ABSTRACT
Objectives
This study aims to investigate the impact of comorbidity with chronic hepatitis B (CHB) on the survival rates and incidence of liver cancer in patients with alcohol‐related liver disease (ARLD).
Methods
Patients with ARLD and those with ARLD co‐morbid with CHB were included in this study and designated as the ARLD group and the ARLD + HBV group, respectively. Propensity score matching (PSM) was then employed to compare survival rates and liver cancer development between these two groups.
Results
Among the 404 patients, 254 were in the ARLD group and 150 in the ARLD + HBV group. After propensity score matching, each group comprised 67 patients. Initially, the ARLD + HBV group exhibited lower 5‐year survival rates compared to the ARLD group (51.3% vs. 70.1%, p < 0.001). However, PSM mitigated this difference, with survival rates now comparable (61.2% vs. 60.9%, p = 0.390). Notably, the ARLD + HBV group showed a higher incidence of liver‐specific mortality after matching (32.6% vs. 6.2%, p = 0.018). Furthermore, although a higher proportion of patients in the ARLD + HBV group developed liver cancer post‐matching, the difference was not statistically significant compared to the ARLD group (15.7% vs. 9.8%, p = 0.170).
Conclusion
Co‐morbidity with CHB in ARLD patients elevates the risk of liver‐related mortality.
Keywords: alcohol‐related liver disease, chronic hepatitis B, liver‐specific mortality, propensity scoring matching
Abbreviations
- 5‐HTOL
5‐hydroxytryptophol
- AH
alcoholic hepatitis
- ALT
alanine aminotransferase
- ARLD
alcohol‐related liver disease
- AST
aspartate aminotransferase
- CDT
carbohydrate deficient transferrin
- CHB
chronic hepatitis B
- EtG
ethyl glucuronide
- GGT
gamma‐glutamyl transferase
- HB
hemoglobin
- HCC
hepatocellular carcinoma
- INR
international normalized ratio
- MDF
Maddery discriminant function
- MELD
model for end‐stage liver disease
- PSM
propensity score matching
- WBC
white blood cell
1. Introduction
Liver diseases, a leading cause of morbidity and mortality, result in 2 million deaths annually worldwide [1]. Within mainland China, hepatitis B infection accounted for 63% of cirrhosis‐related fatalities and 53% of liver cancer‐related deaths, while alcohol intake contributes to 20.0% and 35.5% of such mortalities, respectively [2]. Reports indicate that between 2006 and 2010, among the top 31 hospitals in China, the number of patients admitted for viral hepatitis‐related liver cirrhosis decreased by 10%, whereas hospitalizations for alcoholic liver cirrhosis increased by 33% [3]. This shift in the etiology‐specific hospitalization for liver diseases highlights the need for greater attention to the management of alcoholic liver disease, particularly in patients with coexisting viral hepatitis. This underscores the necessity for a dual approach involving both antiviral therapy and alcohol abstinence.
Prior studies have elucidated the adverse effects of excessive alcohol consumption in patients with chronic hepatitis B (CHB), including delayed clearance of the hepatitis B e antigen, exacerbated cirrhosis progression, and an elevated risk of hepatocellular carcinoma (HCC) [4, 5, 6]. Nevertheless, the synergistic relationship between alcohol and HBV infection remains controversial. While heavy drinking has been shown to have a significant synergistic effect in patients with hepatitis B virus infection [4, 7, 8], mild to moderate or habitual drinking is associated with only a moderate increase in HCC risk, with relative risks ranging from 1.13 to 1.6 [9, 10, 11]. Furthermore, Chung et al. [12] observed no significant impact of hazardous drinking on the effectiveness of 12‐month entecavir antiviral treatment. Consequently, the relationship between hepatitis B virus infection and alcohol consumption remains equivocal.
Previous studies found that patients with both alcoholism and HBV infection had a higher incidence of HCC than those with either condition alone [4, 7] However, both studies reported imbalances in baseline characteristics among the different groups, and no measures were taken to address potential biases. To overcome these limitations, we employed propensity score matching (PSM) in our investigation to balance baseline characteristics, reduce their impact on patient survival and liver cancer development, and thus provide more convincing results.
2. Method
2.1. Patients and Study Design
We conducted a retrospective cohort study involving consecutively hospitalized adult patients with ARLD and ARLD coexisting with CHB at Beijing Ditan Hospital of Capital Medical University from January 2015 to December 2018. Patients with ARLD and those with ARLD combined with CHB were designated as the ARLD group and ARLD + HBV group, respectively. The inclusion and exclusion criteria are as follows.
2.2. Inclusion Criteria
(1) Age ≥ 18; (2) diagnosis of ARLD and alcoholic hepatitis (AH) was according to the EASL Clinical Practice Guidelines: Management of alcohol‐related liver disease [13]; (3) diagnosis of CHB was according to with EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection [14]; (4) diagnosis of live cancer was according to the Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology [15]; (5) complete data.
2.3. Exclusion Criteria
(1) Co‐morbid other viral hepatitis (hepatitis C, hepatitis E, and so on), autoimmune liver diseases or drug‐induced liver injury; (2) history of liver transplantation; (3) diagnosis as liver cancer or underwent hepatectomy before; (4) complication of serious psychological disorder.
This study was approved by the Ethics Committee of Beijing Ditan Hospital of Capital Medical University (NO. JDLY2021‐003‐01), which waived the requirement for informed consent. Demographic and laboratory indicators, as well as imaging data, were collected. Patients were followed for 5 years or until the occurrence of endpoint events, which included death, liver transplantation, or the development of liver cancer.
2.4. Statistical Analysis
Statistical analysis was performed using SPSS version 26 and R version 4.2.2.
A 1:1 PSM procedure was employed to compare the two groups, aiming to minimize the impact of confounding variables. Propensity scores were derived using a logistic regression model that included covariates such as age, gender, daily alcohol consumption, and laboratory parameters. A caliper of 0.05 was applied with a nearest neighbor matching method to ensure the comparability of the matched pairs. Baseline characteristics, including clinical features and laboratory parameters, were compared before and after PSM. Quantitative data conforming to a normal distribution were presented as means ± standard deviations, while medians with interquartile ranges (IQRs) were used for data that were not normally distributed. Differences between groups for quantitative data were assessed using Student's t‐test or the Mann–Whitney U test, as appropriate. Qualitative data were expressed as counts (percentages) and compared using chi‐square tests. The Kaplan–Meier curve was used to estimate survival rates and liver cancer incidence, with differences between groups assessed using the log‐rank test. A two‐tailed p‐value < 0.05 was considered statistically significant.
3. Results
3.1. Patients Screening and Baseline Characteristics
A total of 1050 ARLD patients were hospitalized at Beijing Ditan Hospital from January 2015 to December 2018. After excluding patients with other liver diseases, 404 patients were included in the PSM analysis. These patients were divided into the ARLD group (n = 254) and the ARLD + HBV group (n = 150). Following PSM, which adjusted for covariates such as age, gender, white blood cell (WBC) count, hemoglobin (HB), aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, gamma‐glutamyl transferase (GGT), sodium (Na), international normalized ratio (INR), and daily alcohol consumption, 67 patients remained in each group. The specific process of patient screening and matching is shown in Figure 1.
Figure 1.
Flowchart for screening patients and conducting propensity score matching.
Regarding clinical indicators, the ARLD group had a significantly higher prevalence of cirrhosis (p < 0.001) and ascites (p < 0.001) compared to the ARLD + HBV group. Laboratory parameters revealed that the ARLD group had higher WBC counts (p = 0.003) and lower levels of HB (p < 0.001), ALT (p < 0.001), AST (p < 0.001), and Na (p = 0.001). Additionally, the daily alcohol consumption in the ARLD group was significantly higher than in the ARLD + HBV group (160 vs. 100 g/day, p < 0.001). However, no significant difference was found in disease severity between the two groups, as evaluated by the model for end‐stage liver disease (MELD) score, Maddrey discriminant function (MDF), and Child‐Pugh score (Table 1). After matching, the two groups achieved balance in baseline characteristics (Table 2).
Table 1.
Baseline characteristics before matching.
| Variable | ARLD (n = 254) | ARLD + HBV (n = 150) | p‐value |
|---|---|---|---|
| Clinical characteristic | |||
| Age, year | 54.43 ± 11.014 | 53.00 (47–57.25) | 0.053 |
| Male, n% | 249 (98.0) | 145 (96.7) | 0.510 |
| Relapse, n% | 154 (60.6) | 105 (70.0) | 0.068 |
| Daily alcohol assumption (g/day) | 160 (100–250) | 100 (75–150) | < 0.001* |
| Cirrhosis, n% | 214 (84.3) | 103 (68.7) | < 0.001* |
| Ascites, n% | 175 (68.9) | 73 (48.7) | < 0.001* |
| Varices bleeding, n% | 28 (11.0) | 15 (10.0) | 0.868 |
| Encephalopathy, n% | 40 (15.7) | 26 (17.3) | 0.678 |
| Laboratory parament | |||
| WBC (109/L) | 5.37 (3.84–8.00) | 4.58 (3.43–6.53) | 0.003* |
| HB (g/L) | 107.65 ± 29.64 | 123.40 (104.40–144.38) | < 0.001* |
| PLT (g/L) | 95.40 (62.00–149.00) | 84.40 (58.23–157.25) | 0.216 |
| ALT (U/L) | 26.1 (17.35–44.80) | 63.65 (25.60–374.85) | < 0.001* |
| AST (U/L) | 55.3 (35.25–91.40) | 79.95 (36.03–207.78) | < 0.001* |
| AST/ALT | 1.98 (1.40–2.80) | 1.02 (0.52–1.57) | < 0.001* |
| γ‐GGT (U/L) | 142.10 (49.70–366.75) | 115.15 (55.18–241.05) | 0.073 |
| ALP (U/L) | 99.00 (74.15–126.80) | 102.25 (75.80–133.05) | 0.356 |
| TBIL (μmol/L) | 40.50 (21.45–105.50) | 45.40 (21.63–142.60) | 0.511 |
| ALB (g/L) | 30.90 (25.90–35.40) | 32.30 (27.83–37.23) | 0.089 |
| BUN (mmol/L) | 4.81 (3.39–7.45) | 4.62 (3.53–6.24) | 0.607 |
| Cr (μmol/L) | 66.40 (55.00–82.20) | 69.30 (60.63–78.30) | 0.194 |
| PT‐INR | 1.36 (1.16–1.77) | 1.35 (1.14–1.69) | 0.452 |
| Na (mmol/L) | 138.40 (135.60–141.50) | 140.15 (137.50–142.35) | 0.001* |
| Assessment of disease severity | |||
| MELD | 17.62 (13.96–24.62) | 18.49 (14.19–24.67) | 0.864 |
| MELD ≥ 21, n% | 97 (38.2) | 56 (37.3) | 0.916 |
| MDF | 19.86 (8.73–44.86) | 21.07 (8.26–40.78) | 0.848 |
| Maddery ≥ 32, n% | 89 (35.0) | 48 (32.0) | 0.587 |
| Child pugh A, n% | 50 (19.7) | 35 (23.3) | 0.449 |
| Child pugh B/C, n% | 204 (80.3) | 115 (76.7) | 0.449 |
Note: *p‐value < 0.05 indicated a significant difference.
Abbreviations: ALB, albumin; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; AST/ALT, aspartate transaminase/Alanine transaminase; BUN, blood urine nitrogen; Cr, creatine; HB, hemoglobin; MDF, Maddrey discriminant function; MELD, model for end‐stage liver diseases score; PLT, platelet count; PT‐INR, prothrombin time‐international standardization ratio; TBIL, total bilirubin; WBC, white blood cell; γ‐GGT, γ‐gamma‐glutamyl transferase.
Table 2.
Baseline characteristics after matching.
| Variable | ARLD (n = 67) | ARLD + HBV (n = 67) | p‐value |
|---|---|---|---|
| Clinical characteristic | |||
| Age, year | 52.23 ± 10.00 | 53.70 ± 8.31 | 0.329 |
| Male, n% | 63 (94.0) | 63 (94.0) | 1.000 |
| Relapse, n% | 34 (50.7) | 40 (59.7) | 0.385 |
| Daily alcohol assumption (g/day) | 125 (97.75–250) | 125 (100–200) | 0.843 |
| Cirrhosis, n% | 51 (76.1) | 54 (80.6) | 0.675 |
| Ascites, n% | 37 (55.2) | 37 (55.2) | 1.000 |
| Varices bleeding, n% | 9 (13.4) | 7 (10.4) | 0.791 |
| Encephalopathy, n% | 8 (11.9) | 13 (19.4) | 0.342 |
| Laboratory parament | |||
| WBC (109/L) | 4.72 (3.55–7.05) | 4.20 (3.07–6.36) | 0.395 |
| HB (g/L) | 111.91 ± 33.15 | 116 (99–133) | 0.941 |
| PLT (g/L) | 92.50 (52.38–163.5) | 72 (51–112) | 0.177 |
| ALT (U/L) | 36.7 (22.8–63.15) | 32.5 (23.9–93.9) | 0.527 |
| AST (U/L) | 47.4 (34.7–82.93) | 59 (29–112.8) | 0.344 |
| AST/ALT | 1.42 (0.97–2.20) | 1.27 (0.92–1.93) | 0.812 |
| γ‐GGT (U/L) | 111.95 (34.6–226.55) | 99.2 (34.3–218.4) | 0.739 |
| ALP (U/L) | 92.05 (68.15–122.35) | 97.5 (73.7–130.9) | 0.349 |
| TBIL (μmol/L) | 34.1 (17.38–82) | 44.3 (19.4–114.8) | 0.392 |
| ALB (g/L) | 32.29 ± 7.69 | 30.70 ± 5.85 | 0.201 |
| BUN (mmol/L) | 4.93 (3.54–7.20) | 4.65 (3.72–6.58) | 0.729 |
| Cr (μmol/L) | 63 (55–79) | 66 (59–79) | 0.595 |
| PT‐INR | 1.35 (1.08–1.88) | 1.46 (1.16–1.81) | 0.995 |
| Na (mmol/L) | 139.55 (136.38–142.53) | 139.7 (137.1–141.5) | 0.959 |
| Assessment of disease severity | |||
| MELD | 16.13 (12.73–25.1) | 19.22 ± 7.11 | 0.481 |
| MELD ≥ 21, n% | 24 (35.8) | 24 (35.8) | 1.000 |
| Maddery | 17.07 (5.4–50.25) | 25.64 (7.91–42.51) | 0.874 |
| Maddery ≥ 32, n% | 26 (38.8) | 26 (38.8) | 1.000 |
| Child pugh A, n% | 19 (28.4) | 15 (22.4) | 0.552 |
| Child pugh B/C, n% | 48 (71.6) | 52 (77.6) | 0.552 |
Note: *p‐value < 0.05 indicated a significant difference.
Abbreviations: ALB, albumin; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; AST/ALT, aspartate transaminase/Alanine transaminase; BUN, blood urine nitrogen; Cr, creatine; HB, hemoglobin; MDF, Maddrey discriminant function; MELD, model for end‐stage liver diseases score; PLT, platelet count; PT‐INR, prothrombin time‐international standardization ratio; TBIL, total bilirubin; WBC, white blood cell; γ‐GGT, γ‐gamma‐glutamyl transferase.
3.2. Survival
3.2.1. Cumulative 5‐Year Overall Survival Rate
The median follow‐up time was 52.18 months (50.86–53.51) for patients with ARLD and 53.71 months (52.16–55.27) for patients with ARLD + HBV. A total of 121 patients in the ARLD group and 41 patients in the ARLD + HBV group succumbed by the end of follow‐up. The 1‐, 3‐, and 5‐year cumulative survival rates for the ARLD group were 73.6%, 56.7%, and 51.3%, respectively, while those for the ARLD + HBV group were 84.0%, 78.6%, and 70.1%. Before PSM, patients in the ARLD group demonstrated significantly lower 5‐year survival rates than those in the ARLD + HBV group (p < 0.001) (Figure 2A). Following PSM, 26 patients in the ARLD group and 23 in the ARLD + HBV group died by the end of the follow‐up period. The 1‐, 3‐, and 5‐year cumulative survival rates postmatching were 74.6%, 64.2%, and 61.2%, respectively, for the ARLD group and 85.0%, 77.5%, and 60.9%, respectively, for the ARLD + HBV group. No significant difference in 5‐year survival was observed between the groups postmatching (p = 0.390) (Figure 2B).
Figure 2.
Overall survival curves by different etiology of liver disease. (A) Comparison of survival between the ARLD group and the ARLD + HBV group before propensity score matching. (B) Comparison of survival between the ARLD group and the ARLD + HBV group after propensity score matching.
3.2.2. Liver‐Specific Mortality
The causes of death were further analyzed. Before matching, 31 patients in the ARLD group and 24 patients in the ARLD + HBV group died from liver‐related events. There was no significant difference in 5‐year liver‐specific mortality between the two groups (16.6% vs. 22.5%, p = 0.460) (Figure 3A). However, after PSM, the ARLD + HBV group had a higher liver‐specific mortality compared to the ARLD group (32.6% vs. 6.2%, p = 0.018) (Figure 3B).
Figure 3.
Evaluation of liver‐specific mortality by different etiology of liver disease. (A) Comparison of liver‐specific mortality between the ARLD group and the ARLD + HBV group before propensity score matching. (B) Comparison of liver‐specific mortality between the ARLD group and the ARLD + HBV group after propensity score matching.
3.3. Development of Liver Cancer During Follow‐Up
During the 5‐year follow‐up, 11 patients in the ARLD group and 13 patients in the ARLD + HBV group developed liver cancer. The cumulative incidence of liver cancer at 1, 3, and 5 years was 1.5%, 3.2%, and 8.9% in the ARLD group, and 2.0%, 4.7%, and 9.0% in the ARLD + HBV group, respectively. There was no significant difference in liver cancer development between the two groups at the end of the follow‐up period (p = 0.520) (Figure 4A). After matching, the cumulative incidence rates of liver cancer at 1, 3, and 5 years were 0.0%, 2.0%, and 9.8% in the ARLD group, and 3.0%, 13.4%, and 15.7% in the ARLD + HBV group, respectively. No significant difference was found between the two groups (p = 0.170) (Figure 4B).
Figure 4.
Evaluation of development of liver cancer by different etiology of liver disease. (A) Comparison of development of liver cancer between the ARLD group and the ARLD + HBV before matching. (B) Comparison of development of liver cancer between the ARLD group and the ARLD + HBV after matching.
3.4. Antiviral Status in the ARLD + HBV Group
A total of 133 patients (88.7%) in the ARLD + HBV group received antiviral therapy during the follow‐up period. The remaining 17 patients, who had a negative HBV‐DNA load at baseline, did not receive antiviral treatment. Among those treated, 125 patients (94.0%) received entecavir, six patients (4.5%) received tenofovir disoproxil fumarate (TDF), one patient (0.8%) received Peg‐IFNα‐2a therapy, and one patient (0.8%) received a combination of entecavir and Peg‐IFNα‐2a. Following antiviral therapy, 99 of 133 patients (74.4%) achieved a negative HBV viral load, two patients (1.5%) did not achieve a negative viral load, and data on antiviral status were missing for 32 patients (24.1%). After matching, 59 patients (88.1%) received antiviral therapy, with 47 of them (79.7%) achieving a negative HBV viral load, one patient (1.7%) failing to achieve a negative viral load, and data on antiviral status missing for 11 patients (18.6%). There was no significant difference in the proportion of patients receiving antiviral therapy (p = 0.897) or achieving a negative viral load (p = 0.547) before and after matching.
4. Discussion
Previous research has indicated that patients with both hepatitis B virus infection and heavy alcohol consumption face a significantly higher risk of developing liver cancer compared to those with only one of these factors. However, it is important to note that prior studies have largely overlooked differences in baseline characteristics among various patient groups. Hence, this study balanced the characteristics of patients with ARLD and those with ARLD co‐morbid with CHB to improve comparability. Additionally, liver‐specific mortality was analyzed to obtain more reliable results.
In recent years, novel indicators such as carbohydrate‐deficient transferrin (CDT), 5‐hydroxytryptophol (5‐HTOL), and ethyl glucuronide (EtG) have been proposed as potential tools for identifying patients with alcoholic‐related liver disease (ARLD) [13, 16]. Nevertheless, the AST/ALT ratio remains widely used in clinical practice for this purpose. In this study, patients in the ARLD group exhibited a higher AST/ALT ratio compared to those in the ARLD + HBV group. Notably, the latter group consistently demonstrated a ratio below the threshold of 1.5, which aligns with prior research [4]. Furthermore, disparities were observed in other laboratory indicators such as WBC, HB, and Na between the two patient groups. Although conclusive evidence is lacking, these variations may lead to different outcomes for patients in our study. The use of PSM in this study enables a more accurate comparison of survival rates and cancer incidence between patients with ARLD alone and those with both ARLD and HBV infection.
Patients with ARLD generally experience poor long‐term survival [17, 18]. However, there are limited studies on the survival of patients with ARLD co‐morbid with HBV infection. In this study, the cumulative 5‐year survival rate for the ARLD group was significantly lower than that for the ARLD + HBV group before matching. This difference may be attributed to the higher alcohol consumption observed in the latter group, a factor known to accelerate disease progression in patients with cirrhosis [8, 12]. After adjusting for alcohol consumption and other disparate laboratory indicators, the survival outcomes for both patient groups converged to a comparable level. A 10‐year cohort study by Abassa et al. [4] found that alcohol consumption does not affect the effectiveness of antiviral medications. The high proportion of patients in the ARLD + HBV group who received antiviral therapy and achieved undetectable HBV viral loads likely contributed to the comparable survival rates observed postmatching.
Previous studies have highlighted the synergistic effect of heavy alcohol consumption in promoting the progression to liver cancer, though the exact threshold and quantitative relationship remain uncertain [5, 19, 20]. Lin et al. [7] observed that cirrhotic patients with both alcoholism and HBV infection had a significantly higher 10‐year cumulative incidence of HCC compared to those with alcoholism alone (52.8% vs. 25.6%, p < 0.001). Similarly, Abassa et al. [4] found that patients with alcohol‐induced liver disease co‐morbid with HBV had a significantly higher risk of developing HCC compared to those with alcohol‐induced liver disease alone (52.2% vs. 10.3%, p < 0.001). Our study corroborates these findings, showing a higher likelihood of liver cancer progression among patients in the ARLD + HBV group after matching, although the difference was not statistically significant between the two groups.
Furthermore, extensive research has explored various risk factors associated with liver cancer development. Notably, females are more susceptible to alcohol‐related cirrhosis, with an intake threshold of 84 grams per week, compared to males, who require 168 g per week [21]. Additionally, Ganne‐Carrié et al. [22] highlighted male gender as an independent predictor for HCC incidence (adjusted hazard ratio [HR]: 2.66, 95% confidence interval [CI]: 1.12–6.32). In a meta‐analysis, Abdel‐Rahman et al. [23] identified smoking as a risk factor for HCC development (pooled odds ratio [OR]: 1.55, 95% CI: 1.46–1.65). As discussed, the occurrence of liver cancer is influenced not only by viral infections and alcohol consumption but also by these factors. The development of liver cancer involves a complex interplay of these factors. Further research is essential to unravel the intricate roles of these factors in the etiology and progression of liver cancer.
The study has certain limitations. First, it includes a wide range of disease presentations, from steatosis to alcoholic cirrhosis, which presents a significant challenge for PSM. Additionally, as a retrospective study, it lacks histological evidence for diagnosing ARLD or CHB, which introduces inherent limitations. The small sample size also prevented us from achieving statistical significance regarding liver cancer development. Furthermore, genetic factors and gene polymorphisms may significantly impact patient survival, but these genetic determinants are difficult to match between groups, adding complexity to the analysis. Future prospective studies with larger sample sizes and histological confirmation of liver disease are needed to validate these findings. Moreover, investigating genetic factors and their interactions with environmental exposures could offer further insights into liver disease progression.
5. Conclusion
In summary, this retrospective study compared patients with ARLD to those with concurrent CHB, examining their survival and liver cancer development. We observed a higher risk of liver‐related mortality in ARLD patients with CHB comorbidity. However, further research is essential to confirm the impact of CHB comorbidity on liver cancer development in patients with ARLD.
Author Contributions
Fangfang Duan: writing–original draft, formal analysis, data curation. Shanshan Song: formal analysis. Hang Zhai: data curation. Yazhi Wang: data curation. Jun Cheng: writing–review and editing. Song Yang: writing–review and editing, writing–original draft.
Conflicts of Interest
The authors declare no conflicts of interest.
Transparency Statement
The lead author Song Yang affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Acknowledgments
This study was supported by the High‐level public health talent cultivation project (XKGG‐02‐30), Beijing Municipal Administration of Hospitals Incubating Program (PX2022071) and the Tianqing Foundation of Chinese Foundation for hepatitis prevention and control (TQGB20210050).
Fangfang Duan and Shanshan Song contributed equally to this study.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
- 1. Asrani S. K., Devarbhavi H., Eaton J., and Kamath P. S., “Burden of Liver Diseases in the World,” Journal of Hepatology 70 (2019): 151–171, 10.1016/j.jhep.2018.09.014. [DOI] [PubMed] [Google Scholar]
- 2.World Bank, Country Profiles (World Bank, 2017), https://datacatalog.worldbank.org/dataset/country-profiles.
- 3. Bao X. Y., Xu B. B., Fang K., Li Y., Hu Y. H., and Yu G. P., “Changing Trends of Hospitalisation of Liver Cirrhosis in Beijing, China,” BMJ Open Gastroenterology 2 (2015): e000051, 10.1136/bmjgast-2015-000051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Abassa K. K., Wu X. Y., Xiao X. P., Zhou H. X., Guo Y. W., and Wu B., “Effect of Alcohol on Clinical Complications of Hepatitis Virus‐Induced Liver Cirrhosis: A Consecutive Ten‐Year Study,” BMC Gastroenterology 22 (2022): 130, 10.1186/s12876-022-02198-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Xu H. Q., Wang C. G., Zhou Q., and Gao Y. H., “Effects of Alcohol Consumption on Viral Hepatitis B and C,” World Journal of Clinical Cases 9 (2021): 10052–10063, 10.12998/wjcc.v9.i33.10052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Rehm J., Patra J., Brennan A., et al., “The Role of Alcohol Use in the Aetiology and Progression of Liver Disease: A Narrative Review and a Quantification,” Drug and Alcohol Review 40 (2021): 1377–1386, 10.1111/dar.13286. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Lin C. W., Lin C. C., Mo L. R., et al., “Heavy Alcohol Consumption Increases the Incidence of Hepatocellular Carcinoma in Hepatitis B Virus‐Related Cirrhosis,” Journal of Hepatology 58 (2013): 730–735, 10.1016/j.jhep.2012.11.045. [DOI] [PubMed] [Google Scholar]
- 8. Ribes J., Clèries R., Rubió A., et al., “Cofactors Associated With Liver Disease Mortality in an HBsAg‐Positive Mediterranean Cohort: 20 Years of Follow‐Up,” International Journal of Cancer 119 (2006): 687–694, 10.1002/ijc.21882. [DOI] [PubMed] [Google Scholar]
- 9. Chen C. J., “Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level,” Journal of the American Medical Association 295 (2006): 65–73, 10.1001/jama.295.1.65. [DOI] [PubMed] [Google Scholar]
- 10. Jee S. H., Ohrr H., Sull J. W., and Samet J. M., “Cigarette Smoking, Alcohol Drinking, Hepatitis B, and Risk for Hepatocellular Carcinoma in Korea,” Journal of the National Cancer Institute 96 (2004): 1851–1856, 10.1093/jnci/djh334. [DOI] [PubMed] [Google Scholar]
- 11. Wang L. Y., “Risk of Hepatocellular Carcinoma and Habits of Alcohol Drinking, Betel Quid Chewing and Cigarette Smoking: A Cohort of 2416 HBsAg‐Seropositive and 9421 HBsAg‐Seronegative Male Residents in Taiwan,” Cancer Causes and Control 14 (2003): 241–250, 10.1023/a:1023636619477. [DOI] [PubMed] [Google Scholar]
- 12. Chung W. G., Kim H. J., Choe Y. G., et al., “Clinical Impacts of Hazardous Alcohol Use and Obesity on the Outcome of Entecavir Therapy in Treatment‐Naïve Patients With Chronic Hepatitis B Infection,” Clinical and Molecular Hepatology 18 (2012): 195–202, 10.3350/cmh.2012.18.2.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. European Association for the Study of the Liver , “EASL Clinical Practice Guidelines: Management of Alcohol‐Related Liver Disease,” Journal of Hepatology 69 (2018): 154–181, 10.1016/j.jhep.2018.03.018. [DOI] [PubMed] [Google Scholar]
- 14. European Association for the Study of the Liver , “EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection,” Journal of Hepatology 67 (2017): 370–398, 10.1016/j.jhep.2017.03.021. [DOI] [PubMed] [Google Scholar]
- 15. Benson A. B., D'Angelica M. I., Abbott D. E., et al., “Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology,” Journal of the National Comprehensive Cancer Network 19 (2021): 541–565, 10.6004/jnccn.2021.0022. [DOI] [PubMed] [Google Scholar]
- 16. Jones A. W., “Brief History of the Alcohol Biomarkers CDT, EtG, EtS, 5‐HTOL, and PEth,” Drug Testing and Analysis 16 (2024): 570–587, 10.1002/dta.3584. [DOI] [PubMed] [Google Scholar]
- 17. Duan F., Liu C., Liu Y., et al., “Nomogram to Predict the Survival of Chinese Patients With Alcohol‐Related Liver Disease,” Canadian Journal of Gastroenterology and Hepatology 2021 (2021): 1–8, 10.1155/2021/4073503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Huang D. Q., Mathurin P., Cortez‐Pinto H., and Loomba R., “Global Epidemiology of Alcohol‐Associated Cirrhosis and HCC: Trends, Projections and Risk Factors,” Nature Reviews Gastroenterology & Hepatology 20 (2023): 37–49, 10.1038/s41575-022-00688-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Iida‐Ueno A., Enomoto M., Tamori A., and Kawada N., “Hepatitis B Virus Infection and Alcohol Consumption,” World Journal of Gastroenterology 23 (2017): 2651–2659, 10.3748/wjg.v23.i15.2651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Donato F., “Alcohol and Hepatocellular Carcinoma: The Effect of Lifetime Intake and Hepatitis Virus Infections in Men and Women,” American Journal of Epidemiology 155 (2002): 323–331, 10.1093/aje/155.4.323. [DOI] [PubMed] [Google Scholar]
- 21. Becker U., Deis A., Sorensen T. I., et al., “Prediction of Risk of Liver Disease by Alcohol Intake, Sex, and Age: A Prospective Population Study,” Hepatology 23 (1996): 1025–1029, 10.1002/hep.510230513. [DOI] [PubMed] [Google Scholar]
- 22. Ganne‐Carrié N., Chaffaut C., Bourcier V., et al., “Estimate of Hepatocellular Carcinoma Incidence in Patients With Alcoholic Cirrhosis,” Journal of Hepatology 69 (2018): 1274–1283, 10.1016/j.jhep.2018.07.022. [DOI] [PubMed] [Google Scholar]
- 23. Abdel‐Rahman O., Helbling D., Schöb O., et al., “Cigarette Smoking as a Risk Factor for the Development of and Mortality From Hepatocellular Carcinoma: An Updated Systematic Review of 81 Epidemiological Studies,” Journal of Evidence‐Based Medicine 10 (2017): 245–254, 10.1111/jebm.12270. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.