Table of Content

30 April 2023, Volume 28 Issue 4

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Liver Failure

Analysis of hospitalization costs for patients with HBV-ACLF in Beijing You'an Hospital from 2012 to 2021

LI Shan-shan, XU Man-man, YANG Xue, CHEN Yu

2023, 28(4):  405-409. 

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Objective To investigate the hospitalization cost and influencing factors of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) in Beijing Youan Hospital to provide a reference basis for rational control of patients' hospitalization cost. Methods The data on the first page of 1247 patients hospitalized with a primary diagnosis of HBV-ACLF in our hospital from 2012-2021 were collected. After excluding the influence of price factors, the changing trend and influencing factors of hospitalization costs were analyzed. Mann-Kendall trend test was used to analyze the changes of hospitalization costs with years, and single-factor and multi-factor linear regression methods were used to analyze the influencing factors of hospitalization costs. Results During the decade of 2012-2021, the average hospitalization cost of patients with HBV-ACLF fluctuated from 55373.04 to 62921.70 yuan, and the average daily cost fluctuated from 2,676.42 to 3,172.17 yuan, with no significant change with year, and none of the trend analysis was statistically significant (P<0.05). The cost of medicine always occupied the first place in the composition of hospitalization costs of HBV-ACLF patients (37.7%-64.1%), but showed a decreasing trend with the year, followed by the examination fee (13.7%-18.5%), which showed an increasing trend with the year. Although treatment fees, surgery fees and blood transfusion fees did not account for a high proportion, they also showed an increasing trend with the year, and all trend analyses were statistically significant (P<0.05). Through univariate and multivariate linear regression analysis, the main factors affecting the hospitalization costs of HBV-ACLF patients were hospitalization days (β=0.683, P=0.000) and gender (β=-0.059, P=0.007). The longer the hospitalization days, the higher the hospitalization costs, and the hospitalization costs of male patients were higher than those of female patients. Conclusion The hospitalization cost of HBV-ACLF patients is high which results in the heavy the economic burden. Strengthening the health education of hepatitis B patients, optimizing the hospitalization costs structure, and reasonably shortening the hospitalization time are helpful to reduce the economic burden of HBV-ACLF patients.

Clinical features and survival analysis of patients with liver failure in intensive care unit

NIU Dan, ZHANG Qian-nan, BAI Hui-hui

2023, 28(4):  410-415. 

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Objective To investigate etiology, clinical characteristics, artificial liver treatment and prognosis-related influencing factors of patients with liver failure in intensive care unit (ICU). Methods A retrospective study was used to analyze the etiology, laboratory tests, major complications/comorbidities, mode and timing of artificial liver therapy and prognosis-related influencing factors in 140 patients with liver failure who received artificial liver therapy in our hospital. Results A total of 140 patients with liver failure who received artificial liver support system were followed up for 60 days, 73 patients (52.1%) in the survival group and 67 patients (47.9%) in the death group. There were statistically significant differences in age (t=-2.325, P=0.022), length of stay (t=-3.439, P=0.001), etiology (χ²=50.239, P<0.001) and classification of liver failure (χ²=12.779, P=0.002) between the two groups (P<0.05). APACHE Ⅱ score (t=-6.792, P<0.001), end-stage liver disease model (MELD) (t=-4.079, P<0.001), total bilirubin (TBil) (t=-3.115, P=0.002), international standardized ratio (INR) (t=-3.839, P<0.001), serum creatinine (SCr) (t=-2.408, P=0.018), urea nitrogen (UREA) (t=-2.042, P=0.043), white blood cell (WBC) (t=-4.853, P<0.001) and procalcitonin (PCT) (Z=-3.11, P=0.002)in survival group were significantly lower than those in death group. Prothrombin activity (PTA) (t=3.443, P=0.001) was significantly higher than that in death group (P<0.05). The incidence of acute kidney injury (χ²=7.312, P=0.007) in survival group was significantly lower than that in death group (P<0.05). There was no significant difference in the incidence of hepatic encephalopathy and electrolyte disorder between the 2 groups (P>0.05). Patients in the 2 groups underwent bilirubin adsorption (PBA), plasma exchange (PE), dual plasma molecular adsorption (DPMAS) and dual plasma molecular adsorption combined with plasma exchange (DPMAS+PE) in four different modes of artificial liver treatment, and the difference in their artificial liver treatment modes was not statistically significant (P>0.05), but there was statistical significance in the period of artificial liver therapy (χ²=10.419, P=0.005) between 2 groups (P<0.05). Multivariate COX regression model showed that age (HR=1.04, 95%CI 1.017-1.065, P=0.001), advanced liver failure (HR=4.889, 95%CI 1.103-21.676, P=0.037), APACHE Ⅱ score (HR=1.085, 95%CI 1.032-1.141, P=0.001), INR (HR=3.089, 95%CI 1.178-8.097, P=0.022), TBil (HR=1.006, 95%CI 1.002-1.01, P=0.006), SCr (HR=1.011, 95%CI 1.001-1.021, P=0.032) and PCT (HR=1.023, 95%CI 1.006-1.04, P=0.009) were independent risk factors for prognosis. Conclusion Different modes of artificial liver support system have no significant effect on the survival of patients with liver failure in ICU, but are associated with the timing of patients receiving artificial liver treatment. Age, advanced liver failure, APACHE Ⅱ score, INR, TBIL, SCr and PCT are independent risk factors for prognosis.

Study on the prognosis of acute-on-chronic liver failure and establishment of new score

ZHANG Pu-yang, NIU Qing-hui, XU Chuan-shen, GOU Wei, LI Jin-jin, CAI Jin-zhen

2023, 28(4):  416-422. 

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Objective To investigate the factors related to the prognosis of acute-on-chronic liver failure (ACLF) and the efficacy of common prognostic scoring models in China and abroad, and to analyze the efficacy of single and combined scoring models including alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) indexes in the evaluation of the prognosis of patients with ACLF. Methods The clinical data of patients with ACLF admitted to our hospital from 2010 to 2021 were collected, and the influencing factors of prognosis were analyzed by statistical methods. The prognostic value of the single index of AFP/LDH and the new scoring model for ACLF was analyzed by comparing to common assessment model. Results A total of 159 patients with ACLF were enrolled, with a survival to death ratio of 129∶30 and 111∶48 within 28 and 90 days respectively. Among them, 48 cases were classified as early stage, 58 cases as middle stage and 53 cases as late stage according to the severity of the disease. According to the prognosis within 90 days, patients were divided into survival group and death/liver transplantation group. The baseline indexes including alanine transaminase (ALT) (410 vs 204), aspartate aminotransferase (AST) (296 vs 211), ALT/AST (1.27 vs 0.88), total bilirubin (TBil) (271 vs 349), cholesterol (2.7 vs 2.2), triglyceride (TG) (1.07 vs 0.81), neutrophil count (6.35 vs 6.21), urea nitrogen (3.7 vs 6.0), lymphocyte count (1.45 vs 0.69), neutrophil count/lymphocyte count (2.38 vs 7.04), red blood cell (RBC) count (4.19 vs 3.60), hemoglobin (Hb) (132 vs 119), platelet count (90 vs 74), HBV DNA load (104 vs103), prothrombin activity (PTA) (37.1 vs 30.3), international normalized ratio (INR) (2.09 vs 2.56), MLR(0.37 vs 0.61), serum creatinine (59 vs 64), LDH (221.0 vs 279.5), AFP (82.30 vs 7.66), hepatic encephalopathy, ascites, MELD score (20.57 vs 26.34) and COSSH score (5.05 vs 6.08) between the 2 group were significantly different (P<0.05). There was no significant difference in age, gender, albumin, prealbumin, serum uric acid, direct bilirubin, indirect bilirubin, cholinesterase, serum sodium, serum ammonia, R-glutamyl transpeptidase, ALBI, glutamyl transpeptidase and glutamyl transpeptidase between the 2 groups (P>0.05). AFP, LDH, TBil, TG, RBC, Hb, glutamate/propyl glutamate (GLU), urea nitrogen/creatinine (UREA nitrogen/creatinine) and the new score including AFP and LDH were independent factors for predicting the prognosis of ACLF at 90 days. The predictive value of new scoring model (AUC = 0.87, sensitivity 89.6%, specificity 75.7%, cutoff -0.9909) was better than that of traditional NLR (AUC=0.72, sensitivity 68.9%, specificity 75.2%, Cutoff 3.86), MELD (AUC=0.67, sensitivity 69.6%, specificity 67%, cutoff value 14.64), COSSH (AUC=0.76, sensitivity 75%, specificity 76%, cutoff value 5.37) in patients with ACLF. Conclusion In the study of prognostic factors in patients with ACLF, ADH, TBil, urea nitrogen/creatinine, ALT/AST, erythrocyte, are independent risk factors for predicting the prognosis of ACLF patients within 90 days, while triglyceride, AFP, Hb are independent protective factors. In the study, the new scoring system consisting of the above 8 indicators is more accurate than MELD and NLR in predicting prognosis in all ACLF patients, and the new scoring has higher predictive power than MELD and NLR in the study in hepatitis B patients, but the difference is not statistically significant compared with COSSH, but overall the new scoring still has high predictive power Thus saving the use of clinical organs and providing the best treatment plan.

Viral Hepatitis

Establishment of an accurate prediction system for clinical endpoint events during antiviral therapy for chronic hepatitis B

YANG Mei, LV Yun-hai

2023, 28(4):  423-427. 

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Objective To investigate factors affecting clinical endpoint events during antiviral therapy for chronic hepatitis B (CHB) and establishing an accurate prediction system. Methods A total of 200 CHB patients who received antiviral treatment in our hospital from February 2017 to January 2020 our hospital were selected as the subjects. The clinical data were collected. The time of onset, end or end point of the antiviral treatment was the cut-off time. The risk factors of clinical end point events affecting antiviral treatment were analyzed to establish a prognostic model. The clinical value of different systems including with the end stage liver disease model (MELD), MELD-Na score, Fontana-Index score,hild-Turcotte-Pugh (CTP) score and CTP-Cr score was compared. Results CTP-Cr score (7.51±1.61), MELD-Na score (15.07±6.63), ultrasound score (12.21±3.25), Index score (3.14±1.47), MELD score (10.67±3.36), CTP score (6.58±2.14), Na (127.56±10.15), international normalized ratio (INR) (1.34±0.35), prothrombin time (PT) (14.58±2.14), direct bilirubin (DBil) (19.69±28.66), total bilirubin (TBil) (50.88±57.45) were significantly different from those of CTP-Cr in the group with end-point events score (8.96±1.35), MELD-Na score (22.76±4.91), ultrasound score (18.74±4.29), Index score (4.69±1.69), MELD score (16.74±3.07), CTP score (9.14±2.07), Na (117.96±7.45), INR (1.72±0.28), PT (18.57±2.31), DBil (35.47±30.14), TBil (78.96±80.14), the difference was statistically significant (P<0.05); no end-point event group The incidence of SBP (0.63%), hepatorenal syndrome (0.00%), and hepatic encephalopathy (1.25%) were lower than those of the end-point event group (10.00%, 7.50%, 10.00%) (P<0.05); Multivariate analysis showed that the prognostic risk factors with significant differences were mainly INR,WBC,TBil, and ultrasound score (P<0.05). The receiver operator characteristic (ROC) curves of different systems were conducted, and the area under the curve (AUC) was calculated (Index: 0.807, MELD-Na: 0.827, MELD: 0.804, CTP-Cr: 0.800, CTP: 0.791). The AUC of?the new system A and B were 0.854 and 0.834 respectively. There was no significant difference between CTP-Cr, CTP, prognosis system B and prognosis system A (P>0.05). Conclusion INR, WBC, TBil, hepatorenal syndrome, and ultrasound score are independent risk factors that affect the clinical endpoints of antiviral treatment. New system A based on the basis of INR, TBil, hepatorenal syndrome, and ultrasound has a high value for predicting and evaluating clinical endpoint events.

A study on the impact of grassroots lecture tours on raising awareness of hepatitis C among community health workers

HE Na, HAO Shuai, ZHANG Fen-na, ZHAO Zi-qi, DOU Wen-li, TIAN Ya-wen, LUO Yu-shan, YAN Hong-lin, YANG Yong-qin

2023, 28(4):  428-431. 

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Objective As the gatekeepers of community health, it is important for general practitioners to improve knowledge, diagnosis and treatment of hepatitis C disease to reduce the medical burden in China. Methods To organize hepatitis C diagnosis and treatment specialists to sink into the community to conduct health education rounds on the topic of hepatitis C, and to compile appropriate questionnaires which included four parts: basic information of respondents, knowledge of hepatitis C, understanding of hepatitis C policy, and prevention and treatment of hepatitis C. The above questionnaires were conducted before and after the tour to compare the significance of the grass-roots tour to enhance the awareness of hepatitis C among general practitioners in the community. Results From May 2021 to the end of April 2022, 10 lectures were held at the local community health center, 112 and 105 valid questionnaires were recovered, respectively. The results showed that the mean scores of hepatitis C disease awareness level, policy awareness level and prevention and treatment level of the residents in the host community were 2.89 ± 0.76, 2.37 ± 0.75, and 2.63 ± 0.76, respectively. After the tour, the above scores were 3.82 ± 0.83, 3.55 ± 1.14 and 3.75 ± 0.85, with statistical differences (P<0.05). Through the Hepatitis C theme tour, the proportion of general practitioners'awareness of hepatitis C high-risk groups and transmission routes has increased; The rate of general practitioners (GPs) willing to test invasive subjects for hepatitis C antibodies increased from 57.10% before the round to 75.20% after the round. The rate of GPs willing to test HCV RNA in HCV-positive patients for diagnosis increased from 59.80% before the round to 68.6% after the round. Only 53.6% of GPs were willing to educate patients and 62.5% of general practitioners were willing to refer hepatitis C patients to higher-level hospitals, which increased to 67.6% and 74.3% respectively after the tour. Conclusion The hepatitis C theme tour to the grassroots can not only effectively raise the awareness level of community GPs in hepatitis C prevention and treatment, but also is an important exploration of community-centered hepatitis C elimination model, which is a key step to achieve the strategic goal of “eliminating viral hepatitis by 2030”.

Therapeutic effect of nucleoside/nucleotide analogues on HBeAg-negative chronic hepatitis B patients with normal or slightly elevated alanine aminotransferase

CAO Jing-jing, LI Rong, LI Jing, PAN Feng

2023, 28(4):  432-435. 

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Objective To investigate the therapeutic effect of nucleoside/nucleotide analogues (NAs) on hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT). Methods A total of 102 HBeAg-negative CHB patients from June 2018 to July 2021 in our hospital were included, including 68 males and 34 females, with an average of (41.7±9.2) years. According to the baseline level of serum ALT, the cases were divided into normal ALT group (n=59) and slightly elevated ALT group (n=43) [ALT lower than 2 times the upper limit of normal value (ULN)]. The changes of viral response (VR) rate, hepatitis B virus (HBV) DNA, ALT and liver hardness (LSM) were compared between the 2 groups after NAs treatment. Results The male ratio, ALT, aspartate aminotransferase (AST) and HBV DNA in normal group were 57.6%, (25.4±8.0) U/L, (24.2±8.3) U/L and (4.4±1.0) log₁₀ IU/mL, which were significantly lower than those in mildly elevated ALT group [79.1%, (70.3±17.5) U/L, (52.3±16.2) U/L and (5.2±1.3) log₁₀ IU/mL, P<0.05]. The VR rates of normal ALT group were 49.2% (29/59), 66.1% (39/59), 81.4% (48/59), 84.7% (50/59) and 93.2% (55/59) at the 12th, 24th, 36th, 48th, 72nd and 96th week respectively. The corresponding VR rates in the group with mild elevation of ALT were 41.9% (18/43), 58.1% (25/43), 69.8% (30/43), 76.7% (33/43), 86.0% (37/43) and 95.3% (41/43). Logarithmic rank test showed that there was no significant difference in VR rate between the 2 groups (P>0.05). HBV DNA load decreased significantly during NAs antiviral treatment. In the normal group, after 48 weeks and 96 weeks of treatment, the average level of HBV DNA decreased by (2.8±1.2) log₁₀ IU/mL and (3.7±1.1) log₁₀ IU/mL. The level of HBV DNA in the group with slight elevation of ALT decreased (3.6±1.5) log₁₀IU/mL and (4.3±1.5) log₁₀IU/mL on average. There was no significant difference in the average decline of HBV DNA between the 2 groups (P>0.05). At the 12th, 24th, 36th, 48th, 72nd and 96th week, the normal group's ALT normalization rates were 71.2% (42/59), 86.4% (51/59), 91.5% (54/59), 94.9% (56/59) and 96.6% (57/59), respectively. The ALT normalization rates of the corresponding mildly elevated ALT group were 53.5% (23/43), 76.7% (33/43), 83.7% (36/43), 88.4% (38/43), 95.3% (41/43) and 100% (43/43). There was no significant difference in the normalization rate of ALT between the 2 groups (P>0.05). Thirty-seven HBeAg-negative CHB patients with normal ALT and slightly elevated ALT were examined by FibroScan at 48 weeks after NAs treatment, and LSM was significantly improved [(7.9±3.2) kPa compared with (6.6±2.9) kPa, P<0.05]; FibroScan examination was performed in 25 patients after 96 weeks of NAs treatment, which showed that LSM value was significantly improved after treatment [(8.1±3.3) kPa vs (6.2±2.7) kPa, P<0.05]. Conclusion NAs effectively inhibited the HBV DNA level of HBeAg-negative CHB patients with normal or slightly elevated ALT, and improved the liver histology. Therefore, even HBeAg-negative CHB cases with normal ALT are recommended for antiviral treatment. In addition, significant liver fibrosis is not uncommon in HBeAg-negative CHB patients with normal or mildly elevated ALT, and they should be routinely evaluated for liver fibrosis such as FibroScan.

Influencing factors of disease progression in patients with chronic hepatitis B treated with long-term antiviral therapy

CHEN Wei-hua, TIAN Ling-rong, XI Zhen

2023, 28(4):  436-439. 

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Objective To investigate the effects of long-term antiviral treatment on the progression of chronic hepatitis B (CHB) patients to cirrhosis or from compensated cirrhosis to decompensated cirrhosis, and investigate the influencing factors of disease progression. Methods Based on the real world research method, a retrospective study was conducted. A total of 92 CHB patients treated in our hospital from October 2006 to October 2021 were included. They were divided into progressive deterioration group (27 cases) and non progressive group (65 cases) according to the condition at initiation and endpoints of antiviral therapy. The end point was the occurrence of cirrhosis (stage 5) or death, and October 2021 as the observation endpoint for patients who did not progress to cirrhosis (stage 5) or death. The clinical data from the initial observation to the end point were collected and analyzed retrospectively. The data were analyzed by SPSS 26. The effects of regular antiviral treatment, alcohol consumption, family history, drug resistance, initial treatment condition and age on the progression of CHB were compared between the 2 groups. Analyze the influencing factors of disease progression in CHB patients. Results (1) There were 70 males (76%) and 22 females (24%) were followed up for 5-16 years with a median follow-up of 9 years. By the end point of observation, 27 cases (29%) had significantly progressed and 83 (71%) cases had not significantly progressed by the observation endpoint. (2) The results of χ² test showed that the incidence rate of disease progression in irregular treatment group (χ²=5.050, P=0.025), drinking group (χ²=3.921, P=0.048), with family history group (χ²=3.940, P=0.047), drug-resistant group (χ²=6.185, P=0.013) was significantly higher than that in the control group (P<0.05); In regular antiviral treatment group, the incidence rate of disease progression in patients with age more than 40 years old (χ²=9.113, P=0.004) and patients with cirrhosis stages 3 and 4 at the start of antiviral therapy (χ²=8.134, P=0.004) was significantly higher than that of the control group (P<0.05); (3) The results of logistic regression analysis showed that age at initiation of antiviral therapy (R=1.147, P<0.01), compliance with treatment (R=5.443, P=0.014), severity of the patient at the initiation of antiviral treatment (R=0.434, P=0.039), drug resistance (R=8.862, P=0.032) was correlated with the patient's disease progression (P<0.05). Conclusion Long-term antiviral treatment can effectively delay the progression of CHB patients.

Liver Fibrosis & Cirrhosis

The diagnostic efficacy of Th9 cells and their cytokines for the degree of hepatitis B-related liver fibrosis

WANG Lan, QIU Hong, ZHU Yue-rong, GU Chang, ZHANG Wei-wei, YANG Fan

2023, 28(4):  440-444. 

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Objective To investigate the diagnostic efficacy of Th9 cells and related cytokine IL-9 in combination with multiple indicators for patients with different degrees of liver fibrosis caused by hepatitis B. Methods Two hundred and seven patients with hepatitis B viral infection were selected. They were divided into non-fibrosis group, mild to moderate fibrosis group and severe fibrosis group according to their pathological examination results. The level of Th9 cells in peripheral blood of each patient was detected by flow cytometry. The level of IL-9 was detected by enzyme linked immunosorbent assay (ELISA). The values of FIB-4 (fibrosis index based on the four factors), APRI (aspartate aminotransferase-to-platelet ratio index), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) were calculated. Spearman correlation analysis was used to explore the correlation between each index and the degree of liver fibrosis. Receiver operating characteristic curves (ROC) were drawn and the diagnostic efficiencies of each and the combination of variables were evaluated. Results There were significant differences in the levels of FIB-4 [4.52(2.48~7.99), 4.71(3.33~6.63), 13.09(6.64~19.43)], APRI [1.29(0.64~2.11), 1.39(0.75~1.87), 2.83(1.23~5.55), AAR [1.29(0.90~1.70), 1.35(0.94~1.83), 1.74(1.34~2.32)], RPR [0.13(0.08~0.23), 0.14(0.11~0.21), 0.28(0.20~0.45)]; IL-9 [24.97±3.615, 34.553±5.708, 43.684±6.534] and Th9 cells [0.28±0.085, 0.464±0.103, 0.626±0.098] among the three groups, respectively (P<0.05). The levels of FIB-4, APRI, AAR, RPR, IL-9 and Th9 cells were positively correlated with the stage of liver fibrosis (r=0.740/0.581/0.379/0.714/0.396/0.421, P<0.01); FIB-4, APRI, AAR, RPR, IL-9 and Th9 have better diagnostic efficacy for mild to moderate fibrostic patients and severe fibrostic patients caused by hepatitis B (AUC:0.878/0.831, 0.772/0.745, 0.614/0.678, 0.862/0.818, 0.685/0.588, 0.633/0.578, respectively). The Combination of various variables can improve the diagnostic efficacies for liver fibrosis caused by hepatitis B (AUC: IL-9+Th9, 0.774/0.668; IL-9+Th9+FIB-4, 0.934/0.862; IL-9+Th9+RPR, 0.929/0.818; IL-9+Th9+FIB-4+RPR, 0.943/0.848). Conclusion FIB-4, APRI, AAR, RPR, IL-9 and Th9 cells have better diagnostic efficacies for liver fibrosis caused by hepatitis B, and the diagnostic efficacies of their combinations are better. They were significantly and positively correlated with the stages of liver fibrosis.

The efficacy of on-demand endoscopic therapy in elderly patients with upper gastrointestinal bleeding due to liver cirrhosis

XIN Xiao-rong, CHEN Ping, WU Yun-lin, CAI Bo-er, HE Yun, XIE Ling

2023, 28(4):  445-447. 

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Objective To analyze the effect of on-demand endoscopic treatment on the prevention of gastrointestinal bleeding in elderly patients with liver cirrhosis. Methods A total of 186 elderly patients with liver cirrhosis complicated with upper gastrointestinal bleeding who were treated in the Department of Gastroenterology, Ruijin Hospital North from January 2013 to January 2021 were collected. According to the treatment plan, they were divided into an endoscopic treatment group and a drug treatment group, with 93 cases in each group. All patients in the endoscopic treatment group underwent endoscopic variceal ligation (EVL) for the first time, followed by regular postoperative follow-up and sequential endoscopic treatment in 3～6 months. The patients in the drug treatment group only received drug treatment. The recurrences of bleeding after treatment in these two groups and the risk factors were analyzed. Results Among the 93 patients in the endoscopic treatment group, 13 patients had re-bleeding within half a year after EVL, accounting for 14.0% (13/93); Among the 93 patients in the drug treatment group, 47 patients had rebleeding within half a year, accounting for 50.5% (47/93). There was significant difference in rebleeding rates between the two groups (P<0.05). After one year of follow-up, 7 patients in the endoscopic treatment group had re-bleeding, accounting for 7.5% (7/93); while 27 cases of rebleeding in the drug treatment group, accounting for 29.0% (27/93). There was significant difference between the two groups (P<0.05). However, age, gender, splenectomy and child-Pugh grade had no significant correlation with rebleeding in half a year (P>0.05). Conclusion For elderly patients with upper gastrointestinal bleeding due to liver cirrhosis, on-demand endoscopic treatment is safe and effective. After sequential endoscopic treatment, the recurrent rate of gastrointestinal bleeding significantly lower than those patients with drug treatment alone.

A comparison of transjugular intrahepatic portal-systemic shunt in the treatment of hepatitis B cirrhosis with or without portal vein thrombosis

YI Yan-rong, SHEN Yue-ming, WANG Sai, PENG Xiong-qun, PENG Yu

2023, 28(4):  448-451. 

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Objective To explore the efficacy of transjugular intrahepatic portal-systemic shunt (TIPS) in patients with hepatitis B cirrhosis with or without portal vein thrombosis (PVT). Methods A total of 203 patients with hepatitis B cirrhosis who were successfully treated with TIPS between January 2019 and December 2022 were selected, including 72 patients with PVT and 131 patients without PVT. Data were collected to assess the mortality, shunt dysfunction, and complication rates between these two groups of patients after TIPS operation. Results In PVT group, the platelet count (PLT), hemoglobin (Hb) and total bilirubin levels were (107.2±32.4)×10⁹/L, (76.4±21.7)g/L and (24.6±6.5)mg/dL, respectively, which were statistically different from those of [(65.4±17.7)×10⁹/L, (84.2±26.2)g/L and (33.2±8.4)mg/dL] in the PVT group (P<0.05). A total of twenty-one patients (10.3%) died during follow-up. The causes of death included liver failure (8 cases, 3.9%), multiple organ failure (6 cases, 2.9%), gastrointestinal bleeding (2 cases, 0.9%), hepatorenal syndrome (1 case, 0.5%), sepsis (1 case, 0.5%), cerebral hemorrhage (1 case, 0.5%) and other diseases (2 cases, 0.9%). The cumulative mortality rates of PVT group and non-PVT group at 90 days were 2.6% and 7.5%, and the difference was not statistically significant (P>0.05). The cumulative mortality rates of PVT group and non-PVT group during the whole follow-up period were 10.3% and 16.4%, respectively, without statistical significant difference (P>0.05). There was a statistical difference between PVT group and non-PVT group in varicose bleeding (esophagus and stomach), which was the main indication of TIPS (P<0.05). The main complications of TIPS, the recurrence of varicose bleeding and the recurrence of ascites were similar, but there were significant differences between the two groups in obvious hepatic encephalopathy (P<0.05). During the follow-up period, the cumulative incidence of shunt dysfunction between the two groups was significantly different (P<0.05). Conclusion TIPS is feasible in the treatment of cirrhosis with PVT. Compared with the PVT group, there were no significant differences in the incidence of variceal bleeding and recurrent ascites, but significant differences existed in the incidence of hepatic encephalopathy and shunt dysfunction in patients of the non-PVT group. TIPS represent a potentially viable treatment option for patients with PVT cirrhosis.

Liver Cancer

The efficacy and safety of carrilizumab combined with ramvaritinib in the treatment of unresectable hepatocellular carcinoma

QIAN Hou-long, LI Yang, ZHU Xiang, LU Kui

2023, 28(4):  452-456. 

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Objective To investigate the efficacy and safety of carrelizumab combined with ramvaritinib in the treatment of unresectable hepatocellular carcinoma (HCC). Methods Twenty-six unresectable HCC patients were divided into a control group and an observation group. The control group was treated with ramvaritinib, and the observation group was treated with carrelizumab. The changes of tumor markers, clinical efficacy, follow-up time, survival indexes and major adverse drug reactions were observed. Results After 1 and 3 months of treatment, the levels of serum alpha-fetoprotein (AFP) and abnormal prothrombin (PIVKA-II) in both groups were decreased compared with those before treatment, and the decrease range in observation group was higher than that in control group (P<0.05). The Objective response rate (ORR), local control rate (DCR) and conversion rate in the observation group were significantly higher than those in the control group, and the median response time (mRT) was shorter and the median duration of response (mDR) was longer than that in the control group (P<0.05). The median follow-up time (mFUP), median overall survival (mOS), median progression-free survival (mPFS) and the extent of long diameter reduction of target lesions in the observation group were significantly higher than those in the control group, and the mortality was lower than that in the control group (P<0.05). There was no grade 5 adverse reactions between the two groups, and there was no significant difference in the incidence of grade 3-4 reactions between the two groups (P>0.05). Conclusion The combination of Caririzumab with ramvaritinib may improve the clinical efficacy of ramvartinib on unresectable HCC patients, prolong the patients' survival with high safety.

The efficacy and safety of different doses of apatinib combined with carelizumab in the treatment of advanced liver cancer

ZHU Jia-zuo, ZHAO Ji-guang, CHENG Zhi-yuan

2023, 28(4):  457-460. 

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Objective To explore the efficacy and safety of different doses of apatinib combined with karelizumab in the treatment of advanced liver cancer. Methods Sixty-eight patients with advanced hepatocellular carcinoma admitted from October 2017 to October 2020 in Xuancheng Central Hospital were divided into a high-dose group and a low-dose group with 34 patients in each group. On the basis of 200 mg/time of intravenous infusion of carelizumab, the low-dose group and high-dose group took additional 250 mg/d and 500 mg/d of alpatinib mesylate tablets respectively. The Objective remission rate, adverse reaction rate and 2-year overall survival rate of the two groups after 1 month of treatment were recorded. Results The Objective response rate of the high-dose group was 67.65%, which was higher than that of the low-dose group (41.18%, P<0.05); The difference of disease control rate between the two groups was not statistically significant (P>0.05). The incidence of renal proteinuria and hand-foot syndrome was higher in the high-dose group (P<0.05). The median total survival (OS) was 13 months and 17 months in the low-dose group and high-dose group, and the median progression-free survival (PFS) was 8 months and 9 months, respectively. The total 2-year survival rate was 31.25% and 45.45%, respectively. There was statistically significant difference in PFS curve between the two groups (P<0.05). Conclusion In the treatment of advanced primary hepatocellular carcinoma, appropriately increasing the dosage of apatinib mayl help to improve the efficacy, but the risk of adverse reactions such as renal proteinuria and hand-foot syndrome will be a major concern.

The expression of TREM-1, sCD163 and sB7-H3 in patients with primary liver cancer

QIN Xiao-ping, ZHANG Jing, AI Ping

2023, 28(4):  461-464. 

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Objective To explore the expressions of serum myeloid cell trigger receptor 1 (TREM-1), soluble CD163 molecule (sCD163), and soluble B7-H3 (sB7-H3) test in patients with primary liver cancer and their association with the patients' prognosis. Methods The clinical data of 110 cases of primary liver cancer treated in Zhongxian People's Hospital of Chongqing were collected. They were divided into a poor prognosis group (death, N=45) and a good prognosis group (survival, N=65). The basic information and the levels of TREM-1, sCD163 and SB7-H3 of the two groups of patients were detected. The value of serum TREM-1, sCD163 and SB7-H3 in predicting the poor prognosis of HCC patients were analyzed by receiver operating curve (ROC) and multivariate logistic regression analyses. Results The proportion of tumor size ≥5 cm, liver cirrhosis, vascular invasion, and TREM-1, sCD163, and sB7-H3 levels were all higher in the poor prognosis group than those in the good prognosis group (P<0.05). Tumor size≥5 cm, with liver cirrhosis, with vascular invasion, TREM-1≥3.625 ng/mL, sCD163≥1.520 μg/mL, and sB7-H3≥425.670 pg/mL were the risk factors for poor prognosis in primary HCC patients (P<0.05). Conclusion TREM-1, sCD163, and sB7-H3 tests may have value in predicting the prognosis of primary liver cancer.

Effect of microwave ablation combined with DEB-TACE on immune function and prognosis of patients with advanced hepatocellular carcinoma

LI Hai-xia, WANG Xiu-xiang, GUO Lin, CHAI Mei, LI Yuan-yuan, GAO Ai-hua, SONG Zhao-wei

2023, 28(4):  465-468. 

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Objective To investigate the effects of microwave ablation (MWA) combined with drug-eluting beads(DEB)-transcatheter arterial chemoembolization (TACE) on the prognosis and immune function of patients with advanced hepatocellular carcinoma(HCC). Methods A total of 70 patients with advanced HCC admitted to the hospital from April 2020 to September 2021 were divided into observation group (DEB-TACE combined with MWA, n=35) and control group (TACE combined with MWA, n=35). The two groups of serum indexes, clinical efficacy, immune function and complications were compared. Results The serum levels of Alpha-fetoprotein (AFP), albumin (Alb) aspartate aminotransferase (AST) and total bilirubin (TBil) in the observation group were significantly lower than the control group after 4 weeks of treatment[ (65.23±9.18) ng/mL vs. (123.38±13.46) ng/mL, (33.26±2.61) g/L vs. (36.46±2.93) g/L, (44.24±4.14)μmol/L vs. (49.17±5.23) μmol/L, (24.97±4.25) μmol/L vs. (31.15±5.13) μmol/L, all P<0.05]. After 8 weeks of treatment, CD4+ in the observation group was, significantly higher than control group[(43.51±9.29)% vs. (33.72±8.31)%, (P<0.05)], contrary to CD8+[(24.29±3.35)% vs. (27.14±4.21)%, P<0.05]. The total effective rate in the observation group was higher than the control group[(85.71%) vs. (57.14%), P<0.05]. Between the two groups, there was no difference in the incidence of complications (P>0.05). Conclusion MWA combined with DEB-TACE has a significant and definite curative effect in advanced HCC. Meanwhile, it could also reduce the serum AFP level and improve liver function in patients, which is safe and reliable.

Non-alcoholic Fatty Liver Disease

Development of Prediction Models Based on Machine Learning for Non-alcoholic fatty liver disease

LIU Lu, ZHU Jin-zhou, LIU Xiao-lin, WANG Chao, YI Min-yuen, GAO Jing-wen, XU Chun-fang

2023, 28(4):  469-473. 

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Objective To develop prediction models based on H2O automated machine learning(AutoML) tools for the incidence of Non-alcoholic fatty liver disease (NAFLD). Methods A total of 4,105 subjects were recruited in the study. The data was loaded using H2O AutoML to develop various machine learning models to predict NAFLD. The model was evaluated by ROC curve and confusion matrix, while visualized by SHAP, LIME, and partial dependence plots. Results Twenty-eight machine learning models were fitted. The best model was a gradient boosting machine (GBM) model (Gini 0.80, R2 0.42, LogLoss 0.45). Triglyceride (95%CI: -1.053~-0.887), aspartate aminotransferase (AST) (95%CI: -20.433~-16.927), high density lipoprotein (HDL) (95%CI: 0.232~0.268), ferritin (95%CI: -80.533~-68.607), and blood glucose (95%CI: -0.576~-0.424) were the important variables. The area under ROC in the validation dataset was 0.766 with a sensitivity of 0.715 and a specificity of 0.818, which suggested that the GBM models performed better than the XGBoost models, logistic regression, random forest, and deep learning. Conclusion The prediction model based on H₂O AutoML algorithm provides both promise and insights in screening NAFLD patients.

Evaluation of the relationship between metabolic associated fatty liver disease and cardio-cerebrovascular events in patients with hypertension based on nomogram

XIA Fang, ZHAO Lan, SHI Yi-fu, MENG Xiang-ying, ZHAO Qian, WANG Xiao-jin, SHENG Fu-qiang

2023, 28(4):  474-478. 

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Objective To investigate the clinical features of metabolic associated fatty liver disease (MAFLD) in patients with hypertension and its relationship with cardio-cerebrovascular events. Methods The clinical data of 1385 patients with hypertension in Dahua Hospital, Xuhui District, Shanghai from January 2019 to October 2022 were retrospectively analyzed. The enrolled cases were divided into MAFLD group and non-MAFLD group according to the presence or absence of MAFLD, and the general clinical characteristics of the two groups were compared. The risk factors of cardio-cerebrovascular events in hypertensive patients were analyzed by the binary logistic regression method. Cardio-cerebrovascular events were defined as fatal or non-fatal cardiovascular and cerebrovascular events, including angina, myocardial infarction, stroke, cardiovascular and cerebrovascular death, and heart failure requiring hospitalization or treatment. The independent risk factors of cardio-cerebrovascular events identified by logistic regression were demonstrated by a nomogram model. The concordance index (C-index) and bootstrap resampling were used to evaluate the predictive ability of the nomogram. Results Among the 1385 hypertensive patients, 514 patients were assigned to the MAFLD group, and 871 patients were to the non-MAFLD group. The patients in the MAFLD group were significantly linked to more male gender and higher rates of alcohol consumption, type 2 diabetes and atrial fibrillation, higher levels of body mass index, 24h mean systolic/diastolic blood pressure, total cholesterol, triglycerides and low-density lipoprotein(LDL), lower level of high-density lipoprotein(HDL), and higher incidence of cardio-cerebrovascular events (24.7% vs 17.8%) (P<0.05), when compared to the non-MAFLD group. Univariate and multivariate logistic regression analysis showed that age, smoking, atrial fibrillation, MAFLD, type 2 diabetes, 24h mean systolic blood pressure, total cholesterol, HDL, LDL and glomerular filtration rate were independent factors affecting cardio-cerebrovascular events in hypertension population (P<0.05). The independent risk factors were used to construct a nomogram model, and the calibration curve showed good agreement between the predicted value and the actual observed value. The C-index was 0.70 (95% confidence interval, 0.65-0.72). Conclusion In the hypertension population, patients with MAFLD are more likely to be male, and inclined to have unhealthy lifestyles, suffer from abnormal blood lipid metabolism and comorbidities. MAFLD is independently correlated with cardio-cerebrovascular events in a hypertension population.

Predictive value of serum PCSK9 level for the degree of atherosclerosis in elderly patients with nonalcoholic fatty liver disease

LI Shao-jun, LI Jing, YU Jia-xin

2023, 28(4):  479-482. 

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Objective To investigate the predictive value of serum proprotein convertase subtilisin 9 (PCSK9) level in elderly patients with nonalcoholic fatty liver disease (NAFLD) in predicting the degree of atherosclerosis and prognosis. Methods From April 2020 to April 2021, 254 NAFLD patients who were treated in Tangshan Traditional Chinese Medicine Hospital and Tangshan Artificial Hospital were divided into three groups according to the quartiles of Gensini score: Group 1(Gensini score ≤ 24, n=84); Group 2(24<Gensini score ≤53, n=86) and Group 3(Gensini score>53, n=84). According to whether NAFLD patients had major cardiovascular and cerebrovascular events (MACCE), they were divided into the MACCE group(n=30) and non-MACCE group(n=224). The clinical data among the groups were compared. The relationship between Gensini score and PCSK9 was analyzed by Pearson correlation analysis. The risk factors of MACCE risk were analyzed by Cox risk model, and the predictive value of PCSK9 on the occurrence of MACCE in elderly patients with NAFLD was analyzed by ROC curve. Results hs-CRP, PCSK9, TG, LDL-C, and Lp(a) increased in Group 1 [5.79(4.17,7.81)mg/L, (329.17±50.26)ng/mL, (1.47±0.33)mmol/L, (2.69±0.52)mmol/L, (0.52±0.12)mg/L], Group 2[6.22(4.61,7.58)mg/L, (416.33±55.92)ng/mL, (1.65±0.36)mmol/L, (2.87±0.35)mmol/L, (0.63±0.09)mg/L], and Group 3[7.85(6.21,9.11)mg/L, (498.55±61.28)ng/mL, (1.86±0.24)mmol/L, (3.95±0.48)mmol/L, (0.70±0.11)mg/L] contrary to HDL-C [(1.46±0.25)mmol/L, (1.20±0.22)mmol/L, (1.06±0.27)mmol/L]]. There were significant differences between the three groups (P<0.05); PCSK9 was positively correlated with Gensini score (r=0.657, P=0.000). The age, Gensini score, PCSK9 and LDL-C of the MACCE group[[(72.12±5.54)years, (86.27±5.03)points, (489.71±63.05)ng/mL, (2.88±0.79)mmol/L] were significantly higher than those of the non-MACCE group[(68.63±3.35)years, (61.09±4.52)points, (356.03±51.19)ng/mL, (2.52±0.77)mmol/L, all P<0.05]. Multivariate Cox risk regression analysis showed that Gensini score and PCSK9 were independent risk factors for the risk of MACCE (P<0.05). The AUC of PCSK9 for predicting the occurrence of MACCE was 0.724, the sensitivity was 68.25%, and the specificity was 75.92%. Conclusion Serum PCSK9 is positively correlated with Gensini score in elderly patients with NAFLD, which could be used as a predictor of MACCE in patients.

Other Liver Diseases

Clinical characteristics of HIV-MTB co-infected patients combined with anti-tuberculosis drug-induced liver injury

RUAN Jun, YIN Heng, KOU Guo-xian, YANG cheng-bin

2023, 28(4):  483-486. 

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Objective To analyze the clinical characteristics of anti-tuberculosis drug-induced liver injury(ATB-DILI) patients co-infected with human immunodeficiency virus and mycobacterium tuberculosis(HIV-MTB). Methods The clinical data of 189 cases admitted to the people's hospital of Butuo county in Liangshan prefecture from October 2017 to October 2019 were retrospectively analyzed. Results Among 189 enrolled subjects, 111 cases(58.7%) were young and middle-aged married women, 149 cases(78.8%) were from rural areas, and 135 patients(71.4%) were infected with HIV through heterosexual contact. Most cases of DILI presented with hepatocellular injury(55.6%, Group A), followed by cholecystitis(32.3%, Group B) and mixed type(12.1%, Group C). Patients commonly presented with fatigue and appetit(61.9%), nausea and oil aversio(50.2%), jaundice43.9%), skin itchings(37.6%) and so on. In liver function examination, the ALT level of Group A was higher than that of Group B and Group C[(324.5±127.1)U/L, vs (217.3±86.4)U/L, (243.9±95.3)U/L)]. The ALP level of Group B was higher than that of Group A and Group C[(395.4±156.3)U/L vs (142.7±53.5)U/L, (272.5±101.4)U/L. The CD4+T lymphocyte count(＜200/μL) decreased significantly in 80 cases(42.3%), especially in Group A(175.9±71.3)/μL The abdominal imaging examinations in the three groups varied with no specificity. Conclusion The clinical manifestations of HIV-MTB co-infected patients combined with ATB-DILI are various, mainly presented with digestive system injury, and the prognosis of most patients is good. However, the early screening and intervention of ATB-DILI population in Liangshan prefecture still need to be strengthened.