二维实时剪切波弹性成像诊断慢性肝病肝纤维化的危险因素分析

目的分析影响二维实时剪切波弹性成像技术(2D-SWE)诊断慢性肝病肝纤维化的危险因素。方法选择2018年1月至2020年12月慢性乙型肝炎患者338例进行二维实时剪切波弹性成像检查,且所有患者在7 d内进行肝脏穿刺活检并按病理学分期诊断。同时采集患者临床资料,采用ROC曲线评价二维实时剪切波弹性成像技术诊断慢性肝病肝纤维化的价值。再采用多因素回归性分析影响二维实时剪切波弹性成像技术诊断患者的危险因素。并分析肝脏病理分期、临床资料与LSM值的相关性。结果2组比较,年龄、脾脏厚度、长度、门静脉宽度、谷丙转氨酶、谷草转氨酶差异有统计学意义(P<0.05);年龄、病程、脾脏厚度、脾脏长度、谷丙转氨酶、谷草转氨酶与LSM值呈正相关(P<0.05);肝脏病理分期与LSM值呈正相关(P<0.05);LSM值在肝纤维化的AUC分别为0.762,最佳诊断界值10.08 kPa,敏感性为83.3%,特异性为71.2%。结论慢性肝病肝纤维化患者病程、年龄是影响2D-SWE诊断LSM值的危险因素,且2D-SWE诊断肝纤维化分期有较高的诊断价值。

软肝胶囊治疗慢性肝病肝纤维化临床研究

目的观察软肝胶囊治疗慢性肝病肝纤维化的临床疗效和不良反应。方法将患者随机分为两组,治疗组口服软肝胶囊,辅以西医常规护肝、对症支持治疗,对照组仅予西医常规治疗,均以3个月为1疗程,共治疗1～2个疗程后评效。结果治疗组总有效率高于对照组;两组治疗后中医证候积分及肝功能均明显改善,治疗组优于对照组;治疗组治疗后肝纤维化指标、影像学检测均明显改善,对照组无明显改善。结论软肝胶囊具有明显的抗肝纤维化、逆转肝纤维化、延缓肝硬化进程、护肝、降酶、改善临床症状的作用。

解析肝病治疗仪治疗慢性肝病肝纤维化疗效观察

目的:深入分析肝病治疗仪在进行慢性肝病纤维化治疗中所产生的积极意义。方法:选择在我院进行肝病治疗的48例患者作为实验对象,随机分成两个组别对照实验,各组皆为24例患者,对照组使用常规的治疗方式,治疗组则应用 WLGY -801 肝病治疗仪进行治疗,对比两组患者的治疗效果。结果 治疗组总有效率为83.33%明显高于对照组66.67%( P<0.05),经过对比发现,两组病情均得到环节。治疗组在经过治疗之后,患者的肝纤维化指标得到明显改善,而对照组并无明显变化。结论:肝病治疗仪对于慢性肝纤维化病症治疗的效果比较明显,毒副作用比较小,具备较高的安全性。

肝病治疗仪治疗慢性肝病肝纤维化疗效观察

目的观察肝病治疗仪治疗慢性肝病肝纤维化的临床疗效。方法 48例患者随机分为两组各24例,对照组采用常规治疗,治疗组加用WLGY-801肝病治疗仪治疗,观察两组疗效。结果治疗组总有效率为83.33%明显高于对照组66.67%(P<0.05),与治疗前相比,两组肝功能和中医症状积分均明显改善,但治疗组疗效优于对照组(P<0.05)。治疗组肝纤维化指标治疗后明显改善(P<0.05),对照组无明显改善(P>0.05),治疗组明显优于对照组(P<0.05)。结论肝病治疗仪治疗慢性肝病肝纤维化显示了较好的疗效,无明显毒副作用,安全可靠。

慢性肝病“肝肾精虚”证的客观量化标准

目的:建立慢性肝病"肝肾精虚"证的客观量化指标体系与诊疗标准,提高中医药防治慢性肝病的诊疗水平、临床疗效和服务能力。方法:采用肝损伤与肝再生的现代生物学指标作为考察"肝肾精虚"证的客观量化指标,使"肝肾精虚"的"隐性证候"成为可以准确把握的"显性证候"。结果:建立以肝脏组织学损伤、肝功能减退、再生障碍或紊乱等生物学指标为基础的"肝肾精虚"证的客观量化指标体系及诊疗标准,据此对慢性肝病"肝肾精虚"证的演变规律进行动态监测,判断预后和指导辨证论治。结论:慢性肝病"肝肾精虚"证的客观量化研究是提高中医药防治慢性肝病的诊疗水平、临床疗效和服务能力的有效途径和方法,值得进一步深入研究。

甘露消毒丹加减治疗慢性肝病附加酒精性肝损伤临床观察

目的:运用经方甘露消毒丹加减治疗慢性肝病附加酒精性肝损伤,观察其疗效。方法:慢性肝病附加酒精性肝损伤患者60例,随机分为甘露消毒丹治疗组30例,护肝宁片观察组30例,疗程12周。对照治疗前后肝功主要指标ALT、AST、AKP、GGT、TBIL。结果:治疗组ALT、AST、GGT、TBIL均有明显下降,两组比较有显著性差异(P<0.05)。结论:甘露消毒丹加减治疗慢性肝病附加酒精性肝损伤者,能较好的改善患者的临床症状及肝功能,是治疗本病的有效经方。

83例肝病患者临床与肝组织病理学分析

目的通过对83例肝病患者的临床与肝组织病理学检查的对比研究,以提高临床诊断的准确性。方法用全自动生化分析仪进行血清生化指标检测,ELISA法检测HBV血清标志物,同时进行肝组织病理检查,检测肝组织HBsAg和HBcAg的表达。结果51例血清HBsAg阳性者肝细胞中均有HBsAg和/或HBcAg表达,32例血清HB-sAg阴性者有9例(28.1%)肝组织中有HBsAg和/或HBcAg表达。75例慢性肝病患者中ALT在各炎症分级组间差异无统计学意义(P>0.05),AST和TBIL在不同的肝脏炎症分级组间差异有统计学意义(P<0.05),且炎症分级越高,AST和TBIL升高越明显;ALT、AST、TBIL值在肝脏纤维化S2期最高。以病理诊断为标准,临床慢性肝炎轻度和中度的诊断准确率分别为61.9%(13/21)和62.5%(20/32),肝硬化的临床诊断准确率为40%。结论以肝组织病理检查为金标准,肝病临床诊断的准确率仍较低。为提高慢性肝病的临床确诊率,应尽可能行肝组织病理学检查。

NLRP3炎症小体在慢性肝病及肝损伤中的研究进展

NLRP3炎症小体广泛存在于肝实质和非实质细胞中,它可以感知和识别各种外源性和内源性危险信号,进而促进炎症介质的释放,触发免疫反应与细胞焦亡。近年来,随着对NLRP3炎症小体认识的逐步深入,其异常激活被认为与慢性肝病及肝损伤的发生、发展密切相关。因此,NLRP3炎症小体被认为是相关肝脏疾病治疗的一个重要分子靶点。本文主要讨论了NLRP3炎症小体的调控机制及其在酒精性肝病、非酒精性肝病、肝纤维化、药物性肝损伤中的相关研究进展,并总结了NLRP3炎症小体相关靶点抑制剂在慢性肝病及肝损伤中的应用,从而为NLRP3炎症小体在慢性肝病及肝损伤中的相关研究和新药开发提供理论依据和参考。

Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection

Objective： To observe the recurrence and prognosis of hepatocellular carcinoma （HCC） patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin α1 （Tα1） postoperatively. Methods： From Jan. 2000 to Dec. 2003, 70 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospectively divided into two groups： control group （n=35） received hepatectomy only; treatment group （n=35） received hepatectomy and lamivudine plus Tα1 therapy postoperatively. The suppression of HBV-DNA, HBeAg seroconverted rate, tumor recurrent rate and the median survival for the two groups were observed and calculated. Results： In treatment group and control group, the 2-year HBV-DNA suppression rate was 100% vs. 4% （P=0.0000）; HBeAg seroconverted rate was 73.0% vs. 7.5% （P〈0.05）; the recurrent rate was 10.0 vs 6.5 months （P=0.0032）; the median survival time was 12.5 vs. 6.0 months （P=0.0023）, respectively. Conclusion： Antivirus therapy using lamivudine and Tα1 postoperatively may suppress the HBV reaction, delay the recurrent time and prolong the survival for HCC patients coexisting chronic HBV infection with active virus replication.

Telbivudine:A new treatment for chronic hepatitis B

Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15%-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade merits to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. Approved drugs for chronic hepatitis B treatment include： standard interferon- alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. Unfortunately, these agents are not effective in all patients and are associated with distinct side effects. Interferons have numerous side effects and nucleoside or nucleotide analogues, which are well tolerated, need to be used for prolonged periods, even indefinitely. However, prolonged treatment with nucleoside or nucleotide analogues is associated with a high rate of resistance. Telbivudine is a novel, orally administered nucleoside analogue for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogues, Telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent activity against hepatitis B with a significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment. Telbivudine has been generally well tolerated, with a low adverse effect profile, and at its effective dose, no dose- limiting toxicity has been observed. Telbivudine is one of the most potent antiviral agents for chronic hepatitis B virus and was approved by the FDA in late 2006.

Selection criteria for liver resection in patients with hepatocellular carcinoma and chronic liver disease

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with an annual occurrence of one million new cases. An etiologic association between HBV infection and the development of HCC has been established with a relative risk 200-fold greater than in non-infected individuals. Hepatitis C virus is also proving an important predisposing factor for this malignancy with an incidence rate of 7% at 5 years and 14% at 10 years. The prognosis depends on tumor stage and degree of liver function, which affect the tolerance to invasive treatments. Although surgical resection is generally accepted as the treatment of choice for HCC, new treatment strategies, such as local ablative therapies, transarterial embolization and liver transplantation, have been developed nowadays. With increasing detection of small HCCs from screening programs for cirrhotic patients, it is foreseen that locoregional therapy will play an important role in the near future.

Hepatic steatosis as a possible risk factor for the development of hepatocellular carcinoma after eradication of hepatitis C virus with antiviral therapy in patients with chronic hepatitis C

AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.

Clinical features and management of autoimmune hepatitis

Autoimmune hepatitis(AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis.Its clinical manifestations are highly variable and some-times follow a fluctuating course.Diagnosis is based on characteristic histologic,clinical,biochemical and sero-logical findings.Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required.Liver transplan-tation is generally successful in patients with decompen-sated cirrhosis unresponsive to or intolerant of medical therapy.

Mechanism of T cell hyporesponsiveness to HBcAg is associated with regulatory T cells in chronic hepatitis B

AIM： To study the mechanisms of hyporesponsiveness of HBV-specific CD4^＋ T cells by testing TH1 and TH2 commitment and regulatory T cells. METHODS： Nine patients with chronic hepatitis B were enrolled. Peripheral blood mononuclear cells were stimulated with HBcAg or HBsAg to evaluate their potential to commit to TH1 and TH2 differentiation. HBcAg-specific activity of regulatory T cells was evaluated by staining with antibodies to CD4, CD25, CTLA-4 and interleukin-10. The role of regulatory T cells was further assessed by treatment with anti-interleukin-10 antibody and depletion of CD4^＋CD25^＋ cells. RESULTS： Level of mRNAs for T-bet, IL-12R β2 and IL-4 was significantly lower in the patients than in healthy subjects with HBcAg stimulation. Although populations of CD4^＋CD25^highCTLA-4^＋ T cells were not different between the patients and healthy subjects, IL-10 secreting cells were found in CD4^＋ cells and CD4^＋CD25^＋ cells in the patients in response to HBcAg, and they were not found in cells which were stimulated with HBsAg. Addition of anti-IL-10 antibody recovered the amount of HBcAgspecific TH1 antibody compared with control antibody （P 〈 0.01, 0.34% ± 0.12% vs 0.15% ± 0.04%）. Deletion of CD4^＋CD25^＋ T cells increased the amount of HBcAgspecific TH1 antibody when compared with lymphoo/tes reconstituted using regulatory T cells （P 〈 0.01, 0.03% ± 0.02% vs 0.18% ± 0.05%）.CONCLUSION： The results indicate that the mechanism of T cell hyporesponsiveness to HBcAg includes activation of HBcAg-induced regulatory T cells in contrast to an increase in TH2-committed cells in response to HBsAg.

Gut flora and bacterial translocation in chronic liver disease

Increasing evidence suggests that derangement of gut flora is of substantial dinical relevance to patients with cirrhosis. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen, in particular, predispose to an increased potential for bacterial infection in this group. Recent studies suggest that, in addition to their role in the pathogenesis of overt infective episodes and the clinical consequences of sepsis, gut flora contributes to the pro-inflammatory state of cirrhosis even in the absence of overt infection. Furthermore, manipulation of gut flora to augment the intestinal content of lactic acid-type bacteria at the expense of other gut flora species with more pathogenic potential may favourably influence liver function in cirrhotic patients. Here we review current concepts of the various inter-relationships between gut flora, bacterial translocation, bacterial infection, pro-inflammatory cytokine production and liver function in this group.

Epidemiology of Hepatitis B and Associated Liver Diseases in China

Hepatitis B virus (HBV) infection has long been a critical public health challenge in China. National surveys revealed a prevalence of approximate 10% for chronic HBV infection in general population. HBV has been the leading cause of chronic hepatitis, cirrhosis, and liver cancers in Chinese population and a common pathogen of acute viral hepatitis. Meanwhile, the epidemic provided important opportunities to research the natural history, public health impact, and therapeutic and preventive interventions for HBV in China. In this review, we summarized the selected key epidemiological studies since 1970s regarding HBV infection and its associated liver diseases in China, and provided considerations for future research, prevention and treatment of HBV.

Development of Novel Therapeutics for Chronic Hepatitis B

Chronic infection of hepatitis B virus (HBV) presents one of the serious public health challenges worldwide. Current treatment of chronic hepatitis B (CHB) is limited, and is composed of interferon and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). Interferon is poorly tolerated and is only responsive in a small fraction of CHB patients and NRTIs often face the problem of emergence of drug resistance during long-term treatment. The current treatment of CHB can be improved in several ways including genotyping mutations associated with drug resistance before treatment to guide the choice of NRTIs and suitable combinations among NRTIs and interferon. It is important to continue research in the identification of novel therapeutic targets in the life cycle of HBV or in the host immune system to stimulate the development of new antiviral agents and immunotherapies. Several antiviral agents targeting HBV entry, cccDNA, capsid formation, viral morphogenesis and virion secretion, as well as two therapeutic vaccines are currently being evaluated in preclinical studies or in clinical trials to assess their anti-HBV efficacy.

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA more than 10^5 copies/mL.Compared to HBeAg positive patients, HBeAg negative patients are older and have a lower HBV DNA level and a longer HBV infection history. There is no significant difference in sex ratio, ALT and AST levels and liver histology between the two groups.

A specific gene-expression signature quantifies the degree of hepatic fibrosis in patients with chronic liver disease

AIM： To study a more accurate quantification of hepatic fibrosis which would provide dinically useful information for monitoring the progression of chronic liver disease. METHODS： Using a cDNA microarray containing over 22000 clones, we analyzed the gene-expression profiles of non-cancerous liver in 74 patients who underwent hepatic resection. We calculated the ratio of azanstained： total area, and determined the morphologic fibrosis index （MFI）, as a mean of 9 section-images. We used the MFI as a reference standard to evaluate our method for assessing liver fibrosis. RESULTS： We identified 39 genes that collectively showed a good correlation （r 〉 0.50） between geneexpression and the severity of liver fibrosis. Many of the identified genes were involved in immune responses and cell signaling. To quantify the extent of liver fibrosis, we developed a new genetic fibrosis index （GFI） based on gene-expression profiling of 4 clones using a linear support vector regression analysis. This technique, based on a supervised learning analysis, correctly quantified the various degrees of fibrosis in both 74 training samples （r = 0.76, 2.2% vs 2.8%, P 〈 0.0001） and 12 independent additional test samples （r = 0.75, 9.8% vs 8.6%, P 〈 0.005）. It was far better in assessing liver fibrosis than blood markers such as prothrombin time （r = -0.53）, type IV collagen 7s （r = 0.48）, hyaluronic acid （r = 0.41）, and aspartate aminotransferase to platelets ratio index （APRI） （r = 0.38）. CONCLUSION： Our cDNA microarray-based strategy may help clinicians to precisely and objectively monitor the severity of liver fibrosis.

Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis

Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.