnostic tools to begin an early treatment in population with liver fibrosis and inflammation.

Background and Aims: To evaluate the efficacy of Fuzheng Huayu (FZHY), a Chinese herbal formula, plus entecavir (ETV) in regression of liver fibrosis in chronic hepatitis B (CHB) patients with significant fibrosis/cirrhosis. Methods: The current study was a two-center, randomized, double-blind and placebo-controlled pilot study. Fifty-two currently untreated chronic hepatitis B patients with Ishak fibrosis score ≥3 points were identified and 1:1 randomized into FZHY plus ETV combination and placebo plus ETV groups. The second liver biopsy was performed after 48-week treatment. Necroinflammatory improvement and regression of fibrosis were assessed. Fine changes in different collagen features in paired liver biopsies were evaluated by dual-photon microscopy for both groups. Results: Forty-nine patients completed the full course of treatment; forty-six of them underwent second liver biopsy (for which twenty-two were in the combination group and twenty-four were in the control group). Compared to those in the control group, patients in the combination group had significantly higher rate of fibrosis regression (82% vs. 54%) ( p <0.05). Furthermore, the necroinflammatory improvement was greater in the combination group than in the control group (59% vs. 25%, p <0.05). Among the more than 80 collagen parameters in the dual-photon analysis, 5 decreased significantly in the combination group compared to the control group ( p <0.05). However, no significant improvement was detected in either biochemical, virologic or serologic responses between these two groups at week 48. Conclusions: The combination therapy of FZHY plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in chronic hepatitis B patients with significant fibrosis/cirrhosis. The clinical trial number is ChiCTR-TRC-11001377., Competing Interests: The authors have no conflict of interests related to this publication., (© 2020 Authors.)

Monitoring data were used to analyze the relationships among relative humidity (RH), visibility, and PM 2.5 concentrations. A strong, linear relationship expression between the extinction coefficient and PM 2.5 concentrations at different relative humidities is proposed. The mean correlation coefficient at RH 40%-90% was higher than 0.75 for most of Central and Eastern China, and reached 0.9 in Beijing. Comparatively, the extinction efficiency of PM 2.5 was much larger in Beijing, the Yangzi River Delta Region, and Sichuan than in other regions. However, the influence of RH on visibility varied from region to region. In Beijing, RH dominated the decrease in visibility when RH>90%, while in Guangzhou, this was the case when RH>80%. From 1980 to 1996, the annual variation in PM 2.5 concentrations was not significant in Beijing and the PM 2.5 concentrations were significantly higher than in the 2000s because of the dominant mode of heating. From 1997 to 2009, PM 2.5 concentrations in Beijing showed a slow downward trend, and from 2010 to 2012, showed an upward trend. Since 1980, PM 2.5 concentrations in the entire country have been rising. PM 2.5 concentrations have always been higher in North China than in other parts of the country.

Objective: This study aimed to explore the most up-to-date distribution of hepatitis C virus (HCV) genotypes in China, especially the association between HCV genotypes and patients' characteristics and clinical parameters., Methods: Sera from 483 HCV antibody-positive patients were genotyped using a HCV genotyping chip assay. The distribution of HCV genotypes, clinical parameters, modes of transmission and duration of infection were determined and the relationships among these parameters were analyzed., Results: A total of 424 patients were successfully genotyped. HCV genotypes 1, 2, 3 and 6 were found with a constituent ratio of 72.1%, 12.3%, 10.6% and 5.0%, respectively, in which subtypes 1b (69.1%), 2a (11.6%) and 3a (7.5%) were prevalent. The mean age of patients with genotype 1 and 2 was significantly elder than those with genotype 3 and 6 (P < 0.05). The distribution of HCV genotypes in relation to the mode of HCV transmission was remarkable (P < 0.001). Transfusion of blood and blood products was the main mode of transmission. Most genotype 1 infection (53.1%) was found in the group with a duration of HCV infection of 10-20 years. Genotype 1b was independently associated with age (P = 0.001) and mode of HCV transmission (P = 0.007)., Conclusions: The main HCV subtype was genotype 1b in Chinese patients. The prevalence of HCV genotypes was correlated with age and the mode of HCV transmission. Genotype 3a and 6 may become an increasing threat in the future., (© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Objective: To explore the categories of drugs causing hepatotoxicity and analyze the clinical and histological features of the corresponding drug-induced liver injury (DILI), in order to gain insights into potential diagnostic factors for DILI., Methods: A total of 138 DILI patients treated at our hospital from April 2008 to April 2010 were retrospectively analyzed. The responsible drug for each DILI case was recorded. The Roussel Uclaf Causality Assessment Method (RUCAM) had been used to diagnose DILI. Only cases that had scored as highly probable or probable (more than or equal to 6 points by RUCAM) were included in this study. The patients' general condition, clinical manifestations, and serum biochemical and immunological parameters were assessed. Sixty-six of the patients underwent liver biopsy, and were assessed for liver pathological changes. Clinical and laboratory test data were collected and used to classify the total 138 cases as hepatocellular injury, cholestatic, or mixed hepatocellular-cholestatic types., Results: Within our patient population, the leading cause of DILI was Chinese herb medicine, accounting for 53.62% of cases. Antibiotics were implicated in 7.97% of cases, and dietary supplement in 6.52% of cases. Correlation between the clinical features and histological injury pattern was stronger at the time of biopsy (more than or equal to 3 days after laboratory results) (kappa = 0.63, P less than 0.05) than at the onset of DILI (kappa = 0.25, P less than 0.05). All modified hepatic activity index (HAI) necroinflammatory scores and fibrosis scores were more severe in the cholestatic and mixed injury types than in the hepatocellular injury type (P less than 0.01 and P less than 0.05, respectively)., Conclusion: Chinese herbal medicine, dietary supplements and antibiotics were the main causes of DILI in our patient population. The clinical and histological features correlated well, especially at later stages of DILI. The degree of inflammation and fibrosis was significantly higher in cholestatic and mixed hepatocellular-cholestatic injury types than in the hepatocellular injury type. Assessment of both clinical and pathological features may represent a more accurate diagnostic method for DILI.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/10(6) cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B.

Current guidelines recommend antiviral therapy for chronic hepatitis B (CHB) patients with elevated alanine aminotransferase (ALT) and high viral load. Scant histological data exist for CHB patients with persistently normal ALT (PNALT) because disease progression is thought to be rare. To identify potential predictors of significant histology in the presence of PNALT, we compared the clinical characteristics and histology of Chinese CHB PNALT patients to those in patients with elevated ALT. Percutaneous liver biopsy was performed in 522 CHB patients with Chinese ethnicity who had not had antiviral treatment. Differences in age, ALT, viral load, hepatitis B e antigen (HBeAg) status and liver histology were compared between eligible PNALT (252) and elevated ALT (270) patients. Of the PNALT patients, 38.5% had normal liver histology, 25.4% had significant necroinflammation and/or fibrosis and 8.4% had established cirrhosis. Furthermore, histopathological differences between patients with high-normal ALT (0.5-1.0 x the upper limit of normal (ULN)) and low-normal ALT (≤ 0.5 x ULN) were evaluated. There was a significantly greater prevalence of histopathology in the high-normal group (40.0%) than in the low-normal group (16.6%) (P < 0.001). Multiple logistic regression identified that significant histopathology findings in PNALT patients correlated with age (P < 0.001) and ALT level (P < 0.001), with age >40 years and ALT >0.5 x ULN predicting significant histopathology. Our data indicate that liver biopsy is recommended in CHB patients >40 years of age, particularly when their ALT is 0.5-1.0 x ULN. The findings above provide evidence for indication of antiviral therapy in patients with PNALT and significant histopathological change.

Background: We previously reported on serum N-glycans as markers for the diagnosis of cirrhosis in patients with chronic hepatitis C infection. Our present study aimed to evaluate the use of serum glycan markers for the diagnosis of liver fibrosis in patients with chronic hepatitis B infection., Methods: Patients with hepatitis B virus (HBV) infection (n=173) were diagnosed by clinical laboratory analysis and histological examination. Liver fibrosis was staged using Ishak score. N-glycan profiles of serum proteins were determined by DNA sequencer-based carbohydrate analytical profiling., Results: We found that in HBV patients, like in hepatitis C virus patients, several serum N-glycans were altered during the development of liver fibrosis. We found higher levels of total agalactosylated biantennary glycans in fibrosis patients with HBV infection than in healthy controls. The biantennary (NA2) and the triantennary (NA3) N-glycans decreased significantly (P<0.001) with increased severity of fibrosis. The diagnostic power of serum glycan marker (GlycoFibroTest) [area under the curve (AUC)=0.735) was similar to that of FibroTest (AUC=0.740) for discriminating between moderate and advanced fibrosis (F3-F6) from non- or mild fibrosis (F0-F2). However, GlycoFibroTest (AUC=0.740) was slightly better than FibroTest (AUC=0.696) for distinguishing fibrotic patients (F1 or more) from non-fibrotic patients (F0)., Conclusions: The assay for serum glycan profiling showed satisfactory reproducibility and is a non-invasive blood test for the diagnosis of liver fibrosis. The changes of N-glycan level in serum can be used to monitor or follow-up the progress of fibrosis using specific N-glycan markers.

Objective: To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL)., Methods: HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were examined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy)., Results: Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9+/-1.4) vs (4.1+/-1.1) log(10)copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HAI) > or = to 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAI) > or = to 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, x(2)=0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r=0.626, 0.592, P < 0.01; BCP: r=0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F > or = 3) (AUC = 0.905, 95% CI: 0.771-1.039, P < 0.05) with the cutoff value of 4.5 log(10) copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA is > or = to 10(4) copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 log(10)copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes., Conclusions: Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting significant fibrosis (F > or = 3).

Chronic hepatitis B virus (HBV) infection is a complex interaction between replicating noncytopathic virus and dysregulatory host antiviral immunity. Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immunity via secreting type I interferons. Toll-like receptor (TLR) 9 is involved in major pattern recognition receptors expressed in pDCs. The frequency of pDCs and TLR9 expression in peripheral blood mononuclear cells (PBMC) was determined, using flow cytometry. IFN-alpha production by PBMC was evaluated in vitro in the presence of cytidine phosphate guanosine (CpG) with/without pDCs. The correlation between TLR9, pDCs frequency and viral load was also evaluated. TLR9 expression in pDCs in chronic HBV patients was significantly ( approximately 50%) reduced, supported by approximately 70% reduction of TLR9 mRNA, in comparison to healthy controls, correlating with the impairment of IFN-alpha production in vitro. Furthermore, pDCs frequency in these patients was substantially reduced ( approximately 30%), inversely correlating with serum ALT levels and HBV viral load. HBsAg and HBcAg were detected by immunohistochemistry in pDCs in chronic HBV patients. We conclude that HBV infection results in reduced frequency of circulating pDCs and their functional impairment via inhibiting the expression of TLR9. These data may provide useful information in both basic research and clinical treatment of chronic HBV infection.

Objective: To confirm the diagnostic value of FibroTest-ActiTest (FT-AT) in predicting liver fibrosis and inflammatory activity in patients with chronic hepatitis B (CHB), and to study the discordances between FT and their liver biopsies., Methods: A study was performed on 100 patients with CHB who underwent liver biopsies in our hospital. Serum samples for biochemical markers were taken on the day of their biopsies. Diagnostic accuracies were assessed by ROC curve analysis., Results: The median biopsy specimen size was 15 mm (range: 8-30), with 9 (median) portal tracts (range 5-26). Thirty-nine patients were classified as Ishak F3-F6 in fibrosis and 65 patients as A2-A4 in inflammation. Areas under ROC curve for diagnosis of significant inflammation (A2-A4), significant fibrosis (F3-F6), and cirrhosis (F5-F6) were 0.833 (95% CI: 0.753-0.913), 0.840 (0.750-0.929), and 0.862 (0.721-1.003), respectively. FT less than 0.31 had a NPV of 86% for excluding significant fibrosis, whereas FT > or = 0.72 had a PPV of 92% for predicting significant fibrosis. Among the 26 patients with 2 fibrosis stages of discordances between FT and biopsy, the discordance was attributable to biopsy in 3 cases, to FT in 7, and undetermined in 16., Conclusion: This study confirms the diagnostic value of FT-AT and suggests that 68% of our patients with CHB can be reliably identified by FT without a liver biopsy and with a diagnosis accuracy of 87%.

Objective: To study the histological changes in livers of chronic hepatitis B (CHB) patients with persistently normal serum ALT levels (PNAL)., Methods: 274 CHB patients who had percutaneous liver biopsies and had a detectable viral load (lower limit of detection is 10(3) copies/ml) in our department between October 2003 and February 2007 were included in this study. Among these patients, 139 had PNAL, group A, (with at least 3 normal serum ALT levels, with intervals of more than two months over a period of 12 or more months before the biopsy). The other 135 patients, group B, had abnormal serum ALT levels during the same period. The histological changes in the livers of the two groups of patients were compared., Results: Sixty-six (47.5%) patients with PNAL had normal liver histology, but significant pathohistological changes such as significant necroinflammation, fibrosis and/or cirrhosis were found in 33 (23.7%) patients. Thirteen (9.4%) had established cirrhosis. When compared to patients within (0-0.75)x upper limit of normal (ULN) ALT, patients within (0.76-1.00)x ULN ALT had higher scores of histological changes (43.5% vs. 19.8%, P < 0.05). In the PNAL group, scores of histological changes increased sharply in parallel with an age increase of older than 40 yrs. However neither viral loads nor HBeAg statuses of the PNAL patients had any predictive meaning to the scores of the histological findings., Conclusions: 23.7% of our CHB patients with PNAL, regardless of what their HBeAg statuses or viral load levels were, had significant liver pathohistological changes. Liver biopsies should be considered in CHB patients with PNAL, especially those older than 40 yrs and with a higher ALT within (0.76-1) x ULN.