Indications for antiviral therapies for persistent HBV infection
are based on the need for treatment, related to a range of factors such as age, disease stage, degree of liver disease (inflammation and fibrosis), and risk of further progression to liver cirrhosis and/or HCC. The three key criteria that are currently used in determining whether to treat are histological progression, ALT levels and HBV DNA levels. In numerous reports on factors linked to antiviral therapeutic effects, ALT and HBV DNA levels have been shown to influence the progression of the disease, and are also noted as common factors associated with therapeutic effects for both IFN and NAs. Guidelines from the American Association for the Study of Y-27632 in vitro Liver Roxadustat molecular weight Diseases (AASLD), the European Association for the Study of the Liver (EASL), the Asia Pacific Association for the Study of the Liver (APASL), and the Japanese Ministry of Health, Labour and Welfare (MHLW) research group all nominate these
factors as patient selection criteria, as shown in Table 7. ALT and HBV DNA levels change over the natural course of the disease, and this must be taken into account when deciding when to initiate treatment. 2) 1–2 × ULN >40 years Family history of HCC liver biopsy 2) <1 × ULN liver biopsy 2) ≤2 × ULN >40 years liver biopsy 2) 1–2 × ULN >40 years Family history of HCC liver biopsy 2) <1 × ULN liver biopsy 2) ≤2 × ULN >40 years liver biopsy 4 (<4a) >1 × ULN (>2 × ULNa) Recently a link has been posited between HBsAg levels and carcinogenesis, with some reports claiming that patients with high HBsAg levels (even when the HBV DNA level is less than 4 log copies/mL following HBeAg seroconversion) have higher rates of further progression and cancinogenesis. However there is still insufficient evidence on the link between HBsAg find more levels and long term outcomes, and further studies are required before HBsAg levels can be incorporated into the patient
selection criteria. Recommendations The three key criteria currently used to determine whether to treat persistent HBV infection are histological progression, ALT levels and HBV DNA levels. The question of whether HBsAg levels should be added to these criteria requires further studies. Indications for treatment for chronic hepatitis include abnormal ALT levels, high HBV DNA levels, and presence of histological liver disease. Treatment is therefore not indicated when ALT levels are within the normal range and histological disease is mild or absent altogether – in other words, for HBeAg positive asymptomatic carriers during the immune tolerance phase and inactive carriers following HBeAg seroconversion. Note that in cases of HBeAg-positive chronic hepatitis with elevated ALT levels, there is a 7–16% probability (in annual terms) of the HBeAg seroconversion over the natural course of the disease.