Sclerosing cholangitis following severe trauma: Description of a remarkable disease entity with emphasis on possible pathophysiologic mechanisms

Table 1 Summary of patients‘ characteristics

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Sex	Female	Male	Male	Male	Male
Age (yr)	56	41	56	71	18
Initial event	Room fire	Motorbike accident	Tractor accident	Fall from a raised hide	Power current accident
					and fall
Injuries	Burn injury: 34 % of	Polytrauma with avulsions	Polytrauma with serial	Polytrauma with burst	Burn injury (36 % of body
	body surface (hands,	(left subclavian artery,	rib fracture, hemothorax,	fractures of lumbar spine,	surface), multiple rib
	head, neck, back)	forearm, anterior tibial	pleural effusion, fracture	paraplegia, rib fractures,	fractures, hemothorax,
		artery) and fractures	of right joint ankle	pneumothorax	fractures of the thoracic
		(left humeral shaft,			vertebrae 5 to 9
		pelvis, both lower legs)
Intensive care (d)	58	23	34	26	88
Time from	4	27	4	13	2
occurrence
of cholestasis until
diagnosis (mo)
Treatment start	mo 4	mo 22	mo 4	mo 13	mo 1
with UDCA
Follow-up(mo)	55 (death)	48	41	33	12
Complications	Liver cirrhosis (Child-	Small intrahepatic	unbearable pruritus	liver cirrhosis	-
	Pugh C), variceal	gallstones after 6 mo	during first year,	(Child-Pugh B),
	bleeding, death due	(endoscopically extracted),	liver cirrhosis	recurrent stomal
	to liver insufficiency	liver cirrhosis (Child-Pugh A)	(Child-Pugh A)	bleeding

UDCA: urso deoxycholic acid.

Table 2 Patients’ data and important findings during the early course at the intensive care unit

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Time of increase of liver
function tests > 2× ULN (d)
GGT	101	6	5	4	11
AP	18	18	9	12	15
Bilirubin	36	62	10	8	13
AST	18	52	9	12	16
ALT	18	23	9	7	19
Mechanical ventilation (d)	36;	13;	25;	16;	62;
	PEEPmax. 6 mmHg;	PEEPmax. 10 mmHg;	PEEPmax. 8 mmHg;	PEEPmax. 15 mmHg;	PEEPmax. 20 mmHg;
	FiO2 not documented	FiO2max. 0.6	FiO2max. 0.6	FiO2max. 0.7	FiO2max. 0.6
Severe hypotension	d 1 (2 h)	d 1 (45 min)	d 2 (30 min) and	d 1 (30 min)	None
(systolic blood pressure			d 3 (60 min)
< 70 mm Hg)3
Vasopressor therapy	Dobutamine d 1-8	None	Norepinephrine d 3-5	Norepinephrine d 2-4	None
	dopamine d 1-18		and d 9-17
	norepinephrine d 1-7
Minimum hemoglobin3	7.3 g/dL (d 3)	2.4 g/dL (d 1)	7.2 g/dL (d 3)	8.6 g/dL (d 1)	7.9 g/dL (d 4)
Transfusions (RBC units)3	30	34	10	10	24
Fever (> 38.0 )	d 7-16	d 6-13	d 2-25	d 5-17	d 2- >20
Antibiotics3	Cefotaxim, imipenem,	None	Piperacillin/sulbactam	None	Piperacillin/tazobactam,
	sulbactam, mezlocillin				ciprofloxacin, meropenem,
					levofloxacin, fluconazol

ALT: alanine aminotransferase; AP: alkaline phosphatase; AST: aspartate aminotransferase; FiO2max.: maximum fraction of inspired oxygen; GGT: gamma glutamyl transferase; PEEPmax.: maximum positive end-exspiratory pressure; ULN: upper limit of normal ¹No control of liver function tests between d 4 and 10; ²A bilirubin value 2× ULN was noted only once at d 6;

³Until increase of GGT ≥ 2× ULN.

Table 3 Diagnostic findings in posttraumatic sclerosing cholangitis during the course of the disease (ultrasound, MRT/MRCP, ERCP, and liver histology)

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
1 - 2 mo
Ultrasound	L normal,	L normal,	L normal,	L normal,	L enlarged,
	BD normal,	BD normal,	BD normal,	BD normal,	hyperechoic,
	GB sludge	GB sludge	GB sludge	GB sludge	BD normal,
					GB contracted,
					splenomegaly
ERC	Stenoses and loss of IHBD,	-	IHBD irregular,	-	-
	CBD normal,		CBD normal,
	GB normal		GB normal
MRT/MRCP	-	-	-	L normal, BD	-
				normal, GB normal
4 - 6 mo
Ultrasound	L cirrhosis,	L inhomogeneous,	L inhomogeneous with	-	L enlarged,
			hyperechoic areas
			alongside the IHBD,		BD normal,
	BD normal,	BD normal	BD normal,		BD normal,
	GB stones		GB normal,		splenomegaly
ERC	-		IHBD: multifocal short	-	IHBD irregular,
			strictures and dilatations,		beaded
			CBD normal,		appearance,
			GB normal (Figure 2)		CBD normal,
					GB normal
Liver histology	Substantial cholestasis;	Portal tract inflammation,	Canalicular bile thrombi;	-	-
	inflammation of the portal	occasionally lymphocytes	edematously swollen
	tracts, liver lobules, and	in bile duct epithelium;	portal tracts;
	sporadically the bile ducts;	several necrotic foci with	inflammatory infiltrates,
	feathery degeneration of	foamy macrophages in	esp. around bile ducts;
	hepatocytes;	the liver acini;	occasionally feathery
	fibrosis around bile ducts;	bridging fibrosis;	degeneration of hepatocytes;
	regenerative bile duct	regenerative bile duct	minimal fibrosis
	proliferations	proliferations
12 - 24 mo
Ultrasound	L inhomogeneous cirrhosis	L enlarged, inhomogeneous,	L cirrhosis,	L cirrhosis,	-
		hyperechoic areas segment
		7/8, IHBD slightly dilated,		IHBD slightly dilated,
	BD normal,	CBD normal,	BD normal,	CBD normal,
	GB stones and sludge,	GB stones,	GB normal,	GB normal,
	splenomegaly,	splenomegaly	splenomegaly	splenomegaly
	distinct ascites
ERC	stenoses and loss of IHBD,	IHBD: loss and stenoses	-	IHBD: multifocal	-
		of right-sided bile ducts,		high-grade strictures and
		a long, stretched running		dilatations on the left side,
		left bile duct (suitable to		bile ducts on the right
		liver hypertrophy),		side not presentable,
	CBD normal,	CBD normal,		CBD normal
	GB normal	GB stones
MRT/MRCP	-	L atrophy of right liver,	L macronodular cirrhosis,	-	-
		hypertrophy of left liver;
		reduced signal intensity of
		segments 2 and 3 and
		partly 7 and 8;
		IHBD segmentally dilated,
		CBD pseudoobstruction,	CBD pseudoobstruction,
		GB stones, splenomegaly	splenomegaly
Liver histology	No cholestasis;	-	Occasionally canalicular	Substantial cholestasis (bile
	complete liver cirrhosis		cholestasis; mild	thrombi in dilated canaliculi);
			portal inflammation	occasionally lymphocytes in
			(predominantly	the epithelium of bile ducts;
			lymphocytes); some	numerous regenerative
			regenerative bile duct	bile duct proliferations in the
			proliferations; mild	periphery of portal tracts;
			fibrosis; (sampling error ?)	cirrhosis (Figure 4)

BD: bile ducts; CBD: common bile duct; GB: gallbladder; IHBD: intrahepatic bile ducts; L: liver.

Table 4 Characteristics of posttraumatic sclerosing cholangitis

No former liver disease

Severe life-threatening injury with temporary severe arterial hypotension

Slowly increasing signs of cholestasis

Secondary moderate rise of aminotransferases

PSC-like appearance of intrahepatic bile ducts (multifocal strictures and dilatations)

Exclusion of other liver diseases (esp. hepatic artery thrombosis)