The prevalence of cholelithiasis in the general population ranges from 5.5% to 15% [46]. In CD, the risk of developing gallstones is double (prevalence rate 11–34%), while in UC, no differences in the prevalence of gallstones compared to the general population were identified [46,47]. The risk factors for cholelithiasis in CD patients are age at CD diagnosis, disease duration (>15 years), ileo-colonic localization of the lesions, length of ileal resection (>30 cm), frequency of clinical recurrences (>3), long hospital stay, number of hospitalizations (>3) and total parenteral nutrition [48]. Among the pathophysiological mechanisms underlying cholelithiasis in CD are the following: bile acid malabsorption; solubilization of bilirubin by unabsorbed bile acids in the colon; dysbiosis with bile acid dysmetabolism; reduced gallbladder motility; activation of Th1-mediated immune response; PSC associated with IBD; and hemolysis induced by drugs [49,50,51,52]. The only indication for cholecystectomy remains complicated cholelithiasis [53]. Even in patients with CD who require ileocolonic resection, prophylactic cholecystectomy is not recommended [54]. Navaneethan et al. demonstrated an increased risk of postoperative complications in IBD patients [55].

The prevalence of NAFLD among patients with IBD varies between 33–55% [56,57,58,59]. A study that followed 384 patients with IBD, with no significant alcohol intake, reported the presence of NAFLD in 32.8% of them and the presence of significant liver fibrosis in 12.2% [57]. The independent predictors for NAFLD were higher body mass index (BMI), older age and higher triglycerides [57]. For liver fibrosis, the independent predictors were older age and higher body mass index (BMI) [57]. Extrahepatic diseases, such as chronic kidney disease and cardiovascular disease, proved to be more frequently diagnosed among patients with IBD and NAFLD compared to those with IBD alone [57]. The pathophysiological mechanisms that can explain the increased risk of NAFLD among patients with IBD are chronic relapsing inflammation, an alteration in intestinal microbiota, parenteral nutrition, potentially hepatotoxic drugs and surgery [58,59,60]. Moreover, dysbiosis has been associated with both the severity of IBD and NAFLD, which suggests a pathogenic link between the two conditions [58,59]. Restellini et al. suggested the need to initiate noninvasive screening strategies (transient elastography) among patients with IBD and high-risk factors of NAFLD [57]. The objectives of these screening strategies are early diagnosis and the early initiation of therapeutic measures, such as weight loss or lipid-lowering medication [57]. On the other hand, biological treatments used for IBD, such as infliximab, have been shown to improve liver histological changes in patients with NAFLD [61]. Monitoring adherence to treatment is also necessary. The absence of NAFLD secondary symptoms, such as upper right abdominal pain or asthenia, among some patients with chronic digestive disorders may explain the lower adherence to the therapeutic measures that NAFLD requires [57]. The importance of adherence to treatment derives from the risk of the evolution of this condition toward irreversible liver fibrosis and even cirrhosis.

Granulomatous hepatitis is a rare complication of CD [10]. However, this condition can be secondary to treatment with mesalamine or sulfasalazine, or it can have malignant or infectious etiologies [62,63,64]. From a clinical point of view, granulomas are usually asymptomatic [10]. In extensive disease, hepatomegaly or jaundice can be detected [10]. A diagnosis is usually suggested by imaging identification of a liver mass or an unexplained increase in cholestatic enzymes [65]. A positive diagnosis is established by a liver biopsy [10]. The first-line treatment for granulomatous hepatitis, after the exclusion of infectious etiology, consists of systemic corticosteroids [66]. In case of corticosteroid resistance, immunomodulatory drugs such as azathioprine or methotrexate and anti-TNF-α agents can be used [67]. Paradoxically, cases of granulomatous hepatitis and extrapulmonary sarcoidosis have also been reported in patients with CD who are on anti-TNF-α treatment [68]. Decock et al. identified 90 cases of sarcoidosis-like lesions associated with anti-TNF therapy in the literature [68]. In most cases, these were patients with rheumatic disease (rheumatoid arthritis, ankylosing spondylitis, psoriasiform arthritis) and the most prescribed drug among them was etanercept. Only six patients had IBD as the underlying disease [68]. In 71 of these patients, the partial remission of liver disease was obtained by withdrawing biological treatment, initiating treatment with corticosteroid or both therapeutic measures [68]. The reintroduction of treatment with anti-TNF agents led to the reactivation of liver disease in 7 out of 20 patients [68].

Secondary amyloidosis can be a complication of chronic inflammatory diseases. This condition is rare among IBD patients, occurring in less than 1% of them [46]. If in CD the prevalence of hepatic amyloidosis varies between 0.9–3%, in UC it does not exceed 0.07% [46]. Hepatic amyloidosis is more common in men and the average age at diagnosis is approximately 40 years. Additionally, a more frequent association of this condition with the colonic localization of CD has been reported [46]. The patients are usually asymptomatic, and a diagnosis is suggested by the identification of hepatomegaly during imaging examination. The treatment consists of controlling the underlying CD and reducing the release of acute-phase reactant serum amyloid A [46,69]. Gottenberg et al. claimed that anti-TNFα agents can reduce the release of amyloid precursors and the formation of amyloid deposits, contributing to the clinical improvement of these patients [69]. Another drug with long-term benefits in patients with amyloidosis and CD has been shown to be colchicine [70]. Secondary systemic amyloidosis was associated with an increased risk of infections, sepsis and multi-organ system involvement, but without influencing in-hospital mortality in IBD patients [71].

VTE is a condition with significant morbidity and mortality. In the United States, more than 500,000 hospitalizations and 100,000 deaths attributed to VTE are registered annually [72]. Compared to the general population, patients with IBD have a two-to three-fold higher risk of developing VTE [73]. Bruining et al. reported an incidence rate for portal thrombosis of 1.7% among patients with CD [74]. In patients with IBD undergoing surgery, the incidence rate of superior mesenteric thrombosis can reach up to 4.8% [75]. The pathophysiological mechanisms of VTE in IBD are incompletely elucidated. Currently, the following several risk factors are incriminated: age; genetics factors; pregnancy; active and more extensive disease; hospitalization; surgery; and medications (corticosteroids or tofacitinib) [76]. IBD is characterized by a procoagulant status attributed to the upregulation of inflammatory and coagulation systems [77]. In these patients, during an IBD flare, the following were identified: increased levels of fibrinogen; products of fibrin; thrombin formation; von Willebrand factors; and coagulation factors V, VII, VIII, X, XI and XII [78,79]. During active disease periods, lower levels of antithrombin and protein S, thrombocytosis and increased platelet activity were also highlighted [80,81]. The increased risk of thrombotic events seems to be particular to IBD, not occurring in other chronic inflammatory diseases, such as celiac disease or rheumatoid arthritis [74,82]. Compared to age, there was a significantly higher risk of VTE in young people, but also in elderly patients [83]. Nylund et al. reported an increased risk of VTE among hospitalized IBD adolescents compared to non-IBD hospitalized adolescents [84]. Another study that followed 872,122 patients with IBD reported an increase in the risk of VTE with advancing age [85]. If in the age group 31–40 years, the risk of VTE was 2.1; in the age group 41–50 years, the risk was 2.08; in the age group 51–65 years, the risk was 3.74; in the age group 66–80 years, the risk was 4.04; and in the age group > 80 years, the risk reached 3.06 [86].

The first-line paraclinical investigation that can identify portal vein thrombosis is abdominal ultrasonography, but the gold standard remains the CT scan. The therapeutic management of patients with IBD and portal thrombosis includes the following: cessation of smoking and consumption of oral contraceptives; anticoagulant treatment with low-molecular-weight heparin (LMWH) or warfarin; and, in severe cases, thrombolysis; surgical interventions; or intravascular thrombectomy devices [87].

Currently, there are no clear recommendations regarding VTE prophylaxis among IBD patients. However, all guidelines recommend VTE prophylaxis in hospitalized patients, with no hemodynamically significant bleeding, during an IBD flare [83]. The extent of post-discharge VTE prophylaxis in patients with high thrombotic risk remains unclear [83].

If in the general population the incidence of liver abscess is 8–16 cases/100,000 inhabitants, in patients with CD it can reach up to 11–297 cases/100,000 inhabitants [10]. Compared to the general population, patients with liver abscesses and CD are younger and show more frequent multilocular damage [10]. The pathogenic mechanisms incriminated are portal pyemia with a secondary seeding of germs at the level of liver parenchyma or direct hepatic extension of an intra-abdominal abscess [86]. Other factors with a potential pathological role in the occurrence of liver abscesses are fistulizing disease phenotype, glucocorticoid use, abdominal surgery, diabetes mellitus and malnutrition [86]. The presence of a liver abscess can mimic a CD flare. Thus, these patients can present abdominal pain, fever, diarrhea and leukocytosis [86]. Imaging investigations can identify a liver lesion, but a positive diagnosis is established by the biochemical and bacteriological analysis of purulent aspirate [86]. Treatment involves the administration of antibiotics and in selected cases, ultrasound or CT-guided percutaneous drainage or surgical drainage [88]. Li et al. compared the effectiveness of ultrasound-guided percutaneous catheter drainage (US-PCD) vs. surgical drainage among 120 patients with liver abscesses and septic shock [89]. US-PCD was associated with a shorter extubation time, lower postoperative complication rate, shorter hospital stay and higher survival rate [89]. These authors concluded that US-PCD can be an effective therapeutic method for the drainage of liver abscesses and can improve the prognosis of these patients [89].

Treatment with corticosteroids, immunomodulators and biological agents used in patients with IBD increase the risk of opportunistic infections. Additionally, patients with a history of viral hepatitis are at risk of the reactivation of liver disease because of the immunosuppression induced by these treatments [90]. Most viral reactivations occur at the time of tapering or withdrawing of immunosuppressive therapy [91,92]. This phenomenon can be explained by the response of the immune system to the viral replication with the destruction of infected hepatocytes [91]. The use of two or more immunosuppressive drugs has been shown to be an independent predictor for viral hepatitis B reactivation [93]. Other risk factors for opportunistic infections in IBD patients are older age, malnutrition, chronic diseases, diabetes mellitus or congenital immunodeficiency [94]. The spectrum of clinical manifestations can vary from the absence of symptoms to fulminant, life-threatening hepatitis [91].

The 2021 European Crohn’s and Colitis Organization (ECCO) guidelines recommend serological screening for hepatitis A, B and C viruses, Epstein–Barr virus, varicella zoster virus, cytomegalovirus, measles virus and human immunodeficiency virus (HIV) for all IBD patients before and during immunosuppressive treatment [95]. Additionally, vaccination against hepatitis B is recommended in all seronegative patients (hepatitis B core antibody (anti-HBc) negative and hepatitis B surface antigen (HBsAg) negative) [95]. The goal of vaccination is to obtain an anti-HBs titer > 10 IU/L [95]. A meta-analysis that followed 1688 IBD patients reported a response rate to vaccination of 61% [96]. In patients with IBD and previous HBV infection (anti-HBc positive and HBsAg negative), prophylactic antiviral treatment is not recommended [92]. In patients with IBD and chronic hepatitis B, antiviral treatment with nucleoside analogues is recommended [95]. The use of antiviral treatment in these patients reduces the risk of hepatitis B reactivation from 47.4% to 7.1% [97,98]. The mortality rate in patients with hepatitis B reactivation who receive immunosuppressive treatment is approximately 5% [99].

The prevalence of hepatitis C in patients with IBD varies between 1% and 6% [100]. For patients with IBD and hepatitis C, the ECCO guidelines recommend antiviral treatment [95]. In patients using direct-acting antiviral agents (DAAs), the same guidelines recommend the careful monitoring of disease exacerbation in 2021 [95]. A multicenter retrospective study published in 2022, which followed 79 patients with IBD and hepatitis C treated with DAAs, reported an increased efficiency and safety of this antiviral treatment [100]. A sustained virologic response was obtained in 96.2% of the patients included in the study [100]. Adverse effects were reported in seven patients, five of whom were probably related to DAAs, but in 100% of cases there were mild adverse effects [91]. Thus, in patients with IBD and hepatitis C, antiviral treatment with DAAs seems to be effective, with cure rates > 90% and a good safety profile [100].