A case of cholestatic hepatitis associated with histologic features of acute cholangitis

Figures & data

Table 1 Patient’s laboratory data

Blood count
WBC	5800	3300–9000/μl
Neu	67.44%
Lym	22.4%
Mono	7.8%
Eo	7.8%
RBC	3.77 × 10^4	380–500 × 10^4/μl
Hb	12.3	11.5–15.0 g/dL
Plt	21.9 × 10^3	140–340 × 10^3/μl
Coagulation system
PTINR	1.12	0.85–1.15
Blood chemistry
T-bil	6.7	0.2–1.2 mg/dL
D-bil	5.2	0.0–0.2 mg/dL
AST	182	10–40 IU/L
ALT	376	5–45 IU/L
LDH	282	120–240 IU/L
ALP	936	100–325 IU/L
γ-GTP	772	<30 IU/L
ChE	377	200–452 IU/L
TP	8.7	6.7–8.3 g/dL
ALB	4.5	3.8–5.3 g/dL
T-chol	248	120–219 mg/dL
TG	171	30–149 mg/dL
Na	140	137–147 mEq/L
K	5.1	3.5–5.0 mEq/L
CI	99	98–108 mEq/L
CRP	4.42	<0.3 mg/dL
GIc	97	70–109 mg/dL
TSH	0.821	0.436–3.8 μlU/mL
FT4	0.87	1.0–1.7 ng/dL
Thyroglobulin Ab	0.6 (+)	<0.3 U/mL
Serological examination
lgm-HAAb	(−)	<0.80
HBsAg	(−)
Igm-HBc Ab	(−)
HCV Ab	(−)
HCV RNA	<1.2	<1.2 log lU/mL
EBV-VCA IgM	<10	< ×10
EBV-VCA IgG	×320	< ×10
EBV-EBNA	×1600	< ×10
IgM CMV	(−)	0.8
IgMHEV	(−)
IgG	1907	870–1700 mg/dL
IgG4	80.2	4.8–105.0 mg/dL
IgM	95	46–260 mg/dL
ANA	×40	< ×40
Mitochondria M2Ab	<5.0 (−)	<7.0
P-ANCA	<3.5 (−)	<3.5 U/mL
C-ANCA	<1.3 (−)	<9.0 U/mL
sIL-2R	294	124–466 U/mL
Feritin	452	4.0–62.2 ng/dL
DLST
Pablon	149	<179%
HLA typing
A^*	02:01:01	24:02:01
B^*	40:02:01
C^*	03:04:01
DRB1^*	11:01:01	14:01:01
DQB1^*	03:01:01	05:03:01
DPB1^*	02:01:02	02:02
DQA1^*	01:04	05:05

Abbreviations: WBC, white blood cells; Neu, neutrophils; Lym, lymphocytes; Mono, monocytes; Eo, eosinophils; RBC, red blood cells; Hb, hemoglobin; Plt, platelets; PTINR, prothrombin time international normalized ratio; T-bil, total bilirubin; D-bil, direct bilirubin; AST, aspartate transaminase; ALT, alanine transferase; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; γ-GTP, γ-glutamyl transpeptidase; ChE, cholinesterase; TP, total protein; ALB, albumin; T-chol, total cholesterol; TG, triglyceride; Na, sodium; K, potassium; Cl, chloride; CRP, C-reactive protein; Glc, glucose; TSH, thyroid stimulating hormone; FT4, free thyroxine; Ab, antibody; Ig, immunoglobulin; HBsAg, hepatitis B virus antigen; HCV-Ab, hepatitis C virus antibody; HCV-RNA, hepatitis C virus RNA; EBV, Epstein-Barr virus; VCA, virus capsid antigen; EBNA, Epstein-Barr virus nuclear antigen; CMV, cytomegalo virus; HEV, Hepatitis E Virus, ANA; anti-nuclear antibody; M2 Ab, anti-mitochondrial antibody; P-ANCA, perinuclear anti-neutrophil cytoplasmic antibody; C-ANCA, cytoplasmic anti-neutrophil cytoplasmic antibody; sIL-2R, serum-soluble interleukin-2 receptor; DLST, drug lymphocyte stimulation test HLA, human leukocyte antigen.

Figure 1 Computed tomography (axial image, arterial phase) and endoscopic retrograde cholangiography findings. (A) Computed tomography imaging shows no mass lesion. (B) endoscopic retrograde cholangiography shows no stones in common bile duct and no extrahepatic biliary duct dilatation.

Figure 2 Light microscopic findings of liver biopsy. (A) Bile canalicular cholestasis findings showing edematous and pigmented hepatocytes around the central vein (arrowheads). “C” denotes the central vein. (B) Inflammatory infiltrate is made of polynuclear neutrophils and a varying number of eosinophils. Interlobular bile duct destruction is present in the portal tract. The arrow indicates destructive cholangitis. “P” denotes the portal vein. (C) HE and diastase-digested periodic acid-Schiff show intraepithelial neutrophilic infiltration in the interlobular bile duct. (D) Silver staining shows that basement membrane of the bile duct is preserved, but the nuclear arrangement is irregular. (E) Masson’s trichrome staining yields no evidence of portal fibrosis. (F) Cytokeratin 7 immunostaining shows positive cytoplasmic expression in the bile duct.

Figure 3 Electron microscopic findings. (A) Degenerative bile duct-related epithelial cells (arrowhead) are in an apoptotic process, as inferred from the appearance of condensed polymorphic and fragmented nuclei. The intercellular space adjacent to this degenerative epithelium is remarkably dilated (arrow), implying that bile substances are regurgitated from the lumen to the abluminal side. (B) A canal of Hering (CoH) with markedly dilated lumen (L) and loss of microvilli is lined by two hepatocytes (H1 and H2) and four cholangiocytes (C1–C4) containing deposits of electron-dense biliary substances (arrowhead). The intercellular space adjacent to epithelium is dilated (arrow). Between the two hepatocytes (H1 and H2) is a remarkably dilated bile canaliculus (BC) showing complete loss of microvilli and heavy deposition of biliary substances (arrow). (C) This electron micrograph shows a pseudo-bile ductule, the lumen of which is lined by six hepatocytes containing bile substances. The adjacent bile canaliculus (BC) is dilated with loss of microvilli and deposit of bile substances. The arrow indicates deposition of biliary substances.

Figure 4 Clinical course.

Abbreviations: ALT, alanine transferase; ALP, alkaline phosphatase; T-bil, total bilirubin; γ-GTP, γ-glutamyl transpeptidase; GPT, gutamicpruvate transaminase.