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Correlation between viral load and liver cirrhosis in chronic hepatitis B patients

Lili LIU MM , Jiyao WANG MD , Weimin SHE MM ,

《医学前沿（英文）》 2009年第3卷第3期页码 271-276 doi: 10.1007/s11684-009-0054-1

摘要： The aim of this paper is to investigate the relationship between hepatitis B virus (HBV) DNA levels during the course and the progression to cirrhosis with chronic hepatitis B. A total of 239 chronic hepatitis B patients confirmed by liver biopsy between 2001 and 2007 were followed up for a median of 28 months. Compared with the patients without cirrhosis, the patients progressed to cirrhosis were older and with higher HBV-DNA levels at end point. However, there was no significant difference in cirrhosis progression between different HBV-DNA groups at baseline ( = 0.531). Kaplan-Meier analysis showed higher HBV-DNA level at endpoint had increasing risk of cirrhosis ( = 0.019). The results of Cox model indicated that HBV-DNA levels at endpoint, stage of fibrosis, negative hepatitis B e antigen, and γ-glutamyl transpeptidase at baseline were independent risk factors of cirrhosis. The relative risk ratios were 1.898, 1.918, 8.976, and 1.006, respectively. Progression to cirrhosis in chronic hepatitis B patients is correlated with HBV-DNA levels during follow-up.

关键词： hepatitis B chronic viral load liver cirrhosis

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Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis

null

《医学前沿（英文）》 2013年第7卷第2期页码 255-263 doi: 10.1007/s11684-012-0227-1

摘要：

The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13–15 mg?kg^-1?day^-1) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1–2 but still progressed in patients at stages 3–4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3–4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

关键词： primary biliary cirrhosis ursodeoxycholic acid Chinese biochemical response therapeutic efficacy

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Effects of Decoction on plasma proteome in cirrhosis: preliminary experimental study with rats

LIU Jie, WANG Jiyao, WEI Liming, LU Ye, Jin Hong

《医学前沿（英文）》 2008年第2卷第1期页码 39-44 doi: 10.1007/s11684-008-0008-z

摘要： The aim of this paper is to study the effects of Decoction on the plasma proteome in cirrhotic rats. Twenty-six male Sprague-Dawley (SD) rats were randomly divided into three groups: cirrhotic model group ( = 10), treated with CCl (CCl/olive oil: v/v = 1:1); Decoction intervention group ( = 10), treated with CCl+ Decoction; and normal control group ( = 6), treated with olive oil only. After 8 weeks, blood samples were collected from the inferior vena cava to undergo bi-dimensional electrophoresis (2DE) and analysis by PDQuest 7.3 software. Differential protein spots were cut, enzyme hydrolysis was conducted, and peptide fragments extracted from the mixture underwent mass spectrometry (MS) with MALDI-TOF-TOF-MS. The liver fibrogenesis was assessed using a digital image analysis instrument of Masson’s trichrome stained sections. The fibrosis area of the Decoction was (8.9 ± 3.7)%, significantly smaller than that of the cirrhotic model group [(12.4 ± 4.7)%, < 0.05]. Ten markedly changed protein spots were identified by MALDI-TOF-TOF-MS. Eight of the 10 proteins, including plasma glutathione peroxidase, plasma glutathione peroxidase precursor, prealbumin, haptoglobin, apolipoprotein A-IV precursor, complement C4, inter-alpha-inhibitor H4 heavy chain, and serine/threonine-protein kinase microtubule-affinity regulating kinase 1 (MARK1) were expressed very lowly in the cirrhotic model group while they were expressed highly in the Decoction group. The expression of liver regeneration-related protein LRRG03 and vimentin increased in the cirrhotic model group, and reduced in the Decoction group. Some proteins related to oxidative stress, cell proliferation and transformation have changed in the plasma of cirrhosis induced by CCl. Decoction promotes protein synthesis and plays an anti-fibrotic role by anti-oxidation and accommodation of cell proliferation and transformation.

关键词： Decoction intervention serine/threonine-protein underwent Decoction glutathione peroxidase

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Cryotherapy for cirrhosis-based hepatocellular carcinoma: a single center experience from 1595 treated

null

《医学前沿（英文）》 2015年第9卷第1期页码 63-71 doi: 10.1007/s11684-014-0342-2

摘要：

Cryoablation is a less prevalent percutaneous ablative therapy for hepatocellular carcinoma (HCC), and current evidence about its usefulness is limited. We report our experience in treating 1595 HCC cases with percutaneous cryoablation to give a comprehensive profile about the effectiveness, safety and long-term outcome of this therapy. From January 2003 to December 2013, 1595 patients with 2313 HCC nodules were ablated with 2945 cryoablation sessions in our center. Complete ablation was achieved in 1294 patients for 1893 nodules with a mean diameter of 3.4±2.2 cm. The complete ablation rate was 81.2%, 99.4%, 94.4%, and 45.6% in all tumors, tumors<3 cm, tumors<5 cm, and tumors>5 cm, respectively. Major complications were observed after 80 (3.4%) of the 2945 cryoablations and minor complications were observed after 330 cryoablations with no treatment-related deaths. After a median follow-up of 33.4 months, 937 patients developed different types of recurrence. The 5- and 10-year overall survival was 25.7% and 9.2%, respectively. Cryoablation showed reliable safety and efficacy and should be considered as a promising technique, particularly when a large zone of ablation is required.

关键词： hepatocellular carcinoma percutaneous cryoablation efficacy safety

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Assessment of liver volume variation to evaluate liver function

null

《医学前沿（英文）》 2012年第6卷第4期页码 421-427 doi: 10.1007/s11684-012-0223-5

摘要：

In order to assess the value of liver volumetry in cirrhosis and acute liver failure (ALF) patients, we explored the correlation between hepatic volume and severity of the hepatic diseases. The clinical data of 48 cirrhosis patients with 60 normal controls and 39 ALF patients were collected. Computed tomography-derived liver volume (CTLV) and body surface area (BSA) of normal controls were calculated to get a regression formula for standard liver volume (SLV) and BSA. Then CTLV and SLV of all patients were calculated and grouped by Child-Turcotte-Pugh classification for cirrhosis patients and assigned according to prognosis of ALF patients for further comparison. It turned out that the mean liver volume of the control group was 1 058±337 cm³. SLV was correlated with BSA according to the regression formula. The hepatic volume of cirrhosis patients in Child A, B level was not reduced, but in Child C level it was significantly reduced with the lowest liver volume index (CTLV/SLV). Likewise, in the death group of ALF patients, the volume index was significantly lower than that of the survival group. Based on volumetric study, we proposed an ROC (receiver operating characteristic) analysis to predict the prognosis of ALF patients that CTLV/SLV<83.9% indicates a poor prognosis. In conclusion, the CTLV/SLV ratio, which reflects liver volume variations, correlates well with the liver function and progression of cirrhosis and ALF. It is also a very useful marker for predicting the prognosis of ALF.

关键词： liver volume variation cirrhosis acute liver failure (ALF)

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肝硬化患者胃黏膜微生物菌群特征及其与胃肠道症状的相关性分析 Article

陈燕飞, 郭静, 陈春雷, 石鼎, 方戴琼, 季峰, 李兰娟

《工程（英文）》 2021年第7卷第4期页码 507-514 doi: 10.1016/j.eng.2020.04.014

摘要：

研究表明，肝硬化患者的口腔和肠道微生物群与健康人群存在差异。胃位于口腔和肠道之间，关于其黏膜微生物群结构所知甚少。本研究采用16S rRNA焦磷酸测序技术分析了肝硬化患者和对照组的胃黏膜微生物群。研究发现，组织学和测序法均证实肝硬化患者幽门螺杆菌感染率显著降低。在幽门螺杆菌阴性人群中，可以按细菌组成结构将胃黏膜微生物群分为4个聚类，其中聚类1和2主要是肝硬化患者，聚类3主要是健康人群，而聚类4中肝硬化患者和健康人群各占一半左右。这些不同聚类间的成分和功能存在显著差异。在属的水平上，聚类1和2分别富集奈瑟菌和链球菌。在功能基因分类上，相对而言，聚类2缺乏涉及遗传信息处理以及与聚糖生物合成和代谢相关的功能基因。胃黏膜菌群结构表现为聚类2的患者胃肠道症状更严重，既往内镜下曲张静脉的治疗率显著高于其他组。我们的研究结果表明，在肝硬化中，幽门螺杆菌和非幽门螺杆菌的定植都受到影响。虽然幽门螺杆菌阴性的胃黏膜微生物结构表现出相当大的异质性，但特定的胃微生物群与临床特征之间仍然存在相关性。既往内镜下静脉曲张治疗会引起胃黏膜菌群结构明显改变，从而加重幽门螺杆菌阴性肝硬化患者的胃肠道症状。

关键词：微生物组肝硬化症状静脉曲张胃镜

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γδ T cells in liver diseases

null

《医学前沿（英文）》 2018年第12卷第3期页码 262-268 doi: 10.1007/s11684-017-0584-x

摘要：

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词： γδT cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration

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Current recommendations of managing HBV infection in preconception or pregnancy

null

《医学前沿（英文）》 2014年第8卷第2期页码 158-165 doi: 10.1007/s11684-014-0340-4

摘要：

Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation worldwide. Management of chronic hepatitis B during pregnancy is challenging. Transmission of hepatitis B to infants still occurs perinatally although immunoprophylaxis is widely available for infants born to mothers with chronic hepatitis B infection. The emerging data suggest that initiation of antiviral therapy in the beginning of the third trimester in highly viremic mothers can prevent immunoprophylaxis failure in their infants. The available drug safety data show that lamivudine, telbivudine and tenofovir are generally safe to be used during the pregnancy. In order to minimize the fetal exposure to the antiviral medication, antiviral therapy during the pregnancy should be limited to a selected group of patients with cirrhosis, high hepatitis B viral load, or prior history immunoprophylaxis failure. An elective Caesarean section may reduce the risk of perinatal transmission. For those females planning for pregnancy or in early stage of pregnancy, communication and follow-up among obstetrician, gastroenterologist, and primary care physician are important. In this article, we will review the features of hepatitis B infection before, during and after the pregnancy; the risk factors that increase mother-to-child transmission; safety data on antiviral drug use during pregnancy; and the potential role of Caesarean section in selected cases.

关键词： antiviral therapy Caesarean section cirrhosis hepatitis B immunoprophylaxis mother-to-child transmission pregnancy prevention

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Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

《医学前沿（英文）》 2019年第13卷第6期页码 658-666 doi: 10.1007/s11684-019-0707-7

摘要： Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12–213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (>5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP>5.5 was associated with the presence of cirrhosis ( =0.001), co-existing non-alcoholic steatohepatitis (NASH) ( = 0.035), and GT 1 ( = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis ( = 0.003), Child–Pugh score<6 ( = 0.015), and baseline AFP<10 ( = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child–Pugh score<6, and baseline AFP<10.

关键词： chronic hepatitis C α fetoprotein direct acting antiviral treatment cirrhosis

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Urotensin II receptor antagonist reduces hepatic resistance and portal pressure through enhanced eNOS-dependent HSC vasodilatation in CCl

Ruoxi Zhang, Jing Chen, Diangang Liu, Yu Wang

《医学前沿（英文）》 2019年第13卷第3期页码 398-408 doi: 10.1007/s11684-019-0689-5

摘要： Increased serum urotensin II (UII) levels in human cirrhotic populations have been recently shown, but the long-term effects of UII receptor antagonist on the cirrhosis have not been investigated. To investigate the therapeutic effects of urotensin II receptor (UT) antagonist palosuran on rats with carbon tetrachloride (CCl )-induced cirrhosis, the hepatic and systemic hemodynamics, liver fibrosis, the metalloproteinase-13 (MMP-13)/ tissue inhibitor of metalloproteinase-1 (TIMP-1) ratio, hepatic Rho-kinase activity, and the endothelial nitric oxide synthase (eNOS) activity are measured in CCl -cirrhotic rats treated with palosuran or vehicle for 4 weeks. Primary hepatic stellate cells (HSCs) are used to investigate the changes in UII/UT expression and the effect of palosuran. Compared with the vehicle-treated cirrhotic rats, treatment with palosuran can reduce the portal pressure (PP), decrease the risk of liver fibrosis and the level of α smooth muscle actin, collagen-I (COL-I), and transforming growth factor β expression. However, treatment with palosuran can increase MMP-13/TIMP-1, p-vasodilator-stimulated phosphoprotein (p-VASP), and p-eNOS expression. Moreover, UII/UT mRNA expression increases during HSC activation. MMP-13/TIMP-1, COL-I, and p-VASP are inhibited after palosuran treatment. Our data indicate that long-term administration of palosuran can decrease PP in cirrhosis, which results from decreased hepatic fibrosis and enhanced eNOS-dependent HSC vasodilatation.

关键词： portal hypertension cirrhosis urotensin II palosuran hepatic stellate cell

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Influence of β-elemene on the secretion of angiotensin II and expression of AT1R in hepatic stellate cells

Ling YANG, Rui ZHU, Qingjing ZHU, Dan DAN, Jin YE, Keshu XU, Xiaohua HOU

《医学前沿（英文）》 2009年第3卷第1期页码 36-40 doi: 10.1007/s11684-009-0020-y

摘要： This study aims to investigate the influence of β-elemene on the secretion of angiotensin II (ANG II) and the expression of angiotensin receptor type 1 (AT1R) in hepatic stellate cells (HSCs). , HSC-T6 were cultured for 24 hours and then treated with different doses of β-elemene (2.5, 5 and 10 mg/L). A control group was also set up. The secretion of ANG II in the supernatant was detected by radioimmunoassay. The mRNA expression of AT1R at 4, 12 and 24 h after treatment was detected by reverse transcription-polymerase chain reaction (RT-PCR), respectively. The protein expression of AT1R was detected by western blot. At the 4th h, the ANG II secretion in the supernatant was significantly inhibited by 10 mg/L β-elemene compared with the control group ( <0.05), while 5.0 mg/L and 2.5 mg/L β-elemene had no inhibitory effect on the secretion of ANG II ( >0.05). At the time point of the 12th h, the secretion of ANG II in the supernatant treated with 10 mg/L and 5.0 mg/L β-elemene was significantly lower than the control ( <0.01, <0.05). Following the treatment with 5.0 mg/L and 2.5 mg/L β-elemene for 24 h, significant inhibition of ANG II secretion was observed ( <0.05), but 10 mg/L β-elemene had no such effect. β-elemene significantly reduced the amount of AT1R mRNA in HSCs after the treatment for 4, 12, and 24 h in a dose-dependent manner. The expression of AT1R protein also decreased after the treatment with β-elemene for 24 h. β-elemene can inhibit the secretion of ANG II and the gene and protein expression of AT1R, which may be the mechanism by which β-elemene prevents the progress of hepatic fibrosis.

关键词： liver cirrhosis beta-elemene hepatic stellate cells angiotensin II receptor angiotensin type 1

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血清N-聚糖生物标志物诊断ALT水平正常慢性乙型肝炎患者显著肝纤维化和肝硬化的临床意义 Article

王林, 刘艺琪, 顾启馨, 张驰, 徐蕾, 王蕾, 陈翠英, 刘学恩, 赵鸿, 庄辉

《工程（英文）》 2023年第26卷第7期页码 151-158 doi: 10.1016/j.eng.2023.03.008

摘要：

本研究目的是探讨血清N-聚糖模型在285例丙氨酸转移酶（alanine aminotransferase, ALT）水平正常（＜40 U·L^–1）的慢性乙型肝炎（慢性乙肝）患者中诊断显著肝纤维化和肝硬化的临床意义。入组患者均进行肝组织活检，并使用Ishak评分系统评估患者肝组织纤维化程度。应用基于DNA测序仪的荧光糖电泳技术检测患者血清N-聚糖图谱，每例患者的血清样本中共鉴定出9个N-聚糖峰。利用机器学习算法，即随机森林（random forest, RF）构建更理想的血清N-聚糖模型，以诊断显著肝纤维化（≥ F3）和肝硬化（≥ F5），并比较血清N-聚糖模型和其他纤维化标志物的诊断效能。肝组织活检结果显示，有显著肝纤维化和肝硬化患者分别占63.86%（182/285）和16.49%（47/285），有显著炎症患者为4.91%（14/285）。血清N-聚糖RF-A模型具有很好的诊断显著肝纤维化（≥ F3）的效能，其受试者工作特征曲线下面积（area under receiver operating characteristic curve, AUROC）为0.94，与肝活检的符合率为90.45% 。在诊断肝硬化（≥F5）时，血清N-聚糖RF-B模型的AUROC为0.97，与肝组织活检的符合率为88.94%。血清N-聚糖模型（RF-A和RF-B）的诊断效能优于肝硬度值测量（liver stiffness measurement, LSM）、基于4因子的纤维化指数（fibrosis index based on the four factors, FIB-4）和天冬氨酸转氨酶与血小板比率指数（aspartate aminotransferase-to-platelet ratio index, APRI）。在ALT水平正常的慢性乙肝患者中，血清N-聚糖模型可作为诊断显著肝纤维化或肝硬化的潜在生物标志物。

关键词：肝纤维化慢性乙型肝炎血清N-聚糖 N-聚糖模型丙氨酸转移酶