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    30 September 2022, Volume 27 Issue 9
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    Frontier, Exploration and Controversy Liver Failure
    Clinical characteristics of alcohol-related chronic liver failure
    ZHANG Li-li, HU Jian-hua, WANG Jiu-chong, LI Fei-ran, WANG Bao-hua
    2022, 27(9):  963-965. 
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    Objective To investigate the clinical characteristics and laboratory indexes of patients with alcohol-related chronic liver failure. Methods Laboratory examination results of patients with alcohol-related chronic liver failure admitted to our hospital from January 2018 to June 2021 were retrospectively analyzed. Results A total of 23 cases were enrolled. The incidence rates of jaundice, splenomegaly, ascites, hepatic encephalopathy were 100%, (73.91%), 18 cases (78.26%), and 7 cases (30.43%), respectively. The anemia type of patients in the study was mild to moderate megaloblastic anemia, with Hgb 84.52 ± 20.69 g/L and MCV102.57 ± 10.28f. Eleven cases (47.83%) with elevated alkaline phosphatase (ALP) and 4 (17.39%) with elevated gamma-glutamyl transpeptidase (GGT). The coagulation function of the patients was that prothrombin time (PT) 26.01 ± 6.83s, prothrombin activity (PTA) 35.22 ± 11.48%, international normalized ratio (INR) 2.29 ± 0.60, fibrinogen (FIB) 1.24 ± 0.56 g/L, and platelet (PLT) (57.35 ± 31.15)×109/L. The increase of bilirubin was more obvious and alanine aminotransferase (ALT) were all within the normal reference value range, [total bilirubin (TBil) 165.18 ± 115.12 μmol/L, ALT 23.70 ± 11.09 U/L], and there was a trend of enzyme bile separation. Conclusion Some laboratory indexes of patients with decompensated alcohol-related chronic liver failure or compensated alcohol-related chronic liver failure are different. In patients with compensated alcohol-related chronic liver failure, the disease is more serious and the prognosis is worse.
    Establishment of a prediction model for bacterial infection in patients with HBV related acute-on-chronic liver failure
    ZHENG Hui-fang, LIN Sheng-long, ZHENG Song, HUANG Yu-xin, XIAO Shan-ying, YE Zi-jie, LIN Ming-hua, GAO Hai-bing
    2022, 27(9):  966-972. 
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    Objective To investigate the risk factors of bacterial infection in patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF), and to construct a prediction model. Methods A total of 255 patients with HBV-ACLF admitted to our hospital from January 2015 to December 2018 were enrolled, and the clinical data during 2 days after diagnosis were retrospectively analyzed. Bacterial infection occurred during hospitalization was selected as the clinical outcome. The R programming language was used to analyze the data and construct the nomogram. Lasso regression and logistic regression were used to filter variables, analyze risk factors and construct the prediction model. Efficiency of the constructed model was evaluated by receiver operating characteristic (ROC) curve and calibration plot. The model was internally verified by Bootstrap method. Results Among 255 patients with HBV-ACLF, the proportion of male was 78%, and the incidence rate of bacterial infection during hospitalization was 79.60%. Lasso regression analysis Taking lambda = lambda. 1 se (0.049) as the standard, 7 variables including age, direct bilirubin (DBIL), cholinesterase (CHE), prothrombin time (PT), activated partial thromboplastin time (APTT), C-reactive protein (CRP) and hepatic encephalopathy (HE) were selected as the risk factors through Lasso regression analysis. The logistic regression model was logistic(p)＝-7.1733 + 0.0495 × AGE + 0.4107 × ln(DBIL)-0.0002 × CHE + 0.0350 × PT + 0.0610 × APTT + 0.5212 × ln(CRP) + 1.3582 × (HE=1 or 0). Among the 7 variables, AGE (OR=1.05, 95%CI 1.02-1.09), DBIL (OR=1.51, 95%CI 1.06-2.17), CRP (OR=1.68, 95%CI 1.11-2.62) and HE (OR=3.88, 95%CI 1.37-14.10) were independent risk factors. The specificity of the model was 84.62%, the sensitivity was 69.49%. ROC curve showed the new prediction model (AUC = 85.1%) was superior to CRP(AUC = 71.9%) and PCT (AUC = 65.5%). Conclusion In HBV-ACLF patients, older age, baseline hyper DBIL, low CHE level, prolonged PT, prolonged APTT, elevated CRP, and HE are positively correlated with the occurrence of bacterial infection. The model based on these 7 risk factors performs good in predicting the occurrence of bacterial infection during the hospitalization in patients with HBV-ACLF.
    Metabolic changes of macrophages in LPS-induced liver failure
    GUO Jin, SHI Chun-xia, DENG Wei, ZHANG Lu-yi, CHEN Qian, WANG Yao, GONG Zuo-jiong
    2022, 27(9):  973-977. 
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    Objective During the process of acute liver failure (ALF), endotoxin activated macrophages to release cytokines and induced changes in cellular metabolism. The aim of this study was to investigate the change of the substrates and products of malate dehydrogenase, and to analyze the metabolic changes of mice ANA-1 macrophages in response to lipopolysaccharide (LPS). Methods A total of 16 subjects were enrolled, including 8 ALF cases and 8 were healthy controls. Liquid Chromatograph Mass Spectrometer (LC-MS) was used to analyze the level of the substrates and related metabolite (malate and oxaloacetate). The Mice ANA-1 macrophages cultured in vitro were divided into normal control group and LPS group [treated by LPS (5μg/ml)]. The levels of tumor necrosis factor-α (TNF-α), malate dehydrogenase 1 (MDH1), lactic acid, glucose, adenosine-5'-triphosphate (ATP) were tested. Western-blot was used to detect the intracellular MDH1 protein content. Results Compared with the normal group, the malate increased and oxaloacetate decreased in ALF group (P<0.05). In LPS-induced mice ANA-1 macrophages, the level of TNF-α in supernatant increased [(1722.501 ± 76.261) pg/mL vs (255.010 ± 16.139) pg/mL], P<0.05, which indicates that LPS stimulated macrophages release cytokines. Compared with the control group (15.710 ± 0.302) ng/mL, the level of MDH1(11.831 ± 0.335) ng/mL and protein content in the LPS group were reduced (P<0.05). In addition, the levels of lactate and glucose in ANA-1 cells treated by LPS increased [(0.281 ± 0.016) mmol/L vs (0.081±0.012) mmol/L, (0.081 ± 0.006) μmol/mL vs (0.033 ± 0.004) μmol/mL], and the ATP levels decreased [(61.766 ± 11.982) μmol/gprot VS (130.786 ± 25.386) μmol/gprot], P<0.05. Conclusion During the process of ALF, LPS suppressed the activity of MDH1 in macrophages, induced mitochondrial-related metabolism disorders, resulted in the increase of lactate and glucose, and decrease of ATP production.
    Liver Cancer
    Correlation between transjugular intrahepatic portal shunt and hepatocellular carcinoma: A systematic review and meta-analysis
    MU Zhi-yong, LIU Yu-yi, WANG Jun, CHEN Dong-feng, WEN Liang-zhi
    2022, 27(9):  978-982. 
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    Objective To investigate the incidence of hepatocellular carcinoma (HCC) among liver cirrhosis patients whether treated by transjugular intrahepatic portal shunt (TIPS). Methods Randomized controlled trial, case control studies, chohort studies or cross-sectional study on HCC occurrence in TIPS group and non-TIPS group were retrieved from PubMed, Embase, Cochrane Library, Web of Science, CNKI, WANFANG, CBM and VIP databases. Literature was extracted according to Cochran systematic evaluation method, and NOS scale was used to evaluate literature quality and conduct statistical analysis. Meta-analysis was performed by RevMan5.3. Results A total of 8 studies involving 1,780 patients (755 in TIPS group and 1025 in non-TIPS group) were included. The results of random effects model showed that the incidence rates of HCC in the TIPS and non-TIPS groups were 13.64% (103/755) and 13.56% (139/1025) respectively. There was no significant difference between the 2 groups (OR: 1.65, 95%CI: 0.69 ~ 2.06; P=0.52). Subgroup analysis showed that in viral cirrhosis and mainly covered stents subgroups, there was no significant correlation between TIPS and the occurrence of HCC (P>0.05). However, in mainly bare stents subgroup, the risk of HCC was 1.57 times higher in the TIPS group than that in the non-TIPS group, and the difference was statistically significant (95%CI: 1.06 ~ 2.34, P=0.03). Conclusion Based on current researches, with the widespread application of covered stents in TIPS, the risk of HCC in patients with cirrhosis will not increase.
    Comparative analysis of clinical manifestations and MRI features between hepatocellular carcinoma and sarcomatoid hepatocellular carcinoma
    WANG Qi-hang, GUO Yong-bang
    2022, 27(9):  983-985. 
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    Objective To investigate the clinical manifestations and magnetic resonance imaging (MRI) features of sarcomatoid hepatocellular carcinoma (SHCC) and hepatocellular carcinoma (HCC), and to provide valuable data for differential diagnosis of SHCC. Methods A total of 12 patients (10 males and 2 females) with SHCC admitted to our hospital from January 2010 to June 2021 were enrolled, with an average age of (59.4 ± 11.7) years. Meanwhile, 30 cases of HCC in the same period were included as control group. The clinical manifestations and MRI features of SHCC and HCC patients were compared. T-test and chi-square test were used for comparison. Results The incidence rates of clinical symptoms in SHCC and HCC patients were 9 (75.0%) and 8 (26.7%), the difference was statistically significant (χ2=8.311, P<0.05). In SHCC group, there were 6 cases (50.0%) with hepatitis B virus (HBV) infection and 28 cases (93.3%) with chronic liver disease, which were significantly different from control group [28 cases (93.3%) and 28 cases (93.3%)] (χ2=-10.438, -7.560, P<0.05). The numbers of stage I/II, III/IV in SHCC group were 2 cases (16.7%) and 10 cases (83.3%), which were significantly different from those in control group [19 cases (63.3%) and 11 cases (36.7%)] (χ2=-7.467, P<0.05). In SHCC group, carcinoma antigen 125 (CA125), carcinoma antigen 199 (CA199) and carcinoma embryonic antigen (CEA) increased in 5 cases (41.7%), 4 cases (33.3%) and 3 cases (25.0%), which were significantly different from control group[0 (0), 0 (0) and 0 (0)] (χ2=14.189, 11.053, 8.077, P<0.05). The MRI features of SHCC patients were tumor diameter in (6.1±1.3) cm, 6 (50.0%) with cholangiectasis and 5 (41.7%) with pseudocapsule, which were significantly different from control group [(4.2 ± 1.0) cm, 2 (6.7%) and 25 (83.3%)] (t=7.308, χ2=10.438, -7.292, P<0.05). In SHCC group, "fast-forward and fast-out", continuous enhancement, peripheral enhancement, gradual enhancement, recession and insufficient blood supply were 0 (0), 4 (33.3%), 0 (0), 7 (58.3%), 0 (0) and 1 (8.3%), which were significantly different from control group [28 cases (93.3%), 1 cases (3.3%), 0 (0), 1 case (8.3%) and 0 (0)] (χ2=-36.925, P<0.05). There were 5 cases (41.7%) with intrahepatic metastasis and 4 cases (33.3%) with lymph node enlargement in SHCC group, which were significantly different from control group [4 cases (13.3%) and 1 case (3.3%)] (χ2=4.087, 7.356, P<0.05). Conclusion Clinical symptoms such as abdominal pain, fatigue, fever and jaundice are common in patients with SHCC, and serum tumor markers including CA125, CA199, CEA are abnormally elevated. In addition, false capsule, progressive/continuous enhancement, intrahepatic metastasis and lymph node enlargement are typical MRI features of patients with SHCC. The manifestations above-mentioned will contribute to the differential diagnosis of SHCC.
    The value of T2WI sequence image texture analysis in the differential diagnosis of hepatic infiltrating hepatocellular carcinoma and focal fusion fibrosis
    HU Wei-jie, CHEN Xiao-ping, WU Rong-gang, MA Zhen-chu
    2022, 27(9):  986-989. 
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    Objective To study on the differential diagnosis value of T2 weighted image (T2WI) sequence image texture analysis (TA) of magnetic resonance imaging (MRI) in the differential diagnosis of hepatic infiltrative hepatocellular carcinoma (iHCC) and hepatic focal fusion fibrosis (FFF). Methods Fifty cirrhotic patients with invasive liver cancer were enrolled in the iHCC group. Thirty-two patients with focal fusion fibrosis with complete preoperative magnetic resonance imaging (MRI) data and pathological confirmation of their surgical specimens were enrolled in the FFF group. The clinical data of both groups of patients were collected and retrospectively analyzed. All patients underwent MRI examination and TA sequence analysis on T2WI at one week before the operation. The maximum axial T2WI images of the lesion were selected, and the region of interest (ROI) was manually sketched by Image J Image processing software. The spatial gray co-occurrence matrix (GLCM) texture parameters (entropy, energy, correlation, contrast, deficit distance) and Histogram texture parameters (mean, kurtosis, skewness) were extracted. GLCM and Histogram texture parameters were compared between the two groups. Receiver operating characteristic curve (ROC) was used to evaluate their efficiencies in differential diagnosis of invasive liver cancer and focal hepatic fusion fibrosis. Results The entropy was 7.04±0.29 in iHCC group, which was significantly higher than that of 6.70±0.60 in FFF group (P<0.05). The energy and correlation of the iHCC group were (15.30±7.19) ×10-4 and (15.41±7.28) ×10-4, which were significantly lower than those of (25.02±11.37) ×10-4 and (33.65±14.40) ×10-4 in FFF group, respectively (P<0.05). There were no significant difference in contrast, deficit distance, mean, kurtosis and skewness parameters between the two groups (P>0.05). The entropy, energy and correlation parameters have had certain efficiencies in the differential diagnosis of invasive liver cancer and liver focal fusion fibrosis, and the areas under curves (AUC) were 0.672, 0.701 and 0.812, respectively. Conclusion The entropy, energy and correlation of GLCM texture parameters under T2WI TA are useful in distinguishing infiltrating liver cancer and focal fusion liver fibrosis, which are worthy of further clinical verification.
    The value of magnetic resonance imaging in differentiating the histopathological growth patterns of Liver metastases of colorectal cancer
    GU Yun-rui, GU Ji-yong
    2022, 27(9):  990-993. 
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    Objective To evaluate the value of magnetic resonance imaging (MRI) in differentiating the type of histopathological growth patterns (HGP) of patients with liver metastases of colorectal cancers (CRLM). Methods From January 2010 to January 2022, the clinical and pathological data of 42 patients with CRLM that were confirmed by pathological observation on surgical resection tissues were collected. The average age was (59.4 ± 8.5) years old, including 25 males and 17 females. According to the international expert consensus standard, when there is an advantage (>50%) in promoting the proliferation, replacement or pushing of fibrous tissue in HGPs of CRLM patients, it is classified as promoting the proliferation of desmoplastic HGP (dHGP), replacement HGP (rHGP) or pushing HGP (pHGP), respectively. When the type of dHGP, rHGP or pHGP is less than 50%, it is defined as mixed HGP. The clinical data of CRLM patients with different HGP types were compared, followed by ROC curve analysis and the calculation of diagnostic AUC value. Results Among 42 CRLM patients, dHGP, rHGP and pHGP were 20 cases, 11 cases and 11 cases, respectively, and there was no mixed HGP case. When comparing the general data of rHGP and non-rHGP (dHGP, pHGP), there was no significant difference in the location, pathological type, T stage and N stage of liver metastases (P>0.05). Comparing the MRI findings of CRLM patients with rHGP and non-rHGP, the tumor diameters before and after enhancement was (0.30 ± 0.12) cm and (0.08 ± 0.03) cm, respectively, which had statistically significant difference (P<0.05). There were 11 cases (100%) and 14 cases (45.2%) of rim enhancement in the rHGP and non-rHGP patients, respectively, with statistically significant difference (P<0.05). The AUC value for the combination of the tumor diameter difference before and after enhancement with rim enhancement for distinguishing rHGP from non-rHGP was 0.852 (95% CI: 0.718 ~ 0.986). Conclusion Compared with dHGP and pHGP, rHGP CRLM is more prone to MRI rim enhancement, and the tumor diameter is also significantly increased after enhancement. MRI features such as the difference of tumor diameter before and after enhancement can effectively distinguish rHGP and non-rHGP CRLM patients.
    Predictive value of albumin-bilirubin score in combination with blood ammonia detection for hepatic encephalopathy after resection of primary liver cancer
    CHAI Xiao-zhe, ZHU Xia-feng, WANG Shao-feng, LUP Cheng-lin
    2022, 27(9):  994-998. 
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    Objective To explore the predictive value of albumin-bilirubin (ALBI) score in combination with blood ammonia detection for hepatic encephalopathy (HE) after the resection of primary liver cancer (PLC). Methods Eighty-nine patients who had undergone PLC resection between May 2016 and March 2021 were enrolled in this study. All patients were follow-up for 3 months after the resection. They were divided into HE group and non-HE group according to whether they were complicated with HE after operation. ALBI score and blood ammonia concentration were tested in all patients before operation. The clinical data of the two groups of patients were compared. Logistic regression analysis was used to analyze the influencing factors of HE after PLC resection. Receiver operating curve (ROC) was drawn and the area under the ROC curve (AUC) was used to determine the value of ALBI score combined with blood ammonia for predicting HE. Results Within the 89 patients, 21 cases were complicated with HE (HE group) with an incidence rate of 23.60%; 68 cases were without HE after operation (non-HE group). The proportion of cases with Child-Pugh grade C (57.14%), the levels blood ammonia concentration (56.47±9.58)μmol/L, prothrombin time (PT) (23.86±4.35) s, direct bilirubin (DBIL) (93.27±10.63) μmol/L In the HE group were higher than those of 27.94%, (35.34±6.27) μmol/L, (15.24±3.28)s, and (12.95±2.67)μmol/L in the non-HE group (P＜0.05). The ALBI score (-1.78±0.46) and albumin (ALB) (29.43±6.19) in the HE group were lower than those of (-1.12±0.54) and (33.66±7.84) in the non-HE group (P＜0.05). Logistic regression analysis showed that Child-Pugh grade C, blood ammonia concentration, and ALBI score were all risk factors for HE after PLC resection (95%CI=1.246～7.360, 1.125～6.646, 1.267～7.486, and OR=3.028, 2.735, 3.080, respectively, all P＜0.05). The AUC values (95%CI) of preoperative blood ammonia concentration, ALBI score and the combination of them for predicting postoperative HE after PLC resection were 0.784(0.693～0.875), 0.775(0.683～0.867), and 0.893(0.782~0.941), respectively (P<0.05). Conclusion The preoperative detection of ALBI score and blood ammonia concentration have certain value in predicting the complication of HE after PLC resection, and the combined detection has a higher predictive value.
    Liver Fibrosis & Cirrhosis
    Important roles of UGT2B28, FABP5, and CYP2C9 in the development of rat liver fibrosis induced by abnormal fatty acid metabolism
    SONG Jing-ru, WU Chao, CAO Hong-yan, XIE Dong, WANG Zheng, LIU Lu, WANG Dan, SUN Ming-yu, BIAN Yan-qin
    2022, 27(9):  999-1003. 
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    Objective Purpose Abnormal fatty acid metabolism has been found to be one of the mechanisms of dimethylnitrosamine (DMN)-induced hepatic fibrosis. In this study, we further elucidated the key regulatory genes of fatty acid metabolism in DMN-induced rat model of hepatic fibrosis. Methods The classical rat model of DMN-induced liver fibrosis was replicated. Serum and liver tissues were collected at 2 and 4 weeks of modeling. The serum samples were analyzed for liver function and lipid metabolism. Whole gene microarray was performed with the liver tissues and the microarray data were deeply mined with bioinformatic analysis software. Results Serum ALT and AST levels were (25.28 ± 3.03)U/L and (69.17 ± 5.20)U/L, and (45.83 ± 5.03)U/L and (108.10 ± 17.31)U/L in the model group at 2 weeks and 4 weeks of modeling, respectively, which was significantly higher than those of (25.28 ± 3.03)U/L and (61.44 ± 11.82)U/L in the control group (P<0.05); Similarly, serum TG and FFA levels were (1.11 ± 0.30) and (0.26 ± 0.04), and (0.77 ± 0.10) and (0.49 ± 0.18) mmol/L in the model group at 2 weeks and 4 weeks of modeling, respectively, which was significantly higher than (0.77 ± 0.22) and (0.51 ± 0.18) mmol/L in the control group (P<0.01 for TG, and P<0.05 for FFA). There were 55 shared differential genes (Log Ratio >2) were identified, which were enriched in 9 signaling pathways associated with cell proliferation, fatty acid metabolism, apoptosis, cell death and other biological functions. The shared differential gene UGT2B28 was significantly up-regulated (>5-fold) in 2 weeks and 4 weeks liver samples of the model group, while FABP5 in the liver samples of the model group at 2 weeks and CYP2C9 in the liver samples of the model group at 4 weeks were significantly up-regulated (>5-fold). UGT2B28, FABP5 and CYP2C9 were involved in all processes of lipid metabolism. Conclusion The shared differential genes UGT2B28, FABP5 and CYP2C9 play key roles in the mechanism of liver fibrogenesis associated with abnormal fatty acid metabolism.
    An evaluation on low hemoglobin/red blood cell distribution width ratio for the prognosis of HBV-related decompensate cirrhosis
    GAO Zheng-cong, LEI Zuo-han, GUO Shun-qin
    2022, 27(9):  1004-1007. 
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    Objective To determine the value of hemoglobin/red blood cell distribution (Hb/ RDW) ratio in evaluating the prognosis of patients with hepatitis B virus (HBV)-related decompensate cirrhosis (HBV-DC). Methods 141 patients with HBV-DC admitted from January 2015 to February 2022 were selected, including 116 males and 25 females, with an average age of 52 (46, 64) years. HBV-DC was diagnosed according to the previous standard. One hundred and forty-one cases of HBV-DC were divided into a survival group and a death group according to their survival and death status. Results Of the 41 patients with HBV-DC, 120 survived and 21 died. In the survival group, the scores of TBil, Scr, RDW, INR and MELD were 36.3 (18.0, 99.6) μmol/L, 71.0 (58.7, 83.2) μmol/L, 15.8 (14.8, 17.8)%, 1.3 (1.2, 1.6) and 11.4(6.5, 15.7) points, which were significantly decreased when compared with those of 78.2 (51.0, 239.6) μmol/L, 92.3 (66.6, 125.1) μmol/L, 20.1 (17.3, 21.7)%, 1.6 (1.3, 1.9) and 20.2 (13.1, 22.5) points in the death group, respectively (P<0.05). Hb and Hb/RDW in the survival group were 108 (90, 122) g/L and 6.6 (5.2, 7.8), which were significantly higher than those of 95 (71, 110) g/L and 4.9 (3.9, 5.8) in the death group, respectively (P<0.05). Multivariate logistic regression analysis showed that Hb/RDW and MELD scores were independent risk factors for the deaths of HBV-DC patients (P<0.05). ROC curve analysis for the independent risk factors such as Hb/RDW and MELD score showed that the cutoff point of Hb/RDW in diagnosing the death of HBV-DC patients was 6.0%, with a sensitivity of 85.0% (102/120), a specificity of 66.7% (14/21) and the AUC value of 0.78; The cutoff point of MELD score was 17.4, with a sensitivity of 66.7% (80/120), a specificity of 85.7% (18/21), and the AUC value of 0.80. The AUC value of Hb/RDW combined with MELD score was 0.86. When setting Hb/RDW=6.0% as the cutoff point, the HBV-DC patients were divided into a low Hb/RDW group (n=62) and a high Hb/RDW group (n=79). In the low Hb/RDW group, the scores of Hb, RDW, INR, MELD and the 30-day mortality were 85 (72, 96) g/L, 18.4 (17.0, 20.8)%, 1.5 (1.3, 1.7), 14.2 (9.2, 18.7) and 17 cases (17 cases), which were significantly different than those of 110 (108, 130) g/L, 15.1 (17.3, 21.7)%, 1.3 (1.2,1.5), 11.2 (6.6, 14.9) and 4 cases (5.1%) in the high Hb/RDW group, respectively (P<0.05). Conclusion Hb/RDW and MELD scores are independent risk factors for the death of HBV-DC patients. The combined application of Hb/RDW and MELD scores can effectively predict the prognosis of HBV-DC patients.
    Effects of alcohol consumption on liver function and liver fibrosis progression of hepatitis C patients
    ZHU Xiong-lin, YANG Mei, FENG Xian-hong, Li Xiao-lin, ZHANG Ge-min
    2022, 27(9):  1008-1010. 
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    Objective To explore the effects of different amount of alcohol consumption on liver function and liver fibrosis progression in hepatitis C patients. Methods Hepatitis C Patients treated in our hospital in recent one year and had disease courses of more than 10 years were selected. They were divided into mild alcohol intake group (20g-50g/d) and severe alcohol intake group (more than 50g/d) according to daily amount of alcohol consumption. Liver function and liver fibrosis indicators were detected and compared in both groups of patients. Results The levels of AST (115.12 ± 12.14 U/L), ALT (121.83 ± 11.21 U/L), total bilirubin (TBil) (84.95 ± 6.21 μmol/L) and gamma-glutamyl transferase (γ-GT) (72.31 ± 9.21 U/L) in mild alcohol intake group were significantly lower than those of AST (141.34 ± 12.91 U/L) and ALT (145.57 ± 10.23 U/L), TBil (95.43 ± 5.38 μmol/L) and γ-GT (85.48 ± 8.24 U/L) levels in severe alcohol intake group (P<0.05). Meanwhile, laminin (LN) (162.38 ± 21.34 mg/L), type III procollagen (PC-III) (146.74 ± 23.43 μg/L), type IV collagen (IV-C) (198.57 ± 30.34 μg/L), Hyaluronidase (HA) (245.98 ± 35.78 mg/L) in mild alcohol intake group were significantly lower than those of LN (185.32 ± 18.52 mg/L), PC-III (174.48 ± 19.74 μg/L), IV-C (231.64 ± 27.45 μg/L) and HA (289.74 ± 20.36 mg/L) in the severe alcohol intake group. Conclusion Alcohol consumption are important factors associate with the deterioration of liver function and the progression of liver fibrosis in hepatitis C patients. The patients should be advised to limit alcohol intake for effectively treating liver disease.
    Other Liver Diseases
    Analysis of predictive value of leukocytes telomere length of peripheral blood against drug-induced liver injury induced by tuberculosis drugs
    ZHANG Shu, YU Zhi-yang
    2022, 27(9):  1011-1014. 
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    Objective To analyse the value of leukocytes telomere length (LTL) of peripheral blood in predicting of drug-induced liver injury (DILI) by anti-tuberculosis drugs in patients with tuberculosis (TB). Methods A total of 78 patients with anti-TB drug induced DILI from October 2017 to November 2020 were included, and 100 patients with TB who were not diagnosed with DILI in the same period were selected. Univariate and multivariate analysis were performed to determine the independent predictors of DILI in TB patients, and ROC curve analysis was used to determine the cutoff point of independent predictors of DILI in TB patients, and the diagnostic sensitivity and specificity were calculated. Results According to the clinical data, there were 18 cases (23.1%), 56 cases (71.8%) and 72 cases (92.3%) of rash, fatigue and anorexia in TB patients with DILI (DILI group), compared with 7 cases (7.0%), 23 cases (23.0%) and 28 cases (28.0%) in TB patients without DILI (non-DILI group), with statistically significant (χ2=-9.382, -42.267 and -73.612, P<0.05). The alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (Tbil), international normalized ratio (INR), LTL and model for end-stage liver disease (MELD) scores in DILI group were (232.8 ± 80.1) U/L, (134.8 ± 40.5) U/L, (172.4 ± 62.2) U/L, (2.4 ± 1.0) mg/L, (2.2 ± 0.8), (0.70 ± 0.31) and (17.3 ± 6.3) points, compared with (37.8 ± 8.4) U/L, (36.6 ± 8.5) U/L, (121.5 ± 38.5) U/L, (0.8 ± 0.3) mg/dL, (1.2 ± 0.3), (1.68 ± 0.61) and (8.2 ± 3.2) points in non-DILI group, with statistically significant (t=-60.128, -12.147, -8.136, -17.305, -14.736, 12.018 and -11.114, P<0.05). Multivariate logistic regression analysis was performed with whether TB patients had DILI (assigned value 0 = non-DILI, 1 = DILI) as the dependent variable and rash, fatigue, anorexia, ALT, AST, TBil, INR, LTL and MELD scores as the independent variables. The results showed that rash, fatigue, anorexia, ALT, AST, TBil, INR, LTL and MELD scores were independent predictors of DILI in patients with TB (P<0.05). Receiver operating characteristic (ROC) curve showed that the optimal cut-off point of LTL point in differentiating patients with and without DILI was 0.93, the sensitivity and specificity were 73.1% and 64.0%, respectively, while the area under the curve (AUC) values of AST and ALT were not statistically significant (P>0.05). Conclusion The abnormality of LTL in peripheral blood can reflect the liver injury caused by anti-TB drugs in patients with TB,which is a potential biomarker for early detection of DILI.
    Research hotspots and frontiers of non-alcoholic fatty liver disease and transient elastography: empirical research based on data of Web of Sciense
    YANG Yong-qin, FENG Gong, LI Rong, SUN Xue-mei, CHEN Min, HE Na
    2022, 27(9):  1015-1020. 
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    Objective Transient elastography (TE) has been widely used in nonalcoholic fatty liver disease (NAFLD). The purpose of this study is to help researchers grasp the research topics, research directions, hot spots and frontiers of TE in the field of NAFLD. Methods Based on the literatures about NAFLD and TE included in the Science Citation Index Expanded (SCI-E) in the Web of Science (WOS), author, institution, country and keyword co-occurrence analysis were conducted by using CiteSpace 5.8 software. Co-citation analysis of cited authors, literatures and journals, and drawing visual atlas were conducted. Results After data retrieval and review, a total of 1685 articles were obtained. The United States, China, Italy, Japan and other countries were the most published countries. Major research institutes included the Chinese University of Hong Kong, University of California, Yonsei University, etc. Prolific authors included Wong VWS, Rohit Loomba, etc. High-frequency keywords included transient elastography, fibrosis, diagnosis, fatty degeneration and controlled attenuation parameters. The clustering direction could be divided into NAFLD, non-alcoholic steatohepatitis, hepatocyte steatosis, fibrosis and non-invasive diagnosis. The high-intensity breakout words were biological diagnostic markers, epidemiology, management, fibrosis degree measurement and so on. The research stage of this field could be roughly divided into three periods: exploration period, experience summary period, promotion and application period. Conclusion Visual analysis of TE in NAFLD using Citespace software shows that the application of TE in large-scale epidemiological investigation or disease management is the hot spot and trend of future research in NAFLD.
    Clinical manifestations and etiological analysis of 56 patients with liver abscess
    WANG Jun, YANG Liu-qing
    2022, 27(9):  1021-1024. 
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    Objective To review the clinical data of patients with pathogen-positive liver abscess (LA) and compare it with pathogen-negative liver abscess, so as to provide guidance for clinical condition evaluation and treatment strategy formulation of liver abscess. Methods From January 2017 to December 2020, 62 LA patients (43 males and 19 females) were collected, aged 55 (40, 68) years. To compare the clinical data of patients with pathogen-negative and pathogen-positive LA. According to different pathogenic bacteria, pathogen-positive LA was divided into Escherichia coli group (EC group) and Klebsiella pneumoniae group (KP group), and the clinical data were compared. Results There were 40 patients with pathogen-negative LA and 22 patients with pathogen-positive LA. The patients with pathogen-negative and pathogen-positive LA were 53 (40, 70) years old and 58 (46, 66) years old, and the difference was statistically significant (P<0.05). There were 7 cases (17.5%) and 9 cases (40.9%) of diabetes in pathogen-negative and pathogen-positive LA patients, and the difference was statistically significant (P<0.05). The white blood cell (WBC), neutrophil percentage, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and total bilirubin (Tbil) in patients with pathogen-positive liver abscess were 11.6 (2.6, 18.2)×109/L, 80.2 (36.0, 96.4)%, 56 (22, 214) U/L, 67 (18, 202) U/L and 24.6 (6.8,34.8) μmol/L, compared with 14.5 (3.3, 30.8)×109/L, 86.2 (68.3, 98.6)%、126 (20, 462) U/L, 144 (16, 507) U/L and 28.8 (10.1, 48.4) μmol/L in pathogen-negative LA, the difference was statistically significant (P<0.05). The diameters of abscesses in patients with pathogen-negative and pathogen-positive LA were 4.2 (3.0, 5.8) cm and 5.5 (4.0, 7.0) cm, with statistical significance (P<0.05). The EC and KP pathogens in pathogen-positive LA patients were 16 cases (EC group) and 6 cases (KP group), respectively. According to the clinical data of the two groups, the age, male, diabetes and abdominal pain in EC group were 52 (45,66) years old, 12 cases (75.0%), 9 cases (56.2%) and 4 cases (25.0%), compared with those in KP group [61 (52,70) years old, 2 cases (33.3%), 0 (0) and 4 cases (66.7%)], with statistical significance (P<0.05). The ALP, GGT and TBil in EC group were 115 (14,450) U/L, 126 (12, 480) U/L and 23.7 (9.6, 20.4) μmol/L, which were higher than those in KP group [141 (94, 670) u/l, 170 (84, 507)U/L and 34.5 (18.7, 52.5) μmol/L (P<0.05). There were 3 cases (18.7%), 4 cases (25.0%) and 3 cases (18.7%) with multiple purulent cavities, gas formation of purulent cavities and separation of purulent cavities in EC group, and the difference was statistically significant compared with KP group [5 cases (83.3%), 0 cases (0) and 0 cases (0)] (P<0.05). The treatment strategy is anti-infection combined with ultrasound or CT guided abscess puncture drainage. Three generations of cephalosporins combined with ornidazole and β-lactamase inhibitors were selected as the anti-infection scheme. There were 29 cases (72.5%) and 16 cases (72.7%) of patients with negative and positive LA treated well, respectively, and the difference was not statistically significant (P>0.05). There was no significant difference between the two groups in hospital stay [(18.8 ± 5.2) days vs (17.0 ± 5.0) days, P>0.05]. There was no significant difference in hospitalization time between EC group and KP group [(18.5 ± 5.0) days compared with (19.4 ± 6.0) days, P>0.05]. Conclusion Patients with pathogen-negative LA are younger, so they are less likely to have severe inflammatory reaction and hepatic insufficiency. If pyogenic gas and pyogenic cavity are formed in pathogen-positive LA patients, KP infection is more likely. There is no significant difference in the overall prognosis of LA patients in each group.
    Clinical value of serum TPOAb and 25- (OH) D3 combined detection in patients with intrahepatic cholestasis during pregnancy
    WU Ting, XU Xiao-ying, ZHENG Li
    2022, 27(9):  1025-1029. 
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    Objective To investigate the clinical value of serum thyroid peroxidase antibody (TPOAb) combined with 25 hydroxyvitamin D [25- (OH) D3] in patients with intrahepatic cholestasis of pregnancy (ICP). Methods 90 ICP women who participated in physical examination filing and hospital delivery in the department of obstetrics and gynecology of our hospital from January 2018 to December 2020 were included in the observation group, and 60 healthy pregnant women who delivered in our hospital during the same period were included in the control group. Fasting venous blood samples were collected to determine serum levels of total bile acid (TBA), glycholic acid (CG), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as serum levels of TPOAb and 25- (OH) D3. The observation group was divided into severe and mild subgroups according to the levels of TBA, TPOAb and 25- (OH) D3, and the biochemical indexes between the observation group and the control group were compared. Pearson correlation was used to analyze the diagnostic efficacy of serum TPOAb and 25- (OH) D3 alone and in combination. Results The level of serum TPOAb in severe subgroup was (25.87 ± 4.63) ng/L, which was higher than that in mild subgroup (16.38 ± 3.71) ng/L and control group (9.75 ± 2.36) ng/L. The level of serum 25- (OH) D3 in severe subgroup was (22.37 ± 4.09) μg/mL, which was lower than that in mild group [(29.85 ± 4.63) μg/mL] and control group [(35.26 ± 5.74) μg/mL], the difference was statistically significant (F=17.482, 13.287, P<0.05). TBA, CG, ALT and ALP in high TPOAb subgroup were (48.65 ± 8.34) μmol/L, (410.98 ± 45.67) μmol/L, (92.23 ± 11.75) U/L and (164.75 ± 18.62) U/L, higher than those of low TPOAb subgroup [(22.78 ± 5.03) μmol/L, (249.71 ± 30.54) μmol/L, (67.38 ± 8.34) U/L and (112.65 ± 13.49) U/L], the difference was statistically significant (t=14.361, 11.578, 10.954, 9.803, all P<0.05). TBA, CG, ALT and ALP in high 25- (OH) D3 subgroup were (422.78 ± 5.03) μmol/L, (256.43 ± 31.57) μmol/L, (69.25 ± 8.06) U/L and (109.84 ± 12.36) U/L, lower than those in low 25- (OH) D3 subgroup [(47.29 ± 8.15) μmol/L, (412.59 ± 46.82) μmol/L, (91.72 ± 11.28) U/L and (165.37 ± 19.03) U/L]. The differences were statistically significant (t=13.297, 10.472, 9.716, 12.569, all P<0.05). The incidence of anemia, cesarean section, postpartum hemorrhage, fetal distress, premature delivery, low neonatal weight and other pregnancy outcomes in the high TPOAb subgroup were significantly higher than those in the low TPOAb subgroup. The incidence of pregnancy outcomes in high 25- (OH) D3 group were significantly lower than low 25- (OH) D3 group (P<0.05). After Pearson correlation analysis, the area under the curve (AUC) of serum TPOAb combined with 25- (OH) D3 level was significantly higher than that of single indicator (AUC = 0.763, 0.745, 0.869, P<0.01). Conclusion The combined detection of serum TPOAb and 25- (OH) D3 has high clinical application value for disease diagnosis, disease monitoring and prognosis evaluation of ICP patients.
    Other Liver Diseases
    Establishment of animal models of chronic liver disease and modeling methods
    ZHU Xue-jing, WANG Men-ting, YAN He-xin, HUANG Ren-jie
    2022, 27(9):  1030-1035. 
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    Objective To establish an ideal model of chronic liver injury and evaluate stability of the modeling methods. Methods In this study, the mouse model of non-alcoholic steatohepatitis (NASH), the mouse model of liver fibrosis and the rat model of cirrhosis were induced by the modified high-fat diet (HFD), carbon tetrachloride (CCl4) and thioacetamide (TAA), respectively. Pathological hematoxylin-eosin (HE), oil red O and sirius red (SR) staining were used to observe the structural changes, steatosis and fibrosis of animal liver. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), γ-glutamyltransferase (GGT),glycyl proline dipeptidyl aminopeptidase (GPDA), albumin (ALB), total cholesterol (TC) and triglyceride (TG) were detected by automatic biochemical instrument. Results Compared with traditional diet group (8 mice), the modified HFD group (64 mice) could increase the activities of ALT [(268.7 ± 69.8) vs (35.0 ± 21.9)], AST [(215.0 ± 91.0) vs (34.4 ± 9.4)] and LDH [(560.3 ± 158.5) vs (240.6 ± 101.3)] significantly (all P<0.05), and decrease the activities of TC [(1.5 ± 0.3) vs (2.2 ± 0.2)] and TG [(0.9 ± 0.1) vs (1.6 ± 0.2)] significantly (both P<0.05). In the pathological results, oil red O and HE staining were observed in pathology showed that the hepatic tissue of mice fed with the modified HFD were filled with lipid droplets. Compared with mice injected with olive oil (8 mice), levels of ALT [(8507.3 ± 1083.1) vs (41.8± 29.2)] and AST [(4911.2 ± 644.0) vs (104.0 ± 33.6)] increased significantly (P<0.05) in mice injected with 10% CCl4 (2mL/kg, tiw) for 12 weeks (52 mice). The pathological results of HE and SR staining showed that there was a large number of collagen fibers in the liver tissue of mice injected with CCl4. Compared with mice injected with normal saline (8 rats), levels of ALT [(197.3 ± 131.1) vs (34.0 ± 6.0)], AST [(590.3 ± 457.7) vs (57.5 ± 12.3)], GGT [(10.0 ± 8.4) vs (3.6 ± 3.3)] and GPDA [(290.5 ± 134.4) vs (63.3 ± 14.7)] increased significantly (all P<0.05) and level of ALB [(37.3 ± 1.9) vs (40.9 ± 1.3)] decreased significantly (P<0.05) in rat injected with TAA (200mg/kg, biw) for 16 weeks (37 rats). The pathological analysis of HE and SR staining showed that the liver tissue of rats injected with TAA presented with hepatic fibrosis, proliferation of hepatic fibroblasts and formed pseudo lobules with different sizes. Conclusion Mice were fed with the modified HFD for 2 weeks, the success rate of NASH model was 100%. The model was further aggravated after feeding for 4 weeks. In terms of mice that were injected with 10% CCl4 (2 mL/kg, tiw) for 12 weeks, the success rate of liver fibrosis model was 100%, and the model could be maintained for at least 2 weeks after drug withdrawal. Rats were injected with TAA (200mg/kg, biw) for 16 weeks, the success rate of liver cirrhosis model was 100%, and the model could last for at least 4 weeks after drug withdrawal.
    Establishment and investigation of carbon tetrachloride-induced acute liver injury model in mice
    FU Shuang-nan, GAO Da, GUO Jia-jia, MIAO Ming-san, ZHU Ping-sheng, GONG Man
    2022, 27(9):  1036-1040. 
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    Objective To investigate the stable animal model of carbon tetrachloride (CCl4)-induced acute liver injury in mice, which is convenient for the research and application of new clinical drugs. Methods The Kunming (KM) mice were randomLy divided into blank group, model group, and bifendate group (5.625 mg/kg), and the acute liver injury of mice was replicated by intraperitoneal injection of 0.1% CCl4 solution. The aminotransferase level, liver index, and pathological changes of liver tissue at 3h, 6h, 12h, and 24h after modeling were detected to study the stability of the model. Results After exposure to the model group, alanine aminotransferase (ALT) increased slightly at 3 h [(45.21 ± 13.17) IU/L, P<0.01], and increased significantly at 12 h [(112.30 ± 30.54) IU/L] and 24 h [(121.98 ± 21.66) IU/L] (both P<0.01); AST increased at 3 h [(162.51 ± 28.57) IU/L], 6 h [(192.07 ± 31.05) IU/L], 12 h [(250.75 ± 90.82) IU/L] and 24 h [(274.27 ± 44.02) IU/L] (all P<0.01), but increased significantly at 12 and 24 h; liver index slightly increased at 3 h [(6.72 ± 1.90) g/100 g] and 6h [(6.72 ± 1.90) g/100 g] (both P<0.01). At 12 h [(12.41 ± 1.18) g/100 g] and 24 h [(14.90 ± 2.56) g/100 g] (both P<0.01), the liver pathological changes showed obvious hepatocyte swelling and inflammatory cell infiltration, and the injury degree was more significant at 24 h. Conclusion When the mouse acute liver injury model was prepared by intraperitoneal injection of 0.1% CCl4 solution, the modeling time between 12 h and 24 h was more appropriate.