Background and Aim: Unlike most other countries, in China, liver failure is termed as severe hepatitis. However, there are two differences between liver failure and severe hepatitis: the interval of acute and sub-acute severe hepatitis and the etiology. The aims of this study were to assess the best cutoff time-point to distinguish between acute and sub-acute severe hepatitis caused mainly by hepatitis B virus (HBV; 67.5%) in China and to determine whether the Chinese classifications of severe hepatitis can meet the international criteria based on pathological features and clinical characteristics. Methods: A total of 157 patients with acute, sub-acute and chronic severe hepatitis were involved in the study. Their clinical findings, laboratory data and liver biopsies were retrospectively analyzed. Results: The different incidences of complications between acute and sub-acute severe hepatitis were significant if the cutoff point was set at 15 days or 4 weeks (P < 0.01), but there is no significant differences if the cutoff was 8 weeks. Identifying the better cutoff point with a receiver-operator characteristic curve showed that 28 days was better than 15 days (sensitivity 100% vs 92%; specificity 75% vs 53%). The major differences in histopathology between acute and sub-acute severe hepatitis were: (i) there was a single hepatic necrosis in acute severe hepatitis, but repeated and continuous hepatic necrosis in sub-acute severe hepatitis; and (ii) survivors of acute severe hepatitis had full hepatocyte regeneration in the native liver architecture. Regeneration in survivors with sub-acute severe hepatitis indicated the destruction of nodular architecture; new and old necrosis appeared at the same time. When the cutoff point for acute and sub-acute severe hepatitis was set at 15 days, some sub-acute severe hepatitis cases (full hepatocyte regeneration and one massive necrosis) had an overlap in pathological features with acute severe hepatitis. If the cutoff time-point was set at 4 weeks, the clinical features between acute and sub-acute, as well as the pathological changes, were clearly distinguished. Conclusion: The best cutoff time-point to distinguish between acute and sub-acute severe hepatitis is 4 weeks. This classification meets the international criteria based on the present clinical and pathological results.