Hepatitis C virus‐infected patients with a persistently normal alanine aminotransferase: do they exist and is this really a group with mild disease?

Summary.  Opinion varies on whether or not hepatitis C virus (HCV) infected patients with persistently normal aminotransferase (PNALT) levels represent a group with mild disease. To evaluate the risk of ALT flare and fibrosis progression in patients with PNALT followed up as part of the Trent HCV cohort. Treatment-naïve patients with an elevated ALT ( n  = 1140) or PNALT, the latter defined as either an ALT ≤ 30 IU/L ( n  = 43) or an ALT ≤ 40 IU/L ( n  = 87) on ≥2 occasions in the 6 months following diagnosis, and no ALT > 40 U/L were included. The likelihood of maintaining a PNALT ≤ 30 IU/L was 42.2% and PNALT ≤ 40 IU/L 41.7% at 3 years. The Ishak fibrosis score was ≥3 in 3.7%, 8.3% and 29.6% of patients with PNALT ≤ 30 IU/L, PNALT ≤ 40 IU/L and elevated ALT, respectively. Fibrosis progression between paired biopsies was similar for patients with PNALT ≤ 30 IU/L (0.33 ± 0.94 Ishak fibrosis points/year), PNALT ≤ 40 IU/L (0.35 ± 0.82) and elevated ALT (0.19 ± 0.48). The majority of those defined as PNALT subsequently have an abnormal ALT. They have a similar risk of disease progression to other HCV infected patients and, therefore, warrant the same consideration with regard to treatment.     

Hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum alanine aminotransferase levels

Chronic hepatitis B patients with high-normal serum ALT (levels of 0.5-1x upper limit of normal) are still at risk of liver disease progression. We thus investigated the correlation between serum ALT level and hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum ALT level (PNALT). Baseline clinical and virological features of 414 HBeAg-negative carriers, including 176 (42.5%) with low-normal ALT (levels of less than 0.5x upper limit of normal) and 238 (57.5%) with high-normal ALT, were compared. Compared with HBV carriers with low-normal ALT, those with high-normal ALT were older (41 vs. 37 years, P<0.001) and had a greater frequency of serum HBV DNA level>10(4) copies/ml (63.4% vs. 47.5%, P<0.001) as well as a higher prevalence of basal core promoter T1762/A1764 mutant (36.5% vs. 24.2%, P=0.01). Multivariate analysis showed that factors associated with a high-normal serum ALT level included male sex [odds ratio (OR), 1.82; 95% confidence interval (CI), 1.10-3.01, P=0.019], increasing age (OR, <30 years: 1, reference; 30-39 years: 2.43, 95% CI, 1.18-5.03, P=0.016; 40-49 years: 4.22, 95% CI, 1.99-8.93, P<0.001; >or=50 years: 4.06, 95% CI, 1.69-9.78, P=0.002) and serum HBV DNA level>10(4) copies/ml (OR, 1.83; 95% CI, 1.07-3.13, P=0.027). CONCLUSION: HBeAg-negative patients with persistently normal ALT are not a homogenous group, and those with high-normal ALT share some of the characteristics that have been associated with adverse long-term outcomes.     

Centrilobular necrosis in acute presentation of Japanese patients with type 1 autoimmune hepatitis

AIM:To compare clinicopathological features of acute presentation of type 1 autoimmune hepatitis(AIH) with or without centrilobular necrosis(CN).METHODS:Our study comprised 41 patients with biopsy-proven acute presentation(acute exacerbation phase 36,acute hepatitis phase 5) of type 1 AIH at our hospital from 1975 to 2009.Elevated serum alanine aminotransferase(ALT)(> 5x upper limit of normal) identified acute presentation of the disease.We compared clinicopathological features of these AIH patients with or without CN.The data used for analysis included patient background(age,sex,type of disease,presence of complications with other autoimmune diseases,human leukocyte antigen,and International Autoimmune Hepatitis Group score),clinical parameters at presentation(ALT,alkaline phosphatase,IgG,anti-nuclear antibodies,and anti-smooth muscle antibodies),histology and therapy.RESULTS:CN was found in 13(31.7%) patients with acute presentation(acute exacerbation phase 10,acute hepatitis phase 3) of AIH.Serum IgG levels of patients with CN were significantly lower than those of patients without CN(mean:2307 mg/dL vs 3126 mg/dL,P < 0.05),while antinuclear antibody-negative rates were significantly higher(30.7%vs 3.5%,P < 0.05).However,other clinical features were similar between the two groups.The frequency of advanced fibrosis in patients with CN was significantly lower than in patients without CN(F0-2:84.6% vs 35.7%,F3-4:15.4% vs 64.3%,P < 0.05).Other histological features were similar between the two groups.Although there was no significant difference between groups when evaluated using the revised original score(12 vs 14),the simplified AIH score of patients with CN was significantly lower(6 vs 7,P < 0.05).Frequency of DR4 was similar between patients with and without CN.CONCLUSION:CN is observed in both Japanese patients with acute hepatitis phase and acute exacerbation phase of type 1 AIH,although AIH with CN often shows clinical features of the genuine acute form.     

Alcohol,postprandial plasma glucose,and prognosis of hepatocellular carcinoma

AIM:To identify factors associated with prognosis of hepatocellular carcinoma(HCC) after initial therapy.METHODS:A total of 377 HCC patients who were newly treated at Katsushika Medical Center,Japan from January 2000 to December 2009 and followed up for > 2 years,or died during follow-up,were enrolled.The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis.A similar analysis was performed in 282 patients with tumor stage T1-T3.Additionally,factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence.Finally,214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels,and differences in their causes of death were examined.RESULTS:On multivariate Cox proportional hazards regression analysis,the following were significantly associated with survival:underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C,hazard ratio(HR):0.603,95% CI:0.417-0.874,P = 0.0079],HCC stage(T1/T2 vs T3/T4,HR:0.447,95% CI:0.347-0.576,P < 0.0001),and mean postprandial plasma glucose after initial therapy(< 200 vs ≥ 200 mg/dL,HR:0.181,95% CI:0.067-0.488,P = 0.0008).In T1-T3 patients,uninterrupted alcohol consumption after initial therapy(no vs yes,HR:0.641,95% CI:0.469-0.877,P = 0.0055) was significant in addition to underlying liver disease stage(non-cirrhosis/Child-Pugh A vs B/C,HR:0649,95% CI:0.476-0.885,P = 0.0068),HCC stage(T1 vs T2/T3,HR:0.788,95% CI:0.653-0.945,P = 0.0108),and mean postprandial plasma glucose after initial therapy(< 200 mg/dL vs ≥ 200 mg/dL,HR:0.502,95% CI:0.337-0.747,P = 0.0005).In patients without local recurrence,time from initial to subsequent therapy for newly emerging HCC was significantly longer in the "postprandial glucose within 200 mg/dL group" than the "postprandial glucose > 200 mg/dL group"(l     

聚乙二醇干扰素α-2a联合利巴韦林标准抗病毒治疗慢性丙型肝炎患者疗效再研究*

目的 分析比较应用聚乙二醇干扰素α-2a联合利巴韦林(RBV)抗病毒治疗慢性丙型肝炎(CHC)患者的疗效。方法 2017年2月～2020年4月我院收治的102例CHC患者,采用随机数字表法将其分为对照组50例和观察组52例,分别给予利巴韦林(RBV)联合普通α-2b干扰素治疗或应用RBV联合聚乙二醇干扰素α-2a治疗6个月。采用实时荧光定量PCR法检测血清HCV RNA载量,使用流式细胞仪检测外周血T淋巴细胞亚群。结果 观察组治疗结束时病毒学应答率(ETVR)为88.5%,显著高于对照组的62.0%(P＜0.05),持续病毒学应答率(SVR)为82.7%,显著高于对照组的62.0%(P＜0.05);在治疗结束时,观察组血清ALT水平为(36.8±4.1)U/L,显著低于对照组【(61.5±4.3)U/L,P＜0.05】,血清AST水平为(38.4±3.4)U/L,显著低于对照组【(51.6±3.6)U/L,P＜0.05】;在治疗4 w、12 w和24 w,观察组血清HCV RNA水平分别为(4.6±1.2)Ig IU/mL、(4.1±1.1)Ig IU/mL和 (3.6±0.9)Ig IU/mL,显著低于对照组【分别为(5.1±1.1)Ig IU/mL、(4.7±1.2)Ig IU/mL和(4.2±1.0)Ig IU/mL,P＜0.05】;在治疗结束时,观察组外周血CD3⁺细胞百分比为(73.8±7.5)%,显著高于对照组【(65.6±6.9)%,P＜0.05】,CD4⁺细胞百分比为(49.5±6.3)%,显著高于对照组【(34.8±5.8)%,P＜0.05】,而CD8⁺细胞百分比为(17.6±3.8)%,显著低于对照组【(25.9±4.6)%,P＜0.05】,CD4⁺/CD8⁺细胞比值为(1.0±0.2),显著低于对照组【(1.4±0.3),P＜0.05】。结论 应用聚乙二醇干扰素α-2a联合RBV抗病毒治疗CHC患者疗效尚可,在不能应用直接抗病毒药物的情况下继续应用标准疗法仍可获得一定的抗病毒治疗效果。     

Longitudinal changes in serum HBV DNA levels and predictors of progression during the natural course of HBeAg-negative chronic hepatitis B virus infection

Summary.  We evaluated the longitudinal changes of viraemia and predictors of progression in a prospectively followed cohort of 150 untreated patients with HBeAg-negative chronic hepatitis B virus (HBV) infection. According to the first year of follow-up, 85 patients were classified into inactive carrier state and 65 into chronic hepatitis B (CHB). Serum HBV DNA levels were determined at baseline in all patients, at year-1 in carriers or last pretherapy visit in CHB patients and during alanine aminotransferase (ALT) elevations in carriers progressing to CHB. HBV DNA levels at any occasion were ≥80, ≥2000 or ≥20 000 IU/mL in 81%, 23% or 0% of carriers and 100%, 95% or 83% of CHB patients. The cumulative progression rate from carrier to CHB was 11%, 16%, 24% at 2-, 3-, 4 years and was independently associated with higher baseline ALT (always within traditional normal range) and baseline HBV DNA ≥2000 or ≥5000 IU/mL. In 12 carriers progressed to CHB, HBV DNA increased by >1 log₁₀ IU/mL. During 7.5 months of median follow-up, HBV DNA change ≥1 log₁₀ IU/mL was observed in 49% of CHB patients. In conclusion, serum HBV DNA levels are detectable in the majority of inactive HBV carriers exceeding 2000 IU/mL in only 23% and 20 000 IU/mL in none of them. Carriers have approximately 15% 3-year risk of progression to CHB, which is associated with higher baseline ALT and viraemia ≥2000–5000 IU/mL, and thus should be closely followed. Approximately 20% of HBeAg-negative CHB patients have HBV DNA <20 000 IU/mL with fluctuations >1 log₁₀ occurring in many of them.     

乙型肝炎肝硬化患者外周血dNLR、MLR和SII变化及其临床意义分析

目的 探讨乙型肝炎肝硬化患者外周血衍生中性粒细胞/淋巴细胞比值(dNLR)、单核细胞/淋巴细胞比值(MLR)和系统性免疫性炎症指数(SII)变化及其临床意义。方法 2019年1月～2021年12月我院收治的乙型肝炎肝硬化患者85例和慢性乙型肝炎(CHB)患者85例,采用ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)和IL-17。常规检测血细胞计数。结果 乙型肝炎肝硬化患者血清TBIL和INR分别为(43.1±8.5)μmol/L和(1.3±0.6),显著高于【分别为(19.4±3.0)μmol/L和(1.1±0.2),P<0.05】,而血清ALT和ALB水平分别为(63.6±8.2)U/L和(30.8±4.6)g/L,显著低于CHB组【分别为(104.1±14.9)U/L和(39.0±8.1)g/L,P<0.05】;肝硬化患者血清TNF-α、IL-6和IL-17水平分别为(88.7±11.6)pg/mL、(95.6±12.5)pg/mL和(45.6±8.9)ng/mL,显著高于CHB组【分别为(68.2±9.3)pg/mL、(67.9±9.5)p...     

Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort

AIM:To investigate the evolution of disease phenotypein adult and pediatric onset Crohn’s disease(CD) populations,diagnosed between 1977 and 2008.METHODS:Data of 506 incident CD patients were analyzed(age at diagnosis:28.5 years,interquartile range:22-38 years).Both in-and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database,which included incident patients diagnosed between January 1,1977 and December 31,2008 in adult and pediatric onset CD populations.Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis.RESULTS:Among this population-based cohort,seventy-four(12.8%) pediatric-onset CD patients were identified(diagnosed ≤ 17 years of age).There was no significant difference in the distribution of disease behavior between pediatric(B1:62%,B2:15%,B3:23%) and adult-onset CD patients(B1:56%,B2:21%,B3:23%) at diagnosis,or during follow-up.Overall,the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5-and 10-years of follow-up.Similarly,time to change in disease behaviour from non stricturing,non penetrating(B1) to complicated,stricturing or penetrating(B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis.Calendar year of diagnosis(P = 0.04),ileal location(P < 0.001),perianal disease(P < 0.001),smoking(P = 0.038) and need for steroids(P < 0.001) were associated with presence of,or progression to,complicated disease behavior at diagnosis and during follow-up.A change in disease location was observed in 8.9% of patients and it was associated with smoking status(P = 0.01),but not with age at diagnosis.CONCLUSION:Long-term evolution of disease behavior was not different in pediatric-and adult-onset CD patients in this     

肝细胞癌进展:代谢综合征相关危险因素研究

目的 分析代谢综合征(MetS)对肝细胞癌(HCC)进展的影响。方法 2013年1月～2021年12月中山大学附属第八医院肝胆胰外科收治的HCC患者203例,其中合并MetS者89例,未合并者114例。将存在肝内转移、血管侵犯、肿瘤最大径＞5 cm、淋巴转移和远处转移等肿瘤生物学特征定义为肿瘤进展,应用多因素Logistic回归分析影响肝癌进展的独立危险因素。结果 合并MetS组血糖、血清总胆红素、高密度脂蛋白和甘油三酯水平分别为(6.6±1.4)mmol/L、(48.3±16.2)μmol/L、(0.9±0.3)mmol/L和(1.5±0.8)mmol/L,与未合并组比,差异显著【分别为(5.4±1.9)mmol/L、(22.9±7.2)μmol/L、(1.2±0.3)mmol/L和(1.0±0.5)mmol/L,P<0.05】;合并组HBV感染、发生肿瘤肝内转移、淋巴转移、中心型肥胖和血压升高发生率分别为73.0%、52.8%、32.6%、78.7%和69.7%,与未合并组比,差异显著(分别为86.8%、29.8%、20.2%、39.5%和29.8%,P＜0.05);合并MetS组分患者更容易发生肿瘤进展(P<0.05),经多因素Logistic回归分析显示,低HDL、血糖升高和血压升高是HCC发生肿瘤进展的独立危险因素(P<0.05)。结论 MetS促进HCC患者肝内肿瘤转移和淋巴结转移,导致肿瘤进展,而控制MetS组分是否能帮助抑制或减少肿瘤进展,值得研究。     

替诺福韦治疗不同HBV基因型慢性乙型肝炎患者疗效研究*

目的 探讨替诺福韦治疗不同HBV基因型感染的慢性乙型肝炎(CHB)患者的疗效和血清金属硫蛋白(MT)、白细胞介素29(IL-29)和外周血淋巴细胞程序性死亡受体-1(PD-1)表达的变化。方法 2017年1月～2020年11月我院诊治的CHB患者119例,均接受替诺福韦治疗。采用ELISA法检测血清MT和IL-29水平,使用流式细胞仪检测外周血T 淋巴细胞PD-1表达水平。结果 在本组119例CHB患者中,检出HBV B基因型31例(26.1%),C基因型77例(64.7%),B/C 混合基因型11例(9.2%);基线资料比较,B基因型CHB患者血清ALT和AST水平分别为(154.1±46.7)U/L和(83.3±26.8)U/L,显著高于C基因型患者【分别为(135.8±40.3)U/L和(68.5±20.6)U/L,P＜0.05】或B/C混合基因型患者【分别为(138.9±50.2)U/L和(71.6±23.9)U/L,P＜0.05】,而血清HBV DNA水平为(6.7±1.1)lg copies/ml,显著低于C基因型感染患者【(7.8±1.4)lg copies/ml,P＜0.05】或B/C混合型感染者【(7.4±1.0)lg copies/ml,P＜0.05】;在治疗24 w和48 w末,三组血清ALT复常率无显著性差异(P>0.05),而B基因型和C基因型感染患者血清HBV DNA阴转率分别为96.8%和96.8%,和88.3%和93.5%,均显著高于B/C混合型感染患者(分别为63.6%和81.8%,P<0.05);在治疗48 w,B基因型CHB患者血清MT水平显著高于C基因型或B/C基因型(P＜0.05),血清IL-29水平显著高于C基因型(P＜0.05),而外周血CD4⁺和CD8⁺T淋巴细胞表面PD-1表达水平显著低于C基因型或B/C混合基因型患者(P＜0.05)。结论 不同HBV基因型感染的CHB患者可能对替诺福韦治疗的疗效存在差异,深入了解这些差异可能对研究不同基因型病毒感染患者临床转归有帮助。     

Prognostic role of neutrophil-lymphocyte ratio in operable esophageal squamous cell carcinoma

AIM: To determine the prognostic significance of preoperative serum neutrophil-lymphocyte ratio(NLR) in esophageal squamous cell carcinoma(ESCC).METHODS: Data from 371 eligible patients with ESCC who had undergone surgery with curative intent at our institution between October 2000 and May 2007 were retrospectively recruited for analysis. The cutoff value of NLR was 3.0 as determined by the receiver operating characteristic curve, which discriminated between survival and death; the area under the curve was 0.709, and the sensitivity and specificity were 66.1% and 69.1%, respectively, at the cutoff point. The correlation between the NLR and clinicopathological characteristics was analyzed using a χ2 test. The prognostic influence of the NLR and other clinicopathological factors on cancer-specific survival(CSS) and recurrence-free survival(RFS) was studied using the Kaplan-Meier method. To evaluate the independent prognostic value of NLR, multivariate Cox regression models were applied.RESULTS:The median age of the patients was 57.0years,and 276/371(74.4%)patients were male.The NLR was≤3.0 in 80.1%(297/371)of the patients,and the remaining 19.9%(74/371)had an NLR3.0.Median postoperative follow-up was 66.0 mo[interquartile range(IQR):49.0-76.0 mo],with a follow-up rate of 94%.Follow-up was not significantly different between patients with an NLR≤and3.0(63.13±1.64 vs 61.52±3.66,P=0.711).However,higher preoperative serum NLR was associated with significantly increased risks of higher pathological tumor status(P=0.007).A significant,independent association between high preoperative serum NLR and poor clinical outcome was identified in a multivariate analysis for CSS(HR=1.591;P=0.007)and RFS(HR=1.525;P=0.013).Moreover,when patients were stratified by pathological tumor-node-metastasis(TNM)staging,the adverse effects of preoperative serum NLR on CSS(HR=2.294;P=0.008)and RFS(HR=2.273;P=0.008)were greatest in those patients with stageⅢA disease.CONCLUSION:Preoperative serum NLR is a useful prognostic marker to complement TNM staging for operable ESCC patients,particularly in patients with stageⅢA disease.     

Vascular resection in pancreatic adenocarcinoma with portal or superior mesenteric vein invasion

AIM:To evaluate long-term survival after the Whipple operation with superior mesenteric vein/portal vein resection(SMV/PVR)in relation to resection length.METHODS:We evaluated 118 patients who underwent the Whipple operation for pancreatic adenocarcinoma at our Department of Hepatobiliary Pancreatic Surgery between 2005 and 2010.Fifty-eight of these patients were diagnosed with microscopic PV/SMV invasion by frozen-section examination and underwent SMV/PVR.In 28 patients,the length of SMV/PVR was≤3 cm.In the other 30 patients,the length of SMV/PVR was>3cm.Clinical and survival data were analyzed.RESULTS:SMV/PVR was performed successfully in 58patients.There was a significant difference between the two groups(SMV/PVR≤3 cm and SMV/PVR>3 cm)in terms of the mean survival time(18 mo vs 11 mo)and the overall 1-and 3-year survival rates(67.9%and14.3%vs 41.3%and 5.7%,P<0.02).However,there was no significant difference in age(64 years vs 58years,P=0.06),operative time(435 min vs 477 min,P=0.063),blood loss(300 mL vs 383 mL,P=0.071)and transfusion volume(85.7 mL vs 166.7 mL,P=0.084)between the two groups.CONCLUSION:Patients who underwent the Whipple operation with SMV/PVR≤3 cm had better long-term survival than those with>3 cm resection.     

DAAs治疗丙型肝炎肝硬化患者疗效及安全性研究*

目的 探讨应用直接抗病毒药物(DAAs)治疗慢性丙型肝炎肝硬化(CHC-C)患者的安全性和有效性。方法 2016年3月~2017年10月在我院接受DAAs治疗的CHC-C患者30例,感染HCV基因型均为1b型。将患者分为3组,每组10例。给予A组索非布韦联合利巴韦林,给予B组索非布韦联合雷迪帕韦和利巴韦林治疗,给予C组索非布韦联和达卡他韦合利巴韦林治疗,所有患者均治疗12周。采用荧光PCR法检测血清HCV RNA,使用日立008AS全自动生化分析仪检测血生化指标,采用基因芯片法 或PCR探针法检测HCV基因分型。按照丙型肝炎防治指南的标准,比较各组快速病毒学应答(RVR)、早期病毒学应答(EVR) 、治疗结束时病毒学应答(ETVR)和持续病毒学应答(SVR)。结果 B组和C组RVR和ETVR均为100%,均显著高于A组的40%和50%,差异有统计学意义(P<0.05);在DAAs治疗结束时,A组、B组和C组血清ALT水平分别为(24.2±6.7)IU/L、(22.3±5.6)IU/L和(25.3±4.6)IU/L,血清AST水平分别为(23.2±8.1)IU/L、(24.6±3.8)IU/L和(28.4±4.8)IU/L,无显著性差异(P>0.05);三组血清白蛋白和肾功能指标变化无显著性差异(P>0.05);血清CK水平分别为(63.3±11.8)U/L、(68.5±8.9)U/L和(62.1±10.2) U/L,也无显著性差异(P>0.05);A组出现恶心7例、乏力1例、头痛1例、心悸1例,B组出现恶心4例、乏力3例、头痛1例、心悸1例、皮疹1例,C组出现恶心5例、乏力2例、头痛1例、心悸1例和皮疹1例。结论 DAAs治疗基因1b型HCV感染引发的CHC-C患者近期疗效较好,安全,值得进一步观察。     

索磷布韦/达拉他韦治疗慢性丙型肝炎患者疗效及安全性分析：一项真实世界研究

目的 观察应用索磷布韦/达拉他韦联合或不联合利巴韦林治疗慢性丙型肝炎（CHC）和丙型肝炎肝硬化（LC）患者的疗效和安全性。方法 2016年5月~2017年5月收治的丙型肝炎LC患者129例和CHC患者311例,分别给予索磷布韦/达拉他韦联合利巴韦林或索磷布韦/达拉他韦治疗12周,停药后随访12周。观察停药后12周持续性病毒学应答（SVR12）、生化学应答、肝硬度测量（LSM）和治疗期间不良反应发生情况。结果 治疗2周时,LC组血清TBIL、ALT 和AST 水平分别为（18.10±3.46） μmol/L、（32.48±9.97） IU/L和（31.99±6.65） IU/L,显著低于基线时水平【分别为（20.98±28.64） μmol/L、（97.76±106.43） IU/L和（72.47±80.81） IU/L,P<0.05】,CHC组分别为（20.15±3.48） μmol/L、（35.18±18.47） IU/L和（35.05±13.22） IU/L,显著低于基线时水平【分别为（24.07±18.12） μmol/L、（91.42±54.56） IU/L和（81.06±40.45） IU/L,P<0.05】;CHC组血清HCV RNA为（1.83±2.88） lg IU/ml,LC组为（1.67±2.34） lg IU/ml,显著低于基线时水平【分别为（6.12±1.19） lg IU/ml和（5.91±1.17）lg IU/ml,P<0.01】;CHC组LSM为（8.09±0.90）kPa,LC组为（13.32±1.47） kPa,显著低于基线时水平【分别为（11.81±3.33） kPa和（17.56±9.86） kPa,P<0.01】;两组不同基因型感染者SVR均在94%以上;多因素回归分析显示基线肝硬化或复治是不能获得SVR12的高危因素;主要不良反应为乏力和头痛。讨论 应用索磷布韦/达拉他韦联合利巴韦林治疗丙型肝炎病毒感染患者可获得极高的SVR12和生化学应答率,显著改善肝纤维化程度,且具有良好的安全性。     

Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction

AIM: To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI). METHODS: Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured. RESULTS: Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria.     

恩替卡韦治疗慢性乙型肝炎合并NAFLD患者临床疗效研究

目的 观察应用恩替卡韦治疗慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)患者临床疗效。方法 2018年3月～2020年10月我院诊治的118例CHB患者,其中合并NAFLD患者42例,均接受恩替卡韦治疗12个月。使用流式细胞仪检测外周血CD4⁺和CD8⁺T淋巴细胞亚群水平,并计算CD4⁺/CD8⁺细胞比值,使用FibroScan 502型肝脏弹性检测仪检测肝脏受控衰减参数(CAP)。结果 在治疗12个月末,CHB合并NAFLD组血清天冬氨酸氨基转移酶、丙氨酸氨基转移酶(ALT)和γ-谷氨酰转肽酶及CAP水平分别为(72.3±8.9)U/L、(63.3±9.2)U/L、(76.2±9.8)U/L和(301.1±10.7)dB/m,均显著高于CHB组【分别为(43.2±7.6)U/L、(45.1±8.3)U/L、(48.8±7.7)U/L和(262.7±7.6)dB/m,P<0.05];合并NAFLD组血清总甘油三脂、胆固醇和低密度脂蛋白胆固醇水平分别为(3.5±0.7)mmol/L、...     

代谢相关性脂肪性肝病患者血脂分析*

目的 分析代谢相关性脂肪性肝病(MAFLD)患者血脂状况,观察应用血脂判断MAFLD程度的效能。方法 2021年1月～10月于辽宁中医药大学附属医院体检中心体检发现的MAFLD患者2210例,其中血脂正常组418例,血脂异常组1792例。建立受试者工作特征曲线(ROC),计算曲线下面积(AUC),评估血脂预测MAFLD脂肪变程度的效能。结果 血脂异常组体质指数为(32.8±10.8 )kg/m²,显著大于血脂正常组【(28.4±11.2) kg/m²,P＜0.05】,收缩压为(146.2±21.2 )mmHg,显著高于血脂正常组【(106.3±7.3 )mmHg,P＜0.05】,舒张压为(107.3±11.6 )mmHg,显著高于血脂正常组【(88.6±5.2)mmHg,P＜0.05】,血糖为(6.4±1.9)mmol/L,显著高于血脂正常组【(6.0±1.5)mmol/L,P＜0.05】,血清ALT和GGT水平分别为(42.2±23.8)U/L和(42.5±30.9 )U/L,均显著高于血脂正常组【分别为(38.3±13.7) U/L和(39.3±18.3 )U/L,P＜0.05】;血脂异常组轻度、中度和重度MAFLD患者血清TG、TC和LDL-C水平均显著高于血脂正常组,而血清HDL-C水平显著低于血脂正常组(P＜0.05);以HDL-C=0.84mmol/L为截断点,其AUC为0.72(P＜0.001),诊断轻度MAFLD的灵敏度为84.8%,特异度为52.8%;以TG=2.71mmol/L为截断点,其AUC为0.79(P＜0.001),诊断中度MAFLD的灵敏度为75.7%,特异度为74.4%;以TG=3.35mmol/L为截断点,其AUC为0.86(P＜0.001),诊断重度MAFLD的灵敏度为90.4%,特异度为73.9%。结论 MAFLD患者病程进展与血脂状况息息相关,并且对血糖和血压等也有较大的影响。综合肝脏超声和血生化检查,MAFLD合并血脂异常患者较血脂正常者病情更为严重。积极进行临床干预,阻断病情发展,将使患者获益。     

聚乙二醇化干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎肝硬化患者临床疗效研究*

目的 探讨应用聚乙二醇化干扰素α-2a联合利巴韦林治疗代偿期丙型肝炎肝硬化患者的临床疗效。方法 2003年1月~2016年12月我院就诊的代偿期丙型肝炎肝硬化患者122例,采用随机数字表法分成两组,每组61例。给予对照组常规护肝治疗,给予观察组聚乙二醇化干扰素α-2a联合利巴韦林治疗24~48 w。随访两组24 w。采用实时荧光定量RT-PCR法检测血清HCV RNA,采用全自动生化分析仪检测血生化指标,采用化学发光法检测血清层粘连蛋白（LN）、Ⅲ型前胶原（PC Ⅲ）、透明质酸（HA）,常规使用Fibroscan行肝脏硬度检测（LSM）。结果 在治疗结束时,观察组血清HCV RNA水平为（2.0±0.4） lg IU/ml,显著低于对照组【（3.8±1.3）lg IU/ml,P<0.05】;血清AST和ALT水平分别（46.03±24.05） U/L和（36.32±20.1） U/L,显著低于对照组【（78.7±21.1） U/L和（51.2±20.9） U/L,P<0.05）;观察组血清LN、PCⅢ和HA水平分别为（126.3±29.0）μg/L、（212.3±43.8）μg/L和（211.4±42.0）μg/L,均显著低于对照组【（140.3±32.1）μg/L、（267.5±39.8）μg/L和（329.6±68.4）μg/L,P<0.05】;观察组LSM为（13.6±2.4） kPa,显著低于对照组【（17.6±5.2）kPa,P<0.05】;在随访时发现,观察组血清ALT复常率和持续病毒学应答率（SVR）均显著高于对照组（分别为93.4%对45.9%和72.1%对9.8%,P<0.05）,而疾病进展发生率为3.3%,显著低于对照组的13.1%（P<0.05）。结论 应用聚乙二醇化干扰素α-2a联合利巴韦林抗病毒治疗代偿期丙型肝炎肝硬化患者可显著提高SVR,延缓肝纤维化进展,稳定肝功能指标。     

不同血清ALT水平的乙型肝炎病毒感染者肝纤维化指标变化

目的 研究不同血清谷丙转氨酶(ALT)水平的慢性HBV感染者肝纤维化指标的变化.方法 2018年4月～2020年4月我院诊治的68例慢性HBV感染者(HBV携带者21例,CHB患者47例),根据血清ALT水平不同将患者分为A组(ALT<40 U/L,n=21)、B组(40U/L≤ALT<80U/L,n=24)和C组(A...     

Efficacy of capecitabine and oxaliplatin regimen for extrahepatic metastasis of hepatocellular carcinoma following local treatments

AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in