Published online Aug 8, 2020. doi: 10.4292/wjgpt.v11.i3.48
Peer-review started: January 14, 2020
First decision: April 18, 2020
Revised: May 28, 2020
Accepted: July 1, 2020
Article in press: July 1, 2020
Published online: August 8, 2020
Inflammatory bowel disease (IBD) is a systemic illness that can present with multiple extra-intestinal manifestations. Hepatobiliary (HB) disorders associated with IBD are not uncommon. From an aetiopathogenic perspective, there are multiple layers of evidence suggesting that these disorders are not isolated entities and may share mechanistic pathways. All of these disorders usually manifest with abnormal hepatic biochemical tests. Of the HB complications of IBD, primary sclerosing cholangitis (PSC) carries the most significant clinical implications and remains a highly challenging disease to manage.
Recently, the reported incidence of IBD in paediatrics has increased dramatically. The HB manifestations of IBD have been well studied in children in the industrialized and developed countries. On the other hand, there is a paucity of studies on IBD in low- and middle-income countries (LMICs) such as Egypt.
The main objective was to determine the frequency of HB manifestations in Egyptian paediatric patients with IBDs, to achieve an early diagnosis in order to obtain prompt treatment. Moreover, the risk factors associated with the occurrence of HB complications in patients with IBD were determined.
This study was carried out at the Paediatric Hepatology and Gastroenterology Units of Cairo University Children's Hospital over a 6-mo-period. Patients younger than 18 years of age of both sexes were included. The available data were retrieved from the files of patients diagnosed with IBD as well as newly diagnosed patients. The collected data included a full medical history such as name, age, sex, residence, meticulous family history of IBD and other associated autoimmune illnesses; history of jaundice; abdominal distention; pruritus; bleeding; a history of blood transfusion; and a detailed medication history. A meticulous clinical examination was performed, including the assessment of anthropometric measures and a general and detailed abdominal examination. Laboratory investigations, such as CBC, complete liver functions (ALT, AST, total and direct bilirubin, ALP, GGT, albumin and PT) were performed in all patients. In addition, serum immunoglobulin G, antinuclear antibody, smooth muscle antibody, anti-liver kidney microsomal 1, anti-neutrophil cytoplasmic antibody and anti-Saccharomyces cerevisiae antibody were performed for selected cases suspected of having autoimmune hepatitis (AIH) and/or PSC. Viral markers were assessed in patients suspected of having hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. Abdominal ultrasound was performed in all patients. Endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography was performed for cases suspected of having PSC. Percutaneous liver biopsy was performed when indicated.
We recruited 48 paediatric patients with IBD. Twenty-nine (60.4%) patients were male. Twenty-four (50%) had UC, 11 (22.9%) had CD, and 13 patients had IBD-U. The median (range) of the weight and height by Z score were -1.0 (-5.0-3.0) and -1.2 (-6.6-1.7), respectively. Sixteen patients (33.4%) were on the 3rd percentile or lower for weight, while 13 (27.1%) had short stature. The most common clinical presentation was recurrent abdominal pain, which was present in 47 patients (97.9%), followed by chronic diarrhoea with tenesmus and rectal bleeding. None of our patients presented with ulcerating perianal disease. There was a positive family history of IBD in 9 patients (18.75%). Twelve patients (25%) had other associated diseases: 11 had FMF, and one patient had systemic lupus erythematosus. Therefore, the overall frequency of HB disorders in this study was 27.1% (13 patients). Two patients had cholestatic jaundice, one of them was diagnosed with PSC, and the other patient had PSC/AIH overlap syndrome. Three (6.3%) patients had elevated liver enzymes. Ten (20.8%) patients had echogenic liver suggesting fatty changes.
HB manifestations in paediatric patients with IBD in LMICs are more common than those in the industrialized countries. Investment in research for confounding factors in LMICs is cost-effective, including family genetic studies that can offer an early diagnosis of IBDs in general and specifically for very early-onset IBD. The importance of awareness of the implications and causes of abnormal hepatic biochemical tests in IBD patients is due to the wide range of possible complications and risks associated with the medications used to treat and manage them. Hepatic biochemical tests should be routinely performed in these patients. When abnormalities are detected, a prompt step by step diagnostic approach should be followed until an aetiology is reached. The frequency of HB manifestations in our patients was not low and may be affected by the type of treatment modality and malnutrition. The highest proportion was found in those suffering from an echogenic liver by abdominal ultrasound, and many of these patients received corticosteroids.
Screening for HB manifestations of IBD is mandatory, as many of these complications may be initially asymptomatic. Complete liver function tests and abdominal ultrasound should be performed on a regular basis. A high index of suspicion of PSC should be raised in patients who present with an unexplained cholestatic jaundice or elevated ALP levels. An echogenic liver detected by abdominal ultrasound requires thorough assessment of the patient’s growth and medication history. Liver biopsy may be needed in selected cases for the definitive diagnosis of NAFLD. Drugs used to treat IBD should be administered cautiously, as a majority of them can potentially cause hepatotoxicity. HBV and HCV should be screened for in patients with IBD especially in endemic areas such as Egypt. Patients with IBD have multiple risk factors for HCV and HBV acquisition, including repeated endoscopies, transfusion of blood products and recurrent hospitalizations. Genetic research should include the diagnosis of very early-onset IBD and screening of similar cases in families.