Early Prognostic Predictive System of AECHB and the Diagnosis of Severe Hepatitis B (Liver Failure)

Abstract

This chapter describes the evaluations for the progression of chronic liver diseases, recent achievement for screening and early warning-parameters of AECHB, diagnosis criteria and grading standards of HBV ACLF.

• 1. Several methods have been used to evaluate the progression of chronic liver diseases, including the Child–Turcotte–Pugh (CTP) score, MELD, MESO index, MELD-Na joint formula, iMELD formula, King’s College Hospital (KCH) score, Sequential Organ Failure Assessment (SOFA) score and the Tongji prognostic predictor model (TPPM) score.

• 2. Technologies used for early screening of severe hepatitis B include gene-based diagnostic techniques, such as the polymerase chain reaction, gene sequence analysis, gene chips, and GWAS. Protein-based methods include two-dimensional gel electrophoresis and mass spectrometry; and epigenetic-based methods include assays of DNA methylation and histone modifications. In addition, meta-genomics and systematic biology have been used to analyze microbial sequence and function.

• 3. Early-warning parameters for severe hepatitis B mainly include serum concentrations of ALT, AST, total bilirubin, albumin and pre-albumin, and cholinesterase; and measurements of blood ammonia, prothrombin time and prothrombin activity. Several new parameters related to severe hepatitis B have been identified, including gene mutations (e.g. HBV 1896 site mutation and 1762/1764 double mutation), genetic molecular targets (e.g. CXCL10-201 g/A, IL10-592 t/C, ESR1 IVS1-401 t/C, TBX21-1993 t/C, and ICAM1 R241-E469), immune factors (e.g. TNF-α, reactive oxygen species, reactive nitrogen species, sCD163, hfgl2, HLA-DR, NK cells, CTL, Th17 cells, Treg cells, PD-1/PD-L), and metabolic factors (e.g. lecithin, fat amides and bile acids).

• 4. The clinical diagnosis of severe hepatitis B is mainly based on clinical manifestations, including jaundice, coagulation disorders, hepatic encephalopathy and ascites, and laboratory tests, including prothrombin time, prothrombin activity, international normalized ratio, AST/ALT ratio, and serum concentrations of albumin, bilirubin, cholinesterase, cholesterol, lactic acid, and alpha-fetoprotein.

• 5. At present, there are differences among countries in the standard for diagnosing liver failure. In China, liver failure is referred to as severe hepatitis, whereas, in western counties, liver failure caused by viruses is diagnosed as fulminant hepatitis and refers only to acute liver failure. The main difference is that, in China, the concept of acute fulminant hepatitis has been extended to patients without encephalopathy. In contrast, hepatic encephalopathy II is a necessary condition to diagnose severe hepatitis in the United States, Europe and Japan.

• 6. Liver failure can be subdivided into acute and chronic liver failure. Acute liver failure includes acute and sub-acute liver failure, and chronic liver failure includes acute-on-chronic and chronic decompensated liver failure. To date, hepatic encephalopathy has been necessary for the diagnosis of acute, but not chronic, liver failure, which is characterized by decompensated liver.