Promoting hepatic growth factor in the treatment of heavy type hepatitis and severe chronic hepatitis: a multicenter clinical study

BACKGROUND: The mortality rate of heavy type hepatitisis high. No special treatment is available except generaltreatment. This multicenter clinical study was designed toobserve the safety and efficacy of promoting hepatic growthfactor (PHGF) in the treatment of heavy type hepatitis andsevere chronic hepatitis.METHODS: 347 patients with heavy type hepatitis and 324with severe chronic hepatitis were subjected to administra-tion of 120 μg of PHGF per day for 4 weeks on the basis ofgeneral treatment. Those who were being effectively treat-ed would last additional 2 to 4 weeks. Blood routine, urineroutine, blood urea nitrogen (BUN), blood creatinine(Cr), blood ammonia, alpha fetoprotein (AFP), electro-lyte, alanine transaminase (ALT), aspartate transaminase(AST), serum total bilirubin (TBIL), serum direct biliru-bin (DBIL), prothrombin time activity (PTA), total pro-tein (TP) and albumin (ALB) were detected in the pa-tients before treatment, 2 weeks after treatment, and at theend of the treatment. Any side-effect would be recorded.RESULTS: In the patients with severe chronic hepatitis, thetotal effective rate of the treatment was 88. 9% The levelsof ALT, AST and TBIL decreased significantly (P<0.001),whereas those of PTA and ALB increased significantly (P <0.001), and the level of AFP increased slightly. In patientswith heavy type hepatitis, the total effective rate of thistreatment was 78.4%, and patients at different stage showeddifferent results. The total effective rates of patients withearly, medium and terminal stage heavy type hepatitis were89.9%, 84.8% and 27.5%, respectively. No severe side-effect was shown.CONCLUSION: PHGF is effective and safe in the treat-ment of patients with heavy type hepatitis and severe chro-nic hepatitis. But it should be administered early in patientswith heavy type hepatitis so as to get better curative effects.

Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis

AIM:To determine the utility of connective tissue growth factor(CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus(HBV)-induced chronic liver diseases(CLD-B).METHODS:Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B(CHB) and 39 patients with HBVinduced active liver cirrhosis and 30 healthy individuals.Liver samples from 31 patients with CHB,8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1(TGF-β1) or CCN2 mRNA levels by in situ hybridization,and computer image analysis was performed to measure integrated optimal density(IOD) of CCN2 mRNA-positive cells in liver tissues.Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.RESULTS:Serum CCN2 concentrations were,respectively,4.0-or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals(P < 0.01).There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues(r = 0.87,P < 0.01).The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B(r = 0.85,P < 0.01).Serum CCN2 was a reliable marker for the assessment of liver fibrosis,with areas under the receiver operating characteristic(ROC) curves(AUC) of 0.94 or 0.85 for,respectively,distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.CONCLUSION:Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.

Rifaximin,but not growth factor 1,reduces brain edema in cirrhotic rats

AIM:To compare rifaximin and insulin-like growth factor(IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups:Cirrhosis;Cirrhosis + IGF-1;Cirrhosis + rifaximin;Controls;Controls + IGF-1;and Controls + rifaximin.An oral glutamine-challenge test was performed,and plasma and cerebral ammonia,glucose,bilirubin,transaminases,endotoxemia,brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS:Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups,and improved some liver function parameters(bilirubin,alanine aminotransferase and aspartate aminotransferase).These effects were associated with a significant reduction in cerebral water content.Blood and cerebral ammonia levels,and area-underthe-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals.By contrast,IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION:By reducing gut bacterial overgrowth,only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema,alterations associated with hepatic encephalopathy.

Pancreatic cancer stroma:understanding biology leads to new therapeutic strategies

Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diagnosed with PDA survive past 5 years.Despite development of targeted therapy against other cancers,little progression has been made in the treatment of PDA.Therefore,there is an urgent need for the development of new treatments.However,in order to proceed with treatments,the complicated biology of PDA needs to be understood first.Interestingly,majority of the tumor volume is not made of malignant epithelial cells but of stroma.In recent years,it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells,leading to cancer progression.The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery.Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery.In this review,we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.