A Comparative Study of Phototherapy Versus Phototherapy Plus Ursodeoxycholic Acid in the Treatment of Indirect Hyperbilirubinemia in Neonate

Background: Hyperbilirubinemia is a common neonatal problem. Phototherapy and exchange transfusion is the conventional treatment for indirect hyperbilirubinemia. In the treatment of cholestatic liver disorders, Ursodeoxycholic acid (UDCA) is a bile acid widely used. Few studies have been conducted using UDCA in indirect hyperbilirubinemia. Aim of the study: This study was planned to assess the additive effect of UDCA on reducing indirect hyperbilirubinemia in neonates receiving phototherapy. Material & Methods:This prospective randomized controlled trial was conducted among neonates with indirect hyperbilirubinemia in the neonatal wards of Bangladesh Shishu Hospital and Institute, Dhaka, Bangladesh from June 2018 to July 2020. Finally, 140 neonates were included in the study. Eligible cases were randomized into two groups by the lottery method. Group A (n=70) received phototherapy and Group B (n=70) received UDCA at a dose of 10 mg/kg/day orally twice daily in addition to phototherapy. Total serum bilirubin levels were measured every 12 hours until serumbilirubinlevel falls below 10 mg/dl and then phototherapy was stopped. Demographic data, clinical features, laboratory parameters, outcome variables, and complications were recorded in a pre-format sheet. CBC with PBF, Total and indirect bilirubin, Blood grouping and Rh and typing, CRP, Reticulocyte count, and Coombs test were obtained at enrolment. Comparison of parameters among themselves was done by unpaired t-test and chi-square test. Analyzed outcomes were: time for resolution of jaundice, total duration of phototherapy, length of hospital stays, and adverse effects of the drug. The two groups did not differ statistically in age, sex or weight. The mean total serum bilirubin level measured at 12, 24, 36, 48, and 60 hours of treatment in group A was 16.10±1.43, 14.76±1.45, 13.34±1.68, 11.84±1.35, and, 10.57±0.74 respectively, and in the group, B was,15.18±1.63, 13.18±2.25, 11.39±1.56, 9.84±0.81 and, 9.44±0.46 respectively (p<0.001). The mean duration of phototherapy (64.11±10.8 vs. 47.18±7.51 hours, p<0.001) and length of hospital stay (2.80 ±0.40 vs. 2.19±0.39 days, p=<0.001).Conclusion:The inclusion of UDCA as an adjuvant to phototherapy is more effective in reducing indirect hyperbilirubinemia in neonates.

Risk factors for hepatocellular cancer occurrence in patients with primary biliary cholangitis / 中国肿瘤临床

To investigate the potential risk factors for hepatocellular carcinoma in primary biliary cholangitis (PBC) patients. Methods:The data of 670 PBC inpatients between January 2011 and December 2016 were collected from the database of The First Affiliated Hospital of Zhengzhou University. The potential risk factors were evaluated, and odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed by univariate (unadjusted OR) and multivariate [adjusted OR (AOR)] conditional Logistic regression. Results: In total, 35 PBC patients developed liver carcinoma (5.2%); of these, 4 patients (female) were excluded because of incomplete data for influencing factors and 6 (2 male; 4 female) were excluded as they were diagnosed with hepatocellular carcinoma (HCC) during or before PBC. Therefore, 25 patients were included in the case-control study. Male patients were more likely than female patients to show alcohol in-take, smoking, a family history of malignancy, and serious liver injury (all P<0.05), indicated by the increasing levels of alanine amino-transferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) (P<0.05). Conditional Logistic regression analysis revealed that body mass index (BMI) ≥25 kg/m2 (AOR=1.015, 95% CI: 1.001-1.257, P=0.032) and history of alcohol intake (AOR=10.014, 95% CI: 1.009-91.071, P=0.039) were significantly associated with increased odds of HCC development in PBC patients. Conclusions:The risk factors for PBC-associated liver carcinoma include BMI≥25 kg/m2 and history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from alcohol abstinence and body weight control.

Ursodeoxycholic Acid Ameliorates Pain Severity and Cartilage Degeneration in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1beta (IL-1beta), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1beta, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1beta-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

Effect of ursodesoxycholic acid on JAK/STAT3/COX-2 signal pathway in human hepatocellular carcinoma cells / 肿瘤研究与临床

Objective To investigate the effect of ursodesoxycholic acid (UDCA) on JAK/STAT3/ COX-2 signal pathway in human hepatocellular carcinoma cells and the underlying mechanism of its antitumor effect.Methods In order to obtain the optimal concentration and time of UDCA,MTT assay was used to detect anti-proliferative activities of UDCA on SMMC-7721 cells induced by IL-6 in vitro.Cells were divided into control group,IL-6 group,AG490 (JAK2 inhibitor) group and UDCA group.The protein expressions of STAT3,p-STAT3 and COX-2 were measured by Western blot.Results MTT assay showed UDCA had obvious anti-proliferative activities on SMMC-7721 cells.The optimized concentrations were 50,100,200 μg/ml,the optimized culture time was 48 h.Western blot results showed that the expression of p-STAT3 and COX-2 were remarkably increased in IL-6 group than that in control group.There was no difference of STAT3 expression between the two groups.Compared with IL-6 group,the protein level of COX-2 was decreased in AG490 and UDCA groups,so was the expression of p-STAT3.But there was no change on STAT3 expression in AG490 and UDCA groups.Conclusion UDCA may decrease the proliferation of SMMC-7721 cells via inhibiting phosphorylation of STAT3 and down-regulating COX-2 exprcssion.

Therapy of nonalcoholic steatohepatitis (NASH) – antioxidants and cytoprotective agents.

Pathogenesis of nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) is not completely understood. Because of the role of oxidative stress in the pathogenesis, antioxidants and cytoprotective agents have been used in the treatment of patients with NAFLD/NASH. Various antioxidants and cytoprotective agents used in these patients include Vitamin E, Vitamin C, Betaine, N- acetyl cysteine, silybin, lecithin, beta carotene, metadoxine, selenium and ursodeoxycholic acid (UDCA). Most of the data is available with vitamin E and UDCA, either in isolation or in combination with various agents. The available data on the use of various agents are either experimental or have small number of patients and randomized controlled trials with histological efficacy are sparse. More data is required before any conclusions are drawn regarding the use of anti oxidants and cytoprotective agents in patients NAFLD/NASH.

The Study on the Treatment of Ursodeoxycholic Acid Plus Xiaoyao San in Patients with Primary Intrahepatic Stones / 医学研究杂志

Objective To study the clinical therapeutic effectiveness on primary intrahepatic stones(PIS) treated by Ursodeoxycholic Acid(UDCA) combined with Xiaoyao San.Methods 90 cases of patients with PIS were randomly divided into two groups:the therapeutic group(n=60) and control group(n=30).The therapeutic group treated by UDCA combined with Xiaoyao San for 45 days.And the control group treated by UDCA alone.Then we observed the changes of symptoms as well as B-ultrasonic examine.Results The total effective rate was 86.7% in therapeutic group,higher than that in the control group,60%(P

Efficacy of Combination of Interferon alpha 2a , Ribavirin and UDCA in the Treatment of Chronic Hepatitis C / 대한간학회지

BACKGROUND/AIMS: Although the only therapy of proven benefit for chronic hepatitis C is interferon alpha, the rate of sustained response after treatment with interferon is less than 25%. A 6-month course of combination therapy with interferon and ribavirin was associated with higher rate of long-term response than either interferon or ribavirin alone. Pilot studies suggested that combination of interferon and ursodeoxy-cholic acid (UDCA) resulted in higher biochemical response than interferon alone. We investigated the rates of end of treatment response(ETR) and sustained response(SR) of combination therapy of interferon e2a, ribavirin and UDCA and compared it with interferon a 2a alone. METHODS: Ninty-five naive patients with chronic hepatitis C who have been positive for anti-HCV by 3rd generation EIA and HCV RNA by RT-PCR and had elevated level of ALT over 6 months were included. They were assigned to three groups. Thirty seven patients in group 1 were treated with interferon a 2a (3MU thrice weekly) in combination with ribavirin (600mg/day) and UDCA (600mg/day) for 6 months. Twenty nine patients in group 2 were treated with the same dose of interferon a 2a alone for 6 months. Changes of ALT and HCV RNA were observed over 12 months (average 3029 mos) after the end of treatment in both groups. Twenty nine patients in group 3 were observed over 12 months without antiviral treatment. HCV genotypes were tested by Innop-Lipa in 24 patients in group 1. RESULTS: In group 1, not only ETR (68%) but also 12 month SR rate (54%) was significantly higher than group 2(31%, 21% respectively). There was no difference in relapse rate between two groups. The level of ALT became normalized and HCV RNA negative within 1 month after treatment in most responders in group l. Genotype 1b was associated with lower ETR and SR than non-lb, although not significant stastistically. CONCLUSION: Both the ETR and 12 month SR rate were significantly higher after combination treatment of interferon a 2a, ribavirin and UDCA than interferon e 2a alone in chronic hepatitis C. It is suggested that this combination is preferable to interferon alone in the treatment of naive patients with chronic hepatitis C.