Table of Content

30 November 2021, Volume 26 Issue 11

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Viral Hepatitis

The impact of antiviral treatment with tenofovir on the renal function of patients with chronic hepatitis B

HAN Zong-ru, MIN Xiao-chun, SHEN Qi-gang, YIN You-kuan, WANG Sen

2021, 26(11):  1216-1220. 

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Objective To evaluate the renal safety of tenofovir disoproxil (TDF) in the treatment of chronic hepatitis B (CHB) patients and the risk factors for renal function damage. Methods A total of 113 CHB patients received TDF treatment were collected as TDF treatment group. 65 patients received entecavir (ETV) were collected as ETV treated control group. The patient's clinical data and renal function test were collected at baseline, and 12 and 24 months after treatment. Results After 24 months of treatment, there was no significant difference in the conversion rate of HBV DNA (92.9% in TDF group vs 90.8% in ETV group), the recovery rate of ALT (85.0% in TDF group vs 83.1% in ETV group) and the conversion rate of HBeAg (55.5% in TDF group vs 47.2% in ETV group) between the TDF treatment group and the ETV treatment group(χ²=0.263,P=0.608;χ²=0.110, P=0.740;χ²=0.601,P=0.438). At 24 months of treatment, the blood creatinine level in TDF treatment group was significantly increased, with an average increase of 10.8±4.7 μmol/L (t=2.83,P=0.041),whereas the eGFR level was significantly decreased from baseline, with an average decrease of 11.8±1.5 ml/min/1.732 (t=3.728, P=0.034). A total of 14 patients (12.4%) had renal function impairment (eGFR levels were≥25% lower than baseline), but no patients had chronic kidney disease (CKD). Seven patients developed proximal tubular renal dysfunction. Multivariate logistic regression analysis showed that those patients older than 50 years old (OR: 2.821, 95% CI: 1.084-7.342, P=0.034), with diabetes (OR: 2.072, 95% CI: 1.035-4.150, P=0.040) and with past experience of adefovir dipivoxil (ADV) treatment (OR: 3.162, 95% CI: 1.182-7.737, P=0.024) were independent risk factors associated with renal impairment. Conclusion In CHB patients treated with TDF, eGFR tends to decline and renal impairment may develop with the prolongation of treatment time. Oder age, diabetes, and previous ADV use are risk factors associated with renal impairment. Therefore, the renal function of patients receiving long-term TDF treatment should be carefully evaluated and monitored to prevent the occurrence of adverse reaction.

Analysis of clinical characteristics and risk factors of acute severe hepatitis E

CHEN Ke, CHEN Rong, WANG Xiao-lin, CAI Wei

2021, 26(11):  1221-1223. 

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Objective To analyze the clinical characteristics of patients with acute severe hepatitis E and to explore the risk factors for severe hepatitis. Methods Retrospective analysis of the clinical data of 102 patients with acute hepatitis E admitted to Shanghai Ruijin Hospital from December 1, 2020 to May 31, 2021. According to the guidelines for the diagnosis and treatment of severe hepatitis, the groups were divided into severe and non-severe groups, and the clinical data and laboratory test indexes of the two groups were compared. Results Hepatitis E infection was predominantly disseminated, with clear co-morbidity in 6 cases (5.88%), 65 males and 37 females, mean age (58.16±12.01) years, mean hospitalization days (19.08±15.38) d, no significant difference was seen in the combination of underlying liver disease on whether it progressed to severe disease, and a statistically significant difference was seen in the combination of diabetes mellitus, hypertension and other chronic diseases progressing to severe disease. Conclusion Patients presenting with severe acute hepatitis E are significantly more likely to be male(χ²=7.474, P<0.05), older(F=0.979, P<0.05), and have comorbid underlying disease(χ²=6.544, P<0.05), with a statistically significant difference in length of hospital stay(F=0.791, P<0.05). It was also found that those who progressed to severe disease had lower albumin(Z=3.981, P<0.001), higher total bilirubin(Z=-10.575, P<0.001), and dysfunction of blood coagulation(Z=-4.199, P<0.001).

The efficacy of sofosbuvir-based DAAs treatment on chronic hepatitis C patients with pan-genotypic hepatitis C viral infection

GUO Feng, DOU Jing, XU Qiang, WANG Xiao-bo, MA Yan, YUE Yong-hong, Huxibaiheti, WANG Zhuan-guo, WANG Hong-feng, WANG Xiao-zhong

2021, 26(11):  1224-1227. 

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Objective To evaluate the efficacy of sofosbuvir-based direct-acting antiviral agents (DAA) treatment on chronic hepatitis C patients with pan-genotypic hepatitis C viral infection. Methods A total of 134 Patients diagnosed with chronic hepatitis C in the Liver Diseases Branch of Fourth Affiliated Hospital of Xinjiang Medical University from July 2017 to January 2020 were collected and retrospectively analyzed. These patients received sofosbuvir-based DAAs and completed the recommended treatment course. They had been tested with highly sensitive hepatitis C RNA quantification method during the treatment to observe the sustained virological response (SVR) rate of antiviral treatment. Results Within the 134 patients, 72 were males and 62 were females; 95 patients were <60 years old, 39 patients were ≥60 years old; 121 patients were Han nationality, 13 patients were ethnic minorities; 118 were treatment naïve patients, 16 patients had previous treatment-experience; 59 patients were cirrhotic and 75 were non-cirrhotic; For the infected HCV genotype (GT): 53 patients were GT 1b, 57 patients were GT 2a, 10 patients were GT 3a, 12 patients were GT 3b, 1 patient was of GT 6, and 1 patient was mixed GTs 1b and 2a. For GT1b, 23 patients were treated with sofosbuvir/velpatasvir,16 patients were treated with sofosbuvir plus ribavirin, 11 patients were treated with ledipasvir/sofosbuvir and 3 patients were treated with sofosbuvir plus daclatasvir for 12 weeks. For GT 2a, 32 patients were treated with sofosbuvir/velpatasvir, 5 patients were treated with sofosbuvir/velpatasvir plus ribavirin and 20 patients were treated with sofosbuvir plus ribavirin for 12 weeks. For GT 3, 16 patients were treated with sofosbuvir/velpatasvir for 12 weeks; 6 patients were treated with sofosbuvir plus ribavirins for 12-24 weeks. For GT 6: 1 patient was treated with sofosbuvir plus ribavirin tablets for 12 weeks. For mixed GTs (1b, 2a): 1 patient was treated with sofosbuvir/velpatasvir for 12 weeks. Sofosbuvir-based DAAs treatment of all patients with chronic hepatitis C reached SVR. Conclusion The Sofosbuvir-based DAAs treatment has a high overall SVR and well tolerance in chronic hepatitis C patients with pan-genotypic HCV infection.

Clinical and histopathological features of CHB patients with high viral load but normal or slightly elevated ALT levels

XU Fang, ZHANG Hai-quan, ZHAO Jia-qiang

2021, 26(11):  1228-1230. 

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Objective To analyze the clinical and histopathological features of chronic hepatitis B (CHB) patients with high HBV DNA viral load but normal or slightly elevated alanine aminotransferase (ALT) levels. Methods Three hundred and seventy-eight CHB patients aged (34.8±6.4) years including 206 males and 172 females were collected from January 2016 to September 2020. Scheuer scoring system and histological activity index were used to evaluate the stage of liver fibrosis (F0~F4) and the grade of inflammatory activity of liver tissue (G0~G4). Measurement data are analyzed by t-test; counting data were analyzed by Chi-square test. Results The age, HBV DNA load, ALT level, Aspartate aminotransferase-to-Platelet Ratio Index (APRI), and gamma-glutamyl transpeptidase to platelet ratio (GPR) for patients <F2 stage were (32.8±9.2) years, (8.4±1.0) log₁₀ copies/mL, (45.8±5.5)U/L, (0.40±0.22) and (0.12±0.07), respectively, compared with those of (35.6±5.3)years, (7.6±1.3)log₁₀ copies/mL, (56.8±7.0)U/L, (0.49±0.20) and (0.17±0.08) for patients ≥F2 stage, respectively, the difference was statistically significant (P<0.05). The age, HBV DNA, ALT, AST, FIB-4, APRI and GPR for patients<G2 stage were (33.6±8.4)years, (8.4±1.1)log₁₀ copies/mL, (46.1±5.4)U/L, (32.5±8.2)U/L, (0.19±0.11), (0.40±0.23), (0.12±0.08), respectively, compared with those of (35.2±7.5) years, (7.4±1.4)log₁₀ copies/mL, (56.0±6.8)U/L, (38.7±5.5)U/L, (0.24±0.11), (0.55±0.22), (0.17±0.10) for patients ≥F2 stage, respectively, the difference was statistically significant (P<0.05). Conclusion It is necessary to strengthen the follow-up if the CHB patients are in older age, have normal or slightly elevated ALT, but have continuously increased viral load or abnormal FIB-4, APRI and GPR. Liver biopsy need to be performed whenever necessary.

Relationship between serum ADA, miR-181a, NK cells and HBV DNA load in patients with different clinical types of hepatitis B infection

LI Cheng, ZHANG Wei, CHEN Qu, ZHANG Lei, ZHAO Qiu-jian, LI Yao-ni

2021, 26(11):  1231-1235. 

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Objective To investigate the changes of hepatitis B virus (HBV)-DNA load, adenosine deaminase (ADA), miR-181a, natural killer (NK) cells in patients with different clinical types of hepatitis B after HBV infection, and the relationship between ADA, miR-181a, NK cells and HBV DNA load. Methods One hundred and forty-four patients with HBV infection admitted to our hospital from January 2017 to September 2020 were retrospectively selected as the research objects. According to disease types, they were divided into HBV carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC) and HBV-associated hepatocellular carcinoma (HBV-HCC) groups, of which 37 cases were ASC, 43 cases were CHB, 31 cases were LC and 33 cases were HBV-HCC. Another 30 healthy people with normal physical examination during the same period were selected as a control group. Data of HBV DNA load, serum ADA level, plasma miR-181a level, and the percentage of NK cells in peripheral blood mononuclear cells (PBMC) were collected for comparative analysis. Results HBV DNA load in CHB group was (6.07±0.93) copy/mL, which was significantly higher than those of (5.63±0.82) copy/mL, (5.38±0.73) copy/mL and (4.53±0.42) copy/mL in ASC group, LC group and HBV-HCC group, respectively (P<0.05). HBV DNA load in HBV-HCC group was significantly lower than those in ASC group and LC group (P<0.05). The ADA level of HBV-HCC patients was (49.85±7.23) U/L, which was significantly higher than those of (13.28±3.27) U/L, (21.82±4.83) U/L, (35.83±5.59) U/L, (9.43±2.31) U/L in the ASC, CHB group, LC group and control group, respectively (P<0.05). The ADA level of LC group and CHB group were significantly higher than those in the ASC group and control group (P<0.05), and the ADA level in ASC group was significantly higher than that of the control group (P<0.05). The percentage of NK/PBMC cells in HBV-HCC group was (4.05±0.73)%, which was significantly lower than those of (9.42±2.51)%, (8.43±1.08)%, (5.89±1.34)%, (11.04 ±2.87)% in the ASC group, CHB group, LC group and control group, respectively (P<0.05). The percentage of NK cells in LC group was significantly lower than those of the ASC group, CHB group and control group (P<0.05). The percentage of NK cells in CHB group was significantly lower than those of the ASC group and control group (P<0.05), and the percentage of NK cells in ASC group was significantly lower than that of the control group (P<0.05). The relative expression level of miR-181a in CHB group was (0.71±0.13) 2^-ΔΔCt, which was significantly lower than those of (0.94±0.08)2^-ΔΔCt, (0.94±0.08) 2^-ΔΔCt, (1.23±0.13) 2^-ΔΔCt, (0.98±0.04)2^-ΔΔCt in the ASC group, LC group, HBV-HCC group and control group, respectively (P<0.05), The relative expression level of miR-181a in the HBV-HCC group was significantly higher than those of the ASC group, LC group and control group (P<0.05). In ASC, CHB, LC and HBV-HCC patients, ADA was positively correlated with HBV DNA load (r=0.752, 0.668, 0.413, 0.639, P<0.05), while NK cells were negatively correlated with HBV DNA load (r=-0.631, -0.473, -0.507, -0.434, P<0.05). There was a negative correlation between miR-181a level and HBV DNA load in CHB patients (r=-0.613, P<0.05), and a positive correlation between miR-181a level and HBV DNA viral load in HBV-HCC patients (r=0.510, P<0.05). Conclusion In ASC, CHB, LC and HBV-HCC patients, serum ADA level was positively, whereas the percentage of NK cells was negatively correlated with HBV DNA viral load. The miR-181a level was negatively correlated with HBV DNA load in CHB patients but positively correlated with that in HBV-HCC patients.

An analysis of T lymphocyte level in hepatitis B virus infected patients with different degree of inflammatory gastric mucosal lesions

WANG Yan, XU Na, LI Xiao-xin

2021, 26(11):  1236-1239. 

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Objective To observe the T lymphocyte level in hepatitis B virus (HBV) infected patients with different degree of inflammatory gastric mucosal lesions. Methods A total of 273 HBV infected-patients were enrolled in this study from April 2015 to April 2020, including 85 cases with acute hepatitis B, 93 cases with chronic hepatitis B, and 95 cases with post-hepatitis cirrhosis. They were divided into acute hepatitis B group, chronic hepatitis B group and post-hepatitis cirrhosis group, respectively. In addition, 95 healthy volunteers who had physical examination during the same period were included and assigned into a healthy control group. The CD3⁺, CD4⁺, CD8⁺, and CD4⁺/CD8⁺ levels of T lymphocytes were detected in these three groups of patients after admission (before treatment) and the healthy controls. Gastroscopy was then performed in all patients to record the degree of inflammatory lesions in gastric mucosa. The levels of T lymphocytes in all groups, and the degree of inflammatory gastric mucosal lesions in different patient groups were compared. The association between T lymphocyte levels and the degree of gastric mucosal lesion were analyzed. Results The levels of CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺ in T lymphocytes of healthy group were (67.58±6.81)%, (46.19±4.16)%, (30.17±2.44)%, (1.60±0.41)%; in acute hepatitis B group were (63.24±5.02)%, (43.02±3.77)%, (26.15±2.10)%, (1.33±0.34)%; in chronic hepatitis B group were (55.12±4.22)%, (35.16±2.15)%, (21.16±1.84)%, (1.15±0.27)%; and in post-hepatitis cirrhosis group were (47.15±3.19)%, (28.65±1.41)%, (17.19±1.41)%, (0.94±0.22), respectively, which had significantly difference between the groups (healthy group> acute hepatitis B group>chronic hepatitis B group>post-hepatitis cirrhosis group, P<0.05). Significant difference in the inflammatory degrees of gastric mucosa lesions existed in the patient groups. The percentage of severe chronic superficial gastritis patients in acute hepatitis B group was 3.53%, chronic hepatitis B group was 9.68%, post-hepatitis cirrhosis group was 17.89%. Severe lesions of atrophic gastritis accounted for 7.06% patients in acute hepatitis B group, 20.43% in chronic hepatitis B group, 45.26% in post-hepatitis cirrhosis group, which had significant difference within the groups (acute hepatitis B group<post-hepatitis cirrhosis group<chronic hepatitis B group, P<0.05). The levels of CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺T lymphocytes in mild gastric mucosal inflammatory lesions were (63.84±5.17)%, (42.19±3.55)%, (25.80±2.41)%, (1.28±0.33)%, respectively, while in those of moderate patients were (57.23±4.31)%, (36.21±2.58)%, (20.53±1.72)%, (1.05±0.24)%, respectively, and in those of severe patients were (48.24±3.54)%, (30.78±1.87)%, (17.58±1.06)%, (0.90±0.18)%, respectively, which had significantly difference (severe<moderate<mild, and P<0.05). The correlation analysis confirmed that the level of T lymphocyte was positively correlated with the degree of inflammatory gastric mucosal lesions (P<0.05). Conclusion The levels of CD3⁺, CD4⁺, CD8⁺ and CD4⁺/CD8⁺ in T lymphocytes of HBV-infected patients were significantly decreased, and their expression levels were closely associated with the severity of inflammatory gastric mucosal lesions.

Liver Fibrosis & Cirrhosis

A non-invasive multi-slice spiral CT-based diagnostic model predicts portal hypertension in liver cirrhotic patients

WANG Jian, SHI Pei-mei, SHEN Jie, WEI Yu

2021, 26(11):  1240-1245. 

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Objective To study on the value of noninvasive evaluation of portal hypertension in patients with liver cirrhosis by morphological characteristics of liver and spleen measured by multi-slice spiral CT. Methods Eighty-eight hospitalized cirrhotic patients in Shanghai Changzheng Hospital from September 2016 to December 2020 were enrolled in this study based on the inclusion and exclusion criteria. Patients with liver cirrhosis were divided into non-portal hypertension group, mild portal hypertension group (with esophagogastric varices or hypersplenism alone) and severe portal hypertension group (with both esophagogastric varices and hypersplenism). Add/Remove Structure software was used to measure the total liver volume and spleen volume. Hepatic venous pressure gradient (HVPG) was measured by vascular intervention method. Results There were no significant differences in the distribution of portal hypertension among Child-Pugh A, B and C patients with liver cirrhosis. There was a descendent trend but no significant differences in the associated CT parameters of liver volume within high portal pressure group [(1075.97±399.90) cm³], and the mild portal pressure group [(1053.14±281.21) cm³], and the severe portal hypertension group[(949.87±229.77) cm³]. However, the spleen volume was a good parameter to distinguish patients with portal hypertension. The spleen volume in the non-portal hypertension group was [(397.32±309.49) cm³], in mild portal hypertension group was[(676.55±274.69) cm³], and in severe portal hypertension group was[(903.80±362.33) cm³]. For the distinction of patients with mild and severe portal hypertension by spleen volume, the underlying area of the ROC curve was more than 0.700, reaching 0.894. By multi-regression analysis, the linear evaluation model of portal vein pressure was constructed, and portal vein pressure (mmHg)=-0.08×age-1.06×platelet + 1.89×CRP-1.71×LN total biliarylin + 2.06×spleen volume. This diagnostic model had a very good diagnostic value for portal hypertension, with the ROC curve as high as 0.859 (95%CI 0.759, 0.950), and a diagnostic sensitivity of 80.65%, and specificity of 55.56%. Conclusion The noninvasive evaluation model established by combining serological indexes and imaging parameters is simple and easy. It has preferable value for predicting portal pressure.

Effect of spontaneous portal-systemic shunt on the prognosis of patients with hepatitis B-related liver cirrhosis

YE Dong, ZHANG Jun-xia, LI Jie, ZHANG Dan, LIU Ying, GUO Yong-ze

2021, 26(11):  1246-1249. 

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Objective To analyze the effect of spontaneous portosystemic shunt on the prognosis of chronic hepatitis B patients with liver cirrhosis, and to provide theoretical basis for the clinical treatment and prognostic evaluation of such patients. Methods A total of 72 patients (40 males and 32 females) with an average age of (46.3±8.7) years were enrolled in this study from January 2020 to January 2021. The measured value of portal vein pressure as represented by hepatic venous pressure gradient (HVPG) >10mmHg is defined as portal hypertension, and HVPG <10mmHg is defined as normal portal pressure. The measurement data are expressed as (±s), and compared using t-test between these two groups, while the counting data are expressed as (%) and analyzed with chi-square test. Results There were 35 patients (20 males and 15 females) with portal hypertension, with an average age of (46.0±8.9) years. There were 37 cases (20 males and 17 females) with normal portal vein pressure, with an average age of (46.6±8.4) years. The levels of ALB, ALT, AST, TBIL, PT and PLT in the hypertension group were (23.5±4.3)g/L, (223.2±21.6)U/L, (189.6±30.9)U/L, (78.2±9.3) μmol/L, (18.3±4.3)s and (61.39.3)×10⁹/L, respectively. Compared with those of [(32.0±5.6) g/L, (51.7±11.4) U/L, (45.8±22.3) U/L, (52.1±6.1) μmol/L, (11.9±3.9) s and (95.9±9.6)×10⁹/L] in the normal group, respectively, and the differences were statistically significant (t=10.142, -56.358, 37.445, -11.208, -17.569, 12.120, P<0.05). The internal diameters of portal vein in hypertension group and normal group were (12.3±2.3)cm and (14.6±3.0)cm, respectively, the difference was statistically significant (t=9.126, P<0.05). The depth of ascites in high pressure group and normal group was (79.6±12.3) cm and (53.2±9.6)cm, respectively, and the difference was statistically significant (t=-11.269, P<0.05). There were 14 cases (40.0%) in high pressure group and 1 case (3.1%) in normal pressure group developed gastrointestinal bleeding, with statistical significant difference (χ²=-68.104, P<0.05). Hepatic encephalopathy occurred in 17 cases (48.6%) of high pressure group and 1 case (3.1%) in normal pressure group, and the difference was statistically significant (χ²=-78.345, P<0.05). Ten patients (28.6%) died in high pressure group, which was statistically significant when compared to that of two patients (5.4%) in the normal pressure group (χ²=-30.504, P<0.05). The levels of PCⅢ, IV-C, LN and HA in the hypertension group were (42.1±11.1) ng/mL, (192.2±18.6) ng/mL, (156.0±14.5) ng/mL and (285.3±23.9) ng/mL, respectively, which were significantly higher than those of [(21.8±9.7) ng/mL, (143.9±10.6) ng/mL, (131.2±15.2) ng/mL and (176.9±22.3) ng/mL in the normal pressure group, respectively [t=-16.800, -11.602, -9.786, -13.612, P<0.05]. Conclusion Liver cirrhosis in chronic hepatitis B patients leads to increased portal pressure and compensatory spontaneous portosystemic shunt that may further deteriorate liver function, aggravate liver cirrhosis progression, cause gastrointestinal bleeding and hepatic encephalopathy, and impose adverse effect on the prognosis of patients.

Analysis on the function of antigen-specific CD8+ T cells before and after antiviral treatment in patients with hepatitis B virus-related cirrhosis

GAO De-yong, LOU Xiao-li, MA Shuang, ZHANG Kun-lun, LIU Liang-ming, LIU Hong-xiang

2021, 26(11):  1250-1252. 

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Objective To investigate the number and function of hepatitis B virus (HBV) antigen-specific T cells in peripheral blood before and after antiviral treatment of HBV-related cirrhosis, and its correlation with clinical prognosis. Methods Forty-six patients were selected by HLA-A2 classification test, the percentages of HBV antigen-specific T cells in the peripheral blood were detected before and after treatment by flow cytometry through the major histocompatibility complex (MHC) -antigenic peptide tetramer staining, the cytokines secreting ability and phenotype of the cells were detected. Results Human leukocyte-associated antigens HLA-A2 expressed by antigen-specific CD8⁺T cells were detected in 22 patients, the level of liver function marker alanine aminotransferase (ALT) after treatment (31.29±18.42) was significantly lower than that before treatment (124.05±29.18), (u = 72, P=0.015), and the HBV DNA negative rate was 100%. The number of antigen-specific CD8⁺T cells after treatment (1.15±0.37)% was significantly higher than that before treatment (0.65±0.25)%, (u = 59, P<0.0001). The percentage of cells which secreted interferon (IFN-γ) after treatment (6.86±2.08)% was significantly higher than that before treatment (3.58±1.26)%, (u = 46, P<0.0001). The percentage of HBV epitope-specific CD8⁺T cells which expressed inhibitory factor PD-1 after treatment (0.43±0.19)% was significantly lower than that before treatment (0.76±0.43)%, (u = 131, P<0.05). The percentage of HBV epitope-specific CD8⁺T cells which expressed active factor CD28 after treatment (1.03±0.45)% was significantly higher than that before treatment (0.56±0.26)%, (u = 100, P=0.0006). Conclusion The function of antigen-specific CD8⁺T cells in the peripheral blood of patients with HBV-related cirrhosis is defected. After antiviral treatment, the number and function of antigen specific CD8+T cells are both improved.

The value of contrast-enhanced ultrasonography evaluating splenic blood flow status in the diagnosis of EGVB in patients with hepatitis B related cirrhosis

JU Feng, WANG Dong, SHI Yu-min, ZHU Yan-hong, LI Mei-lin, WANG Xiao-wei, YAO Shang-zhi

2021, 26(11):  1253-1256. 

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Objective To investigate the value of splenic blood flow in diagnosing esophagogastric variceal bleeding (EGVB) in patients with hepatitis B virus (HBV) - related cirrhosis by contrast-enhanced ultrasonography (CEUS). Methods A total of 69 patients with HBV-related cirrhosis complicated by EGVB admitted to our hospital from April 2019 to April 2020 were included in the study. According to the occurrence of EGVB, the patients were divided into bleeding group (n=26) and non-bleeding group (n=43). After admission, CEUS was performed before treatment in both groups. Splenic artery resistance index, splenic artery pulsatility index, splenic vein diameter, mean splenic vein flow, minimum circulation time (MCT), and peak enhancement time (PET) were recorded. The difference of splenic blood flow between the 2 groups was compared, and the values of MCT and PET in the diagnosis of HBV-related cirrhosis complicated by EGVB were analyzed based on receiver operating characteristic (ROC) analysis. Results There was no significant difference in splenic artery resistance index, splenic artery pulsatility index, splenic vein diameter and splenic vein mean flow between the 2 groups (P>0.05). MCT and PET in the bleeding group were significantly higher than those in the non-bleeding group (P<0.05). Both MCT and PET could be used for the diagnosis of EGVB in patients with HBV-related cirrhosis based on ROC analysis. The areas under the curves were 0.775 and 0.866, respectively (P<0.05). Conclusion CEUS can be used in the diagnosis of EGVB in patients with HBV-related cirrhosis. MCT > 5.950 s and PET > 12.270 s are the best cutoff values for diagnosing EGVB in such patients, which is helpful to the clinical treatment.

Liver Cancer

RFA, TACE and secondary hepatectomy for recurrent hepatocellular carcinoma: a 5-year follow-up study

HUANG Yi, WANG Jian-dong, JIN Lei, XU Shi

2021, 26(11):  1257-1259. 

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Objective To collect and analyze the 5-year follow-up information of patients with recurrent liver cancer treated by radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE) and secondary hepatectomy. Methods A total of patients with recurrent liver cancer admitted to our hospital from June 2010 to December 2015 were enrolled. According to the therapeutic methods, they were divided into RFA group (64 cases), TACE group (58 cases) and secondary hepatectomy group (70 cases). The therapeutic effects of the 3 groups were compared, and the complications were observed. All patients were followed up for 5 years, and the deadline was December 2020 or death. Results The effective rates of RFA group, TACE group and secondary hepatectomy group were 95.31%, 87.93% and 98.57, respectively. The effective rate of TACE group was significantly lower than that of secondary hepatectomy group (P<0.05). The incidence of complications in RFA group, TACE group and secondary hepatectomy group was 9.38%, 6.90% and 25.71%, respectively. The overall incidence of complications in secondary hepatectomy group was significantly higher than those in RFA and TACE group (P<0.05). After operation of 1, 3 and 5 years, the tumor free survivals rates of TACE group were significantly lower than those of RFA group and secondary hepatectomy group (P<0.05). Five years after operation, the tumor free survivals rates of secondary hepatectomy group were significantly lower than those of RFA group (P<0.05). One and 3 years after operation, there was no significant difference among the 3 groups (P>0.05). Five years after operation, the cumulative survivals rates of RFA group were significantly higher than those of TACE group and secondary hepatectomy group (P<0.05). Conclusion The treatment efficacy and long-term survival rate of patients treated by TACE are worse than those treated by RFA and secondary hepatectomy. Patients with recurrent liver cancer treated by secondary hepatectomy may have higher risk of complications, and patients treated by RFA have better long-term survival.

Effect of apatinib combined with TACE on serum VEGF/TSGF levels in the treatment for patients with HCC

ZHANG Min-hua, ZHU De-ming, ZHONG Chen

2021, 26(11):  1260-1263. 

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Objective To investigate the effect of apatinib combined with transcatheter arterial chemoembolization (TACE) on serum vascular endothelial growth factor (VEGF)/tumor specific growth factors (TSGF) levels in patients with hepatocellular carcinoma (HCC). Methods A total of 120 patients with HCC admitted to our hospital from August 2018 to August 2020 were selected, and randomly divided into 2 groups on average. The control group was treated with TACE, and the observation group was treated with apatinib combined with TACE. The treatment efficacy of the 2 groups were analyzed, and the levels of VEGF/TSGF, alpha fetoprotein (AFP), matrix metalloproteinase-9 (MMP-9) and the distribution of T lymphocyte subsets CD3⁺, CD4⁺/CD8⁺ were compared before and after treatment. Results The effective rates of the observation group and the control group were 60.00% and 36.67%, respectively, and the difference was statistically significant (P<0.05). In observation group, the level of VEGF/TSGF at 6 days after treatment (411.20±50.21) was significantly lower than that before treatment (500.25±50.23, P<0.05). Three months after treatment, the level of VEGF/TSGF (324.64±51.12) was significantly lower than that before treatment and 6 days after treatment (500.25±50.23, 411.20±50.21, P<0.05). The level of VEGF/TSGF in control group (454.27±49.58) at 6 days after treatment was significantly lower than that before treatment (512.25±55.92, P<0.05), and 3 months after treatment, the level of VEGF/TSGF (532.48±56.48) was significantly higher than that at 6 days after treatment (454.27±49.58, P<0.05). The levels of VEGF/TSGF at 6 days and 3 months after treatment in observation group (411.20±50.21, 324.64±51.12) were significantly lower than those in control group (454.27±49.58, 532.48±56.48, P<0.05). After treatment, the levels of MMP-9 and AFP in the 2 groups were significantly lower than those before treatment (P<0.05), whereas CD3⁺ and CD4⁺/CD8⁺ were significantly higher than those before treatment (P<0.05). After treatment, the levels of MMP-9 [(968.76±201.48) ng/L] and AFP [(489.47±32.49) μg/L] in observation group were significantly lower than those in control group [(1632.49±245.86)ng/L, (743.58±49.58)μg/L, P<0.05], whereas CD3⁺ [(61.58±9.36)%], CD4⁺/CD8⁺ (1.09±0.12) were significantly higher than those in control group [(54.24±8.59)%, 1.34±0.19, P<0.05]. Conclusion Apatinib combined with TACE in the treatment for patients with HCC can effectively regulate the serum VEGF/TSGF levels and inhibit tumor angiogenesis.

The value of gadolinium diamine enhanced MRI and enhanced CT in the diagnosis of hepatocellular carcinoma in Child-Pugh grade A patients

GUO Da-ke, LIU Bing, LIU Bin

2021, 26(11):  1264-1267. 

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Objective To investigate the clinical value of gadolinium diamine enhanced magnetic resonance imaging (MRI) and enhanced computed tomography (CT) in the diagnosis of hepatocellular carcinoma (HCC) in Child-Pugh grade A patients. Methods A total of 114 Child-Pugh grade A patients with HCC admitted to our hospital from December 2018 to December 2020 were selected. All patients underwent gadolinium diamine enhanced MRI and enhanced CT. The detection rate of nodules, enhancement methods and detection rate of capsule between the 2 imaging methods were compared. Results All of the 114 patients were confirmed by pathology, and 150 HCC nodules were found. The sensitivity of gadolinium diamine enhanced MRI in detection of HCC nodules was 94.67%, which was significantly higher than that of enhanced CT (81.33%), (P<0.05). The detection rates of gadolinium diamine enhanced MRI in multiple nodules and HCC nodules <20 mm were 76.76% and 42.25%, respectively, which were significantly better than those of enhanced CT (44.26% and 23.77%), (P<0.05). Gadolinium diamine enhanced MRI and enhanced CT showed a trend of low signal/low density along with time when scanning HCC lesions. All HCC tumor lesions scanned by MRI showed low signals in hepatobiliary phase, with a detection rate of 100%. Ninety tumor nodules with capsules were found in 114 HCC patients, which were confirmed by pathology. The sensitivity of detecting the capsules of HCC nodules through gadolinium diamine enhanced MRI was 85.56%, which was significantly higher than that of enhanced CT 50.00% (P<0.05). There was no significant difference between the 2 imaging methods in observing the features of capsules surround HCC (P>0.05). Conclusion Gadolinium diamine enhanced MRI performs better than enhanced CT in detecting HCC nodules and tumor capsules. Gadolinium diamine enhanced MRI also performs better in showing enhancement characteristics of HCC, which has a higher diagnostic value for hepatobiliary specific phase HCC.

The value of blood supply observed through CTPI in evaluating the prognosis of patients with primary liver cancer after TACE

LI Zhen-zhen, GENG Yun-ping, REN You-you, YOU Guo-qing, ZENG Qing

2021, 26(11):  1268-1271. 

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Objective To investigate the value of blood supply state in evaluating the prognosis of patients with primary liver cancer after transcatheter arterial chemoembolization (TACE) by computed tomography perfusion imaging (CTPI). Methods A total of 257 patients with primary liver cancer who underwent TACE from March 2014 to November 2019 were included in the study. The parameters of the hepatic blood flow (HBF), hepatic artery perfusion index (HPI), time to peak (TTP) and hepatic artery perfusion volume (HAP) were recorded before and after TACE through CTPI. The levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were detected by histopathological biopsy before TACE. The correlations between VEGF, MVD and CT perfusion parameters were analyzed. The therapeutic effects were recorded and the levels of HBF, HPI, TTP and HAP of patients with different effects were compared. The value of CTPI parameters in evaluating the short-term prognosis of patients after TACE was analyzed. Results Three months after TACE, 38 patients got complete remission (CR), 128 patients got partial remission (PR), 36 patients got stable disease (SD) and 55 patients got progressive disease (PD). The Pearson linear correlation analysis showed that VEGF and MVD were positively correlated with HBF, HPI and HAP, and negatively correlated with TTP (P<0.05). The receiver operating characteristic (ROC) curve showed that the HBF, HPI, HAP and TTP were helpful to evaluated the therapeutic effect of TACE (P<0.05). The efficacy index model of Y=X₁+X₂+X₃+X₄ (HBF: X₁, HPI: X₂, HAP: X₃, TTP: X₄) was established according to the results of ROC analysis, the area under curve (AUC) of short-term efficacy was 0.870 (AUC = 0.870, S.E. = 0.025, 95%CI = 0.821-0.919, P=0.000). Conclusion CTPI can be used to evaluate the blood supply of patients with primary liver cancer before and after TACE treatment, and judge the short-term prognosis.

Clinical value of indocyanine green fluorescence navigation in laparoscopic hepatectomy

YAO Han, WANG Jian-dong

2021, 26(11):  1272-1275. 

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Objective To explore the clinical value of indocyanine green (ICG) fluorescence navigation in laparoscopic hepatectomy (LH). Methods 64 PLC patients admitted to hospital for LH from March 2015 to March 2021 were reviewed, including 40 males and 24 females, with an average age of (56.2±9.8) years. The measurement data of skewness and normal distribution were compared by Mann-Whitney U test and independent t test respectively Counting data were compared by χ² test. Results Among 64 PLC patients, ICG fluorescence navigation was performed in 22 cases (ICG group), and the other 42 cases were non-ICG group. Comparing the clinical data, the operation time of ICG group and non-ICG group was 162 (110, 198) min and 192 (124, 248) min, with statistical significance (P<0.05). The intraoperative blood loss of ICG group and non-ICG group was 102 (36, 214) mL and 208 (98, 402) mL, with statistical significance (P<0.05). There were 21 cases (95.4%) with wide cutting edge (>10 mm) and 1 case (4.5%) with narrow cutting edge (< 10 mm) in ICG group, 31 cases (73.8%) with wide cutting edge and 11 cases (26.2%) with statistical significance (P<0.05). Among 22 patients with ICG fluorescence navigation, 14 were given before operation, which were patients with hepatocellular carcinoma; Intraoperative administration was performed in 8 patients with cholangiocarcinoma. There was no significant difference in clinical data (P>0.05). Bright fluorescence imaging was seen in the tumor area before operation, but no imaging was found in normal liver tissue. After ICG injection, the normal liver tissue showed uniform fluorescence development, but the tumor area did not develop. Conclusion ICG fluorescence navigation is safe and feasible in the application of LH. Defining PLC pathological types before operation is helpful to define tumor margin and accurate surgical navigation: preoperative ICG is selected for hepatocellular carcinoma and intraoperative ICG is selected for cholangiocarcinoma.

Other Liver Diseases

Clinical features of 162 elderly patients with drug-induced liver injury - An analysis based on RUCAM

REN Hui-qiong, YAO Jun-di, ZHAO Hong-xin, LU Jin-yu, WU Long-zhi

2021, 26(11):  1276-1278. 

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Objective To investigate the etiology and clinical features of elderly patients with drug-induced liver injury (DILI). Methods A total of 162 patients with DILI admitted to our hospital from June 2014 to December 2020 were selected, and their clinical data were retrospectively analyzed. The Roussel Uclaf Causality Assessment Method (RUCAM) was used to evaluate the relationship between drugs and liver injury. The suspected drugs related to DILI, the clinical manifestations and clinical features of DILI were also analyzed. Results The youngest patient was 68 years old and the oldest was 96, the average age was 91.2. The drugs most likely to induce DILI were Chinese herbal medicine and Chinese patent medicine (68 cases, 41.98%), antibiotic (21 cases, 12.96%) and cardiovascular drugs (13 cases, 8.02%), the RUCAM grades were all more than 3, and there was no significant difference in clinical manifestations among the patients with DILI induced by the three drugs. The numbers of cholestatic injury type, hepatocellular injury type and mixed injury type were 76 (46.91%), 48 (29.63%), 38 (23.46%), respectively. The proportion of severity grade 1, 2, 3 and 4 were 46.29%, 32.72%, 13.58%, 7.41% respectively. Conclusion In the study, we find that traditional Chinese medicine is the main cause of DILI in elder patients, which is worthy of high attention. Clinical manifestations are not significantly different. The most common type is cholestatic DILI. Early intervention can improve the prognosis of patients.

The expression of serum bile acid profile in patients with nonalcoholic fatty liver disease

ZHU Yue, QIAN Xiao-han, JI Guo-zhong, YANG Li-hua

2021, 26(11):  1279-1282. 

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Objective To explore the changes and application value of serum bile acid profile in patients with nonalcoholic fatty liver disease (NAFLD). Methods A total of 60 patients with NAFLD and 54 healthy individuals from Second Affiliated Hospital of Nanjing Medical University were enrolled between July 2019 and July 2020. Clinical data and blood samples were collected and high-performance liquid chromatography-mass spectrometry (LC-MS/MS) was used to determine 15 types of serum bile acid profile. Results Compared with healthy control group, the serum concentration of cholic acid (CA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA) increased and lithocholic acid (LCA) decreased significantly in NAFLD group (P<0.05). There was no obvious differences in serum concentration of deoxycholic acid (DCA), ursodeoxy cholic acid (UDCA), glycolitho cholic acid (GLCA), glycodeoxy cholic acid(GDCA), glycochenodeoxy cholic acid (GCDCA), glycoursodeoxy cholic acid (GUDCA), taurocholic acid (TCA), taurolitho cholic acid (TLCA), taurodeoxy cholic acid (TDCA), taurochodeoxy cholic acid (TCDCA), tauroursodeoxy cholic acid (TUDCA) (P>0.05). In NAFLD group, the serum content of DCA, GCA, GDCA, GCDCA, TCA, TCDCA were positively correlated with the serum level of ALT and AST. BMI (OR: 1.615; 95%CI: 1.224-2.131; P<0.05) and LCA (OR: 0.946; 95%CI: 0.906-0.987; P<0.05) were both associated with the risk of NAFLD. Among the bile acid profile, CA (AUC: 0.640), CDCA (AUC: 0.617)and GCA (AUC:0.634) had the higher diagnostic value for NAFLD. Conclusion The serum bile acid profile in NAFLD patients is significantly changed,which suggests that it may have positive value in diagnosis of NAFLD.

Comparison of laparoscopic resection and laparoscopic microwave ablation in the treatment of hepatic hemangioma

LV Chao, LI Heng-ping, DING Zheng-hua, KONG Diao-diao

2021, 26(11):  1283-1286. 

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Objective To compare the efficacy of laparoscopic resection and laparoscopic microwave ablation in the treatment of hepatic hemangioma. Methods The clinical data of 46 patients with hepatic hemangioma in our hospital from June 2016 to June 2019 were retrospectively analyzed. They were divided into laparoscopic surgery group (group A) and laparoscopic microwave ablation group (group B), with 18 cases in group A and 28 cases in group B. The therapeutic effects of group A and group B on hepatic hemangioma were compared in terms of operation time, intraoperative blood loss, hospital stay and postoperative liver function recovery. Results Compared with group A, group B had obvious advantages in shortening operation time (t=2.797, P=0.008), reducing blood loss (t=3.253, P=0.005) and reducing hospital stay (t=2.065, P=0.045). On the first day after operation, ALT and AST levels in group B were higher than those in group A (P<0.05). The levels of ALT and AST on the third day after operation, the levels of total bilirubin, direct bilirubin and indirect bilirubin on the first and third days after operation, the incidence of postoperative complications and tumor recurrence rate between the two groups were not statistically significant (P>0.05). Conclusion Laparoscopic microwave ablation is safe, feasible and effective, which is worthy of clinical promotion.