Fibrosing cholestatic hepatitis following cytotoxic chemotherapy for small-cell lung cancer

Fibrosing cholestatic hepatitis(FCH) is a variant of viral hepatitis reported in hepatitis B virus or hepatitis C virus infected liver,renal or bone transplantation recipients and in leukemia and lymphoma patients after conventional cytotoxic chemotherapy.FCH constitutes a well-described form of fulminant hepatitis having extensive fibrosis and severe cholestasis as its most characteristic pathological findings.Here,we report a case of a 49-year-old patient diagnosed with small-cell lung cancer who developed this condition following conventional chemotherapy-induced immunosuppression.This is the first reported case in the literature of FCH after conventional chemotherapy for a solid tumor.In addition to a detailed report of the case,a physiopathological examination of this potentially life-threatening condition and its treatment options are discussed.

Severe acute cholestatic hepatitis of unknown etiology successfully treated with the Chinese herbal medicine Inchinko-to (TJ-135)

Severe acute hepatitis of unknown etiology is difficult to treat and often progresses to subacute fulminant hepatitis or late-onset hepatic failure. A 45-year-old wellnourished, healthy man had progressive fatigue and his liver function tests showed severe liver dysfunction. The etiology of sever acute cholestatic hepatitis was unknown. The liver function tests normalized gradually, which excluded high persistent total bilirubin after starting on predonine. A liver biopsy showed chronic active hepatitis with mild f ibrosis (A2, F1). Oral Inchinko-to, a Chinese herbal medicine, at 7.5 g daily was prescribed. The treatment was effective with no adverse effects. We present a successfully treated case and discuss hepatoprotective and choleretic effects of Inchinko-to.

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.

A Case of Severe Cholestatic Hepatitis Induced by a Novel Dual Agonist of Glucagon-like Peptide-1 and Glucosedependent Insulinotropic Polypeptide Receptors

Glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide(GIP)receptor agonists are increasingly used in the management of type 2 diabetes mellitus and obesity due to their ability to stimulate insulin secretion,delay gastric emptying,and suppress appetite.The combination of GLP-1 and GIP agonists improves glycemic control and promotes weight loss.However,the introduction of these novel therapies has raised safety concerns,including the risk of cholestatic hepatitis.We report a case of a patient with obesity who was prescribed a GLP-1/GIP dual-receptor agonist as part of his treatment regimen.Importantly,both before the initiation of this therapy and during the course of treatment,the patient was not taking any other medications.Shortly after receiving four doses of the therapy,the patient developed symptoms of severe cholestatic hepatitis,including jaundice and elevated liver enzyme levels.During hospitalization,no alternative causes for the condition were identified,and a liver biopsy confirmed the diagnosis of druginduced cholestatic hepatitis.This is the first recorded case of cholestatic hepatitis induced by a GLP-1/GIP dual agonist,and it aimed to raise global awareness of this potential side effect.

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.

Clinical study on treatment of chronic viral cholestatic hepatitis with Chishaodanpi decoction

OBJECTIVE: To observe the therapeutic effect of Chishaodanpi decoction(CSDPD) on chronic viral cholestatic hepatitis.METHODS: A total of 107 subjects with chronic viral cholestatic hepatitis were enrolled in our hospital from March 2007 to November 2012. Patients were randomly divided into treatment(54 cases)and control groups(53 cases). The control group was treated with potassium magnesium aspartate,diammonium glycyrrhizinate, glucurolactone, vitamin C, and lamivudine, once a day. The treatment group was treated with modified CSDPD, 100 m L a time, twice a day, in addition to the treatment given to the control group. The patients in both groups were treated for 8 weeks. The main symptoms and signs were recorded every day throughout the clinical trial. Before and after the trial,changes in liver function including total bilirubin(TBil), direct bilirubin(DBil), total bile acid(TBA),and the activities of alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), and γ-glutamyl transferase(γ-GT),were all detected. Adverse reactions were also recorded.RESULTS: There were no differences in gender, age,disease duration, symptoms, signs, or laboratory findings between the two groups(P>0.05). After an8-week treatment, improvements in jaundice, weakness, poor appetite, abdominal distention, and skin itching were significantly better in the treatment group than in the control group(P<0.05). In the treatment group, 43 patients had a significant response to the treatment, seven patients had a response, and four patients had no response, with 21,12, and 20 patients in the control group, respectively. The total effective rate was 92.6% in the treatment group and 62.3% in the control group, which was a significant difference(P<0.05). The levels of TBil, DBil, TBA, ALP, ALT, AST, and γ-GT in both groups were significantly lower after treatment,and were significantly different between the two groups(P<0.05). A few patients in the treatment group had mild adverse effects such as increased bowel movement frequency and mild stomachache. No other adverse reactions were observed in either group.CONCLUSION: CSDPD has a satisfactory therapeutic effect on chronic viral cholestatic hepatitis.

"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.

Celecoxib-induced cholestatic liver failure requiring orthotopic liver transplantation

Selective cyclooxygenase-2 （COX-2） inhibitors are widely used due to their efficacy and good safety profile. However, recent case reports have described varying degrees of liver injudes associated with the use of COX-2 inhibitors. We report the case of a patient who developed acute cholestatic hepatitis progressing to hepatic failure requiring liver transplantation, following a 3-d course of celecoxib for treatment of generalized muscle aches and pains. The clinical presentation, the laboratory data, as well as the liver histopathology were supportive of the putative diagnosis of drug induced liver injury.

Recurrent hepatitis C after liver transplant

End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28 B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5 B polymerase inhibitors and NS5 A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.

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