Hepatitis B, Chronic

This study is part of GBD 2017,1 (link), 20 (link), 21 (link), 22 (link) which was a systematic effort to estimate the levels and trends of burden caused by 359 diseases and injuries by sex, age, year (1990–2017), and location, including seven super-regions, 21 regions, and 195 countries and territories. We modelled the mortality and prevalence of cirrhosis and other chronic liver diseases, hereafter collectively referred to as cirrhosis. We report numbers and age-standardised and age-specific rates for mortality, prevalence, and DALYs, which are the sum of years of life lost (YLLs) due to premature death and years lived with disability (YLDs).1 (link), 20 (link), 21 (link), 22 (link) This study is compliant with the Guidelines for Accurate and Transparent Health Estimates Reporting.
We considered diagnoses coded as B18 and K70–77 in the International Classification of Diseases 10th revision (ICD-10) to be compensated and decompensated cirrhosis. ICD-10 codes B18.0–18.2 were mapped to chronic viral hepatitis B and C in the GBD cause list, B18.8 and 18.9 to other causes, K70 to alcohol-related liver disease, K75.81 to NASH, and the rest of the codes to the category of other causes, which included but was not limited to autoimmune hepatitis (K75.4). The detailed list of ICD-10 codes mapped to the GBD cause list is reported in the appendix (p 4). The causes grouped in the “other chronic liver diseases” category mainly included autoimmune hepatitis, toxic liver diseases, other inflammatory liver diseases, chronic hepatitis not specified, and other diseases of the liver (K76). ICD-10 codes for acute hepatitis were not included in this study. Non-alcoholic fatty liver disease was considered to be a separate entity from compensated and decompensated cirrhosis, and codes for diabetes were also excluded. Finally, deaths caused by hepatocellular carcinoma were excluded because: ICD-10 codes define hepatocellular carcinoma as a cause irrespective of liver cirrhosis; hepatocellular carcinoma can be distinguished from cirrhosis in countries with adequate data; and implications on natural history and management of the two causes are not similar.
Existing evidence shows that ICD-10 coding is valid for defining overall cirrhosis and chronic liver diseases in most of the data sources used to assemble the cause-of-death database but does not have the required accuracy for reporting cirrhosis by the five causes estimated in the current study.23 , 24 (link) The models that we used to split the parent cirrhosis mortality and morbidity into the five causes are described below.

The molecular structure of lamivudine (positive control) and chrysin was drawn by ChemDraw12 (PerkinElmer Informatics, Waltham, MA, USA) as shown in Fig. 1A and B, respectively. The molecular structure of compounds was converted into 3D form, and geometries were optimized in ChemBio3DUltra12 (PerkinElmer Informatics, Waltham, MA, USA). For docking studies, the tested compound chrysin and positive control lamivudine was saved in PDB format. Molecular docking was performed by using Auto dock 4.2 in order to achieve better insights into the binding mechanism of chrysin and lamivudine with HMGB1. Docking guidelines were followed in this docking simulation. To achieve molecular docking, Lamarckian Genetic Algorithm (LGA) was used to define the best potential structures of the ligands that directly interacted with the target protein. Here the ligand was allowed free to explore and interact with the protein's active site in the best possible or threshold energy configuration. Ideal docked configurations were archived and studied for further interaction between receptor-ligand, employing BOVIA Discovery Studio 4.0 to generate 2D interaction plot [34 ]. Docking was eventually visualized by Pymol [35 (link)]. Lamivudine, a nucleoside analogue approved by FDA for the treatment of chronic hepatitis B virus infection, was also docked with the same protein. In the molecular docking analysis, lamivudine was used as a positive control. For protein–ligand interaction, the binding constant (Kb) was calculated using equation (∆G = − RTlnKb (R = universal gas constant, 1.987 kcal/mol/; T = temperature, 298 K) [36 (link)].Fig. 1

A and B represents optimized two-dimensional molecular geometries of anti-HBV compounds lamivudine (nucleoside analogue used as a reference drug in molecular docking analysis only) and chrysin respectively

Chronic hepatitis B was defined as HBsAg positivity for more than 6 months (13 (link)). The diagnosis of compensated cirrhosis was made following liver biopsy, endoscopy, ultrasound, or elastographic evidence of cirrhosis (14 (link)). HCC was diagnosed based on histological or radiological evidence, including computed tomography or magnetic resonance imaging (MRI), and was assessed by clinically experienced physicians (15 (link)).
Demographic characteristics and baseline data, including demographics, complications, blood routine examination, liver function, renal function, coagulation tests, HBV DNA, and alpha-fetoprotein (AFP), were recorded from a computerized database during the 24 h of enrollment. Virological response (VR) was defined as an undetectable HBV DNA load at 1 year. Continuous VR was defined as an undetectable HBV DNA load at the end of the follow-up. Neutrophil–lymphocyte ratio (NLR) was calculated as the neutrophils divided by the lymphocytes. The Model for End-stage Liver Disease (MELD), Child-Turcotte-Pugh (CTP), aspartate transaminase (AST) to platelet ratio index (APRI) score, and fibrosis-4 (FIB-4) scores were calculated according to previous studies (16 (link)–19 (link)). Every 3-6 months, routine laboratory tests and radiological examinations were performed.