Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.

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Intrahepatic cholestasis of pregnancy

S-adenosylmethionine synthesis: molecular mechanisms and clinical implications.

S-Adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.24229

Drug‐induced cholestasis

Alterations have been found to occur in every component of immune response during anaesthesia and surgery. These alterations represent the body's general physiological responses and are mainly dependent on the extent of surgery, as well as other factors such as the patient's age and health status, medication and blood transfusion. Anaesthetic and operative complications have profound effects on these responses. Basically, the immune response to anaesthesia and surgery is a beneficial reaction, needed in local host defences and wound healing and in preventing the body from making autoantibodies against its own tissues. The responses may, however, contribute to the development of postoperative infections and spread of malignant disease. During uncomplicated conventional surgery, the immune response usually passes clinically unnoticed without any harmful effects. Absent responses and excessively high responses, on the other hand, harm the patient. Our understanding of immunological phenomena and our possibilities of controlling mediator activation are now lagging behind the technical advances made in operative treatment. If we want to decrease operative morbidity and mortality to below their present levels, more attention should be directed to immune responses to major surgery, injuries and operative complications with massive mediator release which place the surgical patient at risk. Experimental evidence suggests that results of treatment in injured and operated patients can in the future be improved by controlling immune responses and their mediator systems. Our current level of knowledge of immune responses is already helping us to avoid many immune-mediated complications. However, routine interference with these responses is not indicated.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1399-6576.1992.tb03452.x

Effects of anaesthesia and surgery on the immune response.

Ethynylestradiol-Induced Impairment of Bile Secretion in the Rat: Protective Effects of S-Adenosyl-L-Methionine and Its Implication in Estrogen Metabolism

In order to investigate the effectiveness of microporous cholestyramine in the pharmacological management of intra- and extrahepatic cholestasis, a double-blind placebo-controlled study was carried out in 10 patients. Microporous cholestyramine or placebo 3 g t.i.d. were given orally over a four-week period. The active drug resulted statistically superior to the placebo in reducing itching intensity (p less than 0.01) and serum bile acids (p less than 0.01). A positive linear relationship between itching and serum bile acids (p less than 0.01) was also demonstrated.

Double-blind placebo-controlled clinical trial of microporous cholestyramine in the treatment of intra- and extra-hepatic cholestasis: relationship between itching and serum bile acids.

Influence of S-adenosyl-L-methionine on irreversible binding of ethynylestradiol to rat liver microsomes, and its implication in bile secretion.

Hydroxychloroquine and phlebotomy were compared in the treatment of porphyria cutanea tarda (PCT). Thirty patients received hydroxychloroquine (200 mg twice weekly) for 1 year and thirty-one underwent twice-monthly phlebotomies of 400 ml whole blood each, also for 1 year. Clinical signs of disease improved equally in both groups. At the end of the year, urinary porphyrin excretion had significantly improved in twenty-two out of thirty hydroxychloroquine-treated subjects, but in only eight out of the thirty-one patients who received phlebotomy. Liver histology showed significant regression of steatosis and siderosis in both groups compared with the pretrial biopsy, but the activity of liver disease, as judged by the extent of necrosis, inflammation and fibrosis, worsened in twelve hydroxychloroquine and in seven phlebotomy-treated patients. It is concluded that hydroxychloroquine is more effective than phlebotomy in decreasing porphyrin production. However, further work is needed to assess whether long-term hydroxychloroquine treatment favours the progression of the chronic liver disease associated with PCT.

Rovagnati P

Papers

Ethynylestradiol-Induced Impairment of Bile Secretion in the Rat: Protective Effects of S-Adenosyl-L-Methionine and Its Implication in Estrogen Metabolism

Double-blind placebo-controlled clinical trial of microporous cholestyramine in the treatment of intra- and extra-hepatic cholestasis: relationship between itching and serum bile acids.

Influence of S-adenosyl-L-methionine on irreversible binding of ethynylestradiol to rat liver microsomes, and its implication in bile secretion.

Hydroxychloroquine versus phlebotomy in the treatment of porphyria cutanea tarda

The treatment of retained biliary stones with monooctanoin: report of 16 patients.