Liver Histological Abnormalities Were Better Reflected by Virus Level in Chronic Hbv Infected Patients Aged ≤ 30 Years, Hbeag-Positive and Persistently Normal Alt

doi:10.21203/rs.3.rs-1124279/v1

Background: We analyzed correlations between significant liver histological characteristics and clinical variables in HBV-infected patients and provided recommendations on treatment decisions for patients age younger than 30-year-old.

Methods: Liver biopsy was performed on 161 chronic HBV-infected patients with ALT ≤ 40 U/L from July, 2000 – November, 2019. Median age was 39(18-70) years old. Histologic assessment was based on the Scheuer scoring system.

Results: Significant necroinflammation and fibrosis were observed in 65.2% (105/161) and 52.2% (84/161) patients of all cases. The pathological abnormality was significantly negatively correlated with viral level in HBeAg-positive subjects, and based on ROC curve analysis, the viral level to predict obvious liver pathological changes was 6.7 log10 IU/ml in those patients. Threshold value of ALT (25 U/L) based on the distribution of ALT and virus levels. Patients younger than 30 years old, almost all had significant pathological alteration with HBV-DNA < 6.7 log10 IU/ml; However, the ratio of insignificant liver’s inflammation and fibrosis were 65% and 70% with HBV-DNA levels ≥ 6.7 log10 IU/ml respectively, on that basis, it could have a further rising, reaching 67.5% and 75% combining with ALT ≤ 25 U/L.

Conclusion: Viral load was a better factor to reflect hepatic histological abnormality in Chronic HBV-infected patients with HBeAg-positive and persistently normal ALT whose age ≤ 30 years, 5000000 IU/ml was a suitable threshold.

Gastroenterology & Hepatology

Hepatitis B virus (HBV)

Chronic hepatitis B (CHB)

Hepatitis B e antigen (HBeAg)

Liver disease

Infection

Alanine Transaminase (ALT)

pathology

viral

inflammation

fibrosis

Natural history

Hepatitis B virus (HBV) infection is a major public health problem worldwide. China has the world’s largest burden of HBV infection, the absolute number of HBV - infected people is around 70 million, most of them are carried without immediate treatment (1).

Alanine Transaminase (ALT) level usually indicated liver function. International guidelines recommended observation rather than treatment for patients with ALT levels within the upper limit of normal (ULN) (2–5). However, the 2015 updated guideline of The Asian Pacific Association for the Study of the Liver (APASL) on the management of chronic hepatitis B (CHB), most HBV-infected subjects would not develop hepatic complications. However, 15–40% would develop cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease (2), and these highly related to persistent viraemia (6). A meta-analysis revealed that approximately one fifth of chronic hepatitis B patients with ALT ≤ 40 IU/L might have significant hepatic fibrosis, the approach to such patients should be individualized (7). Moreover, studies from Korea and Indonesia had shown that patients in Immune tolerant phase (IT) had liver histologic damages more or less (8–9), the same phenomenon presented to HBeAg-negative cases (10).

In the latest domestic and foreign practice guidelines for CHB, there was no consensus on the age at treatment or liver biopsy for chronic HBV infection with persistently normal ALT levels (PN-ALT). Age over 35-year-old in guideline of APASL in 2015(2), over 40-year-old in The American Association for the Study of Liver Diseases (AASLD) upgraded in 2018(5) and over 30-year-old in Chinese Society of Hepatology in 2019(3) should evaluate histological severity by liver biopsy or noninvasive tests. Patients with age over 30 years old and high HBV-DNA levels were considered to start antiviral therapy in the 2017 European Association for the Study of the Liver (EASL)(4). The opinions given by most studies were mainly for patients older than 30 years old (11, 12). There was not a clear-cut recommendation to perform drug therapy or liver biopsy before 30 years old.

We analyzed the liver pathological characteristics of chronic HBV-infected patients with PN-ALT and relationships with clinical variables to determine the optimal HBV-DNA threshold value reflecting significant liver tissue damage, and provided recommendations, especially for the HBeAg-positive patients under 30 years of age.

Patients

Patients with chronic HBV infection with PN-ALT underwent ultrasonography-guided percutaneous liver biopsy in the Second Affiliated Hospital of Chongqing Medical University during Between July 2000 and November 2019. Inclusion criteria and exclusion criteria as shown in the Fig 1.

Laboratory assays

All serological measurements were obtained from blood samples three days before the patient underwent liver biopsy. The ULN of serum ALT was defined as 40 U/L. In our study, PN-ALT represented ALT had remained within ULN with at least six months prior to the baseline liver biopsy.

Serum HBsAg, HBeAg were assayed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Serum HBV viral levels were quantified using real-time (RT)-PCR (Roche Diagnostics), the minimum detection limit was 100 IU/ml or 1000 copy/ml. According to the conversion formula 1 Copy≈5 IU, all of them were uniformly converted into IU/ml and finally converted into Log10 IU/L for statistical analysis.

Liver histology

The pathological data of liver were extracted from the pathological system of the Second Affiliated Hospital of Chongqing Medical University. According to Scheuer scoring system (13), Fibrosis was classified as stage(S) 0/1/2/3/4, significant liver fibrosis was defined as S≥2, among which S4 was defined as early cirrhosis or cirrhosis. The grade of inflammatory activity was classified as grade(G) 0/1/2/3/4, Significant inflammation was defined G≥2.

Statistical analysis

Statistical analysis was performed with using the Statistical Package of Social Science Software program (SPSS), version 24. χ2 and Fisher tests were used for categorical variables. The Spearman correlation test was used to reflect the correlation, and receiver operating curve (ROC) analysis was used to determine the optimal threshold of serum HBV-DNA. p<0.05 were considered statistically significant.

1. Baseline characteristics

A total of 161 patients were enrolled at baseline (Table1). There were 59.4% (41/69) patients with G≥2 and 44.9% (31/69) patients with S≥2 in HBeAg-positive patients, which in HBeAg-negative patients were 69.6% (64/92) and 57.6% (53/92). In the univariate analysis of liver pathology in chronic HBV-infected patients with PN-ALT, HBeAg-positive patients had lower age, lower percentage of men, higher HBV-DNA than the HBeAg-negative patients (Table1).

2. Correlation analysis of liver histopathology and clinical variables in HBeAg-positive and HBeAg-negative patients

In HBeAg-positive patients, the necroinflammation and fibrosis of liver were negatively correlated with viral level (r=-0.3, p<0.05) (Fig 2A), while there seemed to be positively correlation between viral load in HBeAg-negative patients, (p>0.05) (Fig 2B). Meanwhile, there were negatively correlation between HBV-DNA and age in HBeAg-positive subjects (r=0.23, p<0.05). No matter how the HBeAg status was, there was no correlation between the histopathological alterations and serum ALT level or age.

3.The HBV-DNA thresholds to reflect significant histological abnormalities in HBeAg-positive patients

Viral levels negatively correlated to significant liver tissue changes in PN-ALT HBeAg-positive patients. Based on ROC curves analysis of serum viral levels, threshold with the optimum sensitivity and specificity for the prediction of significant necroinflammation and fibrosis were determined. The optimum serum HBV-DNA threshold was 6.7 log10 IU/mL (Fig 3A&3B). For HBeAg-positive patients with HBV-DNA ≤ 6.7 log10 IU/ml, 78.8% (33/26) had G≥2, 57.6% (19/33) had S≥2. Nevertheless, these patients with HBV-DNA > 6.7 log10 IU/ml, 42% (15/36) had G≥2, 33.3% (12/36) had S≥2. (Table 2).

4. The decision tree for histopathological alterations in HBeAg-positive patients

We set the ALT cut-off value as 25 U/L. ALT levels > 25 U/L in 72.7% of the people with HBV-DNA in 4.3 - 6.7 log10 IU/ml and 41.4% of the people with HBV-DNA > 6.7 log10 IU/ml (p =0.01) (Fig 4).

According to the decision tree, 53.8% of patients under 30 years old had little inflammation and 57.7% had barely fibrosis. When HBV-DNA was lower than 6.7 log10 IU/ml, obvious inflammation or fibrosis was found in 83% (5/6). When HBV-DNA > 6.7 log10 IU/ml, rate of G<2 increased to 65%, and the proportion S<2 increased to 70%. While ALT was further considered, the incidence of scarcely any inflammation or fibrosis was increased to 67.5% and 75% when ALT ≤ 25 U/L. (Fig 5).

In whole study, there were totally 65.2% with G≥2, 52.2% with S≥2, even 9.3% with early cirrhosis. The histopathological alterations of liver were similarly with research of Kumar M et al (10) and Gui HL et al (14). Previous studies had shown CHB patients with PN-ALT had definitively increased risk of long-term cirrhotic complications and HCC (15, 16). Although there was no consensus on treatment for chronic HBV-infected cases with PN-ALT, early interventions were needed in patients before it progressed to cirrhosis or liver cancer. The current international guidelines for the management of HBV recommended regularly monitor indications mostly the same for chronic HBV-infected, mainly based on serum HBV DNA, ALT levels, the severity of the liver diseases by non-invasive testing and so on (2–5). In addition to, Age was another essential factor, it had been agreed upon in current international guidelines. The most remarkable finding of the present study revealed that recommendations for patients younger than 30 years of age.

In HBeAg-positive infection phase generally with higher HBV-DNA levels and younger age than HBeAg-negative. Chen YC et al (17) concluded patients with HBeAg seroconversion before age 30 had excellent prognosis. In that study, patients with HBeAg seroconversion after age 40 were at significantly higher risk for HBeAg negative hepatitis, cirrhosis, and HCC. That seemed to explain why such high prevalence of liver histopathological abnormalities occurred in our study. In our cohort, the average age of HBeAg-positive patients was younger than HBeAg-negative, 34.4 versus 42.4 years, respectively. This indicated that the age of HBeAg serological conversion was about 40 years old, whereas underlying liver histological changes had occurred in this population, about 60% of HBeAg-positive and 70% of HBeAg-negative patients occurred liver damage, respectively.

At present research, there was a negative relationship in HBeAg-positive patients between serum viral levels and hepatic histopathological alterations, which was consistent with Xie Q et al study (18). In their study showed that patients with HBV DNA levels < 4 log10 IU/ml all had significant fibrosis, whereas the prevalence of significant fibrosis decreased to 35.9% in patients with HBV DNA level ≥7 log10 IU/m. Previous studys had shown a positive relationship between HBV DNA levels and liver fibrosis or inflammation among HBeAg-negative patients (19, 20), our study was inconsistent with that. This might be related to the small sample size. Although the HBeAg-negative HBV-infected patients were older, asymptomatically about 30-40 years, the spontaneous recovery was rare and the long-term prognosis was poor with rapid evolution to cirrhosis and HCC, the annual incidence of cirrhosis was 8–10% (21–22). Therefore, it might reveal that antiviral therapy was needed to all HBeAg-negative HBV-infected patients with PN-ALT without regard to serum viral levels.

Persistent viremia increasing the risk of cirrhosis and Hepatic carcinoma cell had been well documented in a number of studies. The maximal suppression of HBV-DNA as early as possible could reduce the risk of disease progression (23, 24). At our research, we investigated the relationships between clinical variables and hepatic pathology in HBeAg-positive patients. We used ROC to identify the optimal cut-off value of HBV-DNA that reflects obvious hepatic inflammation and fibrosis in HBeAg-positive patients, the value was 6.7 log10 IU/ml, it also reflected the lower limit of viral load of the IT phase. Although the sensitivity and specificity are not perfect, they could guide the clinician in deciding whether to initiate antiviral therapy or more closely followed up. Yenilmez E et al (25) thought HBV-DNA levels between 10⁶ and 10⁸ IU/mL more likely to be in chronic infection stage in HBeAg-positive CHB. Chinese Xie Q’s team (18) study also found the optimal serum HBV DNA cut-off value to evaluate low risk of significant fibrosis was ≥ 6.7 log10 IU/ml, patients with serum HBV DNA levels ≥ 8.5 log10 IU/ ml all had no significant fibrosis.

Studies had shown that using such a definite HBV-DNA cut-off value for treatment was inappropriate, needing to combine with age. At present study, the histopathological inflammation and fibrosis not correlated with age in HBeAg-positive cases, which seemed to be at odds with previous research, in those studies, age was associated independently with significant fibrosis in HBeAg-positive patients (10, 26). This might be related to small number of the population in our study. Andreani et al revealed the median age of loss of tolerance was 30.7 years (27). In Asian countries, most of HBV infection was acquired during the perinatally/early childhood period, and the onset of IT at age 30 or older indicated a prolonged status of infection and might predispose to complications. It had been reported that HBeAg-positive patients over age 30 with generally higher HBV-DNA levels were at significantly higher risk of developing HCC (11). Vlachogiannako’s review suggested that HBeAg-positive patients over 30 years old with vial load more than 20,000 IU/mL should be treated without regard to ALT levels or liver histology (28).

Patients were usually young age during IT stage. The recent Turkish study focused on naive, male and young population. The average age was 22.91 years. All cases, 53.5% had significant fibrosis, 34.4% had significant inflammation (25). As in this study, patients with HBV-DNA > 2×10⁸ IU/mL, the most frequent Fibrosis score was 2 (46.1%), HAI was 4 (22.1%). However, the drawback of this study was that it was highly selective among the population. From our decision tree, patients younger than 30 years of age, HBV-DNA ≥ 6.7 log10IU/ml showed insignificant liver’s inflammation in 65% and insignificant fibrosis in 70%. This is at least a 10% improvement over age and ALT alone in identifying liver tissue damage.

According to guidelines, there was controversial to decrease the treatment threshold for ALT level. And in the literature, high risk of liver fibrosis in HBeAg-positive patients with an ALT level > 0.5 ULN (ULN, 58 IU/L) (29). Lai M et al reported that ALT levels between 25-40 U/L was regarded as high normal, in which histopathological abnormalities were more likely to occur (30). It was clear from the literature mentioned above that the decision to initiate antiviral therapy should not be based on a specific ALT threshold. However, lowering the ALT threshold was worthwhile. According to decision tree, patients younger than 30 years of age, who HBV-DNA levels ≥ 6.7 log10 IU/ml showed 67% were insignificant liver inflammation, 75% were insignificant fibrosis with ALT ≤ 25U/L. This suggested that the evaluation of liver tissue changes in chronic HBV-infected patients under 30 years old was mainly based on the virus level, pathological abnormalities could be further defined by adding the ALT level.

There were several limitations in our study, it's a retrospective, single-center study, with small sample size, existing unavoidable selective bias. At the same time, the cross-sectional span was relatively long, almost nearly 20 years. In the past, ALT was the main indicator for antiviral treatment of CHB, the data was complete, and patients lock of other indicators' data, so we did not include more serological indicators.

In conclusion, it usually required to consider age, viral loads and ALT levels comprehensively when evaluating histopathological abnormality of liver. For chronic HBV-infected patients whose age ≤ 30 years old with PN-ALT and HBeAg-positive, patients with HBV-DNA lower than 6.7 log10 IU/ml should perform liver biopsy to assess the severity of the disease. For patients whose HBV-DNA >6.7log10IU/ml, histology could be further assessed in conjunction with ALT, 25U/L seemed the considerable threshold. The majority of chronic HBV-infected patients with PN-ALT with HBeAg-negative had severe liver histopathological damage, timely viral therapy was necessary.

Data Availability: All data included in this study are available upon request by contact with the corresponding author.

Animal research：Not Applicable.

Consent to Participate: This study had been approved by ethics Committee of the Second Affiliated Hospital of Chongqing Medical University. All patients undergoing liver biopsy had signed Informed consent before the procedure.

Consent to publish: All authors have read and approved the content, and agree to submit this manuscript for consideration for publication in this journal.

Plant Reproducibility: Not applicable.

Clinical Trials Registration: Not applicable.

Funding: This work was supported in part by the National Science and Technology Major Project of China [2017ZX10202203-008], the National Natural Science Foundation of China [No: 81772171] and Chongqing Municipal Health Commission Project (Grant Number: 2022WSJK054). No external funding was received for this study.

Competing Interests: The authors have no conflicts of interest to declare.

Author Contributions: All authors contributed to the study conception and design. Li Wei, Peng Hu and Hu Li were the main investigators. Li Wei, Xiaoqing Liu and Qiao Tang performed Material preparation, data collection and analysis. Li Wei wrote the manuscript. All authors reviewed and approved the final version of the manuscript.

Liu J, Zhang S, Wang Q, Shen H, Zhang M, Zhang Y, Yan D, et al. Seroepidemiology of hepatitis B virus infection in 2 million men aged 21-49 years in rural China: a population-based, cross-sectional study. Lancet Infect Dis 2016;16:80-86.
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016;10:1-98.
Chinese Society of Infectious Diseases CMA, Chinese Society of Hepatology CMA. [The guidelines of prevention and treatment for chronic hepatitis B (2019 version)]. Zhonghua Gan Zang Bing Za Zhi 2019;27:938-961.
European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370-398.
Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS, Jr., et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67:1560-1599.
Papatheodoridis GV, Manolakopoulos S, Dusheiko G, Archimandritis AJ. Therapeutic strategies in the management of patients with chronic hepatitis B virus infection. Lancet Infect Dis 2008;8:167-178.
Chao DT, Lim JK, Ayoub WS, Nguyen LH, Nguyen MH. Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase </= 40 IU/L and significant hepatic fibrosis. Aliment Pharmacol Ther 2014;39:349-358.
Park JY, Park YN, Kim DY, Paik YH, Lee KS, Moon BS, Han KH, et al. High prevalence of significant histology in asymptomatic chronic hepatitis B patients with genotype C and high serum HBV DNA levels. J Viral Hepat 2008;15:615-621.
Lesmana CR, Gani RA, Hasan I, Simadibrata M, Sulaiman AS, Pakasi LS, Budihusodo U, et al. Significant hepatic histopathology in chronic hepatitis B patients with serum ALT less than twice ULN and high HBV-DNA levels in Indonesia. J Dig Dis 2011;12:476-480.
Kumar M, Sarin SK, Hissar S, Pande C, Sakhuja P, Sharma BC, Chauhan R, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology 2008;134:1376-1384.
Kumar S, Ramachandran TM. Immunotolerant Chronic Hepatitis B Infection: When Do I Treat? J Clin Exp Hepatol 2019;9:277-279.
Kennedy PTF, Litwin S, Dolman GE, Bertoletti A, Mason WS. Immune Tolerant Chronic Hepatitis B: The Unrecognized Risks. Viruses 2017;9.
Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991;13:372-374.
Gui HL, Wang H, Yang YH, Wu YW, Zhou HJ, Guo SM, Lin LY, et al. Significant histopathology in Chinese chronic hepatitis B patients with persistently high-normal alanine aminotransferase. J Viral Hepat 2010;17 Suppl 1:44-50.
Yuen MF, Yuan HJ, Wong DK, Yuen JC, Wong WM, Chan AO, Wong BC, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut 2005;54:1610-1614.
Kumada T, Toyoda H, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Kanamori A, et al. Incidence of hepatocellular carcinoma in patients with chronic hepatitis B virus infection who have normal alanine aminotransferase values. J Med Virol 2010;82:539-545.
Chen YC, Chu CM, Liaw YF. Age-specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B. Hepatology 2010;51:435-444.
Xie Q, Hu X, Zhang Y, Jiang X, Li X, Li J. Decreasing hepatitis B viral load is associated with a risk of significant liver fibrosis in hepatitis B e antigen positive chronic hepatitis B. J Med Virol 2014;86:1828-1837.
El-Zayadi AR, Badran HM, Saied A, Shawky S, Attia Mel D, Zalata K. Evaluation of liver biopsy in Egyptian HBeAg-negative chronic hepatitis B patients at initial presentation: implications for therapy. Am J Gastroenterol 2009;104:906-911.
Wang Y, Xu MY, Zheng RD, Xian JC, Xu HT, Shi JP, Li SB, et al. Prediction of significant fibrosis and cirrhosis in hepatitis B e-antigen negative patients with chronic hepatitis B using routine parameters. Hepatol Res 2013;43:441-451.
Hadziyannis SJ, Vassilopoulos D. Hepatitis B e antigen-negative chronic hepatitis B. Hepatology 2001;34:617-624.
Brunetto MR, Oliveri F, Coco B, Leandro G, Colombatto P, Gorin JM, Bonino F. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study. J Hepatol 2002;36:263-270.
Lok AS. Chronic hepatitis B. N Engl J Med 2002;346:1682-1683.
Mani H, Kleiner DE. Liver biopsy findings in chronic hepatitis B. Hepatology 2009;49:S61-71.
Yenilmez E, Cetinkaya RA. Are there optimal alanine aminotransferase and HBV DNA thresholds for discriminating HBeAg-positive chronic infection from chronic hepatitis? An evaluation of 215 young and male cases. Saudi Med J 2019;40:131-139.
Fung J, Lai CL, But D, Wong D, Cheung TK, Yuen MF. Prevalence of fibrosis and cirrhosis in chronic hepatitis B: implications for treatment and management. Am J Gastroenterol 2008;103:1421-1426.
Andreani T, Serfaty L, Mohand D, Dernaika S, Wendum D, Chazouilleres O, Poupon R. Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome. Clin Gastroenterol Hepatol 2007;5:636-641.
Vlachogiannakos J, Papatheodoridis GV. Hepatitis B: Who and when to treat? Liver Int 2018;38 Suppl 1:71-78.
Wong GL, Wong VW, Choi PC, Chan AW, Chim AM, Yiu KK, Chan HY, et al. Clinical factors associated with liver stiffness in hepatitis B e antigen-positive chronic hepatitis B patients. Clin Gastroenterol Hepatol 2009;7:227-233.
Lai M, Hyatt BJ, Nasser I, Curry M, Afdhal NH. The clinical significance of persistently normal ALT in chronic hepatitis B infection. J Hepatol 2007;47:760-767.

Table 1. Baseline data (n=161), univariate analysis of hepatic histological changes in chronic HBV-infected patients with PN-ALT

Variables	Total	G0-1S0-1(47)	G≥2 / S≥2(114)	p
Male, %	101(62.7)	27(57.4)	74(64.9)	0.5
HBV-family history, %	44(27.3)	11(23.4)	33(28.9)	0.4
HBeAg-positive, %	69(42.9)	23(48.9)	46(39)	0.3
age, years	39(18-70)	38±11	39±10	0.12
HBV-DNA (log10), IU/ml	4.4(2.4-8.3)	4.6(2.4-8.3)	4.3(2.4-8.2)	0.2
ALT, U/L	27(9-40)	27(11-40)	27.5(9-40)	0.87
G0/G1/G2/G3/G4, n(%)	0/56(34.8)/82(50.9)/23(14.3)/0
S0/S1/S2/S3/S4, n(%)	22(13.7)/55(34.2)/45(28)/24(14.9)/15(9.3)
ALT, Alanine Transaminase; HBV, Hepatitis B virus; PN-ALT, persistently normal ALT level; G, Inflammation grade; S, Fibrosis stage

Table 2. Characteristics of HBV-DNA subgroup in HBeAg-positive among chronic HBV-infected patients PN-ALT

	HBeAg-positive
Patient characteristics	HBV-DNA (log10IU/ml)
	≤6.7	>6.7	p
N	33	36
Male, n (%)	15(45.5)	15(41.7)	0.75
HBV-Family history, n (%)	12(36.4)	10(27.8)	0.45
Age, years	38±9	31±7.6	0.001
≤30	6(18.2)	20(55.6)
>30	27(81.8)	16(44.4)
ALT, U/L	28(9-40)	25(12-40)	0.15
HBV DNA, log10IU/ml	5.8(2.7-6.7)	7.25(6.7-8.3)	/
Inflammation grade
G0-1	7(21.2)	21(58)	0.002
G2-4	26(78.8)	15(42)	0.002
Fibrosis stage
S0-1	14(42.4)	24(66.7)	0.04
S2-4	19(57.6)	12(33.3)	0.04
ALT, Alanine Transaminase; HBV, Hepatitis B virus; HBeAg, Hepatitis B e antigen; PN-ALT, persistently normal ALT level;

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Liver Histological Abnormalities Were Better Reflected by Virus Level in Chronic Hbv Infected Patients Aged ≤ 30 Years, Hbeag-Positive and Persistently Normal Alt

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