Table of Content

31 January 2024, Volume 29 Issue 1

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Drug-Induced Liver Injury

An analysis of clinical characteristics of liver injury induced by immune checkpoint inhibitors

YANG Si-heng, YIN Rong-kun, CHEN Rong, ZHAO Gang-de, TANG Wei-liang, WANG Wei-jing, XIE Qing, MO Rui-dong

2024, 29(1):  34-36. 

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Objective To analyze the clinical characteristics, treatment, and prognosis of the patients with ICI-induced immune-mediated hepatotoxicity (IMH). Methods A total 14 IMH patients were retrospectively recruited from Department of Infectious Diseases, Ruijin Hospital between September 2019 to September 2022. The characteristics of onset, clinical manifestations, treatment response and the prognosis of IMH patients were summarized and analyzed. Results The 14 patients (median age, 61 years) were mainly males, usually present with jaundice, malaise, and yellow color urine as the main symptoms. The mainly clinical pattern was cholestasis type in 8/12 (66.67%), and 10 patients had grade 3-4 liver injury. The patients were treated with diammonium glycyrrhetate or UDCA basically, and 10 patients were treated with steroids (4/10) or steroids combined with second line immunosuppressive treatment (Mycophenolate Mofetil, 6/10). After treatment, 5 of the 14 patients died or withdrawing treatment due to deterioration of the disease (excluding sudden unexpected death in 2 patients due to other diseases), and 7 patients recovered from IMH. The neutrophil-to-lymphocyte ratio (NLR) in the poor prognosis group was significantly higher than those in the good prognosis group (13.5 vs 3.3, P<0.05). Conclusion Cholestatic type is the main clinical pattern of IMH. Half of the patients recovered after the treatment. The overall prognosis is poor. NLR may be used as a clinical marker to evaluate the prognosis of IMH.

An analysis on the clinical biochemical and pathological characteristics of simple cholestatic type of drug induced liver injury

BAI Huan-huan, FENG Hui-jun, GUO Li-jie, ZHANG Hai-cong, HE Xiao-yan, MENG Shuang, ZHANG Xiang-e

2024, 29(1):  37-40. 

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Objective To analyze the clinical, serum biochemistry and histopathological characteristics of patients with simple cholestatic type of drug induced liver injury (DILI). Methods Thirty-eight patients were diagnosed as simple cholestatic type of DILI with Liver biopsy. The causative drugs, disease course, R value for DILI classification, peak value and changing trend of liver biochemical indexes and histopathology were collected. The correlation between different pathological characteristics and the disease course and liver biochemical indexes were analyzed. Results Simple cholestatic type of DILI was more common in male patients <40 years old, but more common in female patients >40 years old. The most common drugs causing simple cholestatic type of DILI were Chinese herbs (36.8%), the next were antibiotics (13.2%) and antipyretic analgesic drugs (13.2%). Most R values are <2 (mean=1.5). The peak and recovery time of liver biochemical indexes have different characteristics. There was a moderate correlation between the score of canalicular cholestasis and TBil value (r=0.545, P=0.016). The scores of small bile duct degeneration was moderately correlated with the peak value of γ-glutamyl transpeptidase (GGT) (r=0.538, P=0.021).There was no correlation between other pathologic scores and the peak value of liver biochemical indexes (P>0.05).The course of disease was positively correlated with cholestasis in canalicular and hepatocyte (r=0.528, P=0.024; r=0.500, P=0.041). Peak time of TBil was positively correlated with canalicular cholestasis (r=0.672, P=0.002). The normal time of GGT was positively correlated with the degeneration of small bile duct (r=0.551, P=0.018). There was no correlation between other pathologic scores and the peak and recovery time of liver biochemical indexes (P>0.05). Conclusion Simple cholestatic type of DILI has its unique clinical, pathological and hepatic biochemical characteristics and disease evolution course.

An analysis on the effect of plasma exchanges combined with dual plasma molecular adsorption system in the treatment of drug-induced liver failure

ZHOU Xiao-hong, YANG Jing, YUAN Ming-juan

2024, 29(1):  41-43. 

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Objective To explore the efficacy of plasma exchange (PE) combined with dual plasma molecular adsorption system (DPMAS) in the treatment of patients with drug-induced liver failure. Methods A retrospective analysis was conducted on 64 patients with drug-induced liver failure (grade 3 to 4 of drug-induced liver injury) admitted to the department of infectious diseases of Yueyang Central Hospital from June 2020 to February 2021. Among them, 32 were in the PE combined with DPMAS treatment group and 32 were in the drug treatment alone group. Results The clinical efficacy of the two groups post-treatment, the alterations in liver function and coagulation function indicators pre-and post-treatment, as well as the incidence of clinical adverse reactions were compared. The combined use of PE and DPMAS group yielded a significantly higher total effective rate (87.5%) than that of the drug alone group (65.6%). PE combined with DPMAS group had more advantages in reducing bilirubin and improving blood coagulation function (P=0.017 and 0.025, respectively),and there was no statistical difference between the two groups in reducing glutamic pyruvic transaminase and glutamic oxalic transaminase (P=0.497 and 0.103, respectively). Conclusion The incidence of adverse reactions was not significantly different between the two groups.The utilization of both plasma exchange and dual plasma molecular adsorption system is a safe and effective treatment for individuals suffering from drug-induced liver failure.

Liver Fibrosis & Cirrhosis

The characteristics and risk factors of esophageal varices in patients post-liver transplantation

XIANG Lu, ZHANG Li-juan, YANG Jun-lian,ZHANG Da-li, FENG Dan-ni

2024, 29(1):  44-46. 

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Objective To explore the risk factors and characteristics of esophageal varices in patients post-liver transplantation (LT). Methods This is a cross-section study retrospectively analyzed the data of patients post-LT who had a gastroscopy at the General hospital of the 5th medical center of Chinese People's Liberation Army from July 2011 to October 2021. Patients post-LT were classified into patients with and without esophageal varices via gastroendoscopy. Results Fifty-five cases were included in this study, with 26 patients among them with esophageal varices, and 29 cases without esophageal varices. Compared with those patients without esophageal varices, patients with esophageal varices had three characteristics: longer spleen length (117 mm vs 154 mm, P=0.001), lower platelet counts (136×10⁹/L vs 87×10⁹/L, P=0.015), and higher total bile acid level (6.0 μmol/L vs 24.5 μmol/L, P=0.001). Spleen length (OR=1.063, 95%CI=1.01~1.12, P=0.031) was the independent risk factor associated with esophageal varices. The area under the ROC curve for esophageal varices was 0.790 (95%CI=0.647~0.934, P=0.001) at the cutoff value was 143mm, the sensitivity was 91.3%, and specificity was 91.3%. Conclusion Spleen length is the independent risk factor associated with esophageal varices and had good discriminable power for esophageal varices after LT.

Evaluation of hepatic fibrosis by Gd-EOB-DTPA enhanced magnetic resonance imaging

LIU Pu, ZHUO Hong-ping, TAO Guang-ju

2024, 29(1):  47-49. 

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Objective To evaluate the value of gadolinium-ethoxybenzyl-diethylenetriaminepentaaceticacid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) in the evaluation of liver fibrosis degrees of hepatitis B. Methods A retrospective study was performed on chronic hepatitis B patients who underwent Gd-EOB-DTPA enhanced MRI examination enrolled from February 2019 to January 2022. The degree of liver fibrosis in these patients was evaluated according to the pathological results of liver biopsies. The mean signal values of right anterior lobe, right posterior lobe, left lobe, caudate lobe and right erector ridge muscle were measured in T1W1 and enhanced hepatobiliary phase images, and the relative enhancement of liver parenchyma in hepatobiliary phase was calculated. The difference of relative enhancement (RE) ratio of liver parenchyma in different hepatic fibrosis degree was analyzed. Results A total of 102 patients with chronic hepatitis B were enrolled, including 55 males and 47 females, with an average age of 35 years. According to the degree of hepatitis B fibrosis, 21 cases were S0 stage, 18 cases were S1 stage, 29 cases were S2 stage, 20 cases were S3 stage, and 14 cases were S4 stage. The RE ratio of patients with liver fibrosis in S0, S1, S2, S3 and S4 stages were (86.2±9.7)%, (74.1±12.6)%, (70.9±10.7)%, (62.5±13.4)% and (45.6±15.1)%, respectively, the difference was statistically significant (P<0.05). The receiver operating characteristic (ROC) curve of Gd-EOB-DTPA enhanced MRI for evaluating the degree of liver fibrosis in hepatitis B showed an Area Under Curve (AUC) of 86%, an optimal cut-off value of 55%, a sensitivity of 67%, and a specificity of 91%. In patients with obvious liver fibrosis, the RE ratio of hepatobiliary phase was (52.7±6.1)%, which was lower than that of patients without obvious liver fibrosis (78.2±5.3)%, and the difference was statistically significant (P<0.05). Conclusion The more severe the degree of liver fibrosis in patients with chronic hepatitis B, the lower the degree of RE ratio of liver parenchyma in hepatobiliary phase on Gd-EOB-DTPA enhanced MRI. Therefore, Gd-EOB-DTPA enhanced MRI is helpful to evaluate the degree of liver fibrosis in patients with chronic hepatitis B.

A study on the correlation between shear wave elastic imaging parameters and TGF-β1 and TIMP-1 in chronic hepatitis B patients with liver fibrosis

CHEN Wan-feng, XU Ya-chun

2024, 29(1):  50-55. 

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Objective To investigate the correlation between the changes of liver stiffness measurements (LSM) by shear wave elastography (SWE) and serum levels of transforming growth factor β1 (TGFβ1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in chronic hepatitis B (CHB) patients with liver fibrosis. Methods A total of 100 CHB patients with liver fibrosis admitted to the People's Hospital of Hai'an City from July 2020 to December 2022 were included in the observation group. According to the imaging and liver puncture detection results, they were divided into S0 group (n=22), S1 group (n=25), S2 group (n=23), S3 group (n=15) and S4 group (n=15) according to the degree of liver fibrosis. A total of 50 patients who underwent physical examination in our hospital during the same time period were included in the control group. The levels of LSM, serum TGF-β1 and TIMP-1 in the observation group and the control group were detected and compared. The levels of platelet technology, liver function and liver fibrosis indexes were detected and compared in each subgroup of the observation group. The correlation between LSM and TGF-β1 and TIMP-1 was analyzed by Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted to analyze the diagnostic efficacy of LSM combined with TGF-β1 and TIMP-1 for hepatic fibrosis in CHB patients. Results The levels of LSM, TGF-β1 and TIMP-1 in the observation group were 9.32±1.82 kPa, 113.42±10.98 pg/mL and 199.08±23.56 μg/L, respectively. They were higher than 2.41±0.25 kPa, 24.53±5.64 pg/mL and 120.32±14.53 μg/L in the control group, and the differences were statistically significant (t=26.685, 53.758, 21.653, P<0.05). The levels of PLT and serum ALB in CHB patients were gradually decreased, while the levels of serum ALT, AST, γ-GT, TBil, DBil, HA, PC-Ⅲ, Ⅳ-C, LN and FIB-4 index were gradually increased with the increase of hepatic fibrosis stages. The difference was statistically significant (P<0.05). The levels of LSM, TGF-β1 and TIMP-1 in CHB patients were gradually increased with the increase of hepatic fibrosis stages, and the difference was statistically significant (P<0.05). Pearson analysis showed that LSM was positively correlated with TGF-β1 and TIMP-1 in CHB patients with liver fibrosis (rLSM vs TGF-β1=0.564, rLSM vs TIMP-1=0.587, P<0.05). The AUC, sensitivity and specificity of LSM in the diagnosis of liver fibrosis in CHB patients were 0.887, 89.70% and 85.49%, respectively, which were higher than that of serum TGF-β1 and TIMP-1 levels (0.854, 85.64%, 83.78% and 0.821, 83.05%, 80.56%). The difference was statistically significant (P<0.05). Conclusion The levels of LSM by SWE and serum TGF-β1 and TIMP-1 levels were closely correlated with the severity of liver fibrosis in CHB patients with liver fibrosis and LSM had better evaluation efficacy.

The value of instantaneous elastography combined with serum HBsAg and HBV DNA in evaluating the degree of hepatitis B related liver fibrosis

WANG Da-long, WANG Tao, WANG Kang-e

2024, 29(1):  56-59. 

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Objective To investigate the value of instantaneous elastic imaging combined with serum hepatitis B virus surface antigen (HBsAg) and hepatitis B virus gene (HBV DNA) in evaluating the degree of hepatitis B liver fibrosis. Methods From February 2019 to April 2023, 77 patients with chronic hepatitis B were admitted to Huainan Chaoyang Hospital. All patients received liver puncture biopsy to determine the stage of liver fibrosis, and the results showed that 14 cases were in stage S0, 20 cases were in stage S1, 21 cases were in stage S2, 13 cases were in stage S3, and 9 cases were in stage S4. The Mindray Hepatus 5 tester was used to determine the liver hardness value, and the serum HBsAg and HBV DNA levels were tested. Results The liver hardness values of S0-S1, S2, S3 and S4 stages were (6.02±1.41)kPa, (9.11±1.46)kPa, (11.26±1.38) kPa and (13.05±1.59) kPa, respectively. The liver hardness values of S4 stage were higher than those of S3 stage and S3 stage were higher than those of S2 stage. The liver hardness of S2 stage was higher than that of S0-S1 stage (P<0.05). HBsAg levels in stages S0-S1, S2, S3 and S4 were (216.81±42.09) IU/mL, (142.68±35.17) IU/mL, (53.61±11.54) IU/mL, and (26.51±8.14) IU/mL, respectively. HBV DNA in S0-S1, S2, S3 and S4 stages were (1.14×10⁶±1.79×10⁵)IU/mL,(1.06×10⁶±1.54×10⁵)IU/mL, (9.61×10⁵±1.39×10⁵) IU/mL, (8.47×10⁵±1.33×10⁵) IU/mL, respectively. HBsAg level in S0-S1 stage was higher than that in S2 stage, the level in S2 stage was higher than that in S3 stage, and the level in S3 stage was higher than that in S4 stage. HBV DNA level in S0-S1 stage was higher than that in S3 stage and S4 stage, and the level in S2 stage was higher than that in S4 stage (P<0.05). According to ROC analysis, the area under ROC curve of liver hardness value and serum HBsAg and HBV DNA in evaluating the degree of liver fibrosis ≥S2 stage were 0.829 (95%CI: 0.746~0.912), 0.747 (95%CI: 0.678~0.816) and 0.723 (95%CI: 0.778~0.816), respectively. The optimal cut-off values were 7.362 kPa, 148.306 IU/mL, 1.092×10⁶ IU/mL, the sensitivity were 0.774, 0.648, 0.679, and the specificity were 0.920, 0.837, 0.863, respectively. The area under the curve of the combined diagnosis was 0.907 (95%CI: 0.861~0.953), the sensitivity and specificity were 0.910 and 0.958, respectively, P<0.05. Conclusion Instantaneous elastic imaging and serum HBsAg and HBV DNA have good value in the evaluation of chronic hepatitis B patients with liver fibrosis degree ≥S2 stage, and the sensitivity and specificity can be further improved in the combined evaluation.

Clinical characteristics, pathogenic characteristics and influencing factors of hepatitis B-related end-stage liver disease complicated with infection

SI Jin-mei, CHEN Min, XU Xiao-guo, YAN Xue-bing

2024, 29(1):  60-63. 

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Objective To investigate the clinical features, pathogenic features and influencing factors of hepatitis B-related end-stage liver disease (ESLD) complicated with infection. Methods A total of 82 patients with hepatitis B-related ESLD were selected between January 2017 and June 2022, including 51 males and 31 females with an age of 45(34, 60) years. Among them, 34 were not complicated with infection (non-complicated infection group), while 48 were complicated with infection (complicated infection group). The selected ESLD cases met the diagnostic requirements. Single-factor and multi-factor analyses were conducted to analyze the influencing factors of complicated infection in ESLD patients, and information such as infection location, pathogen specimen source, and culture results were collected. Results Univariate analysis indicated that the WBC, CRP, ALT, AST, TBil, Scr, INR, PCT and MELD scores in the complicated infection group were 6.8(4.4, 11.3) ×10⁹/L, 35.8(17.3, 43.8) mg/L, 92(70, 123) U/L, 102(78, 140) U/L, 127.0 (73.8, 250.4) μmol/l, 92.7 (65.5,112.3) μmol/l, 2.0 (1.4,2.3), 6.2 (2.0,9.0) ng/l and 14 (9, 22) points, which were significantly higher than those in the non-complicated infection group [3.7 (3.0, 5.3 ) ×10⁹/L, 11.2 (7.6, 18.9) mg/L, 57 (18, 88) U/L, 54 (24,79) U/L, 37.3(17.9, 80.2) μmol/l, 74.2 (44.8, 97.0) μmol/l, 0.9 (0.7, 1.2), 0.2 (0.1, 2.8) and 7 (5, 11) points, P<0.05]. Additionally, the Alb and PTA levels in the complicated infection group were 28.3(27.8, 31.6) g/L and 45.3(37.9, 50.8) %, which were significantly lower than those in the non-complicated infection group [33.2(30.8, 35.8)g/L and 66.7(49.6, 74.0)%, P<0.05]. In the complicated infection group, 37 cases (77.1%) had single infections and 11 cases (22.9%) had multiple infections. Among the patients with a single infection site, the most common infection was SBP in 18 cases (37.5%), followed by lung infection in 13 cases (27.1%), urinary tract infection in 4 cases (8.3%), and biliary tract infection in 2 cases (4.2%). For patients with multiple infection sites, the most common scenario was SBP combined with lung infection in 10 cases (20.8%), and SBP combined with fungal infection in 1 case (2.1%). A total of 16 pathogens (33.3%) were cultured among the 48 patients, including 9 strains of Bacillus (56.2%), 6 strains of cocci (37.5%) and 1 strain of fungi (6.2%). The bacterial isolates consisted of 7 strains of Escherichia coli (43.7%), 1 strain of Klebsiella pneumoniae (6.2%) and 1 strain of Klebsiella acidogenes (6.2%). Staphylococcal isolates comprised 5 strains of Enterococcus faecalis (31.2%) and 1 strain of Staphylococcus aureus (6.2%). Additionally, there was 1 strain of Candida albicans (6.2%) among the fungal isolates.The resistance rates of Escherichia coli to quinolones such as levofloxacin and ciprofloxacin were 57.1%(4/7) and 42.8%(3/7), respectively, while the resistance rate to cefuroxime was 71.4%(5/7). Escherichia coli exhibited sensitivity to carbapenems such as cefoperazone, sulbactam, meropenem and imipenem. The resistance rate of Enterococcus faecalis to penicillin, levofloxacin and ciprofloxacin were all 80.0%(4/5). Additionally, the resistance rate to tetracycline, gentamicin and streptomycin were 20.0%(1/5), 40.0%(2/5) and 60.0% (2/5), respectively. Conclusion Effective antibiotic treatment plans should be developed for ESLD patients with infections based on the complicated infection site, past antibiotic use history, combined with the epidemic spectrum of pathogenic bacteria and the detection and analysis of drug resistance. This approach will help to prevent further aggravation of infection.

Clinical application value of mNGS in the diagnosis and prognosis of patients with spontaneous peritonitis in cirrhosis

LIN Jia-fu, YU Ting, ZHANG Pei-lin, LIU Xue-tao, WANG Li-heng

2024, 29(1):  64-67. 

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Objective To investigate the diagnosis and prognosis value of metagenomic Next-Generation Sequencing (mNGS) assay in patients with spontaneous bacterial peritonitis by comparing the results of mNGS and ascites culture from patients with liver cirrhosis. Methods Sixty inpatients diagnosed with cirrhosis and met the inclusion criteria were selected from our hospital between March 2021 and March 2023. Ascites specimens were collected using standardized operation, and both ascites culture and ascites mNGS assay were performed. The patients' general clinical data, etiology of cirrhosis, personal medical history, and antibiotic use were recorded. The scoring indexes used included APRI index, FIB-4 index, MELD score, MELD-Na score and Child-Pugh score. Results There was no significant difference in the patients' basic information and etiological composition of cirrhosis (P>0.05). The positive detection rate of ascitic fluid polymorphonuclear leukocyte counting method combined with ascitic fluid mNGS for SBP in cirrhosis was significantly higher than the detection method combined with ascitic fluid culture. The combined counting method and mNGS assay demonstrated a sensitivity of 86.67% and a specificity of 78.86%. Statistical results during the follow-up period revealed that the mNGS positive group had a higher incidence of adverse events, mortality rate, and liver cirrhosis related index scores. The mean MELD scores of the ascites mNGS positive group and the ascites mNGS negative group were 18.25 and 13.11, respectively. As for the mean MELD Na scores, the ascites mNGS positive group reported 23.82 ± 11.77, while the ascites mNGS negative group reported 14.58 ± 11.27. The MELD score and MELD-Na score for patients with mNGS positive ascites were significantly higher than those for patients with mNGS negative ascites. Moreover, the average Child Pugh scores for the two groups of patients were 11.25 and 9.75, respectively. The Child Pugh scores of patients with mNGS positive ascites were significantly higher than those of patients with mNGS negative ascites. Conclusion The combination of PMN count and mNGS was found to be more effective than ascites culture in guiding early treatment. Furthermore, a positive mNGS test was strongly associated with a poor prognosis in patients with cirrhotic SBP. These findings suggest that mNGS test can serve as improtant observational and predictive indicators of patient prognosis, making it a valuable tool for predicting adverse events during follow-up.

Correlation between C/RL-r, APRI, FIB-4 levels and hepatic fibrosis in patients with nonalcoholic fatty liver disease

ZHAO Dong-zhi, LI Guo-dong, CHANG Yuan-yuan, CAO Zhe-li, ZHAO Ya-juan

2024, 29(1):  68-72. 

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Objective To analyze the relationship between the modified caudate-right lobe ratio (C/RL-r), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and the development of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods A total of 153 patients diagnosed with NAFLD treated at Baoding First Central Hospital between February 2021 and December 2022 were included in this study. The patients were divided into non-hepatic fibrosis group (81 cases) and hepatic fibrosis group (72 cases) based on liver puncture and pathology result. MRI scanning was performed to detect C/RL-r and laboratory tests were conducted to calculate the APRI and FIB-4. The analysis aimed to investigate the the correlation between laboratory indices, C/RL-r, APRI, FIB-4 and the presence of liver fibrosis in patients with NAFLD, as well as to identify independent risk factors for liver fibrosis. Additionally, the study sought to evaluate the predictive value of C/RL-r, APRI, FIB-4 for liver fibrosis in NAFLD patients. Results Significant differences were observed in the levels of alanine aminotransferase (ALT) [(42.32±10.21) U/L vs (36.21±7.78) U/L], aspartate aminotransferase (AST) [(45.36±8.72) U/L vs (27.45±5.40) U/L], total bilirubin (TBIL) [(13.52±3.65) μmol/L vs (12.24±2.16) μmol/L], γ-glutamyltransferase (GGT) [(60.53±13.41) U/L vs (53.69±12.44) U/L], triglyceride (TG) [(1.99±0.53) mmol/L vs (1.05±0.33) mmol/L], C/RL-r [(1.15±0.12) vs (0.92±0.09)], APRI [(0.52±0.15) vs (0.32±0.10)] and FIB-4 [(1.47±0.47) vs (0.94±0.30)] between the hepatic fibrosis group and the non-hepatic fibrosis group. The level of high density lipoprotein-cholesterol (HDL-C) [(1.03±0.26) mmol/L vs (1.32±0.45) mmol/L] was significantly lower in the hepatic fibrosis group (t=4.189, 15.453, 2.674, 3.272, 13.322, 13.501, 4.302, 8.405, 4.801, all P<0.05). Furthermore, ALT, AST, TG, C/RL-r, APRI, FIB-4 were positively correlated with liver fibrosis in NAFLD patients (r=0.531, 0.435, 0.571, 0.605, 0.771, 0.716, all P<0.001). High levels of ALT, AST, TG, C/RL-r, APRI and FIB-4 were identified as independent risk factors for liver fibrosis in NAFLD patients (P<0.05). The combination of C/RL-r, APRI, and FIB-4 demonstrated a significantly higher AUC (0.936) in predicting liver fibrosis in NAFLD patients compared to the AUC of C/RL-r (0.767), APRI (0.830), and FIB-4 (0.754) alone (Z=4.495, 3.999, 4.677, all P<0.001). Conclusion Elevated levels of C/RL-r, APRI and FIB-4 are observed in NAFLD patients with liver fibrosis, and the combined detection of these indices demonstrates a high predictive value for the occurrence of liver fibrosis in NAFLD patients.

Correlation analysis of liver stiffness detected by ElastPQ elastography with nonalcoholic fatty liver disease fibrosis score (NFS) and FIB-4 index in the diagnosis of fatty liver

WU Bin-bin, XU Xiao-qin, GU Xing-xing, XIE Qi-hua

2024, 29(1):  73-76. 

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Objective To evaluate liver stiffness and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) measured by ElastPQ elastography, and to investigate their correlation with liver fibrosis index (FIB-4) in the diagnosis of fatty liver. Methods A total of 30 patients with pure NAFLD and 30 patients with type 2 diabetes mellitus (T2DM) combined with NAFLD were selected as observation group 1 and 2, respectively, from the Third People's Hospital of Nantong City, Jiangsu Province, between October 2019 and October 2020. Additionally, 30 healthy subjects from the health examination center of the same hospital during the same period were selected as the comparison group. All participants underwent ElastPQ elastography. The ElastPQ value, NFS score, and FIB-4 index of mild, moderate and severe patients in the two groups were observed. The correlation between ElastPQ value and NFS score and FIB-4 index was analyzed by Spearman correlation analysis. Results The ElastPQ value (6.82±1.54) kPa, NFS score (-0.42±0.12), and FIB-4 index (2.82±0.32) of observation group 2 were significantly higher than those of observation group 1 [(5.75±1.02) kPa, (-1.05±0.25), (2.25±0.16)], respectively. Additionally, the ElastPQ values, NFS score, and FIB-4 index of observation group 1 were higher than those in the comparison group [(4.02±0.11)kPa, (-1.68±0.34), (1.02±0.11)], respectively. These differences were all statistically significant, P＜0.05. The ElastPQ value, NFS score, and FIB-4 index of moderate-severe patients in observation group 1 and observation group 2 were higher than those in moderate patients, and those in moderate patients were higher than those in mild patients, P<0.05 (all differences were statistically significant). ElastPQ value was positively correlated with NFS score and FIB-4 index, P<0.05 (r=4.967, 5.011) (the difference was statistically significant). Conclusion The ElastPQ value demonstrates a gradual increase with the progression of liver fibrosis in NAFLD patients. There is a discernible correlation between the ElastPQ value and the extent of liver fibrosis. Clinically, the ElastPQ value can be measured by color Doppler ultrasound to evaluate the degree of liver fibrosis in NAFLD patients.

Viral Hepatitis

Therapeutic effect of nucles(t)ide analogues and detection of serum HBV RNA in patients with chronic hepatitis B with positive serum HBeAg

LV Gao-yan, WANG Chun-juan

2024, 29(1):  77-80. 

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Objective To investigate the efficacy of nucles(t)ide analogues in the treatment of chronic hepatitis B patients with positive serum HBeAg and to assess the significance of detecting serum HBV RNA. Methods A total of 58 patients with HBeAg positive chronic hepatitis B were treated with nucles(t)ide analogues for 24 weeks between March 2018 and January 2021. The study compared the clinical characteristics before and after treatment, and analyzed the predictive value of serum ALT and HBV RNA in rapid virological response. Results The comparison of clinical characteristics before and after treatment revealed that the levels of total red bilirubin, ALT, HBV DNA and HBV RNA after treatment were (0.2±0.1) mg/dL, (121.5±59.0) U/L, 0.8 (0.5, 0.3)log₁₀copies/mL and 1.4 (1.1, 1.7)log₁₀copies/mL. These values were significantly lower than those of the before treatment group [(0.8±0.3) mg/dL, (168.3 ± 134.6) U/L, 8.4 (5.1, 10.6)log₁₀copies/mL and 7.2 (5.0, 9.9)log₁₀copies/mL (P<0.05)]. The negative rates of serum HBV DNA and HBV RNA were 94.8% and 70.7%, significantly higher than those before treatment [0.0% and 0.0% (P<0.05)]. Serum ALT and HBV RNA were found to have predictive value for rapid virological response, with the AUC values of 0.629 and 0.831 respectively. The best cutoff values for predicting rapid virological response were found to be ≥ 142 for ALT and 1.9 for HBV RNA, with respective sensitivity of 59.0 % and 82.0 %, and specificities of 72.1 % and 80.0 %. The positive predictive values for ALT and HBV RNA were 74.8 % and 86.6 %, while the negative predictive values were 58.2 % and 83.0 %, respectively. Conclusion Nucles(t)ide analogues demonstrate strong efficacy in patients with chronic hepatitis B with positive serum HBeAg. Additionally, serum HBV RNA is identified as a reliable predictor of rapid virological response.

Analysis of hepatitis B reactivation risk warning label in drug instructions based on livertox database

WU Ling, WEI Long, SU Qiong-li

2024, 29(1):  81-84. 

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Objective To investigate and analyze the record of 996 drugs associated with hepatitis B reactivation (HBVr) documented in the livertox database, and to compare this information with the HBVr medication warnings provided in the drug instructions. Methods The HBVr prompt information of drugs in the Livertox database was counted and compared with the HBVr medication warning information in the drug instructions included in the DRUGS.dxy.cn. Results The Livertox database contained information on 47 drugs and 1 drug class, all of which had HBVr risk information prompts and were marketed in China. It was concerning to note that glucocorticoid drugs and 10 drug instructions did not mention HBVr risk information, while 2 drug instructions only partially mentioned the risk. Conclusion Drug manufacturer should promptly update drug descriptions and add warning labels based on the latest HBVr risk information. Clinicians and pharmacists need to enhance medication monitoring for patients with viral infection to promote safe drug use.

Liver Cancer

Assessing the prognostic significance of tumor growth rate in patients with huge hepatocellular carcinoma undergoing transcatheter arterial chemoembolization

CHEN Zong-jie, PENG Xin-jian, WANG Yu-lin, HU Tian-song

2024, 29(1):  85-90. 

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Objective To investigate the prognostic implications of tumor growth rate in patients presenting with huge hepatocellular carcinoma (HCC) initially treated with transcatheter arterial chemoembolization (TACE). Methods The clinical records of patients with huge HCC who underwent TACE treatment at our institution between January 2016 and March 2020 were retrospectively examined. This study involved the collection of demographic, oncological, and serological parameters. The X-tile software was utilized to determine the optimal tumor growth rate threshold for stratifying overal survival(OS) among the cohort. Survival discrepancies based on varing tumor growth rates within 3 years post-TACE were assessed using the Kaplan-Meier method, with intergroup differences evaluated via the Log-rank test. Additionally, A Cox proportional hazards regression model was employed to elucidate factors influencing patient OS. Results The dtermined optimal cutoff value for prognosticating the 3-year survival of patients based on with tumor growth rate was -11.7% per month. Ptiantes were stratified into a low tumor growth rate group(n=52) and a high tumor growth rate group (n=46) according to this threshold,. Kaplan-Meier analysis revealed superior OS in the low tumor growth rate group compared to the high tumor growth rate group(χ²=7.120,P=0.008). The multivariate Cox proportional hazards regression model identified a high tumor growth rate (≥-11.7%/month) (HR=2.153, P=0.006) and the presence of porta vein tumor thrombosis(PVTT) (HR=1.942, P=0.006) as independent predictors of diminished OS post-TACE in patients with huge HCC. Conversely subsequent combination therapy emerged as a protective factor(HR=0.532, P=0.026). Of all patients, 57 (58.16%) received follow-up therapy. For the low tumor growth rate group, combination therapy did not significantly affect OS(P=0.477). Yet, for the high tumor growth rate cohort, post-TACE OS was notably improved in those receiving subsequent combination therapy compared to those without(χ²=4.312,P=0.038). Conclusion Tumor growth rate hodls a discernible prognostic value for patients with huge HCC undergoing TACE as the initial treatment. Those exhibiting a higher tumor growth rate tend to have a relatively poorer prognosis. Notably, patients with a rapid tumor growth rate derive greater benefit from subsequent combination therapy following TACE.

Prognostic impact of metabolic syndrome on outcomes in patients with hepatitis B-related primary hepatocellular carcinoma following hepatectomy

WU Jian, WANG Lian-cai, WANG Ya-feng, DU Chang-shun, XIAO Jian-an

2024, 29(1):  91-94. 

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Objective To investigate the prognostic influence of metabolic Syndrome (MetS) on the postoperative outcomes of patients afflicted with hepatitis B-associated primary hepatocellular carcinoma (HCC) following hepatectomy. Methods Retrospective analyses was performed on 113 HCC patients(89 males and 24 females, mean age 52 years) treated between January 2013 and June 2018. Patients meeting the criteria for HCC and MetS were categorized into MetS and non-MetS groups. Clinical and surgical parameters were compared between these groups. Primary endpoints included overall survival rate and recurrence-free survival rate. Univariate analyses were conduced using T-test, Mann-Whitney U-test, or Chi-square tests as appropriate. Differences in survival rates and recurrence-free survival rates between groups were evaluated using the, log-rank test. Results In the MetS group, the median age was 55 (IQR: 45-62) years, with 27 males(65.8%), a mean BMI of 26.4±4.0 kg/m², a median WBC count of 5.7× 10⁹/L (IQR: 4.2-7.7) and 24 cases (58.5%) of cirrhosis. These metrics were significantly different from the non-MetS group, which had a median age of 50 years (IQR: 43-59), 62 males (86.1%), a mean BMI of 23.0±3.7 kg/m², a median WBC count of 3.5×10⁹/L(IQR: 2.6-4.9), and 11 cases (26.8%) of cirrhosis(P<0.05). Additionally, the MetS group had higher incidences of cirrhosis and steatohepatitis at 58.5%(24 cases) and 26.8%(11 cases), respectively, compared to 34.7%(25 cases) and 9.7%(7 cases) in, the non-MetS group(P<0.05). Liver failure and hyperglycemia were also more prevalent in the MetS group at 12.2%(5 cases) and 26.8%(11 cases) respectively, versus 2.8%(2 cases) and 9.7%(7 cases) in the non-MetS group(P<0.05). Clavien-Dindo grades in the MetS group( 8 cases at 19.5%, 12 cases at 29.3%, 5 cases at 12.2%, 2 cases at 4.9%) differed significantly from those , in the non-MetS group(17 cases at 23.6%, 5 cases at 6.9%, 5 cases at 6.9%)(P<0.05). The comprehensive complication index was significantly higher in the MetS group(median: 8.5, IQR: 0-12.0) compared to the non-MetS group(median: 0, IQR: 0- 8.0)(P<0.05). Over a median follow-up of 42 months(IQR: 4-60), the 5-year overall survival rate was 63.4%(26/41) in the MetS group and 80.5% (58/72) in the non-MetS group, while the recurrence-free survival rates were 51.2% (21/41) and 63.9% (53/72) respectively, both differences being statistically significant (P<0.05). Conclusion When HCC is complicated with MetS, the postoperative complications tend to be more severe, and the overall survival prognosis worsens. This indicates a critical need for meticulous atteintion to metabolic disorders in patients with HCC.

Correlating TRIM3 and FoxO1 in tissues with pathological features and prognosis in primary liver cancer patients

ZHANG Li-li, ZHEN Fei

2024, 29(1):  95-98. 

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Objective To investigate the association between the expression levels of tripartite motif-containing 3 (TRIM3) and forkhead transcription factor O1 (FoxO1) in tissues, and the pathological characteristics and prognostic implications in patients with primary hepatic carcinoma (PHC). Methods Clinical data from 119 patients with PHC treated at Huaian First Hospital Affiliated to Nanjing Medical University from January 2018 to December 2019 were retrospectively analyzed. The study aimed to compare the expression levels of TRIM3 and FoxO1 in liver cancer tissues and adjacent non-tumorous tissues of these patients. Additionally, The pathological characteristics and prognostic outcomes in patients exhibiting varing expression levels of TRIM3 and FoxO1in their PHC tissues were compared. Results In PHC patients, the expression rates of TRIM3 and FoxO1 in liver cancer tissues(46.22 %, 42.02 % respectively) were significantly lower compared to adjacent non-tumorous tissues((75.63 %, 79.83 % respectively)(P<0.05). Patients with positive TRIM3 expression demonstrated a significantly higher incidence of tumors smaller than 5cm, high differentiation and TNM stages Ⅰ-Ⅱcompared to those with negative TRIM3 expression(P<0.05). Similarly, FoxO1 positive patients showed a significantly higher frequency of tumors smaller than 5 cm, single tumors, and TNM stages Ⅰ-Ⅱ compared to FoxO1 negative patients (P<0.05). The 3-year survival rates for patients with positive TRIM3 expression(61.82%) were notably higher than those with negative expression(31.25 %), with a statistically significant difference(Log Rank=10.242, P=0.001). Likewise, the 3-year survival rates were 60.00 % in FoxO1-positive patients and 34.78 % in FoxO1-negative patients, making a significant difference(Log Rank=6.978, P=0.008). Conclusion The expression levels of TRIM3 and FoxO1 in tissues demonstrate a substantial association with both the pathological attributes and the prognostic outlook of PHC patients, indicating their potential as vital prognostic biomarkers for evaluating patint status and predicting clinical outcomes in PHC.

Other Liver Diseases

Surgical management of 93 children with hepatic cystic echinococcosis in Tibet

YE Jun-shan, CHEN Biao, BANGSANG Dun-zhu, DA Wa

2024, 29(1):  99-101. 

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Objective To investigate the clinical profiles and assess the outcomes of surgical interventions for pediatric hepatic cystic echinococcosis. Methods Clinical data of pediatric patients(≤14 years of age) with hepatic cystic echinococcosis, who were treated surgically in the General Surgery Department of the People's Hospital of Tibet Autonomous Region from January 2014 to December 2019, were retrospectively analyzed. The demographic details, clinical manifestations, cyst characteristics, surgical approaches, and postoperative complications were recorded for statistical examination. Results A comprehensive review was conducted on total 93 pediatric cases, comprising 53 males (57.0%) and 40 females (43.0%). Among these, 58 cases (62.3%) were asymptomatic during physical examinations, while 29 cases (31.1%) presented with abdominal pain. The cyst were predominantly located in the right hepatic lobe in 62 cases (66.6%), in the left lobe in 12 cases (12.9%), and in both lobes in 19 cases (20.4%). Multiple internal cysts (≥2) were observed in 34 cases (36.55%), with an average cysts diameter of (9.14±3.16) cm. Surgical interventions included internal cystectomy in 43 cases (46.2%), external cystectomy in 39 cases (41.9%), and complete external capsule remova in, 11 cases (11.8%). Postoperative complications included residual cavity bile leakage in 5 cases, pleural effusion in, 11, residual cavity infection in 1, lung infection in 2, and 1mortality. Over a follow-up- period of 1-4 years, 4 cases experienced recurrence and were managed with oral albendazole and regular B-ultrasound monitoring. Conclusion In pediatric cases, hepatic cystic echinococcosis is predominatly asymptomatic. The cysts are primarily situated in the right hepatic lobe, characterized by a high incidence of multiple occurrences and a thin outer cyst wall. Surgical intervention remains the principal treatment modality, necessitating tailored approaches based on individual patient conditions.

Pediatric portal vein cavernous transformation: a comprehensive review of clinical manifestations, surgical treatment strategies, and outcomes in 40 cases

LIU Luo-hai, LI Shi-qing

2024, 29(1):  102-104. 

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Objective To analyze the clinical characteristics, surgical intervention strategies,, and prognostic outcomes of 40 pediatric patients diagnosed with portal vein cavernous transformation. Methods Between June 2017 and June 2022, 40 pediatric patients diagnosed with portal vein cavernous transformation admitted to our hospital were subjected to a comprehensive analysis of their clinical manifestations, a summary of the surgical treatments administered, and an evaluation of their subsequent outcomes. Results In children, cavernous degeneration of the portal vein typically manifests with clinical symptoms such as abdominal pain, bloating, and splenomegaly, often accompanied by alterations in liver function indicators and esophageal varices as revealed through imaging examination. Forty pediatric cases treated surgically for portal vein cavernous transformation at our institution were retrospectively analysed. The cohort comprised 28 cases (70.0%) undergoing Rex shunt prodedure, 8 cases (20.0%) receiving splenorenal shunt surgery, and 4 cases (10.0%) treated with liver transplantation. Postoperatie survival was 100% among the 40 children. Follow-up assessments indicated that of the children who received Rex shunt, 25 (62.5%) exhibited patent bypass vessels with normal blood flow velocity and no stenosis, while 3 (7.5%) experienced postoperative vascular occlusion. In the splenorenal shunt cohort, 3 (7.5%) did not show a reduction in splenic size or alleviation of esophageal varices, though no cases of hematemesis or melena were reported. Among the liver transplantation recipients, 1 child(2.5%) developed early postoperative hepatic artery thrombosis, which was successfully treated with anticoagulant therapy. Conclusion The clinical manifestations of cavernous transformation of the portal vein in pediatric patients exhibit distinct characteristics. Surgical interventions are tailored based on the developmental status of the portal vein both intra- and extrahepatically. Among the availaboe surgical options, the Rex shunt procedure is notable for its ability to restore the normal anatomy and physiological function of the portal vein system, enhace liver perfusion, and mitigate adverse postoperative outcomes.

Correlation between sTfR, liver/spleen CT ratio and mild cognitive impairment in elderly patients with nonalcoholic fatty liver disease

ZHANG Wei, LIU Qing-lin, ZHANG Man, AN Yang, CAO Mu-han

2024, 29(1):  105-109. 

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Objective To investigate the relationship between serum soluble transferrin receptor (sTfR), liver/spleen CT ratio and cognitive function in patients with nonalcoholic fatty liver disease (NAFLD). Methods A total of 110 elderly patients with NAFLD and 50 healthy people who were treated in Dongfang Hospital of Beijing University of Traditional Chinese Medicine from March 5, 2019 to March 5, 2020 were retrospectively included. The cognitive function was measured using the Montreal Cognitive Function Scale(MoCA). Among them, the elderly patients with NAFLD were classified into MCI group(MoCA>26, 61 cases) and non-MCI group(MoCA <26, 49 cases). Additionally, there were 50 healthy subjects assigned to the control group. The differences in the baseline data of the three groups were collected and compared, and the MoCA was used to evaluate the cognitive function. The Pearson correlation was further used to analyze the correlation between the MoCA score and the above indicators in elderly NAFLD patients, and then logistic regression was performed to analyze the correlation. Risk factors for NAFLD patients with MoCA score < 26 (MCI). Results The ratios of left NAA/Cr, right NAA/Cr, sTfR, liver/spleen CT ratio decreased in the control group, non-MCI group, and MCI group in turn, and the difference between groups was significant (P<0.05); No significant difference was found in the proportion of patients with BMI>25, MocA score, TG and LDL-C levels between the control group and non-MCI group. When compared with the control group and non-MCI group, the proportion of patients with BMI≥25, TG and LDL-C levels were significantly higher, and the MoCA scores were significantly lower (all P<0.05) in the MCI group, . MoCA score in elderly patients with NAFLD was positively correlated with left NAA/Cr, right NAA/Cr, sTfR, liver/spleen CT ratio, and negatively correlated with LDL-C level(P＜0.05). Logistic regression analysis showed that sTfR, liver/spleen CT ratio, BMI≥25, and TG level were risk factors for MCI in elderly patients with NAFLD (P＜0.05). Conclusion sTfR and liver/spleen CT ratio are risk factors for MCI in elderly patients with NAFLD, and both are positively correlated with MCI.