Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.

The aim of the systematic review is to assess the prevalence and risk factors of liver fibrosis in patients with Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD) and to discuss the role of liver fibrosis in the progression to hepatocellular carcinoma (HCC). We performed a structured search in PubMed, Web of Science, Embase, and Scopus up to 3 March 2023 to identify observational studies reporting liver fibrosis in patients with NAFLD and IBD. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) score. A total of 23 studies met our inclusion criteria, including 629,781 patients. A total of 10 cross-sectional, 3 case-control, and 10 cohort studies were included. Fourteen studies had a NOS score ≥ 7 points. NAFLD was diagnosed in 2162/6332 (34.1%) IBD participants. However, NAFLD diagnosis was established in 924/2962 (31.2%) healthy individuals without IBD. Advanced liver fibrosis was found in 116 (11.6%) of 992 IBD patients with NAFLD. Most studies found an association between NAFLD and classic cardiovascular risk factors such as older age, male sex, higher BMI, diabetes, hypertension and dyslipidemia. In addition, metabolic syndrome features were also associated with an increased risk of significant and advanced liver fibrosis. Although no strong association between NAFLD and IBD therapy was reported, some studies associated NAFLD with IBD diagnosis, Crohn’s Disease, a complicated course of IBD, disease activity, and IBD duration. Advanced liver fibrosis was also associated with Crohn’s disease in several studies. In conclusion, NAFLD and advanced liver fibrosis are prevalent and clinically relevant extraintestinal manifestations, so its diagnosis and potential progression to HCC should be carefully considered in daily clinical practice.