Diagnosis of rectal varices via color Doppler ultrasonography

OBJECTIVES: There has been no report on the hemodynamic evaluation of rectal varices by percutaneous color Doppler ultrasonography. Here, we report the usefulness of color Doppler ultrasonography for this purpose. METHODS: Color Doppler ultrasonography was performed in 44 patients: 31 patients with portal hypertension, 7 with liver cirrhosis (LC) without portal hypertension, and 6 non-LC patients. We examined color flow images and measured velocity of blood flow in rectal varices using fast-Fourier transform (FFT) analysis. Next, we performed colonoscopy on these 44 patients as follow-up to confirm findings by color Doppler. Endoscopic findings of rectal varices were evaluated according to the grading system outlined in "The General Rules for Recording Endoscopic Findings of Esophageal Varices" prepared by the Japanese Research Committee on Portal Hypertension. RESULTS: Rectal varices were shown by Doppler color flow images in 27 of the 31 patients (87.1%) with portal hypertension. Blood flow velocity in those 27 rectal varices ranged from 2.0 to 11.6 cm/s (mean 6.5 +/- 2.4 cm/s). Rectal varices were observed in all 27 of these cases by colonoscopy. On the other hand, rectal varices were not observed by colonoscopy in the 7 LC patients without portal hypertension and the 6 non-LC patients not shown to have rectal variceal blood flow via color Doppler ultrasonography. Sensitivity, specificity, and accuracy were 27/27 (100%), 17/17 (100%), 44/44 (100%), respectively, for detection of rectal varices with color Doppler ultrasonography. Next, we compared velocities of rectal varices obtained by color Doppler ultrasonography with colonoscopic findings. Mean velocity (7.1 +/- 2.3 cm/s) in Cb variceal cases (N = 20) was significantly higher than that (4.9 +/- 1.7 cm/s) in the Cw rectal variceal cases (N = 7) (P < 0.05). Mean velocity (8.5 +/- 2.0 cm/s) in the RC-positive cases (N = 9) was significantly higher than that (5.4 +/- 1.8 cm/s) in RC-negative cases (N = 18) (P < 0.01). Mean velocity (9.8 +/- 1.6 cm/s) in rectal bleeding cases (N = 3) was significantly higher than that (6.1 +/- 2.1 cm/s) in patients without bleeding (N = 24) (P < 0.05). Seven days after endoscopic injection sclerotherapy (EIS) treatment, color Doppler ultrasonography showed an extreme decrease in blood flow in all three rectal varices in comparison with values before EIS. CONCLUSIONS: Color Doppler ultrasonography can be considered a very useful noninvasive tool for diagnosis of rectal varices.     

多普勒彩超评估甲氧乙心安联合硝酸异山梨醇酯治疗门静脉高压的效果

目的：评估甲氧乙心安（商品名：倍他乐克）联合硝酸异山梨醇酯（商品名：消心痛）预防肝硬化患者上消化道出血和再出血的效果与安全性。方法：应用多普勒彩超检测２２例肝硬化门静脉高压患者经倍他乐克联合消心痛治疗前后门静脉系统血流动力学变化，并观察治疗前后血压、心率及肝功能变化。结果：治疗前门静脉主干、脾静脉及肠系膜上静脉平均内径较正常组明显增宽，平均血流速度明显减慢，平均血流量明显增多。治疗后三者平均内径无明显变化（Ｐ＞０．０５），但与治疗前比较，平均流速明显减慢，平均血流量明显减少（Ｐ＜０．０５）。结论：倍他乐克联合消心痛降门静脉压治疗安全有效。多普勒彩超对门静脉高压的诊断和治疗评估有重要意义。     

Immune response in addicts with chronic hepatitis C treated with interferon and ribavirin

BACKGROUND: The role played by the immune system in the progression of chronic hepatitis C (CHC) is not completely clear. Opioids may facilitate the outbreak of infections through marked immunomodulating effects on the immune response against a virus. To asses if addicts can be treated successfully with interferon (IFN) during detoxification treatment, we evaluated some immune response mediators in addicts affected by CHC. METHOD: A cohort of heroin users with CHC were enrolled during the detoxification period, divided into two groups and treated with IFN pegilate plus ribavirin (group A treated during methadone administration and group B treated at week 8 after methadone treatment completed). A group of patients with CHC and no history of drug addiction were enrolled as controls. Leukocyte subpopulation NK, CD4+, CD8+ and some cytokines Th1 (IFNgamma, interleukin [IL]2) and Th2 (IL-6, IL-10) were evaluated prior to, during and after methadone treatment. Sustained virological response was evaluated 24 weeks after antiviral treatment was completed. RESULTS: During methadone treatment, significantly (P < 0.05) higher cytokine Th1 and NK and lower cytokine Th2 levels were observed in groups A and B compared with levels obtained before treatment in the same groups. Relapse occurred at 56 +/- 8 weeks in 34/55 group A patients, at 24 +/- 8 weeks in 33/52 group B patients and at 24 +/- 4 weeks in group C, there being a significant difference (P < 0.05) between group A and B and between group A and C. No significant differences between all groups were detected in CD4+ and CD8+ cell counts. CONCLUSIONS: Our results revealed that drug addicts with CHC can be treated successfully with IFN pegilate and ribavirin. This therapy can be recommended during the early phase of detoxification treatment to achieve a sustained response.     

Interferon alfa-2b [correction of alpha-2b]and ribavirin for patients with chronic hepatitis C and normal ALT

OBJECTIVES: Most studies establishing the role of antiviral therapy in patients with chronic hepatitis C (CHC) excluded the patients with normal ALT levels. Small trials with interferon monotherapy suggested a limited efficacy and/or de novo ALT elevations. We sought to evaluate the efficacy of two doses of interferon alfa-2b (IFN) with ribavirin (RBV) in patients with normal ALT [correction]. METHODS: Patients with biopsy-proven CHC with detectable HCV RNA and at least two normal ALT levels three or more months apart were randomized to receive either 3 or 5 million units of IFN thrice a week plus RBV 1,000-1,200 mg. Therapy was stopped at 24 wk if HCV RNA remained detectable and continued for an additional 24 wk if HCV RNA was undetectable. A final HCV RNA level was obtained 24 wk after discontinuation of therapy. RESULTS: Fifty-six patients were randomized and received at least one dose of treatment. The overall rate of sustained virologic response (SVR) was 32%. SVR rates were higher in genotype 2 and 3 patients (80%) than in genotype 1 patients (24%, p = 0.002). There was a tendency toward higher SVR in genotype 1 patients treated with the higher IFN dose (36%vs 10%, p = 0.07). Five patients had mild, transient ALT elevations. No sustained ALT elevations were noted. CONCLUSIONS: Patients with normal ALT had a rate of SVR comparable to that reported in patients with elevated ALT. Higher dose of interferon tended to be more effective in genotype 1 infected patients. De novo ALT elevations were transient and not clinically significant. Patients with CHC should not be excluded from treatment on the basis of ALT alone. Combination therapy with pegylated interferon and ribavirin should be evaluated in these patients.     

Noninvasive measurement of portal venous blood flow in patients with cirrhosis

The present study aims to evaluate the usefulness of combined pulse Doppler-real-time ultrasonography as a noninvasive method for the measurement of portal blood flow in man. This measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension. Ten patients (group 1) were evaluated prior to and after ingestion of a standard meal (Ensure Plus) or placebo. In the remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL) administration or placebo were studied. In group 1, food intake caused a significant increase of portal blood flow (from 1038±539 to 1572±759 ml/min,P<0.02); this effect was due to a significant rise in mean blood velocity (from 18.5±3.7 to 23.9±3.9 cm/sec,P<0.02). In group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985±491 to 625±355 ml/min,P<0.05); a significant decline of mean blood velocity (from 18.8 ±4.5 to 14.5±2.5 cm/sec,P<0.02) was observed. Placebo administration had no significant hemodynamic effects in either group. Our results suggest that Doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension.     

Early decrease in serum IV-7S levels during IFN treatment predicts anti-fibrogenic effect in nonresponders with chronic hepatitis C

Background We evaluated whether early changes in serum levels of fibrogenic markers during interferon (IFN) treatment can predict long-term anti-fibrogenic effects in patients with chronic hepatitis C (CHC).Methods We retrospectively examined the serum levels of N-terminal peptide of type III procollagen (P-III-NP) and 7S domain of type IV collagen (IV-7S) in 56 patients with CHC who were revealed to be IFN-nonresponders. We measured these markers before (T0) and 1 month (T1) after the commencement of IFN therapy, at the end of 24 weeks IFN therapy (T24), and 1 year (T24-1) and more than 2 years (T24-2) after the cessation of IFN therapy. We also measured these markers twice, at intervals of more than 2 years, in 43 IFN-untreated patients with CHC as controls.Results In nonresponders, both P-III-NP and IV-7S levels at T24-2 were significantly decreased compared with those at T0. P-III-NP levels at T1 were significantly decreased compared with those at T0, and remained at significantly low levels until the end of the observation period. IV-7S levels at T1 were not significantly different from those at T0. In patients whose IV-7S levels at T24-2 were decreased compared with those at T0, IV-7S levels at T1 were significantly lower than those at T0. In patients whose IV-7S levels at T24-2 were elevated or unchanged compared with those at T0, IV-7S levels at T1 were significantly higher than those at T0. In unteated patients, both P-III-NP and IV-7S levels at more than 2 years after the initial time were significantly increased compared with those at the initial time.Conclusions An early decrease in IV-7S levels after IFN treatment is a useful indicator of anti-fibrogenic effects in nonresponders.     

Comparison of Doppler ultrasonography and the hepatic venous pressure gradient in assessing portal hypertension in liver cirrhosis

BACKGROUND AND AIM: This prospective study aimed to determine whether Doppler ultrasonography can represent the hepatic venous pressure gradient (HVPG) as an assessment of the severity of portal hypertension and the response to terlipressin, which reduces the portal pressure in liver cirrhosis. METHODS: The HVPG and the Doppler ultrasonographic parameters, such as the portal venous velocity and the splenic venous velocity, the pulsatility and the resistive index of the hepatic, splenic and renal arteries were measured in 138 patients with liver cirrhosis. The changes in the HVPG and the portal venous velocity after administering terlipressin were evaluated in 43 of the 138 patients. The patients who showed a reduction in the HVPG of more than 20% of the baseline were defined as responders to terlipressin. RESULTS: None of the Doppler ultrasonographic parameters correlated with the HVPG. Both the HVPG (28.0 +/- 19.8%) and the portal venous velocity (29.7 +/- 13.2%) showed a significant reduction after terlipressin administration. However, the portal venous velocity decreased significantly, not only in the responders (31.0 +/- 12.0%) but also in the non-responders (25.2 +/- 16.4%). CONCLUSIONS: Doppler ultrasonography does not represent the HVPG, and is therefore not suitable for replacing HVPG as a means of assessing the severity of portal hypertension and the response to drugs which reduce the portal pressure in liver cirrhosis.     

Effect of release‐controlled nifedipine on portal hemodynamics in cirrhotic patients

OBJECTIVE : To evaluate the therapeutic effect of release‐controlled nifedipine on portal hypertension. METHODS : Thirty‐two cirrhotic patients were enrolled to investigate, by using duplex Doppler ultrasonography, differences in portal hemodynamics before and after treatment with release‐controlled nifedipine (30 mg once per day). RESULTS : After taking nifedipine, the diameter, blood velocity and blood flow of the portal vein decreased, but only the change in velocity was statistically significant. After treatment, the congestion index increased, and the blood velocity and blood flow of the splenic vein significantly decreased. The resistance and pulsatile indices of the right hepatic and splenic arteries also decreased markedly. The total hepatic blood flow was elevated slightly and there were no significant changes in mean arterial pressure and heart rate. CONCLUSIONS : The resistance and pulsatile indices of the hepatic and splenic arteries are representative indices of portal resistance. Release‐controlled nifedipine may decrease portal pressure by the following mechanisms: (i) decrease of systemic blood pressure triggers the sympathetic reflex, leading to splanchnic artery constriction and portal blood flow reduction; (ii) dilatation of the portal vein and sinusoids leads to decrease portal resistance; and (iii) dilatation of the collateral veins. Nifedipine has no significant effect on systemic circulation in normotensive cirrhotic patients, therefore it has good prospects as a drug for clinical use in portal hypertension.     

Postoperative portal vein thrombosis in patients with hepatosplenic mansonic schistosomiasis: relationship with intraoperative portal pressure and flow. A prospective study

BACKGROUND/AIMS: Portal vein thrombosis is a frequent postoperative complication after esophagogastric devascularization with splenectomy. The aim of this study was to analyze biochemical, hematological, coagulation blood tests and intraoperative portal vein hemodynamics after surgical treatment of hepatosplenic Mansonic schistosomal portal hypertension. METHODOLOGY: Forty patients with hepatosplenic schistosomiasis with indication for surgical treatment were prospectively studied. All patients underwent routine pre- and postoperative biochemical, hematologic, coagulation blood tests and intraoperative portal hemodynamic evaluation (portal pressure and portal flow) before and after esophagogastric devascularization and splenectomy using a 4-F thermodilution catheter introduced inside the portal vein. RESULTS: Portal vein thrombosis, diagnosed by routine postoperative Doppler ultrasonography was found in 22 patients (55%). It was partial in nineteen and total in three. In patients with postoperative portal thrombosis, we observed a reduction in portal flow of 971 +/- 592 mL/min (42 +/- 16%) at the end of the surgery, while this reduction was of 720 +/- 644mL/ min (33 +/- 30%) in those with postoperative pervious portal vein (p = 0.245). The decrease in portal pressure was the same in both groups: 7.2 +/- 3.0 mmHg (23 +/- 10%) and 7.6 +/- 3.8 mmHg (27 +/- 14%) with and without thrombosis respectively (p=0.759). There was also no significant difference between patients with and without portal vein thrombosis regarding pre- and postoperative hemoglobin level or platelet levels, coagulation tests, portal vein diameter and spleen's weight. CONCLUSIONS: Portal vein thrombosis was observed in 55% of the patients but this complication did not show any correlation with the decrease in portal flow or pressure or with biochemical, hematologic, coagulation blood tests, portal vein diameter or spleen's weight.     

Effect of transjugular intrahepatic portosystemic shunt formation on portal hypertensive gastropathy and gastric circulation

OBJECTIVES: The aim of this study was to investigate the effect of a transjugular intrahepatic portosystemic shunt (TIPS) on portal hypertensive gastropathy (PHG) and gastric hemodynamics. METHODS: A total of 16 patients with cirrhosis and portal hypertensive gastropathy were prospectively studied. Of these, 12 patients underwent TIPS for esophageal varices and four for refractory ascites. Gastric mucosal blood flow (GMBF) was assessed by laser Doppler flowmeter, and total blood flow (TBF) in submucosa and mucosa by near-infrared endoscopy. Portal venous pressure was obtained by a transducer during the TIPS procedure. The severity of portal hypertensive gastropathy was classified as none, mild, or severe. The examinations were performed before and 2 wk after the procedure. RESULTS: TIPS significantly reduced portal venous pressure. PHG improved in all four patients with severe PHG and in five of 12 patients with mild PHG after treatment. Gastric mucosal blood flow increased from 49.0 to 55.6 ml/min/100 g after TIPS. In contrast, TBF decreased from 0.35/s to 0.27/s after treatment. Liver function tests showed no significant changes before and after the procedure. CONCLUSIONS: It is considered that TIPS may have a beneficial effect on PHG at least for a short time. The mechanism by which PHG improves may be closely related to the improvement of the injured gastric perfusion in cirrhotic patients with PHG.     

多潘立酮对肝硬化患者门脉系统血流量的影响

背景:肝硬化病程迁延且内外科治疗效果均不理想,寻找有效的治疗药物一直是该领域研究的热点。目的:探讨多潘立酮对肝硬化患者门脉系统血流量的影响。方法:以20名健康人作为正常对照,用多普勒超声分别测定32例肝硬化患者服用多潘立酮前和服用2周后的门静脉、脾静脉和肠系膜上静脉血流参数。多潘立酮的用法为10mg tid口服。结果:多潘立酮治疗前,肝硬化患者的门静脉血流量(PVF)显著低于正常对照组(P<0.01),脾静脉血流量(SVF)和肠系膜上静脉血流量(SMVF)显著高于正常对照组(p<0.01);治疗后,肝硬化患者的PVF较治疗前无显著差异,SVF和SMVF虽显著低于治疗前(P<0.01),但仍高于正常对照组(P<0.05)。结论:多潘立酮可能对肝硬化患者的内脏高动力循环状态有改善作用。     

Hemodynamic analysis of esophageal varices in patients with liver cirrhosis using color Doppler ultrasound

AIM: To study the portal hemodynamics and their relationship with the size of esophageal varices seen at endoscopy and to evaluate whether these Doppler ultrasound parameters might predict variceal bleeding in patients with liver cirrhosis and portal hypertension. METHODS: One hundred and twenty cirrhotic patients with esophageal varices but without any previous bleeding were enrolled in the prospective study. During a 2-year observation period, 52 patients who had at least one episode of acute esophageal variceal hemorrhage constituted the bleeding group, and the remaining 68 patients without any previous hemorrhage constituted the non-bleeding group. All patients underwent endoscopy before or after color Doppler-ultrasonic examination, and images were interpreted independently by two endoscopists. The control group consisted of 30 healthy subjects, matched to the patient group in age and gender. Measurements of diameter, flow direction and flow velocity in the left gastric vein (LGV) and the portal vein (PV) were done in all patients and controls using color Doppler unit. After baseline measurements, 30 min after oral administration of 75 g glucose in 225 mL, changes of the diameter, flow velocity and direction in the PV and LGV were examined in 60 patients with esophageal varices and 15 healthy controls. RESULTS: The PV and LGV were detected successfully in 115 (96%) and 105 (88%) of 120 cirrhotic patients, respectively, and in 27 (90%) and 21 (70%) of 30 healthy controls, respectively. Among the 120 cirrhotic patients, 37 had F1, 59 had F2, and 24 had F3 grade varices. Compared with the healthy controls, cirrhotic group had a significantly lower velocity in the PV, a significantly greater diameter of the PV and LGV, and a higher velocity in the LGV. In the cirrhotic group, no difference in portal flow velocity and diameter were observed between patients with or without esophageal variceal bleeding (EVB). However, the diameter and blood flow velocity of the LGV were significantly higher for EVB (+) group compared with EVB (-) group (P < 0.01). Diameter of the LGV increased with enlarged size of varices. There were differences between F1 and F2, F1 and F3 varices, but no differences between F2 and F3 varices (P = 0.125). However, variceal bleeding was more frequent in patients with a diameter of LGV >6 mm. The flow velocity in the LGV of healthy controls was 8.70+/-1.91 cm/s (n = 21). In patients with liver cirrhosis, it was 10.3+/-2.1 cm/s (n = 12) when the flow was hepatopetal and 13.5+/-2.3 cm/s (n = 87) when it was hepatofugal. As the size of varices enlarged, hepatofugal flow velocity increased (P < 0.01) and was significantly different between patients with F1 and F2 varices and between patients with F2 and F3 varices. Variceal bleeding was more frequent in patients with a hepatofugal flow velocity >15 cm/s (32 of 52 patients, 61.5%). Within the bleeding group, the mean LGV blood flow velocity was 16.6+/-2.62 cm/s. No correlation was observed between the portal blood flow velocity and EVB. In all healthy controls, the flow direction in the LGV was hepatopetal, toward the PV. In patients with F1 varices, flow direction was hepatopetal in 10 patients, to-and-fro state in 3 patients, and hepatofugal in the remaining 18. The flow was hepatofugal in 91% patients with F2 and all F3 varices. Changes in diameter of the PV and LGV were not significant before and after ingestion of glucose (PV: 1.41+/-1.5 cm before and 1.46+/-1.6 cm after; LGV: 0.57+/-1.7 cm before and 0.60+/-1.5 cm after). Flow direction in the LGV was hepatopetal and to-and-fro in 16 patients and hepatofugal in 44 patients before ingestion of glucose. Flow direction changed to hepatofugal in 9 of 16 patients with hepatopetal and to-and-fro blood flow after ingestion of glucose. In 44 patients with hepatofugal blood flow in the LGV, a significant increase in hepatofugal flow velocity was observed in 38 of 44 patients (86%) with esophageal varices. There was a relationship between the percentage changes in flow velocity and the size of varices. Patients who responded excessively to food ingestion might have a high risk for bleeding. The changes of blood flow velocity in the LGV were greater than those in the PV (LGV: 28.3+/-26.1%, PV: 7.2+/-13.2%, P < 0.01), whereas no significant changes in the LGV occurred before and after ingestion of glucose in the control subjects. CONCLUSION: Hemodynamics of the PV is unrelated to the degree of endoscopic abnormalities in patients with liver cirrhosis. The most important combinations are endoscopic findings followed by the LGV hemodynamics. Duplex-Doppler ultrasonography has no value in the identification of patients with cirrhosis at risk of variceal bleeding. Hemodynamics of the LGV appears to be superior to those of the PV in predicting bleeding.     

Long-term response to interferon plus ribavirin in patients with chronic hepatitis C refractory to interferon.

OBJECTIVE: A sustained response (SR) to interferon (IFN) is only observed in 15-20% of patients with chronic hepatitis C (CHC). The aim of this study was to determine the long-term effectiveness and safety of the treatment with IFN plus ribavirin (RIB) over two years in CHC patients without SR to IFN. DESIGN: A prospective and open longitudinal follow-up study was conducted over 3 years. PATIENTS AND METHODS: A total of 77 CHC patients were included: 63 non-responders (NR) and 14 relapsers (R) to IFN. Patients were treated with IFN (3 MU s.c. three times a week) and RIB (1,000-1,200 mg p.o. daily) for 12 months. Treatment tolerance and viral response (HCV-RNA in serum < 1,000 copies/ml) were assessed after 1, 3, 6 and 12 months of treatment. SR and relapsing rates were subsequently evaluated 6, 12 and 24 months after the end of the treatment, together with those variables capable of predicting SR. RESULTS: At the end of the treatment, 19/77 patients responded (24.7%), 9/63 (14.3%) were non-responders and 10/14 (71.4%) relapsers, and these same patients exhibited SR after 6 months. The SR rate two years after treatment was 22.1% [8/63 (12.7%) NR and 9/14 (64.3%) R]. The relapse rate after 6 months and two years was respectively 0 and 10.5% (2/77). Independent variables capable of predicting SR were negative viremia conversion within the first month of treatment, maintenance of such negative viremia after 6 months, and R status to IFN. Side effects were recorded in 90.9% of cases (70/77), the most frequent being pseudoinfluenza syndrome. Treatment had to be discontinued in 33.8% of patients (26/77). CONCLUSIONS: Combined IFN-RIB therapy for 12 months in CHC patients without SR to IFN obtains a long-term SR of 22.1%, this rate being higher in relapsers to prior IFN therapy (64.3% in R versus 12.7% in NR).     

Early immune-mediated response to ribavirin combined with IFN in patients with chronic hepatitis C.

AIM: This study was to investigate the immunomodulatory effects of ribavirin combined with interferon (IFN)-alpha 2b (R+IFN) compared with consensus IFN monotherapy (IFN-Con) in chronic hepatitis C (CHC) patients. PATIENTS AND METHODS: Thirty-four adult patients with biopsy-proven CHC, who were infected with HCV genotype 2a or 2b, were studied. A 24-week regimen of IFN-alpha 2b (6MU daily for 2 weeks followed by 6MU tiw for 22 weeks) and ribavirin (600-800mg/day for 24 weeks) was given to 17 patients. The other 17 patients were treated with a 24-week regimen of IFN-Con (18MU daily for 2 weeks followed by 18MU tiw for 22 weeks). Flow cytometric determination of cytoplasmic IFN-gamma and IL-4 expression in peripheral blood CD4+ T cells was performed, and the percentage of IFN-gamma+ and IL-4- (Th1), IFN-gamma- and IL-4+ (Th2) cells were calculated before and 3, 7, 14, and 28 days after the start of therapy. RESULTS: In the R+IFN group, the percentage of Th1 cell peaked on day 3, and then decreased to near baseline by day 14, while the percentage of Th2 cell did not change. In the IFN-Con group, the percentage of Th1 cell peaked on day 14 and the percentage of Th2 cell peaked on day 3, and then decreased to near baseline by day 14. CONCLUSIONS: Our results suggest that ribavirin induces an early immune response by peripheral blood CD4+ T cells in CHC patients.     

The effects of selective and non-selective adrenoceptor blockade on the portal blood flow in patients with liver cirrhosis

The effects of different types of adrenoceptor blocking agents on portal venous blood flow were studied in 10 patients with liver cirrhosis by using a duplex Doppler system. Oral atenolol (selective beta 1 blocker), propranolol (non-selective beta blocker), and labetalol (non-selective adrenoceptor blocker) were compared. The drugs were administered at random at an interval of 3 days or more. Hemodynamic measurements were done before and after 1 h, 2 h, and 3 h of therapy. Atenolol and propranolol produced significant decrease in the portal vein cross-sectional area, portal blood velocity, and estimated volume of the portal blood flow. The portal blood velocity decreased by 13.1 +/- 7.2% 3 h after atenolol and by 16.2 +/- 6.5% 3 h after propranolol administration (p less than 0.05). Labetalol had no significant influence on portal venous hemodynamics. These results support the hypothesis that a decrease in portal venous flow induced by beta blockers is at least partly mediated with alpha-adrenergic receptors.     

联合高压氧治疗肝硬化门脉高压疗效观察

目的通过观察肝硬化门脉高压食管胃底静脉曲张患者经高压氧治疗后门静脉系统血流动力学和肝功能的变化,尝试探索高压氧在改善肝功能、预防肝硬化食管静脉曲张再出血维持治疗中的作用.方法2003年1月～2004年12月期间,36例肝炎后肝硬化食管静脉中～重度曲张的住院患者,随机分为3组:高压氧组12例,内科常规联合高压氧治疗2周,每日1次,每次2小时;心得安组12例,心得安10mg及单硝酸异山梨酯20mg,分别为每日3次及2次口服,连续2周;对照组12例内科常规治疗2周.运用彩色多普勒血管超声检测3组患者治疗前后门静脉直径(PV)、脾静脉直径(SV)和门静脉平均血流速度(Vmean)及脾脏厚度的变化,并计算门静脉血流量.同步检测3组患者治疗前后肝功能,前白蛋白(PA)、凝血酶原时间(PT)及吲哚氰绿15min潴留率(ICG15)的变化.结果高压氧组与心得安组血流动力学指标均有不同程度改善,门静脉血流量减少,门脉压力降低;而高压氧组肝功能改善明显优于心得安组及对照组.结论高压氧对防治肝硬化门脉高压食管静脉曲张再出血及改善肝功能具有潜在的治疗作用.     

Technical dilemma in living-donor or split-liver transplant

In partial liver transplantation for adults criteria for the extent of reconstruction of middle hepatic vein tributaries have not been clarified. After hepatic venous and portal anastomoses in living-donor liver transplantation using left liver graft without middle hepatic vein, color Doppler ultrasonography was applied to check venous and portal blood flow. Color Doppler ultrasonography demonstrated absent hepatic venous flow and reversed portal venous flow in the congested area of the left paramedian sector which had been drained by the divided branch of the middle hepatic vein. The area was darkly discolored before arterial reperfusion and under clamping of the artery. Reconstruction of the venous branch was added after arterial anastomosis. Color Doppler ultrasonography revealed restored normal venous outflow and portal inflow after venous reconstruction. Postoperative course of the recipient was uneventful with rapid recovery of liver function. We propose that middle hepatic vein tributaries should be reconstructed if color Doppler ultrasonography demonstrates absent venous flow and reversed portal flow, and if the liver volume excluding the discolored area under occlusion of the hepatic artery is estimated to be insufficient for postoperative metabolic demand.     

Interferon signaling and treatment outcome in chronic hepatitis C

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFNalpha) and ribavirin. It achieves a sustained viral clearance in only 50-60% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFNalpha. In patients with a rapid virological response to treatment, pegIFNalpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFNalpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway.     

不耐受标准治疗方案慢性丙型肝炎患者的低剂量干扰素治疗

目的 针对不能耐受标准治疗方案的慢性丙型肝炎(CHC)患者,探索低剂量干扰素联合利巴韦林长期维持治疗的效果,并分析与疗效相关的可能影响因素. 方法 对于白细胞低下、甲状腺功能异常等多种原因不能耐受标准治疗方案的CHC患者46例,给予个体化低剂量干扰素(标准干扰素60万～300万IU隔日一次,聚乙二醇干扰素50 ～ 90μg/周)联合利巴韦林0.6 ～ 0.9 g/d 长期维持治疗,疗程≥72周.连续变量两组间比较采用t检验或秩和检验,计数资料采用x2检验或Fisher’s exact test检验.结果 93.5％患者(43/46)可耐受不同低剂量干扰素联合利巴韦林长期维持治疗,只有3例不能耐受而被迫停药.不同节点的病毒学应答率为:快速病毒学应答10.9％、早期病毒学应答 30.4％、24周病毒学应答45.7％、48周病毒学应答47.8％.3例患者在治疗过程中肝脏B型超声显示形态学改善.快速病毒学应答、早期病毒学应答、24周病毒学应答者均可在48周时获得较高病毒学应答,尤其24周病毒学应答对48周病毒学应答具有较好预测作用,获得24周病毒学应答者其48周病毒学应答率为95.2％,而24周未获得病毒学应答者其48周未应答率为92.0％.结论 (1)对于不能耐受标准治疗方案的CHC患者予以低剂量干扰素联合利巴韦林长期维持治疗,可以获得较高的48周病毒学应答率(47.8％);(2)24周病毒学应答对48周病毒学应答具有较好预测作用;(3)疗程中严密监测、对症治疗原发病并给予患者足够的依从性教育和心理疏导是治疗得以维持的重要保证.     

硝酸异山梨酯气雾剂对门静脉血流动力学的影响

探讨硝酸异山梨酯以气雾剂的形式应用对门静脉血流动力学的影响。于1999年2月—1999年11月选择肝硬化门脉高压患者31例，利用无创伤自身对照的方法，用彩色超声多普勒检测患者的门静脉直径、血流速度、血流量，脾静脉直径、血流速度及血流量，然后向患者口腔内喷入硝酸异山梨酯气雾剂(商品名：欣舒气雾剂，山东省医药工业研究所制药厂生产)4喷(约含药量2．5mg)，于用药后1分钟、10分钟、30分钟再分别检测以上项目，并进行统计学处理。用硝酸异山梨酯气雾剂后可缩小肝硬化门脉高压患者的门静脉直径、降低门脉血流速度、减少门脉血流量(P＜0．01)，因而可降低门脉压力，对患者的血压和脉搏无显著影响(P＞0．05)其它副作用轻微，并且在1分钟内起效，持续半小时以上。提示：硝酸异山梨能气雾剂可快速降低门静脉压力，从而提出将硝酸异山梨酯以气雾剂的形式用于预防和治疗肝硬化门静脉高压引起的上消化道出血。