Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy （ICP） is apregnancy-specific liver disorder characterizedby maternal pruritus in the third trimester, raisedserum bile acids and increased rates of adverse fetaloutcomes. The etiology of ICP is complex and not fullyunderstood, but it is likely to result from the cholestaticeffects of reproductive hormones and their metabolitesin genetically susceptible women. Equally unclearare the mechanisms by which the fetal complicationsoccur. This article reviews the epidemiology, clinicalfeatures, diagnosis, etiology and management of ICP.     

妊娠期肝内胆汁淤积的临床研究进展

妊娠肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)可导致早产,明显增加围生儿病死率,但其病因及发病机制尚不明确.     

妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症（ICP）为一种妊娠期特有的疾病,其病因不详。该病首次报道于19世纪80年代,于20世纪60年代得到详细报道,属高危妊娠之列。ICP最大的危害是发生胎儿窘迫,常使胎儿突然胎死宫内,并增加母体产后出血的风险。临床主要症状为瘙痒。临床上对ICP的处理存在两种过激的倾向,因此对ICP的诊断需规范化,需排除其他相关性疾病。建议诊断时进行分度,以便合理制定临床治疗方案,避免处理上的盲目性     

Intrahepatic cholestasis of pregnancy

Patients with ICP should be considered to have a high-risk pregnancy. Once the diagnosis of ICP is suspected, usually because of generalized pruritus, it should be confirmed by liver function tests, and other causes of cholestasis should be ruled out. Treatment with UDCA is effective in ameliorating the cholestasis and is especially useful in severe forms or when there is a history of sudden fetal death in a previous pregnancy. The understanding of the pathogenesis of ICP has recently progressed as the result of the discovery of several defects in the MDR3 gene in isolated affected patients. More studies of this and other genes that regulate bile flow, linked with careful clinical observations to rule out unsuspected chronic liver disease not related to pregnancy, should lead to the discovery of the pathogenesis of this enigmatic disorder.     

Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a rare disease occurring mainly during the last trimester of pregnancy. Pruritus, often accompanied by excoriation of the skin but without other skin lesions, and elevated concentrations of bile acids are characteristic for this disorder. We present a 30-year-old woman with pruritus, elevated bile acids, ASAT and ALAT in the 22nd week of pregnancy. Treatment with ursodeoxycholic acid resulted in complete disappearance of the pruritus and normalisation of the bile acids, ASAT and ALAT. A healthy child was born at term. In the differential diagnosis of liver function abnormalities during pregnancy, ICP should be included. ICP responds very well to treatment with ursodeoxycholic acid, with no detrimental effects for mother and child.     

Intrahepatic cholestasis of pregnancy

Opinion statement Intrahepatic cholestasis of pregnancy (or obstetric cholestasis) is a liver disorder that occurs in late pregnancy. Despite the potential adverse maternal and fetal/neonatal outcomes, cholestasis of pregnancy is often neglected and treated expectantly. More research is needed to improve the molecular and genetic understanding of the disease and to define a safe and effective medical treatment that improves clinical outcome. Ursodeoxycholic acid is considered to be a safe treatment option in the third trimester, but further randomized controlled trials are needed before ursodeoxycholic acid treatment can be generally recommended. Ursodeoxycholic acid is preferentially administered to patients with severe cholestasis (onset before week 33 or serum bile acid levels > 70 mmol/L) or to patients with a history of sudden fetal death, while maintaining close obstetric and regular biochemical surveillance (transaminases, bilirubin, and bile acid levels). Ursodeoxycholic acid can decrease pruritus and ameliorate liver tests, but effects on obstetric complications are ambiguous. S-Adenosylmethionine, dexamethasone, and cholestyramine can provide some relief of itching. Because none of these drugs have been shown to be harmful to mother or fetus, the individual woman and her clinician may decide whether to try one of the treatments described.     

Intrahepatic cholestasis of pregnancy in twin pregnancies

To clarify whether the increase in estrogen levels occurring during twin pregnancies (TP) is associated with a greater risk of developing intrahepatic cholestasis of pregnancy (ICP), we followed up 62 consecutive patients with TP and compared them with single pregnancies delivered in our hospital during 1 year. The prevalence of ICP was significantly higher in twin than in single pregnancies (20.9% versus 4.7%, respectively; P less than 0.001). Urinary estriol excretion was also significantly higher in twin compared to single pregnancies, although no quantitative differences were detected in TP with or without ICP. In multiparous patients with a proband TP affected by ICP, the disease recurred only in further TP, emphasizing the important role that estrogens seem to play in the pathogenesis of ICP. In contrast, in multiparous patients with a proband single pregnancy affected by ICP, the disease occurred in 70.5% of their other single pregnancies, suggesting the presence of a metabolic predisposition in these cases. However, in both groups of multiparous women a notable number of single pregnancies were not affected by the disease, supporting the postulate that the pathogenesis of ICP is multifactorial and that some as yet unidentified environmental factor needs to be present in order to develop the disease and also to modulate its expressivity.     

Intrahepatic cholestasis of pregnancy: a past and present riddle

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorders that occurs mainly in the third trimester of pregnancy and is characterized by pruritus and elevated bile acid levels. ICP is regarded as a benign disease with no meaningful consequences to the mother but associated to an increased perinatal risk with increased rates of fetal morbidity and mortality. The pathogenesis of disease is unknown but likely involves a genetic hypersensitivity to estrogen or estrogen metabolites. Mutations or polymorphisms of some hepatobiliary transport proteins may contribute to disease pathogenesis or severity. Treatment is focused on a) reducing symptoms in the mother and b) to provide an adequate obstetric management in order to prevent fetal distress. Currently, only Ursodeoxycholic acid treatment has been proven to be useful and should be considered mainly in patients with severe pruritus or complications in previous pregnancies.     

REVIEW: Intrahepatic cholestasis. A puzzling disorder of pregnancy

Intrahepatic cholestasis of pregnancy is characterized by skin pruritus and a biochemical cholestasis of mild to moderate severity appearing during pregnancy (mainly in the third trimester) and disappearing after delivery. It recurs in 40–60% of future pregnancies. The intensity of pruritus and the laboratory alterations (increased serum bile salts and transaminases in almost all patients, hyperbilirubinaemia in 20% of patients) fluctuate during one pregnancy and also vary in subsequent affected pregnancies. This disease has no meaningful consequences for the mother; in contrast, it is associated with an increased risk of foetal distress, causing premature deliveries and stillbirths. Cholestasis of pregnancy has been recognized in most countries and ethnic groups but its prevalence is higher in Chile (14% of deliveries in 1975 and approximately 4% in 1995) and in Sweden than in other countries. The cause is unknown. Sex hormones, mainly oestrogens and progesterone, appear to be involved in its pathogenesis. An interplay between a genetic metabolic predisposition and some environmental factor(s) is apparently relevant. Clinical and experimental studies suggest that a marginal selenium deficiency could be a dietary pathogenic factor. Some drugs attenuate pruritus and improve maternal cholestasis, but not the foetal prognosis. Ursodeoxycholic acid (UDCA) administration provides a significant improvement in maternal pruritus and in the biochemical abnormalities, with no adverse effects in the mother or child. Recent clinical and experimental studies show that UDCA administration improves maternal disease and foetal prognosis without any detectable adverse effects.     

Review of a challenging clinical issue: Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a reversible pregnancy-specific cholestatic condition characterized by pruritus, elevated liver enzymes, and increased serum bile acids. It commences usually in the late second or third trimester, and quickly resolves after delivery. The incidence is higher in South American and Scandinavian countries (9.2%-15.6% and 1.5%, respectively) than in Europe (0.1%-0.2%). The etiology is multifactorial where genetic, endocrine, and environmental factors interact. Maternal outcome is usually benign, whereas fetal complications such as preterm labor, meconium staining, fetal distress, and sudden intrauterine fetal demise not infrequently lead to considerable perinatal morbidity and mortality. Ursodeoxycholic acid is shown to be the most efficient therapeutic agent with proven safety and efficacy. Management of ICP consists of careful monitoring of maternal hepatic function tests and serum bile acid levels in addition to the assessment of fetal well-being and timely delivery after completion of fetal pulmonary maturity. This review focuses on the current concepts about ICP based on recent literature data and presents an update regarding the diagnosis and management of this challenging issue.     

Intrahepatic cholestasis without jaundice

BACKGROUND:Cholangiocarcinoma(CC),the most common biliary tract malignancy,is frequently seen in advanced unresectable stages and is typically localized extrahepatically.Early diagnosis is unusual because of nonspecific symptoms.Painless jaundice is usually the first sign of tumor. METHOD:We present a patient with a CC(Klatskin tumor) with a complete biliary drainage by an aberrant bile duct without jaundice. RESULTS:A 67-year-old woman presented with persisting elevation of liver parameters.Diagnostic test...     

Intrahepatic cholestasis of pregnancy with marked elevation of transaminases in a black American

Summary A case of intrahepatic cholestasis of pregnancy (ICP) in a black American is presented. This is the first case reported in a black. Marked elevation of transaminases with mild biochemical evidence of cholestasis was initially suggestive of viral hepatitis. A clinical course characterized by pruritis with minimal constitutional symptoms, rapid resolution of biochemical abnormalities after delivery, and negative hepatitis A and B serologies was consistent with the diagnosis of ICP. Review of the classic features of ICP with emphasis on some unusual aspects of the disorder is included.     

Intrahepatic cholestasis after liver transplantation

Biochemical cholestasis after liver transplantation is common and often has no clinical significance if biliary anastomosis strictures and leaks have been excluded. There is no agreed upon definition for severe cholestasis, but it is associated with a worse mortality. There has been little evaluation on risk factors, but these include cryoprecipitate and platelet transfusion intraoperatively, nonidentical blood group, suboptimal graft appearance, inpatient status before transplant, and bacteremia within the first month. Associated causes considered as early (<6 months) include ischemia-reperfusion injury, primary nonfunction, small-for-size graft syndrome, infection, drugs and acute cellular rejection. Late causes include hepatic artery thrombosis, chronic rejection, biliary complications, recurrent viral and cholestatic disease, and posttransplant lymphoproliferative disorder.     

Intrahepatic cholestasis following liver transplantation

Intrahepatic cholestasis following liver transplantation commonly occurs after liver transplantation and may be caused by infections, drugs such as cyclosporine and sulfonamides, and acute or chronic rejection. Less common causes such as fibrosing cholestatic hepatitis or recurrent primary biliary cirrhosis or primary sclerosing cholangitis may also be encountered. Biliary strictures may also be present. Although some disorders may be managed medically, others often require repeat liver transplantation. Prompt recognition and specific treatment can improve the outcome for liver transplant recipients.     

Intrahepatic cholestasis due to azathioprine

Severe intrahepatic cholestasis occurred 13 months following renal homotransplantation in a patient treated with azathioprine and prednisone. The patient had not received other drugs, surgery, anesthesia, or blood transfusions since transplantation. Extrahepatic biliary obstruction was excluded by laparotomy and operative cholangiography. Histologically, marked cholestasis was present with minimal necrosis and inflammation terminally. An awareness of this possible complication is important in the treatment of chronic liver disease with azathioprine.