Professor Hoofnagle of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in his lecture “Treatment of Chronic Viral Hepatitis”, looked at the future direction of chronic hepatitis B treatment. He suggested that long-term treatment with nucleoside analogs until HBsAg is undetectable may be the ideal treatment strategy; to achieve long-term sustained and effective suppression of HBV DNA, viral resistance must be avoided or early intervention is required if resistance occurs; newer nucleoside analogs (entecavir and TDF) have lower resistance rates and stronger antiviral effects, but their long-term efficacy and safety are not yet known. Hoofnagle noted that achieving sustained virologic response (SVR) means improvement in serum ALT and histology, cessation of liver fibrosis progression, and minimal risk of liver cancer, with SVR rates of only 50% with current therapies. A 2005 study showed significant differences in the expression of 18 genes between responders and non-responders. Interferon-stimulated genes (ISG) may already be present in non-responders, and pegylated interferon does not further increase ISG activity; in addition, the virus may inhibit interferon activity. How to break the therapeutic bottleneck? On the one hand, a series of protease inhibitors and polymerase inhibitors have been introduced, and these new drugs combined with pegylated interferon and ribavirin have improved SVR rates; on the other hand, older drugs such as silymarin, nitazoxanide, and S-adenomethionine can be used both for salvage therapy in non-responders and in combination with pegylated interferon and ribavirin to improve SVR rates. In the near future, the addition of certain protease inhibitors to pegylated interferon + ribavirin has increased SVR rates to 75%.