Infected Polycystic Liver Disease- An Unusual Presentation of - - PDF document

Journal of Rawalpindi Medical College (JRMC); 2017;21(3): 308-310 308 Case Report

Infected Polycystic Liver Disease- An Unusual Presentation

• f Extra-renal Autosomal Dominant Polycystic Kidney

Disease (ADPKD)

Mohammad Hourani and Daniyal Nagi

Department of Internal Medicine, Tawam Hospital, Al-Ain, UAE

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive expansion of multiple bilateral renal cysts leading to enlargement and distortion of the kidney and ultimately, end-stage renal disease . ADPKD is the most common inherited cause of kidney disease associated with both PKD1 and non-PKD1 genotypes, can occur as extra-renal manifestation such as Adult Polycystic Liver Disease (APLD) or distinct disease in absence

• f

renal cysts. Typically these are asymptomatic but may be associated with infection or haemorrhage, liver function is typically preserved . 1-3

Case Report

A 91 year old female with no past medical history presented with fever and mild abdominal pain. Blood culture showed bacteraemia (E. coli), ultrasound abdomen showed multiloculate septated intra- abdominal collection involving the epigastric and right upper quadrant. CT scan of the abdomen showed multiple large cystic lesions scattered throughout the liver, of uncertain clinical significance, the largest measuring 7.2 x 6.9 cm (Figure 1), with multiple scattered tiny cystic lesions throughout both kidneys. On the presentation at hospital, the examination revealed a febrile patient, vitally stable with non- tender abdomen. There was no family history of kidney disease. Laboratory investigations showed leucocytosis with high inflammatory markers and deranged liver function test with pattern suggestive of biliary obstruction. Tumour markers (CA 19-9, AFP & CEA) were negative. Echinococcosis and Entamoeba histolytica antibodies were negative. MRCP results showed numerous cysts of variable sizes, noted throughout the liver with predominance for the left

• lobe. Some of the large cysts showed heterogenous

signal intensity. These cysts in the caudate and in segment 6 of the liver showed hyperintense signal on T1-weighted images with fluid level likely representing haemorrhagic components. Although some radicals of the biliary tree appeared inseparable from some peripheral cysts, the intrahepatic biliary ducts were non-dilated. Differential diagnoses included complex hepatic cysts (with haemorrhage and possibility

• f

infection-abscess), biliary cystadenoma/cystadenocarcinoma and less likely type V choledochal cyst (Caroli disease). Multidisciplinary team decided medical treatment with antibiotics without percutaneous intervention. Subsequently, patient started improving clinically, liver function tests, complete blood count and Inflammatory markers returned to the baseline and patient made a satisfactory recovery

Figure 1: CT of the abdomen showing multiple large cyst lesions.

Discussion

Adult liver cystic lesions are classified as hereditary, developmental, neoplastic, inflammatory, or mixed

• lesions. The hereditary forms of polycystic liver

disease (PLD) are associated with autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), or occur as a distinct genetic disease in the absence of renal cysts.5 Autosomal dominant polycystic kidney disease (ADPKD) is an inherited, progressive multisystem disease characterized by the formation and enlargement of cysts in the kidney and other organs (e.g., liver, pancreas, spleen). The incidence of hepatic cysts in ADPKD increases with age from approximately 10% below the age of 30 to greater than 50% percent over the age of 60.4 Two mutations have

Journal of Rawalpindi Medical College (JRMC); 2017;21(3): 308-310 309 been found to cause this disorder: a mutation in the PRKCSH gene that encodes a protein called hepatocystin, and a mutation in the SEC63 gene that encodes for a component of the protein translocation machinery in the endoplasmic reticulum.6 Typically, PLD is asymptomatic, but the symptoms become more frequent with age, and so increase because of increased life expectancy, especially in patients with ADPKD due to dialysis and

• transplantation. Hepatic cysts are more prevalent and

hepatic cyst volume is larger in women than in men, and multiple bile cystic lesions vary from 20 to 30 cm to small microscopic nodules.3 The clinical course of PLD is relatively benign compared with ADPKD. The symptoms that are typically caused by mass effects are hepatomegaly and portal hypertension, ascites, jaundice, haemorrhage, dyspnoea, early satiety and weight loss, gastro-oesophageal reflux, and pain in the lower back region.5 Symptomatic cyst complications include cyst haemorrhage, infection, and rarely torsion, or rupture . Other complications of mass effect are vena cava compression and lower portal vein and bile duct compression that present itself as obstructive jaundice.7 Despite advances in the management of autosomal dominant polycystic kidney disease over the past two decades, infection of liver and kidney cysts remains a serious and potentially threatening complication. It is differentiated from haemorrhage by the clinical presentation (mainly the severity and duration of fever), C-reactive protein (CRP) and white blood cells levels, and the density of the suspected cyst on computed

• tomography. Liver cyst infection
• ccurs

more frequently in patients with large cysts volumes. It can be life threatening and tends to recur. The best radiological imaging technique is positron emission tomography after intravenous injection of [18F]- fluorodeoxyglucose combined with computed tomography.8 Management is based on symptomatic presentation. Often no specific therapy is warranted as therapy is directed toward symptoms and the patient may be

• asymptomatic. In patient with infected cyst; we

recommend initial treatment with a fluoroquinolone guided by culture and sensitivity for the duration of 6

• weeks. However, due to the growing rate of

Ciprofloxacin resistance organisms, the choice of the empirical antimicrobial agent will depend upon the centre-specific resistance rate. Cyst drainage should be considered when cysts are very large and or when infection is resistant to antibiotic treatment. Patient with recurrent liver cyst infection

• r

angiocholitis needs to consider liver transplantation.9 Somatostatin analogues have been tested to help reduce cyst volume and provide symptomatic relief in cases of PLD. A recent pooled analysis of 2 randomized, double-blind, placebo-controlled trial examined 96 patients with PLD treated between 6 and 12 months showed improvement in life quality related to symptoms and hepatomegaly.10 Although a 2008 pilot trial of 16 patient with ADPKD demonstrate that Sirolimus, an mTOR inhibitor, reduced PLD volume by 26%.9 In a systemic review of 54 patients with hepatic cyst infection (Table 1), it is more common in female with mean age of 63. ADPKD was the most prevalent underlying cyst disease. Initial management was through antimicrobial treatment (56%), the rest of the case, initial management involved percutaneous/ surgical intervention. Results showed that first line treatment with antimicrobial alone is associated with high rate of treatment failure (70%). Despite multiple switches in antimicrobials, most of them ultimately required percutaneous drainage or surgery (64%). Nonetheless, recurrent cyst infection was common and developed in 20% of patients. Table 1: Comparison between 54 patients with hepatic cyst infection regarding Gender, mean age, underlying cyst disease, management, and recurrence.12 Gender Male 39%, Female 57% Mean Age 63 ±12 Underlying disease ADPKD: 46%, PCLD: 4%, multiple liver cyst: 15%, multiple kidney cyst: 2%, Management Antimicrobial 56% with Quinolones and Cephalosporin, failed in 70%. Surgical treatment in 31% Recurrence 20% Counselling should be done prior to testing among asymptomatic patients with a family history of

• ADPKD. In children (age less than 18 years), there is

no need for screening since the adverse effects from a pre-symptomatic diagnosis outweigh the current

• benefits. In adults (age greater than 18 years), we

recommend screening potential living, related kidney donors, in other adults, the decision to screen for the disease should be based upon patient's preferences and values, after the benefits and adverse consequences of certainty concerning the diagnosis are fully understood. If screening is performed among asymptomatic patients with a family history of

Journal of Rawalpindi Medical College (JRMC); 2017;21(3): 308-310 310 ADPKD, we recommend imaging of the kidney because of safety and cost, ultrasonography is usually the initial modality.11 Polycystic Liver Disease(PLD) can either co-exist with ADPKD and or occur alone. ADPKD, ARPLD and ADPLD are a group of genetic disorders initiated by mutations in several related genes. Although asymptomatic in most patients, it may cause abdominal discomfort, cyst haemorrhage or infected

• cyst. The progression of the disease occurs throughout

the patient’s life with possible deterioration of renal and liver function. The main diagnostic methods of hepatic involvement are ultrasound, CT, or PET scan. Treatment is highly heterogeneous, first line treatment is with oral Ciprofloxacin. In case of failure, surgical intervention needs to be considered. Screening in adults is upon patient preference with ultrasonography as initial modality.

References

1. Torres VE., Harris PC.,Pirson Y. Autosomal dominant polycystic kidney disease. Lancet 2007;. 14;369(9569):1287-301. 2. Srivastava A. And Patel N. Autosomal dominant polycystic kidney disease. Am Fam Physician 2014;90(5):303-07. 3. Ars E., Bernis C., Fraga G., Martínez V., Martins J. Spanish guidelines for the management of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2014;29( 4):95-105. 4. Drenth JP.,Morsche RH., Smink R. Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease. Nat Genet 2003; 33:345-48. 5. Lantinga MA., Gevers TJ., Drenth JP. Evaluation of hepatic cystic lesions. World J Gastroenterol 2013; 19(23):3543–54 6. Drenth JP., Martina JA., van de Kerkhof R., Bonifacino JS. Polycystic liver disease is a disorder of cotranslational protein processing. Trends Mol Med. 2005;11(1):37–42. 7. Halvorson CR., Bremmer MS. , Jacobs SC. Polycystic kidney disease: inheritance, pathophysiology, prognosis, and

• treatment. Int J Nephrol Renovasc Dis 2010; 2010;3:69–83.

8. Pirson Y. , Kanaan N. Infectious complications in autosomal dominant polycystic kidney disease. Nephrol Ther. 2015;11(2):73-77. 9. Conssen WR and Drenth JP. Polycystic liver disease: an

• verview of pathogenesis, clinical manifestations and
• management. Orphanet J Rare Dis 2014; 2014;9:69-

71.

• 10. Neijenhuis MK., Gevers TJ., Nevens F. Somatostatin

analogues improve health related quality of life in polycystic liver diseases: a pooled analysis of two randomised, placebo- controlled trials. Aliment pharmacol Ther 2015;10:.1111/apt.13301.

• 11. Chapman AB., Devuyst O., Eckardt KU. Autosomal dominant

polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2015; 88:17-19.

• 12. Lantinga M.A., Geudens A., Gevers T.J.G. , Drenth J.P.H

Systemic review: the management of hepatic cyst infection. Alimentary Pharmacology and Therapeutics. 2014;41:253- 61.