Published online Sep 26, 2020. doi: 10.12998/wjcc.v8.i18.4075
Peer-review started: March 21, 2020
First decision: April 8, 2020
Revised: April 23, 2020
Accepted: July 30, 2020
Article in press: July 30, 2020
Published online: September 26, 2020
Primary sclerosing cholangitis (PSC) is a progressive disorder that causes inflammation and scarring of bile ducts, leading to fibrosis, strictures and dilatation of the biliary tree. The etiology and pathogenesis of PSC are currently unknown, although PSC is highly associated with the presence of inflammatory bowel disease (IBD). Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease with specific laboratory and histological findings. It is characterized by elevated serum aminotransferases, increased total IgG and positive autoantibodies, whereas liver biopsy may show interface hepatitis and portal mononuclear cell infiltrate. In some cases, patients may present with variant forms of AIH, in which there is an overlap of AIH and another autoimmune liver disease, such as PSC. Therefore, PSC/AIH overlap syndrome (OS) is a rare disorder characterized by the concomitant occurrence of the biochemical and histological features of AIH and the cholangiography abnormalities found in PSC.
Few cases of PSC/AIH OS have been reported in the literature and many questions are unanswered. Thus, the motivation for this systematic review was to clarify questions regarding the epidemiology, clinical presentation, possible treatments and a better understanding of this syndrome.
The authors report the case of a female patient with AIH and PSC OS associated with ulcerative colitis and systematically review the available cases of AIH and PSC overlap syndrome.
This study was carried out in accordance with the recommendations contained in the preferred reporting items for systematic reviews and meta-analysis protocols guidelines. Searches for studies were run on the electronic databases Scopus, Web of Science, Medline (PubMed), Biblioteca Regional de Medicina, Latin American and Caribbean Health Sciences Literature, Cochrane Library for Systematic Reviews and Opengray.eu. Languages were restricted to English, Spanish and Portuguese and there was no date of publication restrictions. The inclusion criteria were clinical case reports or case series involving autoimmune hepatitis and primary sclerosing cholangitis and the exclusion criteria were studies other than case reports or case series and articles that were not related to the topic. Data, such as patients’ clinical presentation and comorbidities, laboratory results, liver biopsy results and medications used were summarized using descriptive analysis – frequency, means and median, using RStudio and the outcome measured was recovery or death.
Forty-four references were analyzed and a total of 109 patients diagnosed with PSC/AIH OS were included. Of these, 46 (42.59%) were male. Forty-eight (44.44%) patients had IBD. The most common clinical presentation was jaundice, which was present in 31 (28.70%) cases, followed by fatigue and abdominal pain (20.37% and 19.44%, respectively). PSC was identified in small and large ducts (3.70% and 81.48%, respectively). Medications were administered in 63 (58.33%) patients. Of these, 62 (98.41%) patients received steroids; 49 (77.77%) patients received thiopurines (48 on azathioprine and 1 on 6-mercaptopurine) and 7 (11.11%) patients received aminosalicylates (mesalamine); 47 (74.60%) patients received ursodeoxycholic acid. Clinical improvement with these treatments was satisfactory, leading to recovery in 104 (96.30%) patients.
AIH/PSC OS has a good response to treatment with steroids, azathioprine and ursodeoxycholic acid and is generally associated with IBD. It should be suspected in patients with recurrent jaundice, pruritus and abdominal pain with laboratory and imaging tests suggestive of both hepatocellular and cholestatic diseases, especially when associated with IBD. In more severe cases, liver transplantation can be performed with comparable graft and patient survival, as transplantation-free survival in patients with PSC/AIH OS is worse than that in patients with AIH only.
From the present study findings, there is no definitive and highly specific clinical presentation of PSC/AIH OS. Therefore, the gastroenterologist should be aware that patients with laboratory data suggestive of both hepatocellular and cholestatic liver injury should undergo liver biopsy in order to achieve an adequate diagnosis, especially if they have a previous diagnosis of IBD. Also, clinical treatment with steroids, azathioprine, and ursodeoxycholic acid seems to be safe and effective and it seems adequate to consider this association in such cases. If medical treatment fails, liver transplantation is also safe and should be considered earlier than with isolated PSC or AIH. The direction of future research should be clinical trials of possible treatments for PSC/AIH OS, as we expect it to become more common, as the prevalence of IBD has been steadily rising in the past decades.