Focal intrahepatic strictures: A proposal classification based on diagnosis-treatment experience and systemic review

Table 1 Basic clinical data of the patients of focal intrahepatic strictures

No.	Sex	Age	Main symptoms		Bilirubin and ALP before treatment for FIHS		CA199 (ng/mL)	AFP (ng/mL)	History of surgery	Methods for initial diagnosis	Initial diagnosis	Final diagnosis	Location of FIHS	Treatment for FIHS
			Abdominal pain	Fever	T-bil/D-bil (μmol/L)	ALP (U/L)
1	F	65	Mild	-	16.1/0.0	0.0	20.55	8.99	No	MDCT	Suspected ICC	ICC	LLIHD	Left lateral hepatectomy
2	M	70	-	-	16.7/6.2	6.2	13.4	737.00	Yes1	MDCTMRCP	rHCC with BDTT/PVTTLung metastasis	rHCC with BDTT/PVTTLung metastasis	LLIHD	Lenvatinib + Sintilizumab
3	F	60	Mild	-	16.8/8.6	8.6	2270.0	1.61	No	MDCTMRCP	HepatolithiasisSuspected ICC	ASC of liver	LIHD	Left hepatectomy
4	F	67	Mild	-	15.0/0.0	0.0	93.9	2.91	No	USMDCTMRCPERCPSpyglass	Suspected ICC	Hepatolithiasis	LIHD	Left hepatectomy
5	F	49	-	-	21.6/10.4	614.0	11.83	0.90	No	MRCP	Hepatitis	SD-PSC(biopsy)	Multiple IHD	UDCA
6	F	55	-	-	283.5/150.0	279.0	770.0	23.8	No	MDCTMRCPERCP	Suspected PSC	AIH(biopsy)	Multiple IHD	UDCA + MP

¹The patient had histories of hepatectomy for hepatocellular carcinoma (HCC) 19 mo before this admission and resection of the recurrent isolated HCC lesion in abdominal cavity 9 mo before this admission, respectively. T-bil: Total bilirubin; D-bil: Direct bilirubin; ALP: Alkaline phosphatase; AFP: Alpha-fetoprotein; FIHS: Focal intrahepatic strictures; ICC: Intrahepatic cholangiocarcinoma; LLIHD: Left lateral intrahepatic duct; MDCT: Multidetector-row computed tomography; MRCP: magnetic resonance cholangiopancreatography; SD-PSC: small duct primary sclerosing cholangitisprimary; IHD: intrahepatic duct; UDCA: Ursodeoxycholic acid; ASC: Adenosquamous carcinoma; US: Ultrasound; ERCP: Endoscopic retrograde cholangiopancreatography; LIHD: Left intrahepatic duct; rHCC: Recurrent hepatocellular carcinoma; BDTT: Bile duct tumor thrombi; PVTT: Portal vein tumor thrombus; PSC: Primary sclerosing cholangitis; AIH: Autoimmune hepatitis; MP: Methylprednisolone.

Table 2 Imaging and endoscopic diagnosis of focal intrahepatic strictures

No.	Method of examination	Characteristics of FIHS lesion						Characteristics of secondary changes
		Location of FIHS	Enhancement of FIHS lesion in different phases				Imaging diagnosis	Hepatatrophia	Intrahepatic bile duct dilation	Hepatolithiasis
			Plain	Arterial	Portal	Delayed
1	MDCT	Not clear	-	-	faint	faint	Left hepatic lobe atrophy, LIHD dilation, Suspected ICC	+	B2, B3	-
2	MDCT	Confluence of B2/B3	-	+	-	-	rHCC with BDTT/PVTT	-	B2, B3	-
	MRCP		-	+	-	-		-	B2, B3	-
3	MDCT	Confluence of B2/B3/B4	-	-	-	-	Hepatolithiasis, Suspected ICC	-	B2, B3, B4	+
	MRCP		-	-	-	-		-	B2, B3, B4	+
4	US	Not clear	N/A	N/A	N/A	N/A	High-echo lesion in S4	-	LIHD	-
	MDCT	Not clear	-	-	-	-	LIHD dilation	-	LIHD	-
	MRCP	Not clear	-	-	-	-	High T2 signal in S4LIHD dilation, Suspected ICC	-	LIHD	-
	ERCP+Spyglass	Not clear	N/A	N/A	N/A	N/A	Acute cholangitis	N/A	Not clear	-
	IOUS, Choledochoscopy	Confluence of B2/B3/B4	N/A	N/A	N/A	N/A	Acute cholangitis, Hepatolithiasis	-	B2, B3, B4	+
5	MRCP	Multiple small IHD	-	-	-	-	Hepatitis	-	-	-
6	MDCT	Multiple small IHD	-	-	-	-	Acute cholangitis	-	-	-
	MRCP		-	-	-	-	Acute cholangitis, Suspected PSC	-	-	-
	ERCP		N/A	N/A	N/A	N/A	PSC	N/A	-	-

FIHS: Focal intrahepatic strictures; MDCT: Multidetector-row computed tomography; LIHD: Left intrahepatic duct; ICC: Intrahepatic cholangiocarcinoma; B2: Bile duct of segment II; B3: Bile duct of segment III; B4: Bile duct of segment IV; S4: Segment IV; MRCP: Magnetic resonance cholangiopancreatography; US: Ultrasound; ERCP: Endoscopic retrograde cholangiopancreatography; IOUS: Intraoperative ultrasonography; BDTT: Bile duct tumor thrombi; PVTT: Portal vein tumor thrombus; rHCC: Recurrent hepatocellular carcinoma; PSC: Primary sclerosing cholangitis; N/A: Not applicable.

Table 3 Pathological characteristics of focal intrahepatic strictures

No.	Pathological characteristics of FIHS and related lesions
	Location of dilated bile duct	Macroscopic					Microscopic
		Location of FIHS	Features of related lesions				Structure	Pathological diagnosis	Differentiation of malignant FIHS	Surgical margin
			Location of related lesions	Size (cm)	Color	Texture
1	B2, B3	Confluence of B2/B3	ICC: left lateral lobe	ICC: 0.8	Grey white	Jellylike	Tubulo-villous	Peritubular infiltrating type ICC; Partial mucinous adenocarcinoma	Moderate	-
2	-	-	-	-	-	-	-	-	-	-
3	B2, B3, B4	Confluence of B2/B3/B4	ASC: left lobe	ASC: 6.0 (Dilated bile ducts)	Grey white	Hard	Irregular nests of polygonal cells; intercellular bridges	ASC of liver; Hepatolithiasis	Moderate	-
4	B2, B3, B4	Confluence of B2/B3/B4	Hepatolithiasis: B2, B3, B4	Stones: 0.1-0.2	black brown	Hard	Lymphocytes, plasma cells, macrophages infiltration; Fibrosis	Cholangitis; Hepatolithiasis	N/A	N/A
5	-	-	-	-	-	-	Portal inflammation with edema, Fibrosis and proliferation	SD-PSC	N/A	N/A
6	-	-	-	-	-	-	Cloudy swelling of liver cells; cholestasis; inflammatory cell infiltration; proliferation of small bile ducts	AIH	N/A	N/A

FIHS: Focal intrahepatic strictures; ICC: Intrahepatic cholangiocarcinoma; SD-PSC: Small duct primary sclerosing cholangitisprimary; ASC: Adenosquamous carcinoma; B2: Bile duct of segment II; B3: Bile duct of segment III; B4: Bile duct of segment IV; AIH: Autoimmune hepatitis; N/A: Not applicable.

Table 4 Literature review of nature, causes, etiology, pathology and mechanisms of focal intrahepatic strictures

Nature of FIHS	Causes and factors	Etiology	Pathology and mechanisms	Incidence rate
Benign	Surgery and trauma	Hepatobiliary surgery	Physical injury of bile duct and hepatic artery; Ischemia of bile duct	Unknown
		TACE	Chemical injury;Ischemia of bile duct	0.3%[3]
		RFA	Heat damage; Ischemia of bile duct	17%[4]
	Chronic inflammation	Hepatolithiasis/Bacterial infection	Inflammatory response; Mechanical obstruction	70.6%[5]
		Parasite	Inflammatory response; Mechanical obstruction	Case report[6]
		Mycobacterium tuberculosis	Secondary cholangitis and granuloma	16.7%[7]
		HIV cholangiopathy	Inflammatory and immune response caused by cryptosporidium and cytomegalovirus; Ischemia of bile duct caused by injury of hepatic artery	15%-20%[8]
		SD-PSC	Autoimmune response; Bile duct fibrosis	Case report[9]
		LIH-IgG4-SC	Autoimmune response; Bile duct fibrosis	Case report[10]
		Autoimmune pancreatitis	Autoimmune response; Bile duct fibrosis	24.3%[13]
		Follicular cholangitis	Dense fibrosis of muscularis mucosae with follicular hyperplasia	Case report[14]
	Congenital diseases	Caroli's disease	Hepatic fibrosis; Secondary bile duct sclerosis	13%-80%[15,16]
	Benign tumor	IBPMC	Intraductal growth and mechanical obstruction	Case report[17]
Malignant	Primary malignant tumor	Peritubular infiltrating type of ICC	Periductal infiltration and mechanical obstruction	50%-53%[11,18]
		Intratubular growth type of ICC	Intraductal growth and mechanical obstruction
		HCC	Tumor thrombus	11.8%[11]
		ASC of liver	Chronic cholangitis and mechanical obstruction	Case report[19]
	Metastatic malignancy	Metastatic hepatic carcinoma	Intraductal biliary metastasis and mechanical obstruction	Case report[20]

FIHS: Focal intrahepatic strictures; TACE: Transcatheter arterial chemoembolization; RFA: Radiofrequency ablation; SD-PSC: Small duct primary sclerosing cholangitis; LIH-IgG4-SC: Localized intrahepatic IgG4-related sclerosing cholangitis; IBPMC: Intrahepatic biliary papillary mucinous cystadenoma; ICC: Intrahepatic cholangiocarcinoma; HCC: Hepatocellular carcinoma; ASC: Adenosquamous carcinoma.