Congenital Liver Fibrosis Research Articles

A "C" triad: cirrhosis and cholangitis due to Caroli disease.

Abstract Caroli disease (CD) is a rare congenital pathology of probable autosomal recessive inheritance, it is part of the fibrocystic liver diseases and is included in group V of the Todani classification. It is characterized by saccular or cystic dilations of the intrahepatic bile ducts, sometimes associated with congenital liver fibrosis, and is then called Caroli syndrome (CS). The usual clinical manifestation is recurrent abdominal pain secondary to intrahepatic or vesicular stones, and acute cholangitis crises with the consequent formation of intrahepatic abscesses.

A case report of autosomal recessive polycystic kidney disease with noncompaction of ventricular myocardium: coincidence or different manifestations of ciliopathy?

BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is a rare inherited cystic disease characterized by bilateral renal cyst formation and congenital liver fibrosis. Cardiovascular disorders such as noncompaction of ventricular myocardium (NVM) have not been reported with ARPKD.Case presentationA 5-month-old girl was examined after presenting with a fever and turbid urine for one day and was diagnosed as urinary tract infection. Urinary ultrasound showed multiple round, small cysts varying in size in both kidneys. Genetic testing revealed two heterozygous mutations and one exon deletion in the polycystic kidney and hepatic disease 1 gene, indicating a diagnosis of ARPKD. During hospitalization, she was found to have chronic heart failure after respiratory tract infection, with an ejection fraction of 29% and fraction shortening of 13%. When the patient was 15 months old, it was found that she had prominent trabeculations and deep intertrabecular recesses with the appearance of blood flow from the ventricular cavity into the intertrabecular recesses by echocardiography. The noncompaction myocardium was 0.716 cm and compaction myocardium was 0.221 cm (N/C = 3.27), indicating a diagnosis of NVM. Liver and kidney function remained normal during four-year follow-up.ConclusionsThis is the first report of NVM in a patient with ARPKD. It is unsure if the coexistence of NVM and ARPKD is a coincidence or they are different manifestations of ciliary dysfunction in the heart and kidneys.

Caroli disease: an update on pathogenesis.

Caroli disease: an update on pathogenesis.

Caroli Syndrome Associated with Polycystic Kidney and Congenital Heart Disease in Children in Africa

Caroli syndrome (CS) is defined as the association of Caroli disease with congenital liver fibrosis. It is a rare congenital pathology with a global prevalence of less than 1 / 1,000,000 inhabitants. We report a case of CS associated with polycystic kidney disease (PKD). He is a 7 years old boy followed from the age of 2 years for epigastric pain. Abdominal ultrasounds were performed at the ages of 2 years, 4 years and 6 years. They showed hepatomegaly associated with dilation of the intrahepatic bile ducts, hepatic fibrosis and bilateral renal cysts and micro-stones. The child received several hospitalizations, the last of which was at the age of 6 years for abdominal pain, ascites, digestive haemorrhage secondary to portal hypertension and hematuria. On admission, the weight was 19 kg (-2 DS), the size was 119cm (-1 DS) and the BMI was 13.41 (-3DS). The child had no icterus. The abdomen was distended and a painless hepatomegaly was palpated with a hepatic arrow at 12.5cm and stage II splenomegaly. The urine test showed hematuria. The liver test showed an isolated elevation of alkaline phosphatase. The abdominal computed tomography scan showed hepatomegaly, dilation of the intrahepatic bile ducts and the presence of bilateral renal hypodense cystic lesions. The patient received Aldactone, Propanolol, Captopril, a blood transfusion and ursodesoxycholic acid as treatment. The evolution is stationary awaiting surgical management.

Clinical analysis of de novo HBV infection after liver transplantation in non-HBV- related liver disease

Objective: The aim of this study was to summarize and analyze the clinical features and characteristics of de novo HBV infection after liver transplantation in non-HBV-related liver disease. Methods: We retrospectively analyzed the clinical data of 13 patients with new HBV infection in 376 cases of liver transplantation patients with non-HBV related liver diseases from April 2002 to December 2013 in our hospital. Results: Among 376 patients with non-HBV-related liver disease after liver transplantation, 13 patients developed new HBV infection, and the rate of new HBV infection was 3.46%. Of the 13 cases, 5 were males and 8 were females. The follow-up time was 14.7 -128.7 months, and the average time from surgery to new HBV infection was 19.06 months. The primary diseases were as follows: 5 cases of primary biliary cholangitis, 3 cases of alcoholic liver disease, 2 cases of drug-induced liver damage, 1 cases of post-hepatitis C cirrhosis, congenital biliary atresia and congenital liver fibrosis. All patients were positive for HBsAg, HBeAg, anti-HBc, 11 were positive for HBV DNA, and 2 were negative for HBV DNA. 6 cases had abnormal liver function and 7 cases had normal liver function. All patients were treated with antiviral therapy with nucleoside (acid) analogues. HBsAg was negative in 6 patients; HBsAg remained positive in 7 cases, including HBsAg, HBeAg, anti-HBc positive in 6 cases, HBsAg, anti-HBe, anti- HBc was positive in 1 case, HBV DNA was still positive in 1 patient, and HBV DNA was negative in 6 patients; liver function was normal in all patients. Conclusion: Non-HBV- related liver transplantation are high-risk group of new HBV infection, with the highest incidence of autoimmune liver disease. It is speculated that it may be related to the long-term use of hormones after the transplantation. The prognosis of newly diagnosed HBV infection after liver transplantation is fine as long as it can be found and treated early.

Ten-year experience of transjugular intrahepatic portosystemic shunt for noncirrhotic portal hypertension

Transjugular intrahepatic portosystemic shunt (TIPS) is considered to be well suited for the treatment of noncirrhotic portal hypertension (NCPHT) because of a usually severe portal hypertension (PHT) and a mild liver failure, but very less data are available. Records of patients referred for TIPS between 2004 and 2015 for NCPHT were reviewed. No patient should have clinical or biological or histological features of cirrhosis. Twenty-five patients with a wide variety of histological lesions (sinusoidal dilatations, granulomatosis, regenerative nodular hyperplasia, obliterative portal venopathy, or subnormal liver) and a wide variety of associated diseases (thrombophilia, sarcoidosis, common variable immunodeficiency, scleroderma, Castleman's disease, early primitive biliary cirrhosis, congenital liver fibrosis, chemotherapy, purinethol intake, and congenital varices) were included. Two complications occurred during the procedure: one periprosthetic hematoma and the other misposition of a covered stent. During the first month, two other patients had an early thrombosis, another had induced encephalopathy, and one died of early rebleeding. Two of these complications occurred in patients with cavernoma. With a mean follow-up of 39 months, 10 patients experienced at least one episode of spontaneous encephalopathy, with three of these patients requiring a stent reduction. Five patients had a recurrence of their initial symptoms, and one had an asymptomatic hemodynamic dysfunction. TIPS is effective in NCPHT but can be technically difficult, especially in the case of cavernoma. Good liver function does not prevent the occurrence of long-term encephalopathy.

« Le service de pédiatrie était notre deuxième maison »

"THE PAEDIATRICS DEPARTMENT WAS OUR SECOND HOME".: At the age of a few months, Yakub was diagnosed with congenital liver fibrosis then polycystic kidney disease. He has been monitored regularly since then, and has had to be readmitted on several occasions due to complications. Now, aged 15, he is waiting for a liver transplant and is under the care of the adult hepatology department. The transition from paediatrics to the adult services was prepared, in advance, with him and his family. Yakub and his mother's account.

Increased Endoplasmic Reticulum Stress in patients with Congenital Liver Fibrosis caused by germline mutations in a Protein Disulfide Isomerase

Increased Endoplasmic Reticulum Stress in patients with Congenital Liver Fibrosis caused by germline mutations in a Protein Disulfide Isomerase

Jeune syndrome with renal failure

Introduction/Objective. Jeune syndrome (JS) is a rare hereditary ciliopathy characterized by asphyxiating thoracic dystrophy, shortened limbs and brachydactyly. Extraskeletal anomalies such as chronic renal failure (CRF), hepatic fibrosis, and retinitis pigmentosa may be a part of the JATD phenotype. The aim of this study is to present long-term follow-up of JS patients with early progressive kidney disease. Methods. This is a retrospective study of pediatric patients with JS and CRF who were treated at the University Children?s Hospital between January 1980 and December 2014. The patients? data were retrospectively reviewed from the medical records. Results. There were thirteen patients from 11 families, five girls and eight boys mean aged 4.3 years at the time of diagnosis. All of the patients had characteristic skeletal findings, retinal degeneration and an early onset of CRF at age range from 1.5 to 7 years. Five patients had neonatal respiratory distress and congenital liver fibrosis was diagnosed in five patients. One patient died due to complications of CRF, while others survived during follow-up of mean 11 years. IFT140 mutations were found in four genetically tested patients. Conclusion. The average incidence rate of JS with renal phenotype in Serbia was about 0.2 per one million of child population. Long-term survival of JS patients depends on renal replacement therapy, while skeletal dysplasia, growth failure, respiratory and eyes problems have impact on the patients? quality of life.

Hepatopulmonary syndrome in pediatric patients (clinical presentation)

Hepatopulmonary syndrome (HPS) is a rare complication of liver diseases, resulting in lung perfusion disturbances and reduction of blood oxygenation. We report a case of hepatopulmonary syndrome in an 11- year-old-boy with congenital liver fibrosis.

Congenital Liver Fibrosis in a Purebred Spanish Foal

Congenital Liver Fibrosis in a Purebred Spanish Foal

Ciliopathies with Hepatic Involvement the Broad Phenotypical Spectrum of TMEM67 Mutations

Case Study: Ciliopathies are a large group of human disorders caused by dysfunction of the primary cilium. The most important ciliopathies comprise cystic kidney diseases, Joubert syndrome, Meckel–Gruber syndrome and the congenital oculomotor apraxia type Cogan II. Because of major genetic and clinical overlap, a clear cut genotype–phenotype correlation was almost impossible in the past. Recently TMEM67, encoding the transmembrane protein Meckelin, has been in the scientific focus as a genetic cause of various ciliopathies. Mutations in TMEM67 have been reported for nephronophthisis, Meckel-Gruber syndrome, Joubert syndrome, and COACH syndrome (coloboma, oligophrenia, ataxia, cerebellar vermis hypoplasia, and liver fibrosis). There is a wide range of clinical findings in patients with TMEM67 mutations. However, liver involvement in terms of a congenital hepatic fibrosis has been found as a unifying feature in almost all the patients. This makes TMEM67 one of the first ciliary genes with a relatively strong genotype–phenotype correlation. We report four patients with mutations in TMEM67 presenting very different clinical phenotypes, one of them showing oculomotor apraxia. To our knowledge, this is the first time that a compound heterozygous TMEM67 mutation is described in a patient with oculomotor apraxia type Cogan II. All four patients present congenital liver fibrosis and elevated liver enzymes, matching the genotype–phenotype correlation described earlier.

908 Comparison of Transient Elastography and Shear Wave Elastography As Markers for Cirrhosis: Experience at a Tertiary Care Center

Background and Aims: Fibroscan (Echosens,France) is a new non invasive tool for measuring liver stiffness and steatosis. It has mainly developed to evaluate chronic liver disease in adult, but usefulness and appropriate inspection method in children has not been established. We report our experience of Fibroscan to evaluate liver stiffness and steatosis in children. Methods: Pediatric patients diagnosed or suspected to have liver disease were evaluated for controlled attenuation parameter (CAP) and elasticity value (E value) using Fibroscan from August 2013 to November 2014. Results: In total, 20 procedures were performed for 19 patients (14 male, average age 11.5 year). CAP was 100 to 348 dB/m, and E value was 3.2 to 21.3 kPa. E values were higher than 10 kPa in three patients, one after receiving liver transplantation, one post Fontan procedure and one Alstrom syndrome. Liver biopsy was performed in four of them (2 Non-alcoholic steatohepatitis:NASH), 1 congenital liver fibrosis, 1 Wilson's disease) at almost the same time and E value was correlated with histological fibrosis stage (F 1-2) in them. CAP and the degree of steatosis in the liver tissue were correlated in NASH patients. After treatment not only the blood data such as transaminase and HOMA-IR but also CAP and E value of the patient of NASH were improved (CAP 323 to 299 dB/m, E value 7.7 to 4.5 kPa). Conclusion: Fibroscan might be useful for evaluating and following up liver stiffness and steatosis of children with liver disease as well as adult.

906 Evaluating Liver Stiffness and Steatosis in Children Using FibroScan

Background and Aims: Fibroscan (Echosens,France) is a new non invasive tool for measuring liver stiffness and steatosis. It has mainly developed to evaluate chronic liver disease in adult, but usefulness and appropriate inspection method in children has not been established. We report our experience of Fibroscan to evaluate liver stiffness and steatosis in children. Methods: Pediatric patients diagnosed or suspected to have liver disease were evaluated for controlled attenuation parameter (CAP) and elasticity value (E value) using Fibroscan from August 2013 to November 2014. Results: In total, 20 procedures were performed for 19 patients (14 male, average age 11.5 year). CAP was 100 to 348 dB/m, and E value was 3.2 to 21.3 kPa. E values were higher than 10 kPa in three patients, one after receiving liver transplantation, one post Fontan procedure and one Alstrom syndrome. Liver biopsy was performed in four of them (2 Non-alcoholic steatohepatitis:NASH), 1 congenital liver fibrosis, 1 Wilson's disease) at almost the same time and E value was correlated with histological fibrosis stage (F 1-2) in them. CAP and the degree of steatosis in the liver tissue were correlated in NASH patients. After treatment not only the blood data such as transaminase and HOMA-IR but also CAP and E value of the patient of NASH were improved (CAP 323 to 299 dB/m, E value 7.7 to 4.5 kPa). Conclusion: Fibroscan might be useful for evaluating and following up liver stiffness and steatosis of children with liver disease as well as adult.

Liver transplantation in adult patients with portal vein thrombosis: risk factors, management and outcome

Background. Portal vein thrombosis (PVT) is a well recognized complication of patients with end-stage cirrhosis and its incidence ranges from 2 to 26%. The aim of this study was to analyze the results and long-term follow-up of a consecutive series of liver transplants performed in patients with PVT and compare them with patients transplanted without PVT. Patients and methods. Between July 1995 and June 2006, 26 liver transplants were performed in patients with PVT (8.7%). Risk factors and variables associated with the transplant and the post-transplant period were analyzed. A comparative analysis with 273 patients transplanted without PVT was performed. Results. The patients comprised 53.8% males, average age 40, 7 years. PVT was detected during surgery in 65%. Indications for transplantation were: post-necrotic cirrhosis 73%, cholestatic liver diseases 23%, and congenital liver fibrosis 4%. Child-Pugh C: 61.5%. Techniques were trombectomy in 21 patients with PVT grades I, II, IV, and extra-anatomical mesenteric graft in 5 with grade III. Morbidity was 57.7%, recurrence of PVT was 7.7%, and in-hospital mortality was 26.9%. Greater operative time, transfusion requirements, and re-operations were found in PVT patients. One-year survival was 59.6%: 75.2% for grade 1 and 44.8% for grades 2, 3, and 4. Discussion. The study demonstrated a PVT prevalence of 8.7%, a higher incidence of partial thrombosis (grade 1), and successful management of PVT grade 4 with thrombectomy. Liver transplant in PVT patients was associated with an increased operative time, transfusion requirements, re-interventions, and lower survival rate according to PVT extension.

Nephronophthisis type 1 deletion syndrome with neurological symptoms: Prevalence and significance of the association

Type 1 nephronophthisis (NPHP) with homozygous deletions of nephrocystin [NPHP1, DEL] has been considered a pure renal disorder, but co-occurrence of extrarenal symptoms, mainly retinitis pigmentosa, is observed in a subset of patients. Recently, [NPHP1, DEL] has been detected in three patients with Joubert syndrome-related disorders (JSRDs), who associated neurological signs with a peculiar neuroradiological malformation known as the 'molar tooth sign' (MTS). To define the frequency of JSRD spectrum in NPHP1 patients, we re-examined 56 cases with [NPHP1, DEL] and found an overall incidence of 8.9% (five out 56 patients). All had small hyperechoic kidneys and had developed advanced renal failure within 15 years. Two patients presented the complete features of JSRD with cerebello-renal-retinal association and MTS. Two others showed, instead, severe intentional tremor and thick superior cerebellar peduncles on brain magnetic resonance imaging (MRI), and one of them had associated retinopathy. The fifth patient presented with hypotonia, developmental delay, central deafness, and ataxia associated with Leber congenital amaurosis and liver fibrosis but with normal brain MRI. Marked intrafamilial variability of associated extrarenal symptoms was observed in familial cases. Deletion extension did not differ in patients with isolated renal phenotype and in those with associated neurological symptoms. In conclusion, neurological defects varying from subtle involvement of cerebellum with thickened peduncle to both JSRD and diffuse central hypotonia are frequent in [NPHP1, DEL] patients. Prevalence of such association may justify systematic neurological and neuroradiological evaluation.

Intron 2 [IVS2, T-C +4] HFE gene mutation associated with S65C causes alternative RNA splicing and is responsible for iron overload

A patient with congenital liver fibrosis revealed a high transferrin saturation index and iron overload on liver biopsy. He did not carry the most frequent HFE mutations: C282Y or H63D. Heterozygosity was detected for S65C. Unknown HFE mutations were also sought using a combined denaturing high performance liquid chromatography (DHPLC)/direct sequence approach and another point mutation, a transition T-C (nt 4910), at the fourth base of the donor splice site of intron 2 [HFE, intervening sequence (IVS) 2, T-C +4] was found. Family screening revealed that a daughter carried both S65C and [IVS2, T-C +4]. : The existence in our proband of a partly-altered HFE protein in the region encoded by exon 2 might be responsible for the histologically-demonstrated iron overload.

Foscarnet therapy for congenital cytomegalovirus liver fibrosis following prenatal ascites

We report on an infant with multi-system disease including liver fibrosis, right microphthalmia with cataract, interstitial pneumonitis, and hyperechoic lesions in the basal ganglia and in the periventricular and thalamic regions. Prenatal ascites with hepatomegaly concomitantly with detection of cytomegalovirus (CMV) DNA in the amniotic fluid, following recurrent maternal CMV infection, had been shown. Although CMV culture and DNA detection were negative in the urine, the infant was given foscarnet because CMV infection was demonstrated in the liver by DNA detection and immunohistochemical staining. Favorable clinical outcome and absence of CMV in the liver were subsequently shown. Our case suggests that congenital CMV disease following maternal recurrence may not be associated with disseminated infection but only with intracellular infection. The diagnosis should therefore be based on CMV detection in the involved organs. Moreover, this is the first report on the possible efficacy and safety of foscarnet for therapy of immunocompetent infants with congenital CMV disease.

Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure

Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.

Phosphomannoseisomerase deficiency as the cause of protein-losing enteropathy and congenital liver fibrosis.

Phosphomannoseisomerase deficiency as the cause of protein-losing enteropathy and congenital liver fibrosis.