Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management

Abstract

Polycystic liver disease (PLD) is the result of embryonic ductal plate malformation of the intrahepatic biliary tree. The phenotype consists of numerous cysts spread throughout the liver parenchyma. Cystic bile duct malformations originating from the peripheral biliary tree are called Von Meyenburg complexes (VMC). In these patients embryonic remnants develop into small hepatic cysts and usually remain silent during life. Symptomatic PLD occurs mainly in the context of isolated polycystic liver disease (PCLD) and autosomal dominant polycystic kidney disease (ADPKD). In advanced stages, PCLD and ADPKD patients have massively enlarged livers which cause a spectrum of clinical features and complications. Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ. Renal failure due to polycystic kidneys and non-renal extra-hepatic features are common in ADPKD in contrast to VMC and PCLD. In general, liver function remains prolonged preserved in PLD. Ultrasonography is the first instrument to assess liver phenotype. Indeed, PCLD and ADPKD diagnostic criteria rely on detection of hepatorenal cystogenesis, and secondly a positive family history compatible with an autosomal dominant inheritance pattern. Ambiguous imaging or screening may be assisted by genetic counseling and molecular diagnostics. Screening mutations of the genes causing PCLD (PRKCSH and SEC63) or ADPKD (PKD1 and PKD2) confirm the clinical diagnosis. Genetic studies showed that accumulation of somatic hits in cyst epithelium determine the rate-limiting step for cyst formation. Management of adult PLD is based on liver phenotype, severity of clinical features and quality of life. Conservative treatment is recommended for the majority of PLD patients. The primary aim is to halt cyst growth to allow abdominal decompression and ameliorate symptoms. Invasive procedures are required in a selective patient group with advanced PCLD, ADPKD or liver failure. Pharmacological therapy by somatostatin analogues lead to beneficial outcome of PLD in terms of symptom relief and liver volume reduction.

Surgery is the preferred treatment for bile duct hamartomas

“…Therefore, BDH is difficult to diagnose without pathological examination and, once the diagnosis is confirmed, surgical treatment should be preferred due to the potential transformation to cholangiocancinoma. Several studies reported that a proportion of patients with BDH may present with abdominal distension (6), bacterial infections (7), recurring cholangitis and jaundice (8), and portal hypertension (9). Similarly, 2 patients in our study presented with abdominal pain and jaundice.…”

Repeated Minocycline Hydrochloride Injections for Symptomatic Polycystic Liver Disease

“…Symptomatic PLD was controlled by repeated MINO injections given over the course of 14.8 months on average. PLD is a collection of rare human disorders that result from structural changes in biliary tree development [48][49][50] . The biliary tree emerges from the endodermal hepatic diverticulum [48] .…”

Hepatopatía crónica e insuficiencia hepática en un lactante con malformación de la placa ductal

“…Se caracteriza por distintos grados de fibrosis hepática y de dilataciones del árbol biliar; éstas son originadas por una malformación de la placa ductal. [6][7][8] La formación de la placa ductal fue descrita por primera vez por Hammar, en 1926, como una parte importante del desarrollo embriológico de las vías biliares. Posteriormente, Jorgensen propuso que la formación de quistes en el árbol biliar era secundaria a una malformación de ésta.…”

“…Las más importantes son: los complejos de Meyenburg, la fibrosis hepática congénita, la enfermedad poliquística renal autosómica recesiva, la enfermedad poliquística renal autosómica dominante, la enfermedad y el síndrome de Caroli, entre otras. 6,7,11 La placa ductal es una estructura cilíndrica de doble capa que inicia su formación entre las sexta y séptima semanas de la gestación, es la precursora de los conductos biliares intrahepáti-cos y de las glándulas peribiliares intrahepáticas. La placa presenta un proceso de remodelación que empieza en la onceava semana (apoptosis y proliferación celular); en dicho proceso intervienen los cilios y su señalización por numerosas moléculas como proteinasas e inhibidores tisulares de la matriz, metaloproteinasas, tripsinógeno, catepsina, moléculas relacionadas con la apoptosis celular (Bcl-2, Levis Y y C-myc), TGF-a y su receptor, MET, C-erbB2, E-caderina, catetinas (a, b y g), alfa amilasa pancreática, PKR, apomucinasas y el plexo capilar peribiliar.…”