Histologic Disease in Chinese Chronic Hepatitis B Patients With Low Viral Loads and Persistently Normal Alanine Aminotransferase Levels

Wang, Hong; Ru, Guoqing; Yan, Rong; Yin, Zhihua; Wang, Ming Shan; Cheng, Ming

doi:10.1097/mcg.0000000000000544

Cited by 30 publications

(23 citation statements)

References 22 publications

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“…We did not consider immune tolerance as one of the states here, which was common among infants and children, due to less epidemiologic data being available and the largest population comprising chronic HBV infection in adults who were inactive carriers in China [5,[26][27][28].…”

Section: Model Schematicsmentioning

confidence: 99%

Disease burden of chronic hepatitis B and complications in China from 2006 to 2050: an individual-based modeling study

Zheng

Ding

et al. 2020

Virol J

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Background: Chronic hepatitis B has become a major public health problem in China. An accurate depiction of the disease burden has not yet been thoroughly conducted. We aimed to project the disease burden of chronic hepatitis B virus (HBV) infection and related complications by modeling various scenarios. Method: An individual-based Markov model was used to predict disease burden from 2006 through 2050. We simulated 5 scenarios with different annual incidences, diagnoses and nucleotide analog (NA) treatment rates as well as treatment eligibility, which included a natural history without diagnosis or NA therapy, a base case, a World Health Organization (WHO)-proposed target case and two ideal cases. Result: The natural history scenario is projected to have the fewest HBsAg losses (27.59 million) and highest number of HBV-related deaths (27.19 million). With improved diagnosis and treatment rates of NA therapy, ideal cases have fewer HBV-related deaths (14.46-14.77 million) than do WHO-proposed cases (15.13 million) and base cases (16.89 million), but the proportion of HBsAg loss is similar among them. With a reduction in new infections, the prevalence of chronic HBV in 2050 is expected to be a minimum of 27.03-27.49 million under WHO and ideal cases. Conclusion: Ideal scenarios 1 and 2 contribute to the lowest disease burden of HBV and its complications in the future, in which new infection control is more effective than increasing diagnosis, treatment rate and treatment eligibility. However, considering the large existing chronic HBV infected population and the low HBsAg loss rate of NA therapy, it is still difficult to avert the increasing trend of cumulative cirrhosis, DC, HCC, LT, and HBV-related death in all scenarios. If new high-potency drugs are not developed, the disease burden of chronic HBV will remain high in the future.

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Section: Model Schematicsmentioning

confidence: 99%

Disease burden of chronic hepatitis B and complications in China from 2006 to 2050: an individual-based modeling study

Zheng

Ding

et al. 2020

Virol J

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“…Moreover, over half of CHB subjects with normal or mildly elevated ALT values belonged to the patients who possessed advanced liver disease, and most of them showed significant changes in liver pathology, which were in accordance with the outcome of other reports. [33][34][35] On the other hand, the results also suggested that the previous notion that CHB-infected patients with normal biochemical targets had "healthy" livers may be incorrect. Otherwise, the patients might suffer from cirrhosis or even developed liver disease if they only got the diagnosis and guidance according to their clinical data.…”

Section: Discussionmentioning

confidence: 76%

Management of individuals with chronic hepatitis B virus infection and persistent normal or mildly elevated aminotransferase levels

Yan

et al. 2018

J of Cellular Biochemistry

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No consensus exists with respect to positive hepatitis B virus (HBV) DNA results and persistent normal or mildly elevated alanine aminotransferase (ALT). The aim of this study is to investigate the appropriate management and prognosis of these populations with chronic hepatitis B (CHB). A total of 235 subjects with positive HBV DNA results and persistent normal or mildly elevated ALT were enrolled in this study. Liver biopsy and liver stiffness measurements (LSM) were performed in all participants at baseline. Antiviral therapy was initiated in patients with significant hepatic inflammation (G ≥ 2) and/or fibrosis (S ≥ 2). The patients were divided into entecavir and adefovir groups based on HBV DNA load (>2000 IU/mL vs <2000 IU/mL). The liver biopsies were repeated at 72 weeks for the patients received antiviral therapy. We found that 112 subjects were hepatitis B e antigen (HBeAg) positive, and 123 subjects were negative. The corresponding median ALTs were 46 (39.5‐52.5) and 48 (41.5‐57.0) U/mL, respectively. G ≥ 2 and/or S ≥ 2 diseases were present in 48.8% (82/168) of the HBeAg‐positive and 51.2% (86/168) of HBeAg‐negative patients, respectively. In addition, 96 HBeAg‐positive and 72 HBeAg‐negative patients were divided into entecavir and adefovir groups. Meanwhile, liver biopsies had greater diagnostic accuracy for determining cirrhosis than LSM (0.711 vs 1.0, P < 0.0001). At the end of the study period, undetectable HBV DNA levels and normal ALT levels were observed in CHB‐infected patients. Furthermore, the patients showed histologic improvement at 72 weeks compared with baseline measurements (G, 1.72 ± 1.00 vs 0.73 ± 0.88, P = 0.0002; S, 1.484 ± 0.90 vs 0.99 ± 1.13, P < 0.0001). Collectively, liver biopsy enhanced diagnostic accuracy for CHB‐infected individuals with persistent normal or mildly elevated aminotransferase levels. Moreover, antiviral therapy can improve or regress the hepatic fibrosis and cirrhosis.

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“…In hepatitis B patients, CHB might probably develop in those with normal ALT. [25] Clinically, it was found that in patients with NAFLD, the ALT level was influenced by age, gender, metabolic factor, and so on. [26] Therefore, the ALT level could not be used to confirm the reason of inflammation, and also could not reflect the conditions of real inflammation in the hepatic cells.…”

Section: Discussionmentioning

confidence: 99%

The expression of thymosin β4 in chronic hepatitis B combined nonalcoholic fatty liver disease

et al. 2016

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The aim of the study was to detect the expression level of thymosin β4 (Tβ4) in serum and tissues of patients with chronic hepatitis B (CHB) combined nonalcoholic fatty liver disease (NAFLD). The effects of Tβ4 in hepatic steatosis, chronic inflammation, and fibrosis development in CHB combined NAFLD patients were also discussed. The study included 46 patients in the case group with CHB and NAFLD and 42 patients in the control group with CHB. ELISA was applied to detect serum Tβ4 and TNF-α level. Furthermore, the correlation analysis of Tβ4 levels with biochemical index, pathological index, and TNF-α level was performed. The Tβ4 immunohistochemical levels of different inflammation fibrosis levels were compared, and the correlation analysis with TNF expression was performed. The Tβ4 levels in patients with CHB combined NAFLD showed no statistical difference when compared to the control group. In patients with CHB combined NAFLD group, the Tβ4 level had no correlation with ALT, AST, TG, FGP, hepatitis B virus (HBV)-DNA levels, and fat grading, but had negative correlation with inflammation score and fibrosis score (P <0.01). The immunohistochemical results of hepatic tissues showed that the expression intensity of severe inflammation fibrosis group had statistical significance compared with that of slight group, and the Tβ4 expression both in serum and in liver tissue negatively correlated with TNF-α expression. Tβ4 could be involved in the regulation of chronic inflammation and fibrosis and plays a defense role in the disease progression of CHB combined NAFLD patients.

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Histologic Disease in Chinese Chronic Hepatitis B Patients With Low Viral Loads and Persistently Normal Alanine Aminotransferase Levels

Abstract: Among patients presenting with low HBV DNA levels and normal ALT levels, about 38.2% had significant liver disease. Neither serum HBsAg nor HBV DNA levels correlate with liver histology. However, APRI≥0.24 might be considered an indicator of liver biopsy.

Cited by 30 publications

References 22 publications

Disease burden of chronic hepatitis B and complications in China from 2006 to 2050: an individual-based modeling study

Disease burden of chronic hepatitis B and complications in China from 2006 to 2050: an individual-based modeling study

Management of individuals with chronic hepatitis B virus infection and persistent normal or mildly elevated aminotransferase levels

The expression of thymosin β4 in chronic hepatitis B combined nonalcoholic fatty liver disease

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