Bone Marrow-Derived Mesenchymal Stem Cells Isolated from Patients with Cirrhosis and Healthy Volunteers Show Comparable Characteristics

Background and Objectives@#Autologous or allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) have been applied in clinical trials to treat liver disease. However, only a few studies are comparing the characteristics of autologous MSCs from patients and allogeneic MSCs from normal subjects. @*Methods@#and Results: We compared the characteristics of BMSCs (BCs and BPs, respectively) isolated from six healthy volunteers and six patients with cirrhosis. In passage 3 (P3), senescent population and expression of p53 and p21 were slightly higher in BPs, but the average population doubling time for P3–P5 in BPs was approximately 65.3±11.1 h, which is 18.4 h shorter than that in BCs (83.7±9.2 h). No difference was observed in the expression of CD73, CD90, or CD105 between BCs and BPs. Adipogenic differentiation slightly increased in BCs, but the expression levels of leptin, peroxisome proliferator-activated receptor γ, and CCAAT-enhancer-binding protein α did not vary between differentiated BCs and BPs. While ATP and reactive oxygen species levels were slightly lower in BPs, mitochondrial membrane potential, oxygen consumption rate, and expression of mitochondria-related genes such as cytochrome c oxidase 1 were not significantly different between BCs and BPs. @*Conclusions@#Taken together, there are marginal differences in the proliferation, differentiation, and mitochondrial activities of BCs and BPs, but both BMSCs from patients with cirrhosis and healthy volunteers show comparable characteristics.

Measuring Intrahepatic Vascular Changes Using Contrast-Enhanced Ultrasonography to Predict the Prognosis of Alcoholic Hepatitis Combined with Cirrhosis: A Prospective Pilot Study

BACKGROUND/AIMS: Acute hepatic dysfunction combined with alcoholic hepatitis (AH) in alcoholic cirrhosis is related to hepatic hypo-perfusion secondary to intrahepatic necroinflammation, neoangiogenesis, and shunt. The hepatic vein arrival time (HVAT) assessed by microbubble contrast-enhanced ultrasonography (CEUS) is closely correlated with the severity of intrahepatic changes. We investigated the usefulness of HVAT to predict short-term mortality of AH in cirrhosis. METHODS: Thirty-nine patients with alcoholic cirrhosis (27 males) and AH were prospectively enrolled. HVAT study was performed within 3 days after admission using ultrasonic contrast (SonoVue®). The primary outcome was 12-week mortality. RESULTS: Twelve-week mortality developed in nine patients. HVAT was significantly different between the mortality and survival groups (9.3±2.0 seconds vs 12.6±3.5 seconds, p=0.002). The odds ratio of a shortened HVAT for 12-week mortality was 1.481 (95% confidence interval, 1.050–2.090; p=0.025). The area under the receiver operating characteristic curve of HVAT for 12-week mortality was 0.787 (p=0.010). The combination of MDF and HVAT ≥11.0 seconds resulted in an 87.5% survival rate even if the MDF score ≥32; however, HVAT < 11.0 seconds was related with mortality despite a MDF score < 32. CONCLUSIONS: HVAT using microbubble CEUS could be a useful additional index to predict short-term mortality in patients with AH and cirrhosis.

Rifaximin and Propranolol Combination Therapy Is More Effective than Propranolol Monotherapy for the Reduction of Portal Pressure: An Open Randomized Controlled Pilot Study

BACKGROUND/AIMS: Non-selective beta blockers (NSBBs) are currently the only accepted regimen for preventing portal hypertension (PHT)-related complications. However, the effect of NSBBs is insufficient in many cases. Bacterial translocation (BT) is one of the aggravating factors of PHT in cirrhosis; therefore, selective intestinal decontamination by rifaximin is a possible therapeutic option for improving PHT. We investigated whether the addition of rifaximin to propranolol therapy can improve hepatic venous pressure gradient (HVPG) response. METHODS: Sixty-four cirrhosis patients were randomly assigned to propranolol monotherapy (n=48) versus rifaximin and propranolol combination therapy (n=16). Baseline and post-treatment HVPG values, BT-related markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], interleukin-6 [IL-6], and tumor necrosis factor α [TNF-α]), serological data, and adverse event data were collected. HVPG response rate was the primary endpoint. RESULTS: Combination therapy was associated with better HVPG response rates than monotherapy (56.2% vs 87.5%, p=0.034). In combination therapy, posttreatment BT-related markers were significantly decreased (LPS, p=0.005; LBP, p=0.005; IL-6, p=0.005; TNF-α, p=0.047). CONCLUSIONS: Rifaximin combination therapy showed an additive effect in improving PHT compared to propranolol monotherapy. These pilot data suggest that the addition of rifaximin to NSBBs could be a good therapeutic option for overcoming the limited effectiveness of NSBBs.

Successful removal of a foreign body by endoscopic balloon dilatation at the colonic stricture / 영남의대학술지

Most ingested foreign bodies pass readily throughout intestinal tract if they reach the stomach. In some cases, foreign bodies may be impacted behind a luminal constriction but are rare in colon. Here, we report the case of a 59-year-old man who did laparoscopic anterior resection due to sigmoid colon cancer 2 years ago and ischemic colitis was repeated on the anastomosis site. He initially presented with symptoms of abdominal pain 3 months before and melena 1 day before admission. Abdomen computerized tomography showed a 3.2 cm segment of luminal narrowing of the proximal colon involving upstream foreign material stasis. Sigmoidoscopic approaches revealed near complete obstruction on the anal verge of 20 cm and scope passing failed. Balloon dilatations were done on the obstruction site four times all and a foreign body impacted above the obstruction site was removed by an alligator without any complications. The foreign body removed looks like plastic or a shell, about 20 mm in size.

Clinical Implications of the Serum Apelin Level on Portal Hypertension and Prognosis of Liver Cirrhosis

BACKGROUND/AIMS: Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD). METHODS: From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0±12.9 months for decompensation and mortality. RESULTS: A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R2=0.263, p<0.001) and collagen proportional area (R2=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R2=0.356, p<0.001). In a multivariate analysis using a Cox regression hazard model, s-apelin was a weakly significant predictor of decompensation (hazard ratio [HR], 1.002; p<0.001) and mortality (HR, 1.003; p<0.001). CONCLUSIONS: s-apelin showed a significant relationship with CLD severity. However, its significance as a noninvasive biomarker for disease severity and prognosis was weak.

Extranodal natural killer/T-cell lymphoma of the tenosynovium of the hand

No abstract available.

Therapeutic Effects of Mesenchymal Stem Cells for Patients with Chronic Liver Diseases: Systematic Review and Meta-analysis

Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.

The usefulness of non-invasive liver stiffness measurements in predicting clinically significant portal hypertension in cirrhotic patients: Korean data

BACKGROUND/AIMS: Liver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis. METHODS: LSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG > or =10 and > or =12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves. RESULTS: A strong positive correlation between LSM and HVPG was observed in the overall population (r2=0.496, P or =10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG > or =12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively. CONCLUSIONS: LSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.