Experience of a single center with congenital hepatic fibrosis: A review of the literature

Table 1 Syndromes with associated congenital hepatic fibrosis

Associated disorder	Genetic anomaly [chromosome (gene)]	Characteristic clinical features
Caroli syndrome	6p21.1-p12 (PKHD1 gene)	Caroli’s disease - ectasia or segmental dilatation of the larger intrahepatic ducts
Polycystic kidney disease	6p21.1-p12 (PKHD1 gene)	Progressive cystic dilation of the renal tubule (resulting in renal failure), hepatic cysts, cerebral aneurysms, cardiac valvular abnormalities
Joubert syndrome	9q34.3; 11p12-q13; 6q23 (AHI1 gene); 2q13 (NPHP1 gene); 12q21.32 (CEP290 or NPHP6 gene); 8q21 (TMEM67 gene); 16q12.2 (RPGRIP1L gene)	Cerebellar vermis hypoplasia retinitis pigmentosa, nystagmus, ataxia
Senior-Loken syndrome	2q13 (NPHP1, NPHP4, NPHP5 genes); 3q22 (NPHP3 gene)	Cerebellar ataxia and skeletal abnormalities, nephronophthisis, retinal dystrophy, sensorineural hearing loss
COACH syndrome	4p15.3 (CC2D2A gene)	Cerebellar vermis hypo/aplasia, oligophrenia, ataxia, coloboma, polydactyly
Cogan syndrome	2q13 (NPHP1 gene)	Oculomotor apraxia, nephronophthisis, cerebellar ataxia
Arima syndrome	Not yet established	Cerebellar vermis hypoplasia, renal abnormalities, psychomotor retardation
Meckel syndrome	17q23 (MKS1 gene); 8q (TMEM67 gene); 12q (CEP290 gene); 16q12.2 (RPGRIP1L gene); 4p15 (CC2D2A gene); 11q	Microcephaly, renal cystic disease, hypoplastic or ambiguous genitalia, polydactyly, congenital heart defect, cleft palate, ocular defects
Bardet-Biedl syndrome	11q13; 16q21; 3p12-q13 (ADP-ribosylation factor gene); 15q22.3; 2q31; 20p12 (MKKS gene); 4q27; 14q32.11 (tetratricopeptide repeat domain-containing gene); 7p14; 12q; 9q33.1; 4q27; 17q23 (MKS1 gene); 12q21.3 (CEP290 gene)	Rod-cone dystrophy (atypical retinitis pigmentosa), postaxial polydactyly, central obesity, mental retardation, hypogonadism, and renal dysfunction
Alstrom syndrome	2p13 (ALMS1 gene)	Childhood obesity congenital retinal dystrophy, sensorineural hearing loss, endocrinopathies, cardiomyopathy, renal failure
Oral-Facial-Digital type IV - Mohr-Majewski syndrome	Not yet established	Lobulated tongue, pseudo-cleft of lip, hyperplastic frenula, polydactyly, severe bilateral deafness

Table 2 Several antifibrotic agents studied in the setting of hepatic fibrosis of different etiologies[33-43]

Authors	Antifibrotic agent studied	Patient group (n)	Dose used	Therapeutic efficacy
Kershenobich et al[33], 1988	Colchicine	Cirrhosis - all causes (100)	0.6-1.8 mg/d	5-yr survival rates: colchicine 75%, placebo 34%; Histological improvement: colchicine 30%, placebo 0%
Pockros et al[34], 2007	IFN-γ	Cirrhosis - HCV-related (488)	IFN-γ 1b 100 mg and 200 mg	Histological improvement in select group with IFN-inducible T cell a chemoattractant (I-TAC),
Weng et al[35], 2005	IFN-γ	Cirrhosis - HBV-related (99)	50 mg IFN-γ intramuscularly on a daily basis for 3 mo	Histological improvement: treatment group 63%, control group 24.1%
Debernardi-Venon et al[36], 2007	Angiotensin II receptor blockers (candesartan)	Cirrhosis - all causes (47)	8 mg/d	Has been shown to decrease hepatic venous pressure gradient in patients with cirrhotic portal hypertension; studies investigating histological improvement still underway
Neuschwander-Tetri et al[37], 2003	PPAR ligands (rosiglitazone)	NASH associated fibrosis (30)	4-8 mg/d	Significant improvements in zone 3 perisinusoidal fibrosis
Armendáriz-Borunda et al[38], 2006	Pirfenidone	HCV-related fibrosis (15)	1200 mg/d	Histological improvement in 30% of patients
Ferenci et al[39], 1989	Silymarin	Cirrhosis - all causes (170)	140 mg three times daily	4-yr survival rate: silymarin 58%, placebo 39%; no histopathological studies available
Nelson et al[40], 2003	Interleukin-10	HCV related fibrosis (30)	subcutaneously at a daily or thrice weekly dose of 8 pg/kg or a thrice weekly dose of 4 pg/kg	Significant improvements in histology
Poupon et al[41], 2003	Ursodeoxycholic acid	PBC (367)	15-20 mg/kg per day	Significantly delayed progression of histopathological changes
Lieber et al[42,43], 2003	Polyenylphosphatidylcholine	Chronic alcoholics (789)	1.5 g three times daily	No improvement in fibrosis; new study underway

HCV: hepatitis C virus; HBV: Hepatitis B virus; IFN-γ: Interferon-γ; PPAR: Peroxisome proliferator-activated receptor; NASH: Non-alcoholic steatohepatitis; PBC: Primary biliary cirrhosis.