Short summary

Clinical background: Home parenteral nutrition (HPN) is lifesaving for patients with intestinal failure and the incidence has exploded in the last decades. One of the most common and feared complications to HPN is parenteral nutrition-associated liver disease (PNALD).

Aim and design: The aim of this cross-sectional and follow up study is to investigate the feasibility of fibro scanning, shearwave elastography, ultrasonography, bioimpedance measurements, handgrip strength measurements and serological markers in the diagnosis of PNALD in 50 HPN treated patients with short-bowel syndrome at inclusion and after 3 and 6 months. 

Rationale

Clinical background:

Home parenteral nutrition (HPN) is a lifesaving therapy for patients with intestinal failure and the incidence rate has drastically increased over the last decades reaching a prevalence of 20-25 persons per million inhabitants in Denmark. The incidence rate is thus 5-10 times higher than most other European countries. For patients with intestinal failure HPN may prolong their lives for many years after excessive removal of intestine.

HPN is an invasive and expensive therapy which may be associated with several complications, i.e. sepsis, metabolic problems and hepato-biliary dysfunction. These complications may increase the morbidity and mortality of patients on treatment thus impairing their quality of life. Five-year survival rate for patients with a benign diagnosis treated with HPN is about 60% and about 10% of deaths are related to the home parenteral nutrition.

One of the more common complications to HPN is development of hepatic dysfunction, also known as parenteral nutrition-associated liver disease (PNALD). PNALD is characterized by cholestasis, steatosis, and mixed inflammatory changes and can progress to fibrosis and cirrhosis. The development of PNALD is especially common in patients with short bowel syndrome (SBS) occurring in two out of three patients during a period of 6 months, approximately 40% of patients further progress to more advanced stages of liver disease.

The pathogenic mechanisms leading to PNALD are currently unclear. To date, multiple risk factors have been associated with the development of PNALD as disruption of the enterohepatic circulation of bile acids, bile sludging, intestinal stasis with subsequent bacterial overgrowth, metabolic imbalance, early and/or recurrent central venous catheter-related sepsis, excessive glucose intake leading to hyperinsulinism and subsequent steatosis, and high parenteral protein, fat, and/or energy intake, lack/overload of vitamins and minerals. However, no unifying theory has been put forward to explain all of the features of PNALD.

As there is a lack of knowledge about risk factors for PNALD it is important to learn more about the pathophysiology in order to improve prevention. Currently, no specific markers have been identified that predict the degree of hepatocellular dysfunction, the degree of fibrosis and progression to cirrhosis in HPN treated patients. Liver biopsy is currently considered the gold standard for assessing hepatic fibrosis. However, liver biopsy is expensive, invasive, and carries the risk of potentially life threatening complications, thus limiting its repeated application in asymptomatic HPN treated patients. Thus there is a need for a validated, non?invasive procedure which may determine the degree of hepatic fibrosis, cirrhosis and its severity in PNALD patients.

Transient elastography (FibroScan) and shearwave elastography are rapid and non?invasive techniques that measure the stiffness of the liver as an estimate of hepatic fibrosis. These methods, together with serological parameters, have been shown to be of value in the evaluation of fibrosis in other categories of patients with liver disease, i.e. chronic hepatitis. Risk-free methods could be promising diagnostic tools in the diagnosis of chronic liver disease in patients receiving HPN. Nonetheless, the reliability of these methods for diagnosing PNALD at early stages should be investigated further before implementing them in clinical practice.

Description of the cohort

All adult patients attending the out-patient clinic of Department of Medical Gastroenterology receiving HPN will continuously be included in the study from the 1^st of September 2014 until the 31^st of August 2015. Approximately 40 patients will be included at Department of Medical Gastroenterology, Odense University Hospital and about one new patient a week, approximately 10 patients in total, starting parenteral nutrition at Department of Gastroenterology, Rigshospitalet and Department of Medical Gastroenterology, Odense University Hospital.

Key Inclusion Criteria:

• Persons older than 18 years
• Short bowel syndrome
• Receiving parenteral nutrition
• Signed informed consent

Key Exclusion Criteria:

• Predicted lifetime under a half year
• Malignant diagnosis
• Diagnosed liver disease

Data and biological material

All patients will be tested using fibroscans, blood sampling, bioimpedance measurements, hand grip strength measurements and registration of parenteral intake and a 24 hour oral intake interview, and registration of complications related to HPN and the catheter at inclusion and after 3 and 6 months. Ultrasonography and shearwave elastography will only be performed on patients where fibroscanning is impossible.

Collaborating researchers and departments

Department of Medical Gastroenterology, Odense University Hospital

• Medical student and Undergraduate Researcher Sofie Hasling Skadegaard
• Professor and Consultant Jens Kjeldsen, PhD
• Consultant Benedicte Vibjerg Wilson
• Professor Aleksander Krag, PhD

Department of Gastroenterology, University Hospital Copenhagen, Rigshospitalet

• Consultant and Associate professor Palle Bekker Jeppesen, PhD, DMSc