Abstract: Objective To investigate the causes of biochemical persistent nonresponse in chronic hepatitis B(CHB) patients with nucleos(t)ide analogues treatment achieving virologic response, and lead to liver disease progression. Methods From December 2016 to June 2018, 40 CHB patients treated with nucleos(t)ide analogues who had no biochemical response after achieving virological response over 1 month were selected to undergo liver biopsy to explore the cause of liver disease progress. Results Histopathologic examination of 40 liver biopsy samples showed 14 cases of nonalcoholic steatohepatitis(NASH, 35%), 9 cases of autoimmune hepatitis(AIH, 22.5%), 7 cases of drug-induced liver injury(DILI, 17.5%), 5 cases of nonspecific inflammation(12.5%), 3 cases of primary biliary cholangitis(PBC, 7.5%), 1 case of hemochromatosis(2.5%) and 1 case of amyloidosis(2.5%). After comprehensive treatments including lifestyle improvement, immunoregulation, hepatoprotective management and avoidance of hepatotoxic drugs, biochemical indexes were decreased significantly(alanine transaminase: 36.33±18.28 vs. 95.15±19.21, alkaline phosphatase: 101.10±37.96 vs. 123.85±39.29, gamma-glutamyltransferase: 76.50±45.55 vs. 183.15±93.12, P<0.05) and as was liver stiffness values(8.17±4.61 vs. 10.85±5.63, P<0.05). Conclusion The common causes of biochemical persistent nonresponse in CHB patients with nucleos(t)ide analogues treatment achieving virologic response are NASH, AIH, DILI, nonspecific inflammation and PBC, thus liver disease in these patients progress. Therefore, it is necessary to explore the causes of liver disease progression in order to give clinical intervention and improve the prognosis as soon as possible.

Key words: Nucleos(t)ide analogue, Chronic hepatitis B, Virological response, Biochemical nonresponse