Pediatric onset portal hypertension : surgical treatment and outcomes

Background In children various underlying diseases of the liver parenchyma and vasculature may increase portal pressure and eventually lead to complications of portal hypertension (PH). Clinically significant complications include gastroesophageal varices with the risk of variceal bleeding over time, splenomegaly and hypersplenism. The management and outcomes highly depend on the underlying liver disease. Endoscopic interventions, surgical shunt procedures and liver transplantation (LT) are the main treatment options. During the last few decades the outcomes of patients with pediatric onset PH have improved as management protocols of biliary atresia (BA) and LT have evolved and mesoportal bypass was introduced. Despite these advances the long-term outcomes of pediatric onset PH are insufficiently characterized, as are the incidence of underlying diseases and characteristics of disease progression. Aims The general aim of the thesis was to describe outcomes of patients with pediatric onset PH extending into adulthood. Special emphasis was set on surgical treatment, survival, long-term outcomes, and patient reported health. In addition, characteristics of underlying diseases and possible risk factors for portal vein thrombosis (PVT) and sepsis after pediatric splenectomy were addressed. Patients and methods The thesis contains 4 studies with 4 separate study populations. All patients have been treated in the Helsinki University Children’s Hospital. 1) A retrospective hospital record review was performed on 24 consecutive children with extrahepatic portal vein obstruction (EHPVO) referred for operative treatment during 2002-2010. The mesoportal bypass was constructed using both greater saphenous veins. The mphasis of the study was on long-term graft patency and resolution of PH. 2) A retrospective hospital record review was done on 33 consecutive patients diagnosed with autosomal recessive polycystic kidney disease (ARPKD) during 1980-2011. The focus was on the clinical characteristics and management of ARPKD related liver disease in relation to renal failure. 3) A retrospective hospital record and nationwide registry review was done on 141 consecutive children having undergone splenectomy during 1991-2010, out of these 52 patients (37%) were operated laparocopically. The focus was on septic infections, PVT, and causes of death. Out of the 114 survivors, 66 patients (58%) replied to the structured questionnaire, 64 patients (56%) underwent clinical assessment with ultrasonography of the portal venous system and blood tests. 4) The fourth study population includes 126 consecutive patients treated for pediatric onset PH complicated by gastroesophageal varices during 1972-2013. Overall, 14144 upper gastrointestinal endoscopy reports from 1987-2013 were reviewed to identify patients with the underlying condition. Their outcomes were assessed through hospital records and nationwide registries. A questionnaire was sent to all survivors (n=94) of whom 65 (69%) responded. Main results The mesoportal bypass constructed using the greater saphenous veins proved to be a valuable alternative to the internal jugular vein (IJV) graft, allowing long-term resolution of splenomegaly and hypersplenism, and elimination of gastroesophageal varices. Clinically evident PH developed in half of the long-term ARPKD survivors necessitating endoscopic and/or surgical interventions in 30%. After pediatric splenectomy none of the patients developed PVT and sepsis was associated almost exclusively with an underlying immunodeficiency with a high mortality rate. Overall, the fourth study population (n=126) contained 19 underlying disorders including BA (35%), EHPVO (35%) and ARPKD (7%). During the median follow-up of 15 (range 6 months – 43 years) years patients underwent median 9 (1-74) upper gastrointestinal endoscopies. Esophageal varices were first observed at the median age of 4 (4 months – 18 years) years, 112 (89%) patients underwent median 6 (1-56) sclerotherapy or banding sessions, and 61 (48%) experienced median 2 (range 1-20) variceal bleeding episodes. Forty-eight surgical shunt procedures were performed to 41 (36%) patients and 38% underwent LT. Portal hypertensive biliopathy was diagnosed in 4 patients. LT was necessary due to hepatopulmonary syndrome in two patients, hepatic encephalopathy in two patients and for one patient due to hepatorenal syndrome. The overall survival was 75% and the median age at death was 9 (6 months – 29 years) years. None of the deaths were related to variceal bleeding and all EHPVO patients survived. The patient reported perception of health on a scale of 1-10 was 9 (range 4-10), and 86% reported no current symptoms attributable to esophageal varices. Conclusions Various heterogenous diseases cause PH in children, BA and EHPVO being the most common underlying diseases accounting for 2/3 of the patients in Finland. The management and outcomes highly depend on the underlying disease. Despite a multimodal interdisciplinary approach with prophylactic endoscopic treatment combined with surgical procedures long-term morbidity remains high and continues in adulthood. Mortality was related to complications of advanced liver disease and its treatment, but not to variceal bleeding. The patient reported health of long-term survivors was good.