Effect of Sinisan on Oxidative Stress in Cholestatic Hepatitis Rats Based on Nrf2/HO-1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveBased on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway， this paper explores the effect of Sinisan （SNS） on liver oxidative stress injury in cholestatic hepatitis rats and its mechanism. MethodThirty 6-week-old male SD rats were randomly divided into a control group， model group， low and high dose groups of SNS （2.5 and 5 g·kg-1） and ursodeoxycholic acid group （UDCA， 63 mg·kg-1）， with six rats in each group. Rats were administrated for seven consecutive days. On the 5th day， the control group was given olive oil of 10 mL·kg-1， and the other groups were given alpha-naphthalene isothiocyanate （ANIT） of 80 mg·kg-1. The serum biochemical indicator levels of cholestasis and the content of antioxidant factors in rat liver were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in liver tissue. The relative mRNA and protein expressions of Nrf2， HO-1， and quinone oxidoreductase 1 （NQO1） in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the model group showed a significant increase in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）. There were obvious pathological changes in the model group such as the disordered arrangement of hepatocytes， obvious congestion and necrosis in the portal area， infiltration of inflammatory cells， and destruction of the interlobular bile duct. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly down-regulated in the model group （P<0.05， P<0.01）. Compared with the model group， the groups of SNS showed a significant decrease in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）， and the pathological liver injury was obviously improved. The necrotic area was reduced， and the infiltration of inflammatory cells was decreased. In addition， there was a small amount of extravasated blood in the interlobular vein. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly up-regulated （P<0.05， P<0.01）. ConclusionSNS can significantly improve liver injury in cholestatic hepatitis rats， and its mechanism may be related to the inhibition of oxidative stress response mediated by the Nrf2/HO-1 signaling pathway.

Effects observation of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis / 中国生化药物杂志

Objective To investigate the clinical effects of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis. Methods 100 patients with chronic cholestatic hepatitis were selected from Pingyang Hospital of traditional Chinese medicine from February 2011 to November 2016. They were randomly divided into the study group (n=50) and the control group (n=50). The control group was given routine treatment, the study group on the basis of routine therapy was given modified Yinchenzhufu decoction. The clinical efficacy and adverse reactions (drug related) during the 8 weeks of continuous treatment were recorded in two groups of patients with chronic cholestatic hepatitis. Results After treatment, the total efficiency in the study group of patients with chronic cholestatic hepatitis was 90.00% and the control group was 72.00%, and there was significant difference between two group (P<0.05); there was no statistical significance in adverse reactions of treatment in the study group, compared with the control group. Conclusion The application of the basic method of treatment for chronic cholestatic hepatitis plus modified Yinchenzhufu decoction could significantly improve the clinical efficacy.

Effects observation of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis / 中国生化药物杂志

Objective To investigate the clinical effects of Yinchenzhufu decoction combined routine treatment in treatment of chronic cholestatic hepatitis. Methods 100 patients with chronic cholestatic hepatitis were selected from Pingyang Hospital of traditional Chinese medicine from February 2011 to November 2016. They were randomly divided into the study group (n=50) and the control group (n=50). The control group was given routine treatment, the study group on the basis of routine therapy was given modified Yinchenzhufu decoction. The clinical efficacy and adverse reactions (drug related) during the 8 weeks of continuous treatment were recorded in two groups of patients with chronic cholestatic hepatitis. Results After treatment, the total efficiency in the study group of patients with chronic cholestatic hepatitis was 90.00% and the control group was 72.00%, and there was significant difference between two group (P<0.05); there was no statistical significance in adverse reactions of treatment in the study group, compared with the control group. Conclusion The application of the basic method of treatment for chronic cholestatic hepatitis plus modified Yinchenzhufu decoction could significantly improve the clinical efficacy.

A case of amoxicillin-induced hepatocellular liver injury with bile-duct damage / 대한간학회지

Amoxicillin, an antibiotic that is widely prescribed for various infections, is associated with a very low rate of drug-induced liver injury; hepatitis and cholestasis are rare complications. Here we present a case of a 39-year-old woman who was diagnosed with abdominal actinomycosis and received amoxicillin treatment. The patient displayed hepatocellular and bile-duct injury, in addition to elevated levels of liver enzymes. The patient was diagnosed with amoxicillin-induced cholestatic hepatitis. When amoxicillin was discontinued, the patient's symptoms improved and her liver enzyme levels reduced to near to the normal range.

"""Dose-effect-response"" Relationships of Paeoniae Radix Rubra on α-Naphthylisothiocyanate-induced Acute Cholestatic Hepatitis in Rats" / 中草药·英文版

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 administrated with vehicle or PRR [(1,9,18,36,54,72,and 81 g/(kg·d)] 3 d before and 2 d after α-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) after α-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 ameliorate α-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.

Hepatitis colestásica inducida por flutamida. Presentación de un caso / Cholestatic hepatitis induced by flutamida. Presentation of a case

La flutamida es un antiandrógeno no esteroideo, utilizado como terapia a largo plazo para el cáncer de próstata. Entre los efectos secundarios se incluye toxicidad hepática, la cual es muy rara vez reportada. Se presenta el caso de un adulto de 71 años con cáncer de próstata que desarrolla episodio de hepatitis colestásica durante tratamiento con flutamida. Luego de suspender la flutamida el paciente recupera progresivamente su función hepática, pero presenta recurrencia más severa al reiniciar la droga.No se justifica el reinicio del tratamiento luego de un primer episodio de hepatitis tóxica y es necesario tener en cuenta la toxicidad hepática del fármaco, cuando se decide indicarlo como tratamiento.

Flutamide is a nonsteroidal antiandrogen, used like therapy a long term for the prostate cancer. Between the indirects effects the hepatic toxicity is included, which is very rarely reported. The case of an adult of 71 years old with prostate cancer appears that develops episode of cholestatic hepatitis during treatment with flutamide. After to suspend flutamide the patient it recovers progressively his hepatic function, but he presented a recurrence more severely upon reintroduction of the drug.The resumption of the treatment after a first episode of toxic hepatitis is not justified and is necessary to consider the hepatic toxicity of the drug, when it is decided to indicate it like treatment.

A Case of Acute Q Fever with Severe Acute Cholestatic Hepatitis

Minimal hepatic dysfunction can be common in acute Q fever, but severe acute cholestatic hepatitis is rarely reported. We report on a 55-year-old male with acute Q fever and severe acute cholestatic hepatitis. He complained of fever, jaundice, ascites, and restlessness on admission. A liver biopsy revealed the presence of compact fibrin-ring granulomas. Serologic titers for C. burnetii IgM and IgG were 2048:1 and 1024:1, respectively. C. burnetii DNA was detected by a nested polymerase chain reaction on the liver tissue.

Cholestatic Hepatitis Caused by Tongyeong Strain of Orientia tsutsugamushi / 감염과화학요법

In Korea, the clinical manifestation of scrub typhus in humans appears to be severe in the northern regions of the country and mild in the southern areas. Studies on the geographic distribution of the serotype of Orientia tsutsugamushi revealed that the Boryong serotype is predominant in the southern Korean peninsula, whereas the Gilliam, Karp, and Gilliam-Karp serotypes prevail in the northern or central peninsula. We report a case of severe scrub typhus caused by the Japanese Gilliam type of Orientia tsutsugamushi in a 66-year-old woman from Tongyeong, a city located in the southern part of Korean peninsula. The patient was admitted to the hospital with fever on August 29th, 2001. Scrub typhus complicated by shock, pneumonitis, and encephalitis was diagnosed. Additionally, markedly elevated alkaline phosphatase levels was observed, which necessitated an ultrasonographic examination, which showed an ill-defined hyperechogenic mass on the right hepatic lobe. Liver biopsy showed cholestatic hepatitis and blood culture showed growth of O. tsutsugamushi. Gene sequencing of the amplicons of a polymerase chain reaction using primers for the amplification of the gene encoding the 56-kDa protein of O. tsutsugamushi revealed a nucleotide sequence that matched Yonchon strain of O. tsutsugamushi.

Cholestatic Hepatitis Caused by Tongyeong Strain of Orientia tsutsugamushi / 감염과화학요법

In Korea, the clinical manifestation of scrub typhus in humans appears to be severe in the northern regions of the country and mild in the southern areas. Studies on the geographic distribution of the serotype of Orientia tsutsugamushi revealed that the Boryong serotype is predominant in the southern Korean peninsula, whereas the Gilliam, Karp, and Gilliam-Karp serotypes prevail in the northern or central peninsula. We report a case of severe scrub typhus caused by the Japanese Gilliam type of Orientia tsutsugamushi in a 66-year-old woman from Tongyeong, a city located in the southern part of Korean peninsula. The patient was admitted to the hospital with fever on August 29th, 2001. Scrub typhus complicated by shock, pneumonitis, and encephalitis was diagnosed. Additionally, markedly elevated alkaline phosphatase levels was observed, which necessitated an ultrasonographic examination, which showed an ill-defined hyperechogenic mass on the right hepatic lobe. Liver biopsy showed cholestatic hepatitis and blood culture showed growth of O. tsutsugamushi. Gene sequencing of the amplicons of a polymerase chain reaction using primers for the amplification of the gene encoding the 56-kDa protein of O. tsutsugamushi revealed a nucleotide sequence that matched Yonchon strain of O. tsutsugamushi.

The value of treating cholestatic hepatitis with tolynicate and naphthylacetia acid and Dansen Root rejected fluid / 中国实用内科杂志

Objective To evaluate the value of treating chotestatic hepatitis with tolynicate and naphthylacetia acid,and Dansen Root rejected fluid.Methods All patients were divided into Control Group treated with Potassium magnessium aspartape,Glucurolactone etc,and Treating Group treated with tolynicate and naphthylacetia acid,and Dansen Root re- jected fluid;The change of clinical symptom,jaundice decreasing and recovery of hepatic function were observed respec- tively.Results The change of clinical symptom,jaundice decreasing and recovery of hepatic function of Treating Group were better,and there are significant difference (P

Expressions of ?-smooth muscle actin and collagen type Ⅰ,Ⅲ in biopsy liver tissue from patients with fibrosing cholestatic hepatitis / 中国医师进修杂志

Objective To observe expressions of ?-smooth muscle actin(?-SMA) and collagen type Ⅰ,Ⅲ deposition in the liver tissues, and to evaluate potential mechanism of fibrosis in patients with fibrosing cholestatic hepatitis (FCH) by collagen synthesis. Method Immunohistochemical staining was used to detect the expressions of ?-SMA and contents of type Ⅰ,Ⅲ collagen proteins, which were from the specimens of the biopsy liver in 9 cases with FCH associated with hepatitis virus B (HBV) developed following renal transplantation and in 5 cases without liver disease(control group), respectively. Results The expressions of ?-SMA and type Ⅰ,Ⅲ collagen proteins in the patients with FCH were significantly higher than those in the control group. The expression and distribution pattern of ?-SMA and type Ⅰ,Ⅲ collagen proteins were almost identical, and quantitative analysis showed a positive correlation (P

An Unusual Combination of Relapsing and Cholestatic Hepatitis A in Childhood

Clinical variants of hepatitis A include the prolonged, relapsing and cholestatic forms. Here, the first childhood case of hepatitis A, with a combination of the relapsing and cholestatic forms is presented, a 14-year old boy. In the first phase of the illness, while the AST and ALT levels were declined, th total and direct bilirubin and GGT were increased. The patient was thought to have the cholestatic form of hepatitis A. Du to intense pruritus and high bilirunbin levels, ursodeoxycholic acid (UDCA) therapy was started. On the 17th day, the decreased AST and ALT levels began to increase, reaching levels as high as 484 U/L and 862 U/L, respectively. The UDCA treatment was stopped on the 64th day. On the 164th day, all his laboratory parameters were within normal limits, but the anti-HAV IgM was still positive.

A Case of Acute Cholestatic Hepatitis Associated with Orlistat / 대한간학회지

Orlistat(Xenical(R), Roche) is considered a safe and effective drug to treat obesity by reduced absorption of 30% digested fat. To date, no serious adverse effects affecting the liver have been published except a case of subacute hepatic failure leading to liver transplantation in a young women with moderate obesity treated with orlistat. We report a case of acute cholestatic hepatitis in a young woman with moderate obesity treated with orlistat: a 33-year-old female admitted for the evaluation of jaundice. Abdominal ultrasonography, ERCP, routine chemistry, viral markers, and a fine needle biopsy of liver were performed. Microscopic findings of the liver biopsy specimen were compatible with acute cholestatic hepatitis. After steroid therapy, liver function was improved.

Three Cases of Ticlopidine-induced Cholestatic Hepatitis

Ticlopidine hydrochloride is world-wide used antiplatelet agent that inhibit ADP pathway. Its clinical side effects are the change of the blood picture, allergic skin reaction and gastrointestinal symptoms. We report three patients with severe cholestatic hepatitis caused by ticlopidine. They developed jaundice about 20days after taking ticlopidine (500 mg/day). Infectious and immunological etiologies were excluded by serology. There was no history of alcohol or drug abuse. Their symptoms were gradually subsided for a few months after discontinuing ticlopidine.

Four cases of ticlopidine-induced cholestatic hepatitis / 대한내과학회지

Ticlopidine, a potent antiplatelet agent, is widely used for treatment of coronary artery disease and cerebrovascular disease. Adverse effects has been reported in 10% to 20% of patients receiving ticlopidine. The most commom adverse effects were gastrointestinal disturbance, skin rash, but cholestatic hepatitis with jaundice was rare (0.1% incidence). We have recently experienced four cases of ticlopidine-induced cholestatic hepatitis after coronary artery stent insertion. Jaundice developed within 1 month of starting ticlopidine at recommended daily doses. In all cases, jaundice resolved and serum liver enzymes improved over a period of months after drug withdrawal. Therefore, clinicians should be aware of the reversible condition of ticlopidine-induced cholestatic jaundice that slowly resolves after drug withdrawal.

A Case of Acute Cholestatic Hepatitis Caused By the Seeds of Psoralea-corylifolia / 대한간학회지

The potential hepatotoxicity of herbal remedies is usually ignored in daily life. One such compound, Boh-Gol-Zhee (in Chinese, Bu Ku Zi), appeared to be the cause for acute cholestatic hepatic injury in the following case. Psoralea corylifolia is known to contain a sufficient amount of phyto-estrogen. Some alternative medicine therapists claim that Psoralea corylifolia is effective for the treatment of osteoporosis. So far, at least 35 chemical components in the fruits of Psoralea corylifolia have been identified. High concentrations of phyto-estrogen, such as genistein, have been found in the leaves of Psoralea corylifolia. Phyto-estrogen has structural similarity to estrogen and exhibits beneficial effects on osteoporosis under estrogen-deficient conditions. The authors observed a case of acute cholestatic hepatitis in a post-menopausal woman caused by seeds of Psoralea corylifolia in amounts over 10 times the usual dose. Other possible causes of liver injury were excluded by laboratory tests and imaging studies. After discontinuation of this remedy, elevated liver enzyme and total bilirubin rapidly returned to normal. Liver biopsy showed zone 3 necrosis, degenerating cells, cholestasis and infiltrations with inflammatory cells. This case stresses the need to warn the potential hepatotoxicity of Psoralea corylifolia seeds, especially in a large dose.

Sulindac-induced Cholestatic Hepatitis and Acute Pancreatitis in a Patient having Systemic Sclerosis with Anti-RNP Antibody: report of a case / 대한류마티스학회지

Sulindac is a commonly used nonsteroidal anti-inflammatory drug (NSAID). It is relatively economical and seems to be less nephrotoxic due to its property of minimal renal prostaglandin inhibition. Although hepatic injury has been infrequently reported for nearly all NSAIDs currently on the market, sulindac has more commonly been associated with hepatotoxicity. In addition, it has been known that sulindac is the agent to have a definite association with pancreatitis. We describe a 37-year-old woman who developed cholestatic hepatitis and acute pancreatitis in association with sulindac. This patient met the diagnostic criteria of both mixed connective tissue disease and systemic sclerosis, in which the disease classification needs to be clarified. While being treated with sulindac, close observation and periodic liver function test seem to play an important role.

A case of flutamide-induced acute cholestatic hepatitis: a case report

Flutamide, an oral nonsteroidal, antiandrogenic, anilid compound which inhibits the uptake and binding of androgens to nuclear receptors in the prostate, is used with or without LH-RH analogues for treatment of patients with metastatic carcinoma of the prostate. Clinically significant hepatotoxicities such as toxic hepatitis, cholestatic hepatitis, hepatic failure, and even death have rarely been reported in the English literature, but no case has been reported in Korea. A 75-year-old man with metastatic carcinoma of the prostate had taken flutamide (750 mg/day) for 7 months and suddenly developed jaundice and general weakness. The findings of blood chemistries were compatible with cholestatic hepatitis, but ultrasonography, viral marker and auto-antibody studies did not reveal any attributable causes. Histologic examination of a sono-guided liver biopsy only disclosed centrilobular cholestasis, nuclear glycogenosis and mild sinusoidal lymphocytic infiltration. Discontinuation of flutamide resulted in an almost full recovery of the patient's liver function in 2 months. We, herein, report a case of flutamide-induced acute choestatic hepatitis with a brief review of the literature.