A Five Year Experience of Acute Intrahepatic Cholestasis in Patients with Sickle Cell Disease at a Large Teaching Hospital in London

Background:

Acute intrahepatic cholestasis (AIC) is a rare but severe form of sickle hepatopathy, caused by sickling within hepatic sinusoids, leading to vascular stasis, hypoxic damage and can lead to acute hepatic failure. It is characterised by a combination of clinical, laboratory and radiological features. There is tender hepatomegaly, hyperbilirubinaemia without evidence of extrahepatic biliary obstruction, coagulopathy and thrombocytopenia. Transaminitis, if present is mild or moderate.

AIC has a high fatality rate if not treated promptly. Although there is a dearth of evidence on how to treat AIC, the most frequently recommended intervention is by exchange blood transfusion. We report our experience of managing patients with this rare yet serious complication of sickle cell disease at a large tertiary centre over the course of 5 years.

Methods:

A retrospective review of adult patients who attended the sickle cell service from 1^st January 2010 to 30^thJune 2015 was undertaken. All patients who had had a bilirubin level greater than 300umol/L were identified. Patients with evidence of ‘secondary’ causes of hyperbilirubinaemia such as biliary sepsis, acute biliary or extrahepatic duct dilatation were excluded.

For the remaining patients, clinical notes were reviewed for history of tender right upper quadrant, peak bilirubin levels, coagulation studies, ferritin, ultrasonography or other liver imaging, pre-existing co-morbidities and immediate and long-term clinical outcome were recorded.

Results:

We identified 16 cases of AIC in 15 patients, out of an excess of 582 patients who attended the Sickle Cell Department over the course of 5 years. In three of these cases, there was also an associated generalised vaso-occlusive crisis. There were 10 male and five female, all of whom had sickle cell anaemia (HbSS), with a median age of 30years (20-48 years).

In terms of pre-existing liver disease, one patient had autoimmune hepatitis; another two had chronically deranged liver functions with radiological features suggestive of cirrhosis.

Age	Sex	Peak bilirubin; conjugated%	INR	APTR	Thrombocytopenia	Concurrent crisis (VOC)	Outcome
25	F	398; 65%	1.28	1.17	No	No	Alive
25	F	386; 61%	1.22	1.97	No	No	Alive
36	M	299; 69%	1.28	1.33	No	Yes	Alive
20	M	299; 63%	1.49	1.22	No	No	Alive
37	M	693; 74%	1.37	1.54	No	No	Alive
38	F	671; 100%	1.21	1.41	Yes	No	Alive
25	F	686; 83%	1.07	1.53	Yes	No	Alive
25	M	585; 78%	1.25	1.14	No	No	Alive
34	M	450; 88%	1.12	1.58	Yes	No	Alive
30	M	694; 96%	2.59	3.77	Yes	No	Deceased
48	M	719; 66%	3.00	2.33	Yes	No	Deceased
22	M	975; 98%	4.0	>5	No	No	Deceased
25	F	310; N/A	1.47	2.06	Yes	Yes	Alive
25	M	1043; 99%	3.43	>5	Yes	No	Deceased
44	F	478; 100%	1.33	1.40	No	No	Alive
46	M	644; 91%	2.08	1.2	Yes	No	Deceased

The findings on ultrasonography included increased liver reflectivity, hepatomegaly and in two cases, cirrhosis. Choledolithiasis was present in 6 cases, with no evidence of gall bladder infection, inflammation or duct obstruction. Cholecystectomy had been performed in 3 cases; two of these patients had chronically dilated intrahepatic ducts.  

All patients received transfusions to lower the Haemoglobin S% to less than 30%. Eleven patients received exchange blood transfusions within 72hours of presentation. The remainder, who had received transfusion recently (majority at local hospital) received further transfusions within a week of admission to keep HbS% <20%.

Seven of the 11 patients who recovered now have normal transaminases with mildly elevated bilirubin levels. Three patients have markedly elevated transaminases and bilirubinaemia, two of whom had previous cholecystectomy and chronically dilated intrahepatic ducts. The third has a heterogenous liver with features of sickle hepatopathy and probable early features of liver fibrosis, while the fourth went on to have a successful liver transplant.

There were 5 deaths; all in male patients aged between 22 and 48 years. Two had established cirrhosis; one also had autoimmune hepatitis and CMV viraemia. A third patient had liver biopsy evidence of fibrosis, while a fourth had a CT description of liver with a nodular contour. The fifth patient,was previously fit and well and adenoviraemia was diagnosed.

Discussion:

Our experience supports the view that AIC can successfully be reversed by timely exchange blood transfusion, and suggests that underlying liver disease and viraemia confer a poor outcome, irrespective of age.