PURPOSE: The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. MATERIALS AND METHODS: From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. RESULTS: Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. CONCLUSION: COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia.
Biliary Atresia/complications/enzymology/*surgery ; Child ; Child, Preschool ; Chronic Disease ; Cyclooxygenase 2 Inhibitors/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/etiology/pathology/*prevention & control ; Male ; *Portoenterostomy, Hepatic ; Thiazines/*therapeutic use ; Thiazoles/*therapeutic use

Laparoscopic liver resection (LLR) is becoming widely accepted for the treatment of hepatocellular carcinoma (HCC). Laparoscopic left lateral sectionectomy and minor laparoscopic liver resection are now considered standard approaches, especially for tumors located in the anterolateral segments of the liver. Laparoscopic left lateral sectionectomy in adult donors is also gaining acceptance for child liver transplantation in many centers. Major LLRs, including left hepatectomy and right hepatectomy, have been recently attempted. Laparoscopic donor hepatectomy is becoming more popular owing to increasing demand from young living donors who appreciate its minimal invasiveness and excellent cosmetic outcomes. Several centers have performed total laparoscopic donor right hepatectomy in adult-to-adult living donor liver transplantation. Many meta-analyses have shown that LLR is better than open liver resection in terms of short-term outcomes, principally cosmetic outcomes. Although no randomized control trials have compared LLR with open liver resection, the long-term oncologic outcomes were similar for both procedures in recent case-matched studies.
Carcinoma, Hepatocellular/complications/pathology/*surgery ; Humans ; Laparoscopy ; Liver Cirrhosis/complications ; Liver Neoplasms/pathology/*surgery ; Neoplasm Recurrence, Local ; Prognosis

Laparoscopic liver resection (LLR) is becoming widely accepted for the treatment of hepatocellular carcinoma (HCC). Laparoscopic left lateral sectionectomy and minor laparoscopic liver resection are now considered standard approaches, especially for tumors located in the anterolateral segments of the liver. Laparoscopic left lateral sectionectomy in adult donors is also gaining acceptance for child liver transplantation in many centers. Major LLRs, including left hepatectomy and right hepatectomy, have been recently attempted. Laparoscopic donor hepatectomy is becoming more popular owing to increasing demand from young living donors who appreciate its minimal invasiveness and excellent cosmetic outcomes. Several centers have performed total laparoscopic donor right hepatectomy in adult-to-adult living donor liver transplantation. Many meta-analyses have shown that LLR is better than open liver resection in terms of short-term outcomes, principally cosmetic outcomes. Although no randomized control trials have compared LLR with open liver resection, the long-term oncologic outcomes were similar for both procedures in recent case-matched studies.
Carcinoma, Hepatocellular/complications/pathology/*surgery ; Humans ; Laparoscopy ; Liver Cirrhosis/complications ; Liver Neoplasms/pathology/*surgery ; Neoplasm Recurrence, Local ; Prognosis

BACKGROUND/AIMS: Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). METHODS: The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. RESULTS: The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. CONCLUSION: CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.
Angiogenic Proteins/genetics/metabolism ; Animals ; Bile Ducts/surgery ; C-Reactive Protein/*analysis/genetics/metabolism ; Cells, Cultured ; Disease Models, Animal ; Hepatic Veins/abnormalities ; Hepatocytes/cytology/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Lithocholic Acid/pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/etiology ; Liver Diseases/metabolism/*pathology ; Male ; Microscopy, Fluorescence ; Mitochondria/drug effects/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Serum Albumin/genetics/metabolism

OBJECTIVETo explore the clinical and pathological factors influencing the prognosis of patients with hepatocellular carcinoma (HCC)(≤5 cm) after hepatectomy.

METHODSTwo hundreds and nineteen cases with HCC(≤5 cm) undergoing hepatectomy in Cancer Hospital, Chinese Academy of Medical Sciences between December 2003 and July 2013 were collected. The alpha fetoprotein (AFP) level, tumor number, tumor size (diameter), liver cirrhosis, vascular invasion, capsular invasion, differentiation, surgical methods, resection margin, the way of treatments, the situation of recurrence and time to recurrence were analyzed. Log-rank test and the stepwise Cox proportional-hazards models were used to compare the prognosis, respectively.

RESULTSThe 1-, 3-, 5- and 10- year overall survival rates were 95.9%, 85.3%, 67.8% and 53.3% respectively in all patients.Single factor analysis indicated that vascular invasion, capsular invasion, tumor size, hepatic vascular occult, liver cirrhosis, tumor differentiation, AFP, the way of treatments, the situation of recurrence and time to recurrence can affect the prognosis significantly (all P<0.05). The multifactor analysis showed that AFP, tumor differentiation, liver cirrhosis, capsular invasion, tumor size and the situation of recurrence and time to recurrence were independent prognostic factors (all P<0.05).

CONCLUSIONThe prognosis of patients with HCC(≤5 cm) underwent hepatectomy are affected by multi-factors, such as AFP, tumor differentiation, liver cirrhosis, capsular invasion, tumor size and the situation of recurrence and time to recurrence.

Carcinoma, Hepatocellular ; diagnosis ; surgery ; Hepatectomy ; Humans ; Liver Cirrhosis ; diagnosis ; pathology ; Liver Neoplasms ; diagnosis ; surgery ; Neoplasm Recurrence, Local ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; alpha-Fetoproteins ; analysis

INTRODUCTIONMinimally invasive hepatectomy (MIH) for patients with hepatocellular carcinoma (HCC) is technically challenging, especially with large posteriorly located tumours or background of liver cirrhosis. This is a case-control study comparing the long-term oncological safety of HCC patients who underwent MIH and open hepatectomy (OH). Most of these patients have liver cirrhosis compared to other studies.

MATERIALS AND METHODSSixty patients were divided into 2 groups, 30 underwent MIH and 30 underwent OH for HCC resection. The patients in both groups were matched for extent of tumour resection, age and cirrhosis status. Patient characteristics, risk factors of HCC and all oncological data were studied.

RESULTSNegative resection margins were achieved in 97% of patients in both groups. The mean blood loss during surgery was significantly lower in the MIH group compared to the OH group (361 mL vs 740 mL; 95% CI, 222.2, 734.9; P = 0.04). Hospitalisation is significantly shorter in MIH group (7 days vs 11 days; 95% CI, 6.9, 12.2,; P = 0.04). Eight patients (27%) in the MIH group and 13 patients (43%) in the OH group developed HCC recurrence (P = 0.17). One, 3 and 5 years disease-free survival between MIH and OH groups are 76% vs 55%, 58% vs 47%, and 58% vs 39% respectively (P = 0.18). One, 3 and 5 years overall survival between MIH and OH groups are 93% vs 78%, 89% vs 70%, and 59% vs 65% respectively (P = 0.41).

CONCLUSIONMIH is a safe and feasible curative treatment option for HCC with similar oncological outcomes compared to OH. MIH can be safely performed to remove tumours larger than 5 cm, in cirrhotic liver, as well as centrally and posterior located tumours. In addition, MIH patients have significant shorter hospitalisation and intraoperative blood loss.

Blood Loss, Surgical ; Carcinoma, Hepatocellular ; complications ; pathology ; surgery ; Case-Control Studies ; Disease-Free Survival ; Hepatectomy ; methods ; Humans ; Laparoscopy ; Length of Stay ; Liver Cirrhosis ; complications ; Liver Neoplasms ; complications ; pathology ; surgery ; Margins of Excision ; Minimally Invasive Surgical Procedures ; methods ; Neoplasm Recurrence, Local ; epidemiology ; Tumor Burden

Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.
Animals ; Cell Differentiation ; Cell Proliferation ; Hepatocytes/immunology/metabolism/pathology/*transplantation ; Humans ; Liver/immunology/metabolism/pathology/physiopathology/*surgery ; Liver Cirrhosis/diagnosis/immunology/metabolism/physiopathology/*surgery ; Liver Regeneration ; *Mesenchymal Stem Cell Transplantation/adverse effects ; *Mesenchymal Stromal Cells/immunology/metabolism/pathology ; Phenotype ; Regenerative Medicine/*methods ; Risk Factors ; Signal Transduction ; Treatment Outcome

BACKGROUND/AIMS: To investigate the efficacy and longterm outcome of esophageal variceal ligation (EVL) plus propranolol in comparison with propranolol alone for the primary prophylaxis of esophageal variceal bleeding. METHODS: A total of 504 patients were retrospectively enrolled in this study. 330 patients were in propranolol group (Gr1) and 174 patients were in EVL plus propranolol group (Gr2). The endpoints of this study were esophageal variceal bleeding and mortality. Association analyses were performed to evaluate bleeding and mortality between Gr1 and Gr2. RESULTS: EVL was more applied in patients with high risk, such as large-sized varices (F2 or F3) or positive red color signs. Total 38 patients had bleeds, 32 in Gr1 and 6 in Gr2. The cumulative probability of bleeding at 120 months was 13% in Gr1 versus 4% in Gr2 (P=0.04). The predictive factors of variceal bleeding were red color signs (OR 2.962, P=0.007) and the method of propranolol plus EVL (OR 0.160, P=0.000). 20 patients died in Gr1 and 12 in Gr2. Mortality rates are similar in the two groups compared, 6.7% in Gr1 and 6.9% in Gr2. The cumulative probability of mortality at 120 months was not significantly different in the two groups (7% in Gr1, 12% in Gr2, P=0.798). The prognostic factors for mortality were age over 50 (OR 5.496, P=0.002), Child-Pugh class B (OR 3.979, P=0.001), and Child-Pugh class C (OR 10.861, P=0.000). CONCLUSIONS: EVL plus propranolol is more effective than propranolol alone in the prevention of the first variceal bleeding in patients with liver cirrhosis.
Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Esophageal and Gastric Varices/*pathology ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage/*drug therapy/mortality/surgery ; Humans ; Ligation ; Liver Cirrhosis/etiology ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Proportional Hazards Models ; Propranolol/*therapeutic use ; Retrospective Studies ; Severity of Illness Index ; Survival Rate

OBJECTIVETo study the clinical features, pathologic findings and prognosis of patients with dysplastic nodules of liver (DN) and early hepatocellular carcinomas (eHCC).

METHODSOne hundred and forty-five archival cases previously diagnosed as DN or eHCC or well-differentiated HCC during the period from 2000 to 2009 were retrieved and reevaluated with the new diagnostic criteria by two experienced pathologists, according to International Consensus Group for Hepatocellular Neoplasia (ICGHN) 2008. Immunohistochemical study (EnVision method) for CD34, HSP70, glutamine synthetase, glypican 3 and Ki-67 was carried out. The original diagnosis and diagnosis after review were compared and correlated with the survival data of the patients, with statistical analysis.

RESULTSWith the new criteria, 16 cases were diagnosed as low-grade DN, 50 cases as high-grade DN, 72 cases as DN with microinvasion, 7 cases as advanced HCC. Slide review showed no diagnostic discrepancy in 112 cases (77.2%). Amongst the 33 (22.8%) underdiagnosed cases, there were 7 cases of advanced HCC initially diagnosed as DN or DN with microinvasion and 26 cases of eHCC initially diagnosed as high-grade DN. Kaplan-Meier analysis showed that the diagnosis of high-grade DN or early HCC carried no statistically significant difference in overall survival (P = 0.778, 0.677) or disease-free survival (P = 0.949, 0.700) in all patients and in patients with no history of HCC. The co-existence of advanced HCC in patients with DN or eHCC significantly correlated with overall survival (P = 0.004) but not with disease-free survival (P = 0.079).

CONCLUSIONSThe new diagnostic criteria by ICGHN 2008 are useful in delineating high-grade DN and eHCC. The overall survival and disease-free survival of patients with eHCC or high-grade DN undergoing hepatectomy show no statistically significant difference. Patients with DN or eHCC have better prognosis than patients with advanced HCC, though there is still a high risk of tumor recurrence.

Antigens, CD34 ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; surgery ; Cell Transformation, Neoplastic ; Disease-Free Survival ; Female ; Follow-Up Studies ; HSP70 Heat-Shock Proteins ; metabolism ; Hepatectomy ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen ; metabolism ; Liver Cirrhosis ; metabolism ; pathology ; surgery ; Liver Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Survival Rate

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.
Bilirubin/blood ; Creatinine/blood ; Electrocardiography ; Fatal Outcome ; Hepatorenal Syndrome/*drug therapy ; Humans ; Intestinal Mucosa/pathology ; Intestines/surgery ; Liver Cirrhosis/diagnosis/therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Necrosis/*chemically induced/surgery ; Tomography, X-Ray Computed ; Vasoconstrictor Agents/*adverse effects/*therapeutic use