1.Accuracy of multivariate discriminant analysis versus fibrosis-4 in evaluating the liver fibrosis degree in patients with chronic HBV infection
Hongyu LIU ; Xiaoting LI ; Jianning JIANG ; Chao JIN ; Cailian CAI ; Keshan WANG ; Fangpeng LING ; Bingling FAN ; Minghua SU
Journal of Clinical Hepatology 2025;41(4):677-683
ObjectiveTo investigate the accuracy of multiple discriminant analysis (MDA) versus fibrosis-4 (FIB-4) in assessing liver fibrosis degree in patients with HBV infection, as well as the possibility of MDA as an indicator for disease progression. MethodsA total of 263 patients with HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from April 2010 to April 2024 were included, and their clinical data were collected. According to the results of pathological examination, they were divided into non-significant fibrosis group (F<2) with 126 patients and significant fibrosis group (F≥2) with 137 patients. The correlation of MDA and FIB-4 with liver fibrosis degree was analyzed, and MDA and FIB-4 were compared in terms of their accuracy in assessing significant liver fibrosis. A total of 62 patients completed follow-up, and according to the presence or absence of progression to liver cirrhosis at the last follow-up visit, they were divided into progressive group with 21 patients and non-progressive group with 41 patients; the efficacy of MDA and FIB-4 in diagnosing disease progression was analyzed and compared. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Bonferroni method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data. The Spearman’s correlation coefficient was used for correlation analysis. The Wilcoxon signed rank sum test was used for the analysis of baseline data and data at the end of follow-up, and the binary Logistic regression analysis was used to investigate the influencing factors for progression to liver cirrhosis. The receiver operating characteristic (ROC) curve was used to investigate the diagnostic efficacy of indicators, the Z-test was used for comparison of the area under the ROC curve (AUC), and the paired chi-square test was used for comparison of the sensitivity, specificity, and accuracy of the two indicators. ResultsThe correlation coefficient between FIB-4 and liver fibrosis degree was 0.378, while the correlation coefficient between MDA and liver fibrosis degree was -0.325 (both P<0.001). FIB-4 had an AUC of 0.688, a sensitivity of 64.96%, a specificity of 68.87%, a positive predictive value of 67.42%, a negative predictive value of 63.36%, an accuracy of 65.40%, and a cut-off value of 1.01, while MDA had an AUC of 0.653, a sensitivity of 52.55%, a specificity of 78.57%, a positive predictive value of 72.73%, a negative predictive value of 60.37%, an accuracy of 65.02%, and a cut-off value of 0.29, suggesting that compared with FIB-4, MDA had a lower sensitivity (P=0.004) and a higher specificity (P=0.001). The progressive group had a significantly higher age than the non-progressive group at baseline (t=2.611, P=0.011). For the progressive group, there was an increase in FIB-4 and a reduction in MDA from baseline to the end of follow-up (both P<0.001), while the non-progressive group showed no significant changes (both P>0.05). The multivariate Logistic regression analysis showed that aspartate aminotransferase (odds ratio [OR]=0.940, 95% confidence interval [CI]: 0.885 — 0.998, P<0.05) and MDA (OR=0.445, 95%CI: 0.279 — 0.710, P<0.001) were independent influencing factors for disease progression. MDA had an AUC of 0.893 and an optimal cut-off value of -0.01 in diagnosing the disease progression of liver cirrhosis. ConclusionMDA has a comparable accuracy to FIB-4 in the diagnosis of significant liver fibrosis, and MDA<-0.01 has a high accuracy in diagnosing the progression of liver fibrosis to liver cirrhosis, which can help to reduce the need for liver biopsy in clinical practice.
2.Effectiveness of fibrosis-4 versus aspartate aminotransferase-to-platelet ratio index in evaluating liver fibrosis degree in patients with chronic HBV infection
Xiaoting LI ; Bobin HU ; Hongyu LIU ; Chao JIN ; Cailian CAI ; Keshan WANG ; Yanchun WEI ; Jianning JIANG ; Minghua SU
Journal of Clinical Hepatology 2024;40(12):2424-2429
ObjectiveTo investigate the performance of fibrosis-4 (FIB-4) versus aspartate aminotransferase-to-platelet ratio index (APRI) in predicting advanced liver fibrosis and disease progression in patients with chronic HBV infection. MethodsA total of 497 patients with chronic HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from February 2013 to December 2022 were enrolled, among whom 404 were enrolled in a retrospective study and 75 were enrolled in a prospective study. Related indicators were collected, including demographic features (sex and age), biochemical indices (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), and platelet count, and FIB-4 and APRI were calculated. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve (AUC) was used to assess the ability of APRI and FIB-4 in evaluating liver fibrosis degree and disease progression in patients with chronic HBV infection. ResultsIn the retrospective analysis, compared with the FIB-4<2.67 group, the FIB-4≥2.67 group had a significantly higher proportion of the patients who were diagnosed with liver cirrhosis or hepatocellular carcinoma (66.19% vs 47.54%, χ²=12.75, P<0.001). The medians of FIB-4 and APRI increased significantly with liver fibrosis degree from F0 to F4 (H=42.5 and 35.9, both P<0.001). As for the fibrosis stage of F0-F4, the median of FIB-4 was significantly higher than that of APRI in the patients with the same fibrosis stage (H=59.71, P<0.001). FIB-4 and APRI had a similar AUC for predicting stage F3 fibrosis (0.67 vs 0.65, Z=0.71, P=0.480), while FIB-4 had a higher AUC for predicting stage F4 fibrosis than APRI (0.72 vs 0.64, Z=10.50, P<0.001). In the prospective study cohort, FIB-4 and APRI showed an increasing trend over time in predicting disease progression (chronic hepatitis B to liver cirrhosis), with an AUC of 0.718 (95% confidence interval [CI]: 0.476 — 0.760) and 0.555 (95%CI: 0.408 — 0.703), respectively, and FIB-4 had a significantly higher accuracy than APRI in predicting disease progression (χ2=12.44, P<0.001). ConclusionFIB-4 and APRI can be used to evaluate advanced liver fibrosis (F3 and F4) and predict disease progression, and FIB-4 is superior to APRI in certain aspects.
3.Diagnostic value of serum extra-spindle pole-like protein 1 in the progression of hepatitis B virus-related liver fibrosis
Long HUANG ; Hongqian LIANG ; Aoli REN ; Minghua SU ; Bobin HU ; Qingmei LI ; Tumei SU ; Qianbing YIN ; Yanfei FENG ; Jianning JIANG
Journal of Clinical Hepatology 2024;40(9):1785-1789
Objective To investigate the clinical diagnostic value of extra-spindle pole-like protein 1(ESPL1)in the progression of hepatitis B virus(HBV)-related liver fibrosis.Methods A total of 228 patients with HBV infection who were admitted to The First Affiliated Hospital of Guangxi Medical University from June 2017 to August 2023 were enrolled.The transient elastography system FibroScan was used to determine liver stiffness measurement(LSM)for all patients,and according to the LSM value,they were divided into non-liver fibrosis group with 80 patients,mild liver fibrosis group with 83 patients,advanced liver fibrosis group with 30 patients,and liver cirrhosis group with 35 patients.ELISA was used to measure the serum level of ESPL1.The Kruskal-Wallis H test was used for comparison of the serum level of ESPL1 between the four groups;the Spearman correlation analysis was used to investigate the correlation between ESPL1 and LSM;the receiver operating characteristic(ROC)curve was used to analyze the value of serum ESPL1 in predicting the progression of liver fibrosis.Results The liver cirrhosis group had a significantly higher serum level of ESPL1 than the non-liver fibrosis group and the mild liver fibrosis group(both P<0.05),and the advanced liver fibrosis group and the mild liver fibrosis group had a significantly higher serum level of ESPL1 than the non-liver fibrosis group(both P<0.05).The correlation analysis showed that there was a positive correlation between serum ESPL1 and LSM in the patients with HBV infection and varying degrees of liver fibrosis(r=0.515,P<0.001).Serum ESPL1 had an area under the ROC curve(AUC)of 0.809 in predicting liver cirrhosis and an AUC of 0.638 in predicting advanced liver fibrosis,with a sensitivity of 87.5%and 100%,respectively,and a specificity of 59.7%and 31.3%,respectively.Conclusion There is a certain correlation between serum ESPL1 and HBV-related liver fibrosis,and higher serum ESPL1 may indicate a higher degree of liver fibrosis.Serum ESPL1 is expected to become one of the serum markers for assisting in the diagnosis of liver cirrhosis and an important clinical method for dynamically monitoring the progression of liver fibrosis in patients with HBV infection.
4.Research progress on sepsis-associated liver injury
LIU Zhihong ; QIN Yaqin ; SU Minghua
China Tropical Medicine 2023;23(12):1358-
Sepsis is an inflammatory disorder syndrome caused by the infection of pathogenic microorganisms, which organ dysfunction due to the dysregulated response of the body to the infection. Sepsis is a dangerous disease with a high fatality rate. The liver, an important organ involved in human biological transformation, energy metabolism, and cytokine production. Its role in sepsis is like a "double-edged sword" because the liver acts as not only an important defense line of the body against microorganisms but also a common target of inflammatory disorders and damage, making it one of the most vulnerable organs in sepsis. The liver contributes to pathogen clearance through immune responses, but the resulting inflammatory reactions can also lead to tissue and organ damage. Sepsis liver injury is an independent risk factor for poor prognosis in sepsis patients, and preventing its occurrence and promoting early recovery can partially inhibit disease progression and reduce mortality rates. However, the pathogenesis of sepsis liver injury is not yet fully understood, and there is a lack of early and effective means of diagnosis and treatment. In-depth research on its pathogenesis will provide a better understanding of its occurrence and development, further supporting the theoretical basis for the treatment of sepsis liver injury and identifying some new targets for sepsis treatment, ultimately reducing the mortality of sepsis.
5.Efficacy of entecavir versus tenofovir disoproxil fumarate in treatment of chronic hepatitis B patients with high viral load
Huikun ZHOU ; Jianning JIANG ; Minghua SU ; Rongming WANG ; Bobin HU ; Deli DENG ; Huilan WEI ; Xianshuai LIANG ; Wenming HE ; Rongsheng GUO
Journal of Clinical Hepatology 2022;38(3):532-536
Objective To investigate the efficacy of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) and the treatment measures for poor response in previously untreated chronic hepatitis B (CHB) patients with high viral load. Methods A total of 165 CHB patients who received antiviral therapy and met the inclusion criteria in Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, from June 2016 to July 2021 were enrolled. The patients enrolled had a baseline HBV DNA level of > 6lg copies/ml and were previously untreated CHB patients who had used ETV or TDF for 48 weeks, and quantitative real-time PCR was used to measure HBV DNA. Virologic response rate was calculated after 48 weeks of treatment; a logistic regression analysis was used to investigate the influencing factors for the response of HBV DNA < 500 copies/mL and HBV DNA < 100 copies /mL at 48 weeks; a stratified analysis was performed to compare the virologic response rate of HBV DNA < 500 copies /ml and HBV DNA < 100 copies/ml after 48 weeks between the patients with different ages, sexes, baseline HBV DNA levels, baseline alanine aminotransferase (ALT) levels, types of first-line medication, and HBeAg statuses. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups, and the binary logistic regression model was used for multivariate analysis. Results After 48 weeks of treatment, 85.5% (141/165) of the patients achieved an HBV DNA load of < 500 copies/mL, and 66.1% (109/165) of the patients achieved an HBV DNA load of < 100 copies /mL, with no significant difference in treatment outcome between the ETV group and the TDF group. The multivariate logistic regression analysis showed that sex( OR =2.793, 95% CI : 1.197-6.517), baseline HBV DNA( OR =0.369, 95% CI : 0.142-0.959), baseline ALT( OR =4.556, 95% CI : 1.770-11.732), and baseline HBeAg( OR =0.120, 95% CI : 0.033-0.429) were influencing factors for complete virologic response(all P < 0.05). For the patients with normal ALT (≤40 U/L) at baseline, 75.6% (34/45) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and 53.3% (24/45) achieved an HBV DNA load of < 100 copies/mL, with no significant difference in treatment outcome between the ETV group and the TDF group. For the patients with abnormal ALT (> 40 U/L) at baseline, 89.2% (107/120) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and the proportion of such patients in the TDF group was significantly higher than that in the ETV group (96.1% vs 84.1%, χ 2 =4.386, P =0.036); 70.8% (85/120) achieved an HBV DNA load of < 100 copies/mL, the proportion of such patients was no significant difference between the TDF group and the ETV group (78.4% vs 65.2%). The response of HBV DNA < 100 copies/ml of the normal baseline ALT group and the abnormal baseline ALT group, there were no significant differences between the patients aged≤30 years and aged > 30 years (77.8% vs 47.2%, 85.2% vs 66.7%). For the patients who did not achieve complete virologic response (HBV DNA ≥100 copies/mL) after 48 weeks of treatment, 87.9% (29/33) achieved complete virologic response after the original treatment regimen was prolonged for 48 weeks, and 100% (9/9) of the patients achieved complete virologic response after switching to or adding the first-line nucleos(t)ide analogues (NUCs) without cross-resistance sites with the original regimen for another 48 weeks. Conclusion The patients aged > 30 years should receive antiviral therapy as early as possible, regardless of viral load and ALT level, especially those with a family history of liver cirrhosis or hepatocellular carcinoma; the patients aged ≤30 years who have a normal ALT level and a high viral load should consider initiating antiviral therapy after providing informed consent. For the patients with poor response after 48 weeks of treatment, first-line NUCs without cross-resistance sites with the original regimen should be switched to or added in time.
6.Epidemiological features and antiviral response of genotype 6 chronic hepatitis C
Jinni HUANG ; Jianning JIANG ; Dandan LIANG ; Shiyu LONG ; Guozhen DONG ; Man SU ; Jijiao LI ; Chunling TENG ; Ping ZHANG ; Minghua SU
Journal of Clinical Hepatology 2022;38(4):793-797
Objective To investigate the epidemiological features and antiviral response of patients with genotype 6 chronic hepatitis C (CHC) in Guangxi, China. Methods A total of 97 patients with genotype 6 CHC who were admitted to The First Affiliated Hospital of Guangxi Medical University from December 2012 to December 2020 were enrolled, among whom 62 patients were given antiviral therapy. The 62 patients receiving antiviral therapy were divided into interferon group with 22 patients and direct-acting antiviral agent (DAA) group with 40 patients. Related data were collected, including general demographic data, HCV RNA, liver function, routine blood test results, and renal function. The chi-square test was used for comparison of categorical data between groups. Results Among the 97 patients, there were 69 male patients (71.1%) and 28 female patients (28.9%), with a mean age of 41.97±10.12 years, and the patients aged 30-40 years accounted for 47.4% (46/97). Of all 97 patients, 95 (97.9%) had genotype 6a, 1 had genotype 6e, and 1 had genotype 6xa. Among the 65 patients with a definite route of infection, 41 (63.1%) had intravenous drug use, 14 had medical-related operations, 9 had blood transfusion, and 4 had sexual contact as the route of infection. For the interferon group, the rapid virologic response (RVR) rate at week 4 was 81.8% (18/22), the rate of undetectable virus at the time of drug withdrawal (Epoint) was 86.4% (19/22), the rate of sustained virologic response at 12 weeks after drug withdrawal (SVR12) was 81.8%, and the rate of sustained virological response at 24 weeks after drug withdrawal (SVR24) was 81.8%; 1 patient in this group experienced recurrence. All 40 patients in the DAA group were previously untreated patients (33 patients without liver cirrhosis and 7 patients with compensated liver cirrhosis), with an overall RVR rate of 87.5%(35/40), an Epoint rate of 100%, and an SVR12 rate of 100%, and there was no treatment failure or recurrence. Although different DAA regimens had different RVR rates, they all had a SVR12 rate of 100%. The patients with compensated liver cirrhosis and other diseases had a SVR12 rate of 100%. Conclusion Intravenous drug addiction is the main route of infection for patients with genotype 6 CHC in Guangxi, and CHC is more common in men, with genotype 6a as the main subtype. DAA treatment has a higher virologic response rate than interferon treatment, with an SVR12 rate of 100%. There is no significant difference in SVR12 rate between the patients with compensated liver cirrhosis and those without liver cirrhosis.
7.Time phased scheduling and Disease grading management to achieve efficient rescue of batches of COVID-19 infected patients in shelter hospital
Ying SUN ; Minghua SU ; Xiaohong ZHANG ; Jiajia LI ; Tingting LUO ; Yun ZHANG ; Feng CHEN ; Tao JIANG ; Tong WU ; Xiaobo HUANG ; Kang CHEN ; Chuanzhu LV
Chinese Journal of Emergency Medicine 2022;31(8):1110-1115
Objective:To introduce how to quickly set up a doctor team to achieve efficient treatment of batchs COVID-19 patients in Changchun GongTi shelter hospital.Methods:A cross-sectional study was conducted to analyze the basic situation of the doctors who supported the Changchun Gongti shelter hospital. The workload is the total number of patients from April 3 to 28, 2022. At the beginning of the task, the first week and the third week of the task, the five point scoring method was used to reflect the doctor's physical and mental state, stress state and rescue achievement. The time phased scheduling and disease grading management were fully implemented after 10 days of operation in the shelter. The doctors' ward round efficiency and self scoring changes before and after the implementation of the plan were compared, and the rescue results were summarized.Results:Total of 56 doctors (the Sichuan medical assistance team to Changchun), who undertook the work of Changchun Gongti shelter Hospital, came from 12 professional departments of 14 hospitals. By internal and external linkage-time phased scheduling and information-based patient zoning and grading management, the admission time of batch patients was shortened from (14.64±10.09) min to (6.80±5.10) min per person( P<0.05), the number of patients that each doctor can view per hour ranges from (28.50±12.26) to (68.43±19.95) ( P<0.01). A total of 1 293 patients were treated. There were no deaths, no accidents and no mild illness to severe illness in shelter hospital. 35 doctors completed a continuous survey. Before and after the implementation of those measures, the average physical state scores and the psychological state scores of doctors improved ( P=0.03), the self-score of stress feeling decreased ( P<0.01), and the self-score of professional achievement increased ( P<0.01). Conclusions:To adapt to the characteristics of emergency treatment for batch COVID-19 patients, the internal and external linkage-time phased scheduling and information-based patient zoning and grading management could help the temporarily convened doctors deal with a large number of patients efficiently, reduce work stress and exposure risk in shelter hospital.
8.Clinical features of talaromycosis marneffei in human immunodeficiency virus negative and human immunodeficiency virus positive patients
Linman LI ; Jianning JIANG ; Mengfeng JIANG ; Jinni HUANG ; Dandan LIANG ; Shiyu LONG ; Guozhen DONG ; Minghua SU
Chinese Journal of Infectious Diseases 2021;39(6):328-332
Objective:To compare the similarities and differences of clinical characteristics of human immunodeficiency virus (HIV)-negative and HIV-positive patients with talaromycosis marneffei (TSM).Methods:The clinical data of 175 inpatients diagnosed with TSM in First Affiliated Hospital of Guangxi Medical University from May 2012 to April 2019 were retrospectively analyzed. The patients were divided into HIV-positive group and HIV-negative group according to the results of HIV confirmation test. The clinical manifestations, laboratory examination indicators (white blood cell count, hemoglobin, albumin, CD4 + T lymphocyte count and C-reactive protein (CRP)) between the two groups were compared. Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Among 175 TSM patients, 85 were HIV-positive and 90 were HIV-negative patients. The main clinical manifestations of fever and lymphadenopathy in the HIV-positive group and HIV-negative group were 71 (83.53%) cases and 73 (81.11%) cases, 50 (58.82%) cases and 47 (52.22%) cases, respectively, and there were both no statistical differences ( χ2=0.175 and 0.771, respectively, both P>0.05), while respiratory symptoms, weight loss and subcutaneous masses were 62 (72.94%) cases and 81 (90.00%) cases, 73 (85.88%) cases and 56 (62.22%) cases, one (1.18%) case and 16 (17.78%) cases, respectively, the differences were all statistically significant ( χ2=8.514, 12.630 and 13.737, respectively, all P<0.01). Hemoglobin in HIV-positive group and HIV-negative group were 90.50 (77.00, 113.95) g/L and 88.65 (72.85, 99.93) g/L, respectively. The difference was statistically significant ( Z=2.023, P=0.043). The ratios of albumin<30 g/L, CRP>10 mg/L in the two groups were 69.41%(59/85) and 60.00%(54/90), 94.37%(67/71) and 94.19%(81/86), respectively, and the differences were both not statistically significant ( χ2=1.693 and 0, respectively, both P>0.05). The ratios of cases with white blood cell counts >10×10 9/L and CD4 + T lymphocyte count<50/μL in the positive and negative groups were 3.53%(3/85) and 81.11%(73/90), 80.77%(63/78) and 1.75%(1/57), respectively, the differences were both statistically significant ( χ2=107.095 and 82.467, respectively, both P<0.01). Conclusions:In TSM patients, HIV-negative with subcutaneous masses, and increased white blood cell counts are common. Decreased body weight and CD4 + T lymphocyte count<50/μL in HIV-positive patients are more common than HIV-negative patients.
9.Liver histological status and clinic outcome in HBeAg-negative chronic hepatitis B with low viral load
Deli DENG ; Jianning JIANG ; Minghua SU ; Rongming WANG ; Weiwei ZANG ; Xiaozhang LING ; Huilan WEI ; Xianshuai LIANG ; Huikun ZHOU ; Wenming HE ; Rongsheng GUO
Chinese Journal of Hepatology 2020;28(12):1013-1017
Objective:To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients.Methods:A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient’s clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients.Results:Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion:For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.
10.Risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis treated with long-term nucleos(t)ide analogues
Weiwei ZANG ; Minghua SU ; Xiaozhang LING ; Rongming WANG ; Bianchuan CAO ; Yulong WU ; Deli DENG ; Huilan WEI ; Xianshuai LIANG ; Jianning JIANG
Chinese Journal of Hepatology 2020;28(8):679-685
Objective:To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs).Methods:The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The 2 test was used for rate comparison. Results:The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion:The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

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