Congenital hepatic fibrosis (CHF) is a rare genetic disorder characterized by biliary dysgenesis due to ductal plate malformation which is the primary structure of the liver that eventually forms the bile ducts, in some cases like CHF the ductal plate doesn’t develop correctly , instead of forming a complete bile duct , a malformed ducts surrounded by excess fibrous tissue causing a liver scarring and an increased blood pressure in the liver (portal hypertension) . the CHF can be related with other conditions such as polycystic kidney disease (ARPKD ) .
Due to its rarity and non-specific presentation, CHF is often underdiagnosed or misdiagnosed, particularly in its early stages. Many patients are identified when they present with complications of portal hypertension, such as splenomegaly, ascites, or gastrointestinal bleeding. Early recognition and management of CHF are critical to prevent the progression of liver disease and improve long-term outcomes. This case report highlights a 21-year-old girl with CHF who initially presented with abdominal pain,blood vomiting, hepatomegaly, and Abdominal distension,these symptoms prompted further investigation,including liver biopsy Which showed a portal hypertension and a genetic testing that confirmed an autosomal recessive polycystic kidney disease (ARPKD) due to compound heterozygous mutations in the PKHD1 gene.
The patient had normal blood pressure and heart rate , she was slightly jaundice in the sclera , the biomedical analysis showed a mild anemia HGB 75g/L, a thrombocytopenia with a ratio of PLT 37×10/L, and WBC 1.48×10/L . Bone marrow biopsy showed erythroid reactive hyperplasia in the bone marrow tissue; Bone marrow fluorescence hybridization showed that there were no abnormalities in BCR-ABL, F1P1L1/CHIC2/PDGFRA and PDGFRB (5q32) genes in bone marrow cells.
The ultrasound analysis demonstrated a Hepatomegaly, splenomegaly and signs of portal hypertension along with Multiple strong echoes in both kidneys ,which looked like stones or calcifications, the contrast- enhanced CT scan showed intrahepatic stenosis of the inferior vena cava, figure 1 small blocked right hepatic vein and middle hepatic vein, and collateral circulation these results were similar to Bud-chiari syndrome (BCS ), but the opposite has been proved after liver biopsy ,a small sample of liver tissue was taken from the patient to be examined under a microscope which is the definitive method for diagnosing liver diseases and determining whether it is CHF or not .it revealed a dense fibrosis around the bile ducts in the portal areas and portal hypertension , creating fibrosis bands with the liver , along with dilated bile ducts within the fibrosis and an abnormality in the ductal plate which is a key feature of Congenital hepatic fibrosis (CHF) as it is shown in figure2.
| Characteristics | II (Patient) | I1 (Father) | I2(Mother) |
| HGB | HGB 75g/L | NA | NA |
| WBC | 1.48×10/(9)L | NA | NA |
| PLT | 37×10/(9)L | NA | NA |
| Folic Acid | FOL>40.00ng/mL(↑) | NA | NA |
| RET | 2.11% (↑) | NA | NA |
| Creatinine | CR 86μmol/L， | NA | NA |
| GFR | 83.19ml/min (↓) | NA | NA |
| ALBUMIN | ALB 38.7g/L (↓) | NA | NA |
| Fibroscan | LSM 18 6 kpa | NA | NA |
| PKHD1 | |||
Sanger Sequencing was the main procedure taken for this study A blood sample was collected from the patient and Genomic DNA was extracted from peripheral blood leukocytes for genetic analysis. The PKHD1 gene was selected for sequencing, as it is known to be associated with both CHF and ARPKD , later a PCR was used to amplify specific exons of the PKHD1 gene .
The Sequencing was conducted in both forward and reverse directions for accuracy. The fluorescent signals from the labeled nucleotides were detected by the sequencer, generating a series of peaks (chromatograms) corresponding to the DNA sequences. Figure3[wz1]
The sequencing of the PKHD1 gene revealed two compound heterozygous mutations in the patient These mutations were inherited from the father and mother separately :
exon21, c.2107>A(p.Asp 703Asn) : missense mutation that alters an Amino acid, affecting the protein structure
Exon32 c.4820A>G(p.tyr1607Cys) : nonsense mutation resulting in a truncated protein
Both mutations were confirmed in multiple sequencing runs, ensuring the accuracy of the results. These mutations have previously been reported in association with CHF and ARPKD, and both are pathogenic, causing abnormal development of bile ducts and kidney cysts.
This genetic diagnosis, obtained via Sanger sequencing, confirmed congenital hepatic fibrosis due to compound heterozygous mutations in the PKHD1 gene .This case of congenital hepatic fibrosis (CHF) associated with autosomal recessive polycystic kidney disease (ARPKD) shows the essential role of genetic testing in diagnosing and managing complex genetic disorders with multisystem involvement. CHF, often associated with mutations in the PKHD1 gene, presents clinically with a range of hepatic and renal complications, including periportal fibrosis, bile duct malformations, and progressive renal cysts. The overlap of clinical features between CHF and other liver and kidney conditions can make the diagnosis challenging based solely on clinical findings. Genetic testing, in this case, was instrumental in confirming the diagnosis, identifying the causative mutations, and helping clarify the patient’s prognosis.
This mutations is known as pathogenic variant linked to CHF and ARPKD, both her parents electropherograms showed clear peaks of (C and T) at the sites marked by the red arrows figure4 , which indicates heterozygosity, where one Allele has Cytosine (C) and the other a Thymine (T) , These results confirm compound heterozygous mutation related to ARPKD and CHF , This mutation may impair the function of fibrocystin/polyductin, figure 5 the C/T heterozygosity in the sequencing results reflects the c.2107G>A (p.Asp703Asn) mutation , showing that the individual is heterozygous for this variant, this mutation is expressed in our patients due to a second pathogenic mutation on the second allele of PKHD1 inherited from the father ? [fh3]
the fibrocystin is a protein crucial for bile ducts and kidneys development , Without functional fibrocystin, patients experience progressive hepatic fibrosis, portal hypertension, and kidney dysfunction.
Knowledge of these mutations allowed for a targeted patient-specific approach to treatment, surveillance, and genetic counseling for the family.
Management of CHF requires a multidisciplinary approach, as demonstrated in this case. The patient’s portal hypertension was managed with beta-blockers to prevent variceal bleeding, and renal function was closely monitored due to the presence of kidney cysts and mild renal impairment. Additionally, genetic counseling informed the family about the 25% recurrence risk for future siblings, an essential aspect of care in autosomal recessive disorders. By understanding the specific mutations and inheritance pattern, the family was equipped with valuable information for potential prenatal and preimplantation genetic diagnosis.
carriers of this mutation do not develop symptoms but can pass it to the offspring
This case highlights how advances in genetic testing, such as Sanger sequencing, enhance diagnostic precision in complex genetic conditions. The ability to identify specific mutations not only facilitates accurate diagnosis but also improves our understanding of the underlying pathophysiology, supports early intervention, and enables family planning. As genetic testing becomes more accessible, it is likely to become a cornerstone in the personalized management of multisystem genetic disorders.
This case demonstrated that while CHF and Budd-Chiari syndrome can both lead to portal hypertension and liver dysfunction, key differentiators such as the acute nature of symptoms, imaging findings of hepatic venous obstruction, and genetic testing results were critical in distinguishing BCS as a separate, superimposed condition. The distinction between these conditions allowed for targeted treatment of BCS (such as anticoagulation) without confusing it with CHF progression, thereby providing more precise and effective management for the patient. Our case illustrates as well the pivotal role of genetic testing in confirming the diagnosis, guiding treatment, and providing essential information for genetic counseling. The identification of compound heterozygous mutations in the PKHD1 gene (c.2107G>A and c.4820A>G) provided a definitive diagnosis, allowed for tailored clinical management, and facilitated family counseling. This case underscores the value of a comprehensive, multidisciplinary approach in managing CHF, leveraging genetic testing to improve diagnostic accuracy, optimize care, and empower families with knowledge of inheritance patterns and risks.
PKHD1,fibrocystin, Congenital hepatic fibrosis (CHF), Sanger sequencing , mutations .
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[wz1]You can go look at the way others describe it in the literature I sent you
[wz2]The images should be combined and combined into one big picture
[fh3]Can you site the mutation for me ?
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