To our knowledge, this study is the first systematic investigation of the etiological composition or prognostic criteria for each LF subclass. In this multicenter retrospective cohort study, the Department of Infectious Diseases of the Fifth People's Hospital of Wuxi (Wuxi Infectious Disease Hospital) is the designated LF treatment center of Wuxi city. It is the central unit of "One City and One Center for Nonbiological Artificial Liver Treatment". The number of patients is relatively small at two participating tertiary general hospitals in southeastern China, where LF patients are also being treated in other public hospitals. In recent decades, there have been limited reports on the proportions of HBV-LF in southeast China, so it is impossible to speculate on the morbidity or mortality trends of HBV-LF. In some studies conducted in southwestern and northern China 1, 12, the incidences of HBV-LF were 91.6% (years: 2000–2012) and 69.2% (years: 2002–2011), respectively, whereas, in our study, it was 64.52% (years: 2018–2020). According to statistical analysis in southwest China, 87.3% of ACLF patients were mainly caused by HBV infection, which is the leading cause of SALF and ACLF 12. Current guidelines and recommendations suggest that the ACLF data include the ACLF and SALF subclasses 6, 7, and we used consistent classification criteria for calculation and comparison. In contrast, our ACLF incidence rate in this study was reduced to 80.27% (297/370, recalculated based on Fig. 1C), and our data were lower than those in Southwest China a decade ago 1.
The morbidity and mortality rates of LF are affected by regional economic development and medical services. Southeast China is a region with a developed economy and medical technology, so further assessment of the morbidity and mortality rate of HBV-LF in southeastern China and an understanding of the economic burden of health care are needed. Similar to previous data in northern and southwestern China 1, 12, the short-term mortality rate in HBV-LF patients is significantly higher than in non-HBV-LF patients. However, it has been shown that our overall SS rate is higher than before 2012 12. That is, timely intervention is the key to preventing deaths and obtaining a successful treatment. Therefore, if the subclasses of LF can be predicted and diagnosed earlier, the timely use of artificial liver support will help to reduce the incidence of hepatic encephalopathy and death 16, 21. LF can be induced by liver diseases of various etiologies, resulting in impaired or decompensated liver function and alterations in its composition, detoxification, drainage, biotransformation function, and other abnormalities 22. LF patients have different causes or trigger factors, including hepatotropic viruses, drugs, alcohol, genetic disorders, and cirrhosis. In the past 30 years, with the explosive growth of China's economy and the improvement of social openness, alcohol consumption has significantly improved, and alcoholic cirrhosis has shown an upward trend growth 23. The outcome of alcohol-related cirrhosis may be different from HBV-related cirrhosis. Alcoholic cirrhosis is more likely to lead to hepatic encephalopathy and LF. Patients with HBV-related cirrhosis are at increased risk of liver cancer and hypersplenism 24. Similarly, the highest proportion of the sex ratio (M/F) of LF patients in our study was 76:9 (8.44), occurring in the HBV-CLF subclass, which predominantly had underlying diseases cirrhosis and liver cancer. However, the incidence of non-HBV-LF was similar to other countries, caused by pharmaceuticals, Chinese herbal medicines, anti-tuberculosis drugs, infections, and alcoholism.
Our study also has several important findings. First, age, the number of hospitalization days, PT-INR, and AT III values are likely to be used as prognostic criteria for the outcomes of LF subclass patients. In addition, drug- or alcohol-induced non-HBV-LF patients who received early non-biological artificial liver support therapy recovered more quickly than the HBV-LF group. However, our previous study showed that the success rate of non-biological artificial liver therapy in LF individuals reached only 55.56% 25, and cirrhosis and liver cancer remain the leading causes of LF death. Furthermore, our study showed that SALF was the main subclass of the HBV-LF group in Wuxi, with the incidence of HBV-LF decreasing from 8.36% in 2018 to 6.24% in 2020 (Supplementary Table 3).
Accumulating studies have demonstrated the value of clinical predictive markers or mortality models for the outcomes of ACLF patients, including the TBil, MELD score, PT-INR, and neutrophil-lymphocyte ratio (NLR) values 21, 26. The MELD score is accepted worldwide as an effective and reliable indicator of prognosis for LF patients and is used to assess the entire course of treatment 6, 21. However, there was a lack of detailed predictive evaluation for each LF subclass. Furthermore, because the definition of ACLF varies in Eastern and Western countries, the triggering event and prognosis may also be different 4, 5. Hence, this study aims to calculate meaningful diagnostic criteria by analyzing a single cause. In addition, based on previous studies, the neutrophil-lymphocyte ratio (NLR) has been identified as a potential marker of HBV-LF survival and prognosis 26. Here, we calculated the ALT, PT-INR, TBil, and AT III values and found that the PT-INR value (≥ 2.05, AUC = 0.726) in the HBV-SALF subclass showed a higher ROC curve that could be used as a predictive indicator of outcomes for patients with HBV-SALF (sensitivity of 57.14%, specificity of 84.62%). In addition, the PT-INR value can also be used as a predictive indicator of outcomes for patients with non-HBV-SLF (≥ 1.92) or non-HBV-ACLF (≥ 2.11). However, the AT III level (≤ 24.50%) can be used as a predictive outcome indicator for patients with HBV-ALF. Therefore, the above initial indicator values can be used as a new reference for the prognosis of outcome for each LF subclass patient. In summary, the AT III value as a prognostic criterion for the LF subclass is also the first time to propose compared with the previous studies.