Shear wave elastography results correlate with liver fibrosis histology and liver function reserve

AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. METHODS: Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. RESULTS: At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures: significantly lower with F4 (P = 0.037) and F3 (P = 0.032) as compared to F0 and significantly lower with F4 as compared to F2 (P = 0.032). CONCLUSION: SWE LSM shows a good correlation with histologic fibrosis grading and pharmacologic quantitative liver function reserve in experimental severe fibrosis and cirrhosis.     

Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

AIM:To identify factors that influence long-term liver function following radiofrequency ablation(RFA)in patients with viral hepatitis-related hepatocellular carcinoma.METHODS:A total of 123 patients with hepatitis B virus-or hepatitis C virus-related hepatocellular carcinoma(HCC)(n=12 and n=111,respectively)were enrolled.Cumulative rates of worsening Child-Pugh(CP)scores(defined as a 2-point increase)were examined.RESULTS:CP score worsening was confirmed in 22patients over a mean follow-up period of 43.8±26.3mo.Multivariate analysis identified CP class,platelet count,and aspartate aminotransferase levels as significant predictors of a worsening CP score(P=0.000,P=0.011 and P=0.024,respectively).In contrast,repeated RFA was not identified as a risk factor for liver function deterioration.CONCLUSION:Long-term liver function following RFA was dependent on liver functional reserve,the degreeof fibrosis present,and the activity of the hepatitis condition for this cohort.Therefore,in order to maintain liver function for an extended period following RFA,suppression of viral hepatitis activity is important even after the treatment of HCC.     

Expression of metastasis suppressor gene nm23 in human hepatocellular carcinoma

AIM: To investigate the relationship between the expression of nm23-Hi mRNA and the metastatic potential of hepatocellular carcinoma (HCC). METHODS: The expression of nm23-H1 mRNA was detected in 24 cases of HCC by in situ hybridization using digoxigenin-labeled nm23-H1 antisense cRNA probe. Twenty-four HCC specimens were divided into two groups according to the following criteria: (1) metastasis in portal lymph nodes; (2) the number of tumors in the liver; (3) cancerous emboli in the portal vein; and (4) the existence of satellite lesions. We named those meeting criteria (1) or (2) and (3), or (3) and (4) high metastatic potential (n = 6); and the others formed the low metastatic potential group (n = 18). RESULTS: Positive results of in situ hybridization showed granules or masses in the cytoplasm. In the low metastatic potential group strong staining was obtained in ten specimens, while in the high metastatic potential group there was none. Three negative results were found in the high metastatic potential group, and one in the low metastatic potential group (P < 0.05). The expression of nm23-H1 mRNA was not correlated with some clinical factors, such as tumor size or the background liver disease. CONCLUSION: The expression of nm23-H1 mRNA is inversely correlated with HCC metastatic potential, and can be considered as an index which indicates the metastatic potential of HCC.     

Adult-to-adult living donor liver transplantation for acute liver failure in China

AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation(AALDLT) for acute liver failure(ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio(INR) ≥ 1.5] and degree of mental alteration without pre-ex-isting cirrhosis and with an illness of 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic(ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B(n = 18),drug-induced(n = 1) and indeterminate(n = 1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe(n = 17) and dual graft(n = 3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-torecipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65%(13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients.Multivariate analysis showed that waiting duration was independently correlated with increased mortality(P = 0.014).Furthermore,ROC curve revealed the cut-off value of waiting time was 5 d(P = 0.011,area under the curve = 0.791) for determining the mortality.The short-term creatinine level with different recipient's waiting duration was described.The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration 5 d(66.7% vs 9.1%,P = 0.017).In addition,all donors had no residual morbidity.Furthermore,univariate analysis did not show that short assessment time induced the high morbidity(P = 0.573).CONCLUSION:Timely AALDLT for patients with ALF greatly improves the recipient survival.However,further systemic review is needed to investigate the optimal treatment strategy for ALF.     

Acceptance of living liver donation among medical students: A multicenter stratified study from Spain

AIM: To analyze the attitude of Spanish medical students toward living liver donation(LLD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain(n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire(PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student′s t test, χ2 test and logistic regression analysis.RESULTS: The completion rate was 95.7%(n = 9275). 89%(n = 8258) were in favor of related LLD, and 32%(n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude:(1) age(P = 0.008);(2) sex(P 0.001);(3) academic year(P 0.001);(4) geographical area(P = 0.013);(5) believing in the possibility of needing a transplant oneself in the future(P 0.001);(6) attitude toward deceased donation(P 0.001);(7) attitude toward living kidney donation(P 0.001);(8) acceptance of a donated liver segment from a family member if one were needed(P 0.001);(9) having discussed the subject with one's family(P 0.001) and friends(P 0.001);(10) a partner's opinion about the subject(P 0.001);(11) carrying out activities of an altruistic nature; and(12) fear of the possible mutilation of the body after donation(P 0.001).CONCLUSION: Spanish medical students have a favorable attitude toward LLD.     

超声造影联合血清CA19-9鉴别诊断胆管细胞癌与肝细胞癌应用研究

目的 探讨肝内胆管细胞癌(ICC)与肝细胞癌(HCC)患者超声造影(CEUS)和血清糖类抗原19-9(CA19-9)水平变化特征。方法 经组织病理学检查诊断的ICC患者48例和HCC患者78例,进行CEUS检查,常规检测血清CA19-9。建立鉴别诊断ICC与HCC的多指标二元Logistic回归方程,探索其诊断ICC的价值。结果 45.8%ICC患者以肿瘤周围环状增强为主,显著高于HCC患者的2.6%(P<0.05);58.3%ICC患者造影剂显著廓清,而94.9% HCC呈弱或无廓清(P <0.05);ICC组廓清时间为(54.6±10.2)s,显著早于HCC组【(76.1±25.1)s,P <0.05】;72.9%ICC患者血清CA19-9升高,显著高于HCC组的19.2%(P<0.05);建立多指标联合的二元Logistic诊断模型方程为:Logit(P)=-4.030+2.640×增强模式+2.486×廓清时间+2.579×廓清程度+2.731×血清CA19-9 (U/ml),该模型识别ICC的AUC为0.943,其敏感度和特异度分别为79.2%和93.6%。结论 熟悉ICC与HCC的超声造影表现特征,结合血清CA19-9水平,可以帮助鉴别这两种肿瘤。     

Survival outcome of patients with spontaneously ruptured hepatocellular carcinoma treated surgically or by transarterial embolization

AIM: To evaluate clinical outcomes of patients that underwent surgery, transarterial embolization (TAE), or supportive care for spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: A consecutive 54 patients who diagnosed as spontaneously ruptured HCC at our institution between 2003 and 2012 were retrospectively enrolled. HCC was diagnosed based on the diagnostic guidelines issued by the 2005 American Association for the Study of Liver Diseases. HCC rupture was defined as disruption of the peritumoral liver capsule with enhanced fluid collection in the perihepatic area adjacent to the HCC by dynamic liver computed tomography, and when abdominal paracentesis showed an ascitic red blood cell count of > 50000 mm 3 /mL in bloody fluid. RESULTS: Of the 54 patients, 6 (11.1%) underwent surgery, 25 (46.3%) TAE, and 23 (42.6%) supportive care. The 2-, 4and 6-mo cumulative survival rates at 2, 4 and 6 mo were significantly higher in the surgery (60%, 60% and 60%) or TAE (36%, 20% and 20%) groups than in the supportive care group (8.7%, 0% and 0%), respectively (each, P < 0.01), and tended to be higher in the surgical group than in the TAE group. Multivariate analysis showed that serum bilirubin (HR = 1.09, P < 0.01), creatinine (HR = 1.46, P = 0.04), and vasopressor requirement (HR = 2.37, P = 0.02) were significantly associated with post-treatment mortality, whereas surgery (HR = 0.41, P < 0.01), and TAE (HR = 0.13, P = 0.01) were inversely associated with posttreatment mortality. CONCLUSION: Post-treatment survival after surgery or TAE was found to be better than after supportive care, and surgery tended to provide better survival benefit than TAE.     

Neurotensin receptor 1 overexpression in inflammatory bowel diseases and colitis-associated neoplasia

AIM: To explore the association of neurotensin receptor 1 (NTSR1) with inflammatory bowel diseases (IBD) and colitis-associated neoplasia. METHODS: NTSR1 was detected by immunohistochemistry in clinical samples of colonic mucosa with IBD colitis, colitis-associated raised low-grade dysplasia (LGD) including dysplasia-associated lesions or masses (DALMs, n = 18) and adenoma-like dysplastic polyps (ALDPs, n = 4), colitis-associated high-grade dysplasia (HGD, n = 11) and colitis-associated colorectal carcinoma (CACRC, n = 13), sporadic colorectal adenomatous polyp (SAP, n = 17), and sporadic colorectal carcinoma (SCRC, n = 12). The immunoreactivity of NTSR1 was semiquantitated (as negative, 1+, 2+, and 3+) and compared among different conditions.RESULTS: NTSR1 was not detected in normal mucosa but was expressed similarly in both active and inactive colitis. LGD showed a significantly stronger expression as compared with non-dysplastic colitic mucosa, with significantly more cases showing > 2+ intensity (68.75% in LGD vs 32.26% in nondysplastic mucosa, P = 0.001). However, no significant difference existed between DALMs and ALDPs. CACRC and HGD showed a further stronger expression, with significantly more cases showing 3+ intensity than that in LGD (61.54% vs 12.50% for CACRC vs LGD, P = 0.022; 58.33% vs 12.50% for CACRC/HGD vs LGD, P = 0.015). No significant difference existed between colitis-associated and non-colitic sporadic neoplasia. CONCLUSION: NTSR1 in colonic epithelial cells is overexpressed in IBD, in a stepwise fashion with sequential progress from inflammation to dysplasia and carcinoma.     

胃癌患者血清肿瘤标志CA50和CEA的意义

目的比较胃恶性和良性病变血清人类结肠癌抗原 CA50和 CEA 的变化。方法用放射免疫法测定33例健康对照和86例胃部疾病(胃癌34例,胃溃疡27例和慢性萎缩性胃炎25例)患者血清 CA50和 CEA 含量,胃癌包括窦部27例,体部3例和底部9例,组织学类型包括腺癌21例,上皮癌4例和未分类9例;胃溃疡包括窦部18例,体部3例和底部9例;萎缩性胃炎均伴有肠上皮化生。结果与正常人比较,胃癌血清 CA50(112.67±38.36 kU/L vs 16.26±6.14 kU/L,P<0.01)和 CEA(10.28±3.76μg/L vs 3.12±1.03 μg/L,P<0.01)明显升高;CA50(>22 kU/L)阳性率在胃癌是53.0%(18/34),CEA(>5 μg/L)阳性率是55.8%(19/34);CA50和 CEA 升高呈正相关(r=0.648,P<0.01)。胃癌手术后(n=21),血清 CA50(46.4±25.9 kU/L,P<0.01)和 CEA(6.85±2.43μg/L,P<0.01)有明显下降。胃溃疡和萎缩性胃炎血清 CAS0(P<0.05)轻度升高,而 CEA 无明显变化(P>0.05)。结论血清 CAS0和 CEA 升高可作为诊断晚期胃癌的指标,胃癌手术后血清 CA50和 CEA 明显降低,提示联合测定血清CA50和 CEA 对晚期胃癌的诊治有一定临床意义。     

Antifibrotic effects of ambrisentan,an endothelin-A receptor antagonist,in a non-alcoholic steatohepatitis mouse model

AIM: To examine the effects of the endothelin type A receptor antagonist ambrisentan on hepatic steatosis and fibrosis in a steatohepatitis mouse model.METHODS: Fatty liver shionogi(FLS) FLS-ob/ob mice(male, 12 wk old) received ambrisentan(2.5 mg/kg orally per day; n = 8) or water as a control(n = 5) for 4 wk. Factors were compared between the two groups, including steatosis, fibrosis, inflammation, and endothelin-related gene expression in the liver.RESULTS: In the ambrisentan group, hepatic hydroxyproline content was significantly lower than in the control group(18.0 μg/g ± 6.1 μg/g vs 33.9 μg/g ± 13.5 μg/g liver, respectively, P = 0.014). Hepatic fibrosis estimated by Sirius red staining and areas positive for α-smooth muscle actin, indicative of activated hepatic stellate cells, were also significantly lower in the ambrisentan group(0.46% ± 0.18% vs 1.11% ± 0.28%, respectively, P = 0.0003; and 0.12% ± 0.08% vs 0.25% ± 0.11%, respectively, P = 0.047). Moreover, hepatic RNA expression levels of procollagen-1 and tissue inhibitor of metalloproteinase-1(TIMP-1) were significantly lower by 60% and 45%, respectively, in the ambrisentan group. Inflammation, steatosis, and endothelin-related m RNA expression in the liver were not significantly different between the groups.CONCLUSION: Ambrisentan attenuated the progression of hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing procollagen-1 and TIMP-1 gene expression. Ambrisentan did not affect inflammation or steatosis.     

Duodenal epithelial transport in functional dyspepsia: Role of serotonin

AIM: To investigate functional duodenal abnormalities in functional dyspepsia (FD) and the role of serotonin (5-hydroxytryptamine, 5-HT) in mucosal ion transport and signalling. METHODS: Duodenal mucosal biopsies were obtained from 15 patients with FD and 18 healthy controls. Immunohistochemistry was used to study the number of 5-HT-containing cells and real-time polymerase chain reaction for expression of 5-HT receptors 1A, 1B, 2A, 2B, 3A, 3B, 3C, 3D, 3E, 4 and 7, as well as expression of the serotonin re-uptake transporter (SERT) gene SLC6A4 and tryptophan hydroxylase 1 (TPH1). Biopsies were mounted in Ussing chambers for evaluation of basal and 5-HT-stimulated short-circuit current (SCC). RESULTS: Conductance was lower in FD [42.4 ± 4.7 mS/cm² (n = 15) vs 62.5 ± 4.5 mS/cm² (n = 18), P = 0.005]. 5-HT induced a dose dependent rise in SCC in both FD (n = 8) and controls (n = 9), the rise was lower in FD (P < 0.001). Mean number of 5-HT stained cells per high power field was the same [34.4 ± 8.4 in FD (n = 15) and 30.4 ± 3.7 in controls (n = 18), P = 0.647]. The following genes were highly expressed: 5-HT receptor HTR3E, HTR4, HTR7, SERT gene (SLC6A4) and TPH1. Differences in expression levels were observed for HTR3E (higher expression in FD, P = 0.008), HTR7 (lower expression in FD, P = 0.027), SLC6A4 (higher expression in FD, P = 0.033) and TPH1 (lower expression in FD, P = 0.031). CONCLUSION: Duodenal ion transport in response to exogenous 5-HT is abnormal in FD patients and associated with high expression of the HTR3E receptor and the serotonin transporter.     

Circulating insulin-like growth factor-binding protein 3 as prognostic biomarker in liver cirrhosis

AIM: To investigate the prognostic significance of insulin-like growth factor-binding protein 3(IGFBP-3) in patients with cirrhosis.METHODS: Prospective study that included two cohorts: outpatients with stable cirrhosis(n = 138) and patients hospitalized for acute decompensation(n = 189). Development of complications, mortality or liver transplantation was assessed by periodical phone calls and during outpatient visits. The cohort of stable cirrhosis also underwent clinical and laboratory evaluation yearly(2013 and 2014) in predefined study visits. In patients with stable cirrhosis, IGFBP-3 levels were measured at baseline(2012) and at second re-evaluation(2014). In hospitalized subjects, IGFBP-3 levels were measured in serum samples collected in the first and in the third day after admission and stored at-80 ℃. IGFBP-3 levels were measured by immunochemiluminescence.RESULTS: IGFBP-3 levels were lower in hospitalized patients as compared to outpatients(0.94 mcg/mL vs 1.69 mcg/m L, P 0.001) and increased after liver transplantation(3.81 mcg/m L vs 1.33 mcg/mL, P = 0.008). During the follow-up of the stable cohort, 17 patients died and 11 received liver transplantation. Bivariate analysis showed that death or transplant was associated with lower IGFBP-3 levels(1.44 mcg/mL vs 1.74 mcg/m L, P = 0.027). The Kaplan-Meier transplant-free survival probability was 88.6% in patients with IGFBP-3 ≥ 1.67 mcg/mL and 72.1% for those with IGFBP3 1.67 mcg/mL(P = 0.015). In the hospitalized cohort, 30-d mortality was 24.3% and was independently associated with creatinine, INR, SpO_2/FiO_2 ratio and IGFBP-3 levels in the logistic regression. The 90-d transplant-free survival probability was 80.4% in patients with IGFBP-3 ≥ 0.86 mcg/mL and 56.1% for those with IGFBP3 0.86 mcg/mL(P 0.001). CONCLUSION: Lower IGFBP-3 levels were associated with worse outcomes in patients with cirrhosis, and might represent a promising prognostic tool that can be incorporated in clinical practice.     

Suppository naproxen reduces incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial

AIM: To determine the efficacy of rectally administered naproxen for the prevention of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP).METHODS: This double-blind randomized control trial conducted from January 2013 to April 2014 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 324 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients received a single dose of Naproxen(500 mg; n = 162) or a placebo(n = 162) per rectum immediately before ERCP. The overall incidence of PEP, incidence of mild to severe PEP, serum amylase levels and adverse effects were measured. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and elevation of the serum amylase level to 3 × the upper normal limit(60-100 IU/L) within 24 h after ERCP. The severity of PEP was classified according to the duration of therapeutic intervention for PEP: mild, 2-3 d; moderate 4-10 d; and severe, 10 d and/or necessitated surgical or intensive treatment, or contributed to death.RESULTS:PEP occurred in 12 %(40/324) o f participants, and was significantly more frequent in the placebo group compared to the naproxen group(P 0.01). Of the participants, 25.9%(84/324) developed hyperamylasemia within 2 h of procedure completion, among whom only 35 cases belonged to the naproxen group(P 0.01). The incidence of PEP was significantly higher in female sex, in patients receiving pancreatic duct injection, more than 3 times pancreatic duct cannulations, and ERCP duration more than 40 min(P s 0.01). There were no statistically significant differences between the groups regarding the procedures or factors that might increase the risk of PEP, sphincterotomy, precut requirement, biliary duct injection and number of pancreatic duct cannulations. In the subgroup of patients with pancreatic duct injection, the rate of pancreatitis in the naproxen group was significantly lower than that in the placebo(6 patients vs 23 patients, P 0.01, RRR = 12%, AR = 0.3, 95%CI: 0.2-0.6). Naproxen reduced the PEP in patients with ≥ 3 pancreatic cannulations(P 0.01, RRR = 25%, AR = 0.1, 95%CI: 0.1-0.4) and an ERCP duration 40 min(P 0.01, RRR = 20%, AR = 0.9, 95%CI: 0.4-1.2).CONCLUSION: Single dose of suppository naproxen administered immediately before ERCP reduces the incidence of PEP.     

Combined acoustic radiation force impulse,aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse(ARFI), aspartate aminotransferase to platelet ratio index(APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B(CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage(all P 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI(P 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage(Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI(Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.     

Age-dependent slowing of enteric axonal transport in insulin-resistant mice

AIM:To investigate retrograde tracer transport by gastric enteric neurons in insulin resistant mice with low or high glycosylated hemoglobin(Hb).METHODS:Under anesthesia,the retrograde tracer fluorogold was superficially injected into the fundus or antrum using a microsyringe in KK Cg-Ay/J mice prior to onset of type 2 diabetes mellitus(T2DM;4 wk of age),at onset of T2DM(8 wk of age),and after 8,16,or 24 wk of untreated T2DM and in age-matched KK/HIJ mice.Six days later,mice were sacrificed by CO 2 narcosis followed by pneumothorax.Stomachs were removed and fixed.Sections from fundus,corpus and antrum were excised and mounted on a glass slide.Tracer-labeled neurons were viewed using a microscope and manually counted.Data were expressed as the number of neurons in short and long descending and ascending pathways and in local fundus and antrum pathways,and the number of neurons in all regions labeled after injection of tracer into either the fundus or the antrum.RESULTS:By 8 wk of age,body weights of KKAy mice(n=12,34±1 g) were heavier than KK mice(n=17,29±1 g;F(4,120)=4.414,P=0.002] and glycosylated Hb was higher [KK:(n=7),4.97%±0.04%;KKAy:(n=6),6.57%±0.47%;F(1,26)=24.748,P<0.001].The number of tracer labeled enteric neurons was similar in KK and KKAy mice of all ages in the short descending pathway [F(1,57)=2.374,P=0.129],long descending pathway [F(1,57)=0.922,P=0.341],local fundus pathway [F(1,53)=2.464,P=0.122],local antrum pathway [F(1,57)=0.728,P=0.397],and short ascending pathway [F(1,53)=2.940,P=0.092].In the long ascending pathway,fewer tracer-labeled neurons were present in KKAy as compared to KK mice [KK:(n=34),302±17;KKAy:(n=29),230±15;F(1,53)=8.136,P=0.006].The number of tracer-labeled neurons was decreased in all mice by 16 wk as compared to 8 wk of age in the short descending pathway [8 wk:(n=15),305±26;16 wk:(n=13),210±30;F(4,57)=9.336,P<0.001],local antrum pathway [8 wk:(n=15),349±20;16 wk:(n=13),220±33;F(4,57)=8.920,P<0.001],short ascending pathway [8 wk:(n=14),392±15;16 wk:(n     

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     

Visualizing the hepatic vascular architecture using superb microvascular imaging in patients with hepatitis C virus: A novel technique

AIM: To identify the hepatic vascular architecture of patients with hepatitis C virus(HCV) using superb microvascular imaging(SMI) and investigate the use of SMI in the evaluation of liver fibrosis.METHODS: SMI was performed in 100 HCV patients. SMI images were classified into five types according to the vascular pattern, and these patterns were compared with the fibrosis stage. Moreover, the images were analyzed to examine vascularity by integrating the number of SMI signals in the region of interest ROI [number of vascular trees(VT)]. The number of VT, fibrosis stage, serum parameters of liver function, and CD34 expression were investigated.RESULTS: There was a significant difference between SMI distribution pattern and fibrosis stage(P 0.001). The mean VT values in each of the fibrosis stages were as follows: 26.69 ± 7.08 in F0, 27.72 ± 9.32 in F1, 36.74 ± 9.23 in F2, 37.36 ± 5.32 in F3, and 58.14 ± 14.08 in F4. The VT showed excellent diagnostic ability for F4 [area under the receiver operator characteristic(AUROC): 0.911]. The VT was significantly correlated with the CD34 labeling index(r = 0.617, P 0.0001).CONCLUSION: SMI permitted the detailed delineation of the vascular architecture in chronic liver disease. SMI appears to be a reliable tool for noninvasively detecting significant fibrosis or cirrhosis in HCV patients.     

近20年妊娠急性脂肪肝患者预后变化和死亡原因分析

目的 分析近20年我科诊治的妊娠急性脂肪肝(AFLP)患者的临床特征。方法 2002年1月～2011年12月北京佑安医院收治AFLP患者25例(A组),2012年1月～2022年1月收治28例(B组),对比分析两组临床表现、并发症、病死率变化和死亡原因。结果 A组和B组血清总胆红素水平分别为 (239.8±104.2)μmol/l和【(161.9±107.7)μmol/l, P=0.052】, A组肝功能异常率为12.0%,显著低于B组的42.9%(P=0.006);A组剖宫产率为76.0%,显著低于B组的100.0%(P=0.020);A组与B组DIC(40.0%对3.6%,P=0.001)和失血性休克发生率(24.0%和3.6%,P=0.028)存在显著性差异,而产后出血(48.0%对25.0%,P=0.081)无显著性差异;B组产妇病死率为3.6%而胎儿无死亡,显著低于A组的24.0%和12.1%(P<0.05)。结论 DIC和大出血是10年前AFLP产妇的主要死亡原因,近10年AFLP母婴病死率明显下降,但肝衰竭进展仍较常见,仍需早期识别和处理。     

余甘子提取物对非酒精性脂肪性肝病大鼠外周血Treg细胞及肝组织LXRα/FAS通路表达的影响*

目的 探讨余甘子提取物对非酒精性脂肪性肝病(NAFLD)大鼠外周血Treg细胞及肝组织LXRα/FAS通路表达的影响。方法 将48只SD大鼠随机分对照组、模型组、多烯磷脂酰胆碱及小剂量、中剂量和大剂量余甘子处理组,在造模成功后,给予对照组生理盐水灌胃,给予模型组多烯磷脂酰胆碱处理,另给予不同剂量的余甘子灌胃处理,连续给药6周。采用ELISA法检测血清TNF-α、IL-17和IL-10水平,使用流式细胞术检测血CD4⁺IL-17⁺和CD4⁺CD25⁺Treg细胞百分比,采用WB法检测肝组织LXRα和FAS蛋白表达。结果 与模型组比,大剂量余甘子提取物处理组肝组织病理学损伤显著改善,血清ALT、AST、TC、TG水平显著降低(P<0.05);血清TNF-α和IL-17水平显著降低,分别为(34.7±0.9)pg/ml和(3.2±0.2)pg/mL,而IL-10水平显著升高,为(4.8±0.2)pg/mL(P<0.05);大剂量余甘子处理组CD4⁺IL-17⁺百分比为(1.1±0.6)%,显著低于模型组[(1.9±0.4)%,P<0.05],CD4⁺CD25⁺Treg百分比为(1.5±0.6)%,显著高于模型组[(0.9±0.2)%,P<0.05];小、中、大剂量余甘子提取物处理组肝组织LXRα和FAS蛋白表达显著减弱[分别为(1.8±0.1)和(2.0±0.2),P<0.05]。结论 余甘子提取物可改善NAFLD大鼠肝组织病理学损伤,可能与其对炎性细胞因子、Th17/Treg细胞和LXRα/FAS通路因子的表达产生了某种影响有关。     

上海市900例老年住院结核病患者营养状况调查分析

目的 分析上海市老年结核病住院患者营养状况及其风险因素,为早期营养干预老年结核病住院患者提供依据。方法 连续性收集2018年8月1日至2019年8月1日同济大学附属上海市肺科医院结核病区住院超过24 h且确诊为结核病的1100例≥65岁老年患者,剔除无体质量记录、严重糖尿病、严重高血压、肝肾功能不全,以及神志不清者,最终纳入900例。对纳入患者的临床相关资料[包括患者性别、年龄、临床诊断、并发症、治疗次数、出入院日期、营养风险筛查量表(NRS 2002)分值]及营养相关指标[血红蛋白(Hb)、血清总蛋白(TP)、血清白蛋白(ALB)、血清前白蛋白(PAB)、视黄醇结合蛋白(RBP)、预后营养指数(PNI)、中性粒细胞/淋巴细胞比值(NLR)等因素]进行统计,分析影响老年结核病患者营养风险发生的危险因素。900例老年结核病患者中,443例(49.22%)NRS 2002≥3分者纳入有营养风险组,457例(50.78%)NRS 2002<3分者纳入无营养风险组。结果 因素分析显示,有营养风险组患者在75~和80~90岁组[18.28%(81/443)和18.51%(82/443)]、BMI<18.5[40.41%(179/443)]、治疗2次及以上[25.51%(113/443)]、结核性胸膜炎[21.67%(96/443)]方面的分布均明显高于无营养风险组[分别为9.19%(42/457)和8.75%(40/457)、0.00%(0/457)、17.51%(80/457)、13.13%(60/457)](χ²=51.350,299.500, 8.818, 16.280;P=0.000,0.000,0.012,0.000)。营养相关临床指标检测结果显示,有营养风险组患者的TP[(64.88±0.34)g/L]、ALB[(34.15±0.23)g/L]、PAB[(138.60±3.26)g/L]、Hb[(113.60±0.84)g/L]、RBP[(26.32±0.50)g/L]、PNI[(39.61±0.35)]均低于无营养风险组患者[分别为(67.30±0.28)g/L、(38.18±0.16)g/L、(194.10±3.22)g/L、(126.70±0.79)g/L、(34.32±0.22)g/L、(45.51±0.26)][F=19.496, 79.334, 34.030, 22.808,21.326, 72.464;P值均=0.000];而NLR(5.44±0.32)和住院时间[(6.61±0.17)d]明显高于无营养风险组患者[分别为(3.29±0.14),(5.53±0.13)d][F=6.335, P=0.012;F=5.994,P=0.015]。结论 老年结核病患者营养风险发生率较高,且与年龄、治疗次数呈正相关、与BMI呈负相关,并表现为有营养风险组患者的TP、ALB、PAB、Hb、RBP、PNI均明显低于无营养风险组患者,严重影响临床治疗效果、延长住院时间。