Sei Jin Chang

Acute Hemodynamic Effects of Octreotide and Terlipressin in Patients with Cirrhosis: A Randomized Comparison

BACKGROUND:Octreotide and terlipressin are widely used in acute variceal hemorrhage to reduce the bleeding rate. They purportedly act by mesenteric arterial vasoconstriction, thus reducing portal venous flow (PVF) and portal pressure. Little is known about the immediate-early hemodynamic effects of these drugs.AIM:To compare the acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis.PATIENTS:Forty-two cirrhotic patients with a history of variceal bleeding were randomized to receive either octreotide 100 μg intravenous bolus followed by a continuous infusion at 250 μg/h (n = 21), or terlipressin 2 mg intravenous bolus (n = 21).METHODS:Mean arterial pressure (MAP), heart rate (HR), hepatic venous pressure gradient (HVPG), and PVF, assessed by duplex Doppler ultrasonography, were measured before and at 1, 5, 10, 15, 20, and 25 min after the start of drug administration.RESULTS:Octreotide markedly decreased HVPG (−44.5 ± 17.8%) and PVF (−30.6 ± 13.6%) compared to the baseline at 1 min (p < 0.05). Thereafter, both variables rapidly returned toward the baseline, and by 5 min, no significant differences in HVPG (−7.1 ± 28.9%) and PVF (10.2 ± 26.2%) were noted. A similar transient effect on MAP and HR was observed. Terlipressin significantly decreased HVPG (−18.3 ± 11.9%) and PVF (−32.6 ± 10.5%) at 1 min (p < 0.05) and sustained these effects at all time points. The effects on arterial pressure and HR were also sustained.CONCLUSIONS:Octreotide only transiently reduced portal pressure and flow, whereas the effects of terlipressin were sustained. These results suggest that terlipressin may have more sustained hemodynamic effects in patients with bleeding varices.

Histological subclassification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical stage and grade of portal hypertension

BACKGROUND & AIMSnFurther histological subclassification of cirrhosis may be useful because of heterogeneity of severity within cirrhosis. We aimed to determine the relationship between histological subclassification and clinical stage of cirrhosis as well as grade of portal hypertension.nnnMETHODSnOne hundred-twenty-three biopsy-proven cirrhosis patients, whose clinical stage of cirrhosis and hepatic venous pressure gradient (HVPG) could be estimated, were included in this prospective study. Histology of cirrhosis was blindly subclassified using the Laennec fibrosis scoring system semi-quantitatively without knowledge of the clinical stage or the HVPG results. The Laennec system subclassifies cirrhosis as mild - thin septa, moderate - at least two broad septa, and severe - at least one very broad septum or many minute nodules. Clinical stages were determined by the presence or absence of varices, ascites, and variceal hemorrhage. Biological and laboratory data were also collected.nnnRESULTSnAlcohol intake was the most common cause of cirrhosis in this cohort (87, 70.7%). Histology of cirrhosis subclassified using the Laennec scoring system significantly correlated with both the clinical stage of cirrhosis (p < 0.001) and HVPG (mild: 8.1 ± 2.6 mm Hg, moderate: 12.4 ± 3.3mm Hg, severe: 16.3 ± 4.0 mm Hg, p < 0.001). With higher grades of histological subclassification of cirrhosis, increased frequency in both severe portal hypertension (HVPG ≥ 12 mm Hg) and episodes of variceal hemorrhage were observed (p < 0.001).nnnCONCLUSIONSnHistological subclassification of cirrhosis by the Laennec fibrosis scoring system is tightly correlated with both the clinical stage of cirrhosis and grade of portal hypertension. This suggests that cirrhosis should be subclassified into different stages according to its histological severity.

Hepatic vein arrival time as assessed by contrast-enhanced ultrasonography is useful for the assessment of portal hypertension in compensated cirrhosis.

The measurement of the hepatic venous pressure gradient (HVPG) for the estimation of portal hypertension (PH) in cirrhosis has some limitations, including its invasiveness. Hepatic vein arrival time (HVAT), as assessed by microbubble contrast‐enhanced ultrasonography (CEUS), is negatively correlated with the histological grade of liver fibrosis because of the associated hemodynamic abnormalities. Anatomical and pathophysiological changes in liver microcirculation are the initial events leading to PH. However, the direct relationship between HVAT and PH has not been evaluated. The present study measured both HVPG and HVAT in 71 consecutive patients with compensated cirrhosis and analyzed the relationship between the two parameters (i.e., the derivation set). Results were validated in 35 compensated patients with cirrhosis at another medical center (i.e., the validation set). The derivation set had HVPG and HVAT values of 11.4 ± 5.0 mmHg (mean ± standard deviation; range, 2‐23) and 14.1 ± 3.4 seconds (range, 8.4‐24.2), respectively; there was a statistically significant negative correlation between HVPG and HVAT (r2 = 0.545; P < 0.001). The area under the receiver operating characteristic curve (AUROC) was 0.973 for clinically significant PH (CSPH; HVPG, ≥10 mmHg), and the sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios for CSPH for an HVAT cut‐off value of 14 seconds were 92.7%, 86.7%, 90.5%, 89.7%, 6.95, and 0.08, respectively. In addition, a shorter HVAT was associated with worse Child‐Pugh score (P < 0.001) and esophageal varices (P = 0.018). In the validation set, there was also a significant negative correlation between HVAT and HVPG (r2 = 0.538; P < 0.001), and AUROC = 0.953 for CSPH. HVAT was significantly correlated with PH. These results indicate that measuring HVAT is useful for the noninvasive prediction of CSPH in patients with compensated cirrhosis. (HEPATOLOGY 2012;56:1053–1062)

Job stress and depressive symptoms among Korean employees: the effects of culture on work

ObjectiveThis study was conducted to investigate the association between depressive symptoms and job stress, as measured by the KOSS, among Korean employees in small- and medium-sized enterprises, and examined which components of stress are involved in the risk for depression among males and females.MethodsData were collected from a work-stress survey of full-time employees of small- and medium-sized enterprises in Incheon, South Korea. A total of 3,013 participants were included in the analysis. Job stress was measured using 24 items (7 sub-scales) of the short form of Korean occupational stress scale (KOSS-SF), and depressive symptoms were evaluated using Center for epidemiologic studies depression scale (CES-D).ResultsAfter adjustment for confounding variables, most of subscales of job stress contributed to an increased risk of depressive symptoms, and job insecurity (male; ORxa0=xa02.02, 95%CI: 1.61–2.40, female; ORxa0=xa01.95, 95%CI: 1.42–2.70) and occupational climate (male; ORxa0=xa01.84, 95%CI: 1.49–2.28, female; ORxa0=xa01.78, 95%CI: 1.30–2.49) showed strong associations in both male and female. Other subscales revealed different effects for males and females; for males, job demands (ORxa0=xa01.68, 95%CI: 1.43–2.20), inadequate social support (ORxa0=xa01.55, 95%CI: 1.23–1.94), and lack of rewards (ORxa0=xa01.88, 95%CI: 1.48–2.37) were associated with depressive symptoms, whereas for females, organizational injustice (ORxa0=xa01.62, 95%CI: 1.14–2.30) was associated with depressive symptoms.ConclusionThese results indicate that job stress may play a significant role in increasing the risk of depressive symptoms, and that further preventive efforts and research are needed to reduce job stress and address health problems caused by job stress among Korean employees.

Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective nonrandomized study

Background and Aims: Alterations in the Doppler hepatic vein (HV) waveform are associated with cirrhosis and portal hypertension. We prospectively evaluated the correlation between the extent of abnormal Doppler HV waveforms expressed as damping index (DI) and the hepatic venous pressure gradient (HVPG) and response to propranolol in patients with cirrhosis.

Current trends in the epidemiological and pathological characteristics of gastrointestinal stromal tumors in Korea, 2003-2004.

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patients survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patients survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patients survival, but the mechanism still needs to be clarified through future studies.

Captopril reduces portal pressure effectively in portal hypertensive patients with low portal venous velocity

BackgroundThe effect of an angiotensin II blockade in lowering the portal pressure in patients with liver cirrhosis and portal hypertension is controversial. This prospective study was undertaken to evaluate the portal hypotensive effect of captopril compared to that of propranolol, and to determine the factors that contribute to a successful reduction in the portal pressure after longterm captopril administration in patients with liver cirrhosis.MethodsThe hepatic venous pressure gradient (HVPG) and portal venous velocity (PVV) were measured both before and 3 months after initiation of the administration of captopril (n = 29) or propranolol (n = 29) in cirrhotic patients with a variceal bleeding episode. Patients who showed a reduction in the HVPG of more than 20% of the baseline were defined as being responders.ResultsAt 3 months, the mean reduction in the HVPG after captopril was less than that after propranolol (−3.0 ± 9.3% vs −28.5% ± 4.1%; P ≪ 0.05). However, of the 29 patients receiving captopril, 9 were classified as being responders. On multivariate analysis with parameters including age, cause, Child-Pugh score, HVPG, and PVV, only low PVV was found to be a significant independent factor for responders (PVV ≪ 12u2009cm/s; odds ratio [OR], 12.2; 95% confidence interval [CI], 1.47–102.40) in the captopril group.ConclusionsLongterm captopril administration reduces the portal pressure effectively in cirrhotic patients with a low PVV. This suggests that the reduction in portal pressure after captopril administration is a result of improved portal venous outflow brought about by a decrease in the intrahepatic vascular resistance. When the PVV is below 12u2009cm/s, a captopril trial might be useful in preventing variceal bleeding in portal hypertensive patients.

Beneficial effects of candesartan, an angiotensin‐blocking agent, on compensated alcoholic liver fibrosis ‐ A randomized open‐label controlled study

Recent studies have shown that the renin‐angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo. However, no study was done in humans with alcoholic liver disease.

Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model

BackgroundAngiotensin blockade such as with an angiotensin II receptor blocker (ARB) or angiotensinconverting enzyme inhibitor (ACEI) has antifibrotic properties. The aim of this study was to evaluate and compare the antifibrotic effect between ARBs and ACEIs.MethodsCommon bile duct-ligated (BDL) adult Sprague-Dawley rats were allocated to five groups (each group, n = 8) as follows: G1, BDL without drug; G2, BDL + captopril 100 mg/kg per day; G3, BDL + ramipril 10 mg/kg per day; G4, BDL + losartan 10 mg/kg per day; G5, BDL + irbesartan 15 mg/kg per day. Four weeks post-BDL, hepatic fibrosis was analyzed histomorphologically using Batts and Ludwig scores. α-Smooth muscle actin (α-SMA) expression by immunohistochemical staining, hydroxyproline contents of liver tissue by spectrophotometry, and angiotensin receptor, collagen, procollagen, and transforming growth factor β (TGF-β) expressions were evaluated by real-time reverse transcriptase-polymerase chain reaction. Angiotensin receptor expression was also determined by Western blotting.ResultsBatts and Ludwig scores were 3.8, 2.6, 2.4, 1.8, and 1.6 in G1, G2, G3, G4, and G5, respectively. Histologically, ARB groups (G4, G5) showed significant suppression of hepatic fibrosis compared with ACEI groups or the control. Expressions of α-SMA (%) and the content of hydroxyproline (μg liver tissue) were significantly lower in ARB groups (G4, G5) than in ACEI groups (G2, G3) (P < 0.05). Also, ARB reduced the expression of angiotensin receptor, collagen, procollagen, and TGF-β1 compared with ACEI. Western blot analysis showed that the expression of angiotensin receptor was inhibited in both ARB and ACEI groups.ConclusionsBoth ARB and ACEI attenuate hepatic fibrosis through inhibiting hepatic stellate cell activation, and the inhibitory effect of ARBs on hepatic fibrosis is superior to that of ACEIs in the BDL rat model.

Portal hypertensive gastropathy: correlation with portal hypertension and prognosis in cirrhosis.

BackgroundPortal hypertensive gastropathy (PHG) is a common endoscopic finding in patients with cirrhosis. However, the relationship between PHG and portal hypertension is controversial. Furthermore, nothing is known regarding the correlation between PHG and prognosis in patients with cirrhosis.MethodsThe hepatic venous pressure gradient (HVPG), endoscopic PHG grade, Child–Pugh score, and model for end-stage liver disease (MELD) score were assessed at baseline and were followed prospectively in 331 cirrhotic patients (284 males, 85.8%; mean age, 52.16xa0±xa09.05xa0years) from January 2001 to April 2009. The relationship between PHG with HVPG and survival was investigated.ResultsThe HVPG was significantly higher in patients with severe PHG than in those with mild or no PHG (absent, 4.9xa0±xa01.7xa0mmHg; mild, 10.7xa0±xa04.1xa0mmHg; severe, 15.6xa0±xa04.6xa0mmHg; Pxa0<xa00.001). During follow-up, 28 patients (8.5%) died from liver-related disease. In the Cox regression analysis, severe PHG (none and mild vs. severe) (hazard ratio 1.153, 95% confidence interval: 1.048–1.269) showed a significantly high relative risk of mortality, and in the Kaplan–Meier analysis, severe PHG showed a significantly shorter expected survival time than none or mild PHG (median survival time, 77.6xa0±xa09.6xa0months in severe PHG; log-rank test, Pxa0=xa00.030).ConclusionsPHG was associated with portal hypertension severity and prognosis in patients with cirrhosis.