Unique pattern of fibrosing cholestatic hepatitis after liver transplantation

To explore the pathological features and thedifferential diagnosis of recurrent HBV after livertransplantation.Methods: One case of liver transplantation for HBVcirrhosis was subjected to liver biopsises on time post-operatively.Results: 25 days after liver transplantation, serologicHBsAg, HBeAg and HBV-DNA of the patient becamenegative, but HBsAg was positive again on day 58 af-ter liver transplantation. Histopathological examina-tion showed balloon-like changes of hepatocytes withfragmental necrosis, fibrosis in the portal areas andaround the portal veins, cholestasis in some hepato-cytes and canaliculi, and positive HBsAg and HBcAgwith immunohistochemical staining. Clinically hepaticenzyme levels progressively increased, maintained forsome time, and decreased rapidly at last. Stubborn hy-poproteinemia was associated with the aggregation ofgeneral condition of the patient.Conclusions: Fibrosing cholestatic hepatitis (FCH) is aspecial type in recurrent infection of HBV after livertransplantation. It has a serious clinical process andspecific pathological changes different from those ofthe usual HBV.

"Dose-effect-response" Relationships of Paeoniae Radix Rubra on α-Naphthylisothiocyanate-induced Acute Cholestatic Hepatitis in Rats

Objective To investigate the hepatoprotective effects of Paeoniae Radix Rubra(PRR)at different doses against α-naphthylisothiocyanate(α-NIT)-induced acute cholestatic hepatitis in rats.Methods Rats were ig admini-strated with vehicle or PRR[(1,9,18,36,54,72,and 81 g/(kg·d)]3 d before and 2 d afterα-NIT(60 mg/kg)ig administration.The general status of rats,histopathology of liver,serum alanine aminotransaminase,aspartate aminotransaminase,total bilirubin,direct bilirubin,and alkaline phosphatase levels,were observed at respective time points(24 and 48 h)afterα-NIT administration.Using cluster analysis and correspondence analysis,the 'dose-effect-response'relationships of PRR were evaluated.Results The results showed that compared with model group,the serum biochemistry index significantly decreased with the increasing of PRR dosage(P<0.01), and the change and necrosis of hepatic cellula,and inflammatory cell infiltration were gradually alleviated. However,the improvement was not obviously found in the low-dose group[1 g/(kg·d)].The cluster analysis and correspondence analysis results showed that different doses of PRR could significantly ameliorateα-NIT-induced acute cholestatic hepatitis of rats in a dose-dependent manner.Conclusion The experiments show that administration doses of PRR in clinical use should be added properly in order to gain the expectant therapeutic effect,especially in the treatment of heavy acute cholestasis hepatitis.

Network pharmacology assessment of Qingkailing injection(清开灵注射液)treatment of cholestatic hepatitis

OBJECTIVE:To investigate the targets and mechanisms of action of Qingkailing injection(清开灵注射液,QKL)in the treatment of cholestatic hepatitis.METHODS:A network pharmacology method was implemented using drug and disease databases to target QKL and cholestasis hepatitis,respectively.The functional protein association network STRING database was used to construct a protein-protein interaction network using R language and the Bioconductor toolkit.The org.Hs.eg.db and cluster Profiler packages were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis,which explored biological functions and pathways of potential targets.Targets were then visualized using Cytoscape 3.6.0 software.RESULTS:We screened 121 compounds in QKL and identified 112 targets for the treatment of cholestatic hepatitis.QKL played a role in the treatment of cholestatic hepatitis through 305 biology process terms,15 cellular component and 29 molecular function terms.The mechanism of QKL action was mainly related to tumor necrosis factor,mitogen-activated protein kinase,and PI3 K-Akt signaling pathways.CONCLUSION:The treatment of cholestatic hepatitis by QKL involved multiple targets,biological functions,and signaling pathways that are closely associated with the disease.

A Patient with Acute Liver Injury after Sulfamethoxazole/Trimethoprim Treatment for Pyelonephritis

Background: Sulfamethoxazole/Trimethoprim is a commonly used drug in a variety of clinically indicated scenarios, but it is not without side effect. Case-reports have stated that adverse reactions secondary to Sulfamethoxazole/Trimethoprim can present very early in the course of treatment, especially in patients who have a higher predisposition. Thus, the burden is placed on the clinician to be wary of these side effects and be able to recognize them in the correct clinic scenario. Objective: To discuss the risk of developing cholestatic hepatic dysfunction secondary to treatment with sulfamethoxazole/trimethoprim. Methods: We present the history, physical findings, laboratory investigations, and clinical course of a 47-year-old African-American female who developed cholestatic hepatic dysfunction after treatment with sulfamethoxazole/trimethoprim for pyelonephritis. Results: Drug-induced liver injury is a rare complication of sulfamethoxazole/trimethoprim therapy and only 20% of cases are secondary to cholestatic hepatic dysfunction. Our patient, who had been on sulfamethoxazole/trimethoprim for 7 days for pyelonephritis, presented to our hospital with a clinical picture consistent with hepatic injury;her laboratory investigations were noteworthy for an elevated white blood cell count, platelet count, and elevated transaminases, along with alkaline phosphatase levels greater than 2 times the upper limit of normal. Promptly following the discontinuation of sulfamethoxazole/trimethoprim, our patient improved clinically and her liver enzymes down-trended during the course of her hospital stay. She returned to normal at her 4 month follow up, thus confirming the diagnosis of cholestatic hepatic dysfunction secondary to sulfamethoxazole/trimethoprim. Conclusion: Cholestatic hepatic dysfunction is a form of drug-induced liver injury and a rare complication of sulfamethoxazole/trimethoprim treatment. The majority of cases resolve following discontinuation of the offending medication. However, a small percentage of patients may progress to liver failure and ultimately require liver transplantation. Clinicians should be aware of these risks to avoid delaying the discontinuation of sulfamethoxazole/trimethoprim.

Effects of ursodeoxycholic acid on intrahepatic cholestasis in rats

Objective To investigate the effects of treatment with ursodeoxycholic acid (UDCA) on intrahepatic cholestasis in rats, and to explore its mechanism Method Rats suffering from intrahepatic cholestasis were treated with UDCA Their serum alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), γ glutamyl transpeptidase (γ GT), total cholesterol (TCH), bile flow, total bile acid excretion, total Na + and TCH of bile were measured before and after treatment In addition, the changes of liver tissue under microscrope were observed and recorded Results Compared with the control group, serum ALT, ALP, TBIL, DBIL, γ GT and TCH of rats in the treatment group decreased, while bile flow, total bile acid excretion, total Na + and TCH decreased significantly Degeneration of hepatocytes, infiltration of inflamed cells and proliferation of small bile ducts in the treatment group were improved under microscope ####Conclusion UDCA may have therapeutic effects on cholestatic hepatitis The mechanism may involve in its hydrophilicity, choleretic effect and immune modulation