Therapeutic Drug Monitoring as a Tool for the Clinical Outcome Prediction in Vedolizumab-Treated Patients: An Italian Pilot Study.

Over the years, vedolizumab (VDZ) has emerged as a more effective target therapy for inflammatory bowel disease. The aim of this work was to analyze a cohort of inflammatory bowel disease patients, evaluating the association between VDZ serum concentrations at 6 months from starting therapy and their clinical and biochemical indexes within one year of treatment, correlating drug levels with response and clinical remission. Forty patients treated with VDZ were enrolled. Drug concentrations were quantified through ELISA methods. VDZ levels correlated with hemoglobin levels at twelve months of therapy (p = 0.03) and with clinical remission at twelve months of therapy (p = 0.03); patients who reached clinical remission showed higher VDZ concentrations. A VDZ cut-off value of 43.1 µg/mL was suggested, predicting clinical remission at twelve months of therapy. A statistically significant association between VDZ levels at T6 and calprotectin <250 µg/g at T12 was found (p = 0.04). Furthermore, the optimal threshold value of VDZ levels at T6 associated with calprotectin <250 µg/g at T12 was identified: through levels higher than 45.2 µg/mL, we were able to predict remission one year after therapy. In the final regression multivariate model, no factor was retained as a predictor of clinical remission at one year of treatment. In conclusion, this is the first pilot study reporting a possible VDZ serum cut-off value able to predict not only the clinical remission at twelve months of therapy but also the calprotectin level, which is very important, as it is a surrogate marker of mucosal healing.

Helicobacter pylori in Inflammatory Bowel Diseases: Active Protagonist or Innocent Bystander?

Helicobacter pylori (H. pylori) infection is a prominent entity within human infectious diseases which cause chronic gastritis, peptic ulcers, gastric malignancies, and extragastric disorders. Its persistent colonization can lead to a systemic inflammatory cascade, potentially instigating autoimmune responses and contributing to the pathogenesis of autoimmune diseases. While the specific etiopathogenesis of inflammatory bowel diseases (IBDs) is still unknown, it is widely recognized that immunological, genetic, and environmental factors are implicated. Various bacterial and viral pathogens have been implicated in the pathogenesis of IBDs. Numerous studies suggest a correlation between H. pylori infection and IBDs. While subject to debate, this link suggests that the bacterium's presence somehow impacts the progression of IBDs by modifying the diversity of the gut microbiota, consequently altering local chemical profiles and disrupting the pattern of gut immune response. However, epidemiological evidence indicates a protective role of H. pylori infection against the onset of autoimmune diseases. Additionally, laboratory findings demonstrate H. pylori's capacity to promote immune tolerance and restrict inflammatory reactions. The aim of this review is to elucidate the proposed mechanisms and confounding factors that underlie the potential association between H. pylori infection and IBDs.

Correlation between Polymorphisms of Vitamin D Metabolism Genes and Perianal Disease in Crohn's Disease.

Although the role of vitamin D (VD) in the pathogenesis and progression of Crohn's disease (CD) is known, the association between single-nucleotide polymorphisms (SNPs) of genes linked to vitamin D pathway and CD risk is still under study. Furthermore, no significant association has been previously found between these SNPs and perianal CD (pCD), a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, and recto-vaginal fistula. Among the mechanisms involved in its pathogenesis, local inflammation and intestinal microbiota alteration are recognized. VD seems to act on these elements. The aim of this study was to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters, and receptors involved in the VD pathway and the occurrence of pCD. Blood samples of 206 patients with CD, including 34 with pCD, were analyzed for VDR, CYP27B1, CYP24A1, and GC genetic variants. VDR Apal Aa genotype and VDR BsmI Bb genotype resulted in an association with pCD (p = 0.01 and p = 0.02, respectively). Our study demonstrates for the first time the impact of the polymorphisms of genes associated with the VD pathway on the onset of pCD. Future multicenter studies are needed to confirm these data.

A prospective, multicenter, three-cohort study evaluating contrast-induced acute kidney injury (CI-AKI) in patients with cirrhosis.

BACKGROUND & AIMS: Nephrotoxicity of intravenous iodinated contrast media (ICM) in cirrhosis is still a debated issue, due to scarce, low-quality and conflicting evidence. This study aims to evaluate the incidence and predisposing factors of acute kidney injury (AKI) in patients with cirrhosis undergoing contrast-enhanced computed tomography (CECT). METHODS: We performed a prospective, multicenter, cohort study including 444 inpatients, 148 with cirrhosis (cohort 1) and 163 without cirrhosis (cohort 3) undergoing CECT and 133 with cirrhosis (cohort 2) unexposed to ICM. Kidney function parameters were assessed at T0, 48-72 h (T1), 5 and 7 days after CECT/enrollment. Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) was measured in 50 consecutive patients from cohort 1 and 50 from cohort 2 as an early biomarker of tubular damage. RESULTS: AKI incidence was not significantly increased in patients with cirrhosis undergoing CECT (4.8%, 1.5%, 2.5% in cohorts 1, 2, 3 respectively, p = n.s.). Most AKI cases were mild and transient. The presence of concomitant infections was the only independent predictive factor of contrast-induced AKI (odds ratio 22.18; 95% CI 2.87-171.22; p = 0.003). No significant modifications of U-NGAL between T0 and T1 were detected, neither in cohort 1 nor in cohort 2 (median ΔU-NGAL: +0.2 [-7.6 to +5.5] ng/ml, +0.0 [-6.8 to +9.5] ng/ml, respectively [p = 0.682]). CONCLUSIONS: AKI risk after CECT in cirrhosis is low and not significantly different from that of the general population or of the cirrhotic population unexposed to ICM. It mostly consists of mild and rapidly resolving episodes of renal dysfunction and it is not associated with tubular kidney injury. Patients with ongoing infections appear to be the only ones at higher risk of AKI. IMPACT AND IMPLICATIONS: Nephrotoxicity due to intravenous iodinated contrast media (ICM) in patients with cirrhosis is still a debated issue, as the available evidence is limited and based on very heterogeneous studies, often conducted on small and retrospective cohorts. In this prospective three-cohort study we found that intravenous administration of ICM was associated with a low risk of AKI, similar to that of the general population and to that of patients with cirrhosis unexposed to ICM. Patients with ongoing infections were the only ones to have a significantly increased risk of contrast-induced AKI. Therefore, the actual recommendations of performing contrast imaging studies cautiously in cirrhosis do not seem to be reasonable anymore, with the exception of infected patients, who have a significantly higher risk of contrast-induced AKI.

Metformin and Hepatocellular Carcinoma Risk Reduction in Diabetic Patients with Chronic Hepatitis C: Fact or Fiction?

BACKGROUND: Patients with chronic hepatitis C (CHC) and concomitant type 2 diabetes mellitus (DM) show a higher risk of developing hepatocellular carcinoma (HCC). Successful antiviral therapy has reduced the incidence of post-therapy HCC, but the presence of DM still represents an unfavourable predictive factor even in cured patients. Metformin (MET) is recommended as a first-line therapy for DM, and its use is associated with a significant reduction in HCC among diabetic patients with chronic liver disease of different etiology, but very few studies specifically address this issue in patients with CHC. AIM: the aim of this review is to evaluate whether the use of MET induces a significant decrease in HCC in diabetic patients with CHC, treated or untreated with antiviral therapy. METHODS: A search of PubMed, Medline, Web of Sciences and Embase was conducted for publications evaluating the role of MET in reducing the risk of HCC in patients with DM and CHC, with no language and study type restrictions up to 30 June 2023. Only studies fulfilling the following inclusion criteria were considered: (1) data on the incidence of HCC in the follow-up of diabetic patients with CHC only; (2) follow-up ≥24 months; (3) sufficient data to establish the rate of diabetic patients with CHC treated with metformin or other antidiabetic medications; and (4) data on the type of antiviral treatment and the clinical outcome. RESULTS: Three studies met the inclusion criteria. A prospective cohort study considering only patients with DM and untreated advanced CHC, or non-responders to interferon (IFN) therapy, showed that the use of MET was associated with a significant decrease in HCC incidence, liver-related death and liver transplants. A recent retrospective study focusing on a large-scale nationwide cohort of patients with CHC in Taiwan successfully treated with IFN-based therapy stratified patients into 3 groups: non-MET users, MET users and non-diabetic patients, with 5-year cumulative rates of HCC of 10.9%, 2.6% and 3.0%, respectively, showing a significantly higher HCC risk in non-MET users compared with MET users and with non-diabetic patients, while it was not significantly different between MET users and non-diabetic patients. In a recent Italian cohort study focusing on 7007 patients with CHC treated and cured with direct-acting antiviral agents (DAAs), a combined effect of DM and MET therapy was found, showing a higher incidence of HCC in diabetic patients not taking MET compared with those without DM and those with DM taking MET. CONCLUSION: according to the current evidence, the use of MET should be encouraged in diabetic patients with CHC in order to reduce the risk of HCC; however, a well-designed randomized controlled trial is needed to establish the generalizability of the beneficial effects of MET in this particular subset of patients.

Inflammatory Bowel Disease: Emerging Therapies and Future Treatment Strategies.

Inflammatory bowel disease (IBD) is a term used to represent a group of chronic, relapsing inflammatory disorders of the gastrointestinal tract. Crohn's disease (CD) and ulcerative colitis (UC) are the two major clinical forms. The global incidence and prevalence of IBD have increased over the last 2-4 decades. Despite the specific etiopathogenesis of IBD still being unknown, it is widely recognized that immunological, genetic, and environmental factors are implicated. A greater understanding of the multiple signaling pathways involved has led to the development of biologic therapies in the last two decades. Although these treatments have dramatically transformed the course of IBD, there is not a definitive cure and available therapies may cause adverse events (AEs), limiting their use, or have an inadequate effect in some patients. In this context, emerging therapies addressing new specific pathogenetic mechanisms have shown promising efficacy and safety data in early clinical trials. The purpose of this review is to highlight the available clinical trial data for these new drugs, such as more preferential JAK inhibitors, anti-IL-23 antibodies, sphingosine-1-phosphate receptor modulators, anti-integrin therapies, and other small molecules that are currently under research. We will emphasize the potential significance of these agents in shaping future treatment options.

Excellent outcome in patients with primary biliary cholangitis in Northwest Italy followed up for up to 30†years.

OBJECTIVE: Primary biliary cholangitis (PBC) is a rare chronic autoimmune cholangiopathy, characterized by a variable course and response to treatment. We aimed to describe long-term outcomes of PBC patients referred to three academic centres in Northwest Italy. METHODS: This is an ambispective cohort study of PBC patients (retrospective component: diagnosis before 1 January 2019; prospective component: thereafter), including 302 patients: 101 (33%) followed up in Novara, 86 (28%) in Turin, 115 (38%) in Genoa. Clinical features at diagnosis, biochemical response to therapy and survival were analyzed. RESULTS: Among the 302 patients (88% women, median age 55 years, median follow-up 75 months), alkaline phosphatase (ALP) levels significantly decreased during treatment with ursodeoxycholic acid (UDCA, P < 0.0001) and obeticholic acid (P < 0.0001). At multivariate analysis, ALP at diagnosis was predictive of 1-year biochemical response to UDCA [odds ratio 3.57, 95% confidence interval (CI) 1.4-9, P < 0.001]. Estimated median survival free of liver transplantation and hepatic complications was 30 years (95% CI 19-41). Bilirubin level at diagnosis was the only independent risk factor for the combined outcome of death, transplantation or hepatic decompensation (hazard ratio, 1.65, 95% CI 1.66-2.56, P = 0.02). Patients presenting with total bilirubin at diagnosis ≥0.6 times the upper normal limit (ULN) had a significantly lower 10-year survival compared to those with bilirubin <0.6 times ULN (63% vs. 97%, P < 0.0001). CONCLUSION: In PBC, both short-term response to UDCA and long-term survival can be predicted by simple conventional biomarkers of disease severity, obtained at diagnosis.

Hepatic encephalopathy increases the risk for mortality and hospital readmission in decompensated cirrhotic patients: a prospective multicenter study.

Introduction: Hepatic encephalopathy (HE) affects the survival and quality of life of patients with cirrhosis. However, longitudinal data on the clinical course after hospitalization for HE are lacking. The aim was to estimate mortality and risk for hospital readmission of cirrhotic patients hospitalized for HE. Methods: We prospectively enrolled 112 consecutive cirrhotic patients hospitalized for HE (HE group) at 25 Italian referral centers. A cohort of 256 patients hospitalized for decompensated cirrhosis without HE served as controls (no HE group). After hospitalization for HE, patients were followed-up for 12 months until death or liver transplant (LT). Results: During follow-up, 34 patients (30.4%) died and 15 patients (13.4%) underwent LT in the HE group, while 60 patients (23.4%) died and 50 patients (19.5%) underwent LT in the no HE group. In the whole cohort, age (HR 1.03, 95% CI 1.01-1.06), HE (HR 1.67, 95% CI 1.08-2.56), ascites (HR 2.56, 95% CI 1.55-4.23), and sodium levels (HR 0.94, 95% CI 0.90-0.99) were significant risk factors for mortality. In the HE group, ascites (HR 5.07, 95% CI 1.39-18.49) and BMI (HR 0.86, 95% CI 0.75-0.98) were risk factors for mortality, and HE recurrence was the first cause of hospital readmission. Conclusion: In patients hospitalized for decompensated cirrhosis, HE is an independent risk factor for mortality and the most common cause of hospital readmission compared with other decompensation events. Patients hospitalized for HE should be evaluated as candidates for LT.

Prognostic Value of Simple Non-Invasive Tests for the Risk Stratification of Incident Hepatocellular Carcinoma in Cirrhotic Individuals with Non-Alcoholic Fatty Liver Disease.

Hepatocellular carcinoma (HCC) represents a relevant disease burden in cirrhotic patients with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the prognostic value of simple non-invasive tests (NITs) (AAR, APRI, BARD, FIB-4) for the stratification of HCC risk development in a cohort of 122 consecutive cirrhotic individuals with NAFLD. Over a median follow up of 5.9 (3.2-9.3) years, 13 (10.7%) developed HCC. Only FIB-4 was associated with HCC risk (HR = 1.27, 95% CI 1.03-1.58, p = 0.027). After evaluating different established FIB-4 cut-offs, the lowest cut-off of 1.45 allowed the ruling out of a greater number of patients with a minimal risk of HCC than the 1.3 cut-off (23 vs. 18 patients). Conversely, the cumulative incidence of HCC using the highest cut-off of 3.25 (rule in) was distinctly higher than the 2.67 cut-off (19.4% vs. 13.3%). After multivariate Cox regression analysis, these cut-offs were independently associated with HCC after adjusting for sex, BMI and T2DM (HR = 6.40, 95% CI 1.71-24.00, p = 0.006). In conclusion, FIB-4 values of <1.3 and >3.25 could allow for the optimal stratification of long-term HCC risk in cirrhotic individuals with NAFLD.

Identification of the Best Cut-Off Value of PIVKA-II for the Surveillance of Patients at Risk of Hepatocellular Carcinoma Development.

Patients with cirrhosis are at risk of hepatocellular carcinoma (HCC) development and, according to current guidelines, should undergo surveillance by ultrasound at six month intervals. Due to the known limitations of surveillance strategies based on ultrasonography, the use of tumor biomarkers, although debated, is common practice in many centers. The aim of the study was to identify the best cut-off value for one of such biomarkers, protein induced by vitamin K absence, or antagonist-II (PIVKA-II). We retrospectively enrolled 1187 patients with liver cirrhosis: 205 with a diagnosis of HCC (median age 67 years, 81.0% males) and 982 without tumor (median age 64 years, 56.2% males). During a median follow-up (FU) of 34.6 (11.4−43.7) months, 118 out of 982 (12.0%) patients developed HCC. Serum PIVKA-II was assessed by chemiluminescence immunoassay on the Lumipulse® G600 II platform (Fujirebio, Tokyo, Japan). In the overall cohort (n = 1187), PIVKA-II showed an area under the curve (AUC) of 0.802 for HCC detection. The best cut-off value that maximized sensitivity was 50 mAU/mL (sensitivity = 80%, specificity = 64%). In the 982 patients without HCC at baseline, PIVKA-II > 50 mAU/mL was associated with an increased risk of HCC development during the FU (HR = 1.74, 95% CI 1.21−2.51; p = 0.003)). In conclusion, the evaluation of serum PIVKA-II showed a good performance for HCC detection; a cut-off value > 50 mAU/mL could be suitable for the surveillance of patients who are at risk of developing HCC.

The Predictive Role of Extracellular NAPRT for the Detection of Advanced Fibrosis in Biopsy-Proven Non-Alcoholic Fatty Liver Disease.

Intrahepatic oxidative stress is a key driver of inflammation and fibrogenesis in non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the role of extracellular Nicotinamide phosphoribosyltransferase (eNAMPT) and extracellular nicotinic acid phosphoribosyltransferase (eNAPRT) for the detection of advanced fibrosis. eNAMPT and eNAPRT were tested in 180 consecutive biopsy-proven NAFLD patients and compared with liver stiffness (LS) and the FIB-4 score. eNAMPT was similarly distributed across fibrosis stages, whereas eNAPRT was increased in patients with advanced fibrosis (p = 0.036) and was associated with advanced fibrosis (OR 1.08, p = 0.016). A multiple stepwise logistic regression model containing significant variables for advanced fibrosis (eNAPRT, type 2 diabetes, age, male sex, ALT) had an area under the curve (AUC) of 0.82 (Se 89.6%, Sp 67.3%, PPV 46.7%, NPV 93.8%) when compared to that of LS (0.79; Se 63.5%, Sp 86.2%, PPV 66.0%, NPV 84.8%) and to that of the FIB-4 score (0.73; Se 80.0%, Sp 56.8%, PPV 44.9%, NPV 86.6%). The use of eNAPRT in clinical practice might allow for the better characterization of NAFLD patients at higher risk of disease progression.

Who Should Not Be Surveilled for HCC Development after Successful Therapy with DAAS in Advanced Chronic Hepatitis C? Results of a Long-Term Prospective Study.

Background and aims: The identification of patients with Hepatitis C Virus (HCV)-positive advanced chronic liver disease (aCLD) successfully treated by Direct Acting Antiviral Agents (DAAs) who really benefit from Hepatocellular Carcinoma (HCC) surveillance programs is still a matter of debate. We performed a long-term prospective cohort study on F3-F4 HCV-positive patients achieving Sustained Virologic Response (SVR) after DAAs treatment in order to identify patients who can safely suspend surveillance. Methods: 1000 patients with HCV-positive aCLD obtaining SVR by DAAs from January 2015 to December 2017 were divided into four groups according to baseline elastographic, ultrasonographic, clinical and biochemical features: (1) Group 1: 324 patients with Liver Stiffness Measurement (LSM) ≥ 9.5 ≤ 14.5 kPa, FIB-4 < 3.25 and APRI < 1.5 (2) Group 2: 133 patients with LSM ≥ 9.5 ≤ 14.5 kPa, FIB-4 ≥ 3.25 and/or APRI ≥ 1.5 (3) Group 3: 158 patients with LSM > 14.5 kPa, FIB-4 < 3.25 and APRI < 1.5 (4) Group 4: 385 patients with LSM > 14.5 kPa, FIB-4 ≥ 3.25 and/or APRI ≥ 1.5. FIB-4 and APRI scores were calculated at baseline and at SVR achievement. Each patient was surveiled twice-yearly by ultrasound for a median follow-up of 48 months. Results: among Group 1 patients, 1/324 (0.3%) developed HCC (0.09/100 patients/year [PY]), compared to 6/133 (4.5%) Group 2 patients (1.22/100 PY, p = 0.0009), 10/158 (6.3%) Group 3 patients (1.68/100 PY, p = 0.0001), 54/385 (14.0%) Group 4 patients (4.01/100 PY, p < 0.0001). HCC incidence was significantly lower in Group 2 compared to Group 3 (p = 0.004) and in Group 3 compared to Group 4 (p = 0.009). HCC risk fell in patients showing a decrease of FIB-4/APRI scores. Conclusions: the risk of HCC occurrence is negligible in about 90% of HCV-positive patients with baseline LSM ≥ 9.5 ≤ 14.5 kPa plus FIB-4 < 3.25 and APRI < 1.5 achieving SVR. Among this particular subset of patients, FIB-4/APRI scores may represent an accurate and inexpensive tool to distinguish patients not needing long-term HCC surveillance.

Epidemiology of Inflammatory Bowel Diseases: A Population Study in a Healthcare District of North-West Italy.

The burden of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. The aim of the present study was to investigate the clinical characteristics and the changing in epidemiology of IBD in the Healthcare District Bra, an area of North-West Italy accounting for 57,615 inhabitants as of 31 December 2021. Clinical and demographic data were retrieved from administrative databases and the medical records of general practitioners (n = 39) at Verduno Hospital. Prevalence and incidence rates were calculated for the time span 2016-2021 and compared to the 2001-2006 period. IBD prevalence was 321.2 per 100,000 population in 2021 and, compared with 2006 (200 per 100,000 population), the prevalence has increased at a rate of +46%. Similarly, the average incidence has increased from the period 2001-2006 (6.7 per 100,000 population/year) to the period 2016-2021 (18.0 per 100,000 population/year) at a rate of +169%; such an increase was greater for CD than UC. In the 2016-2021 period, the mean age at diagnosis was 42.0 ± 17.4 years and 30.9% required at least one hospitalization, while 10.9% of patients underwent at least one surgery. In conclusion, the prevalence and incidence of IBD distinctly increased over a two decade period in the Healthcare District Bra paralleling the results of previous surveys from other Italian regions. These data warrant specific interventions to improve patients' management and resources' allocation.

Cross-Sectional and Longitudinal Performance of Non-Invasive Tests of Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

Background and aims: Non-invasive tests (NITs) are needed in clinical practice to replace histology for the identification of liver fibrosis and prognostication in Non-Alcoholic Fatty Liver Disease (NAFLD). Novel collagen-derived fibrogenesis markers including N-terminal type III collagen pro-peptide (PRO-C3) are among the most promising tools in this field. The aim of this study was to assess the diagnostic accuracy of PRO-C3, the derivative ADAPT score, and other NITs for the identification of advanced fibrosis (stages 3-4) and changes over 12 months of follow-up. Methods: In this longitudinal study, 96 patients with biopsy-proven NAFLD were evaluated at baseline, of which 50 underwent a follow-up visit after 12 months. Clinical-biochemical parameters, liver stiffness (LS) by transient elastography, PRO-C3, and other NITs (ADAPT, FIB-4, NFS, APRI) were collected at baseline and follow-up. Results: LS showed the best accuracy for the identification of advanced fibrosis, with Area under the Receiving Operator Curve (AUROC) 0.82 (0.73-0.89) for a cut-off value of 9.4 kPa. Among the other NITs, the ADAPT score showed the best accuracy, with AUROC 0.80 (0.71-0.88) for a cut-off of 5.02 (Se 62%, Sp 89%, PPV 74%, NPV 83%). The comparison between the AUROC of LS with that of ADAPT was not statistically different (DeLong test p value 0.348). At follow-up, LS was slightly reduced, whilst PRO-C3 displayed a significant increase from baseline median 11.2 ng/mL to 13.9 ng/mL at follow-up (p = 0.017). Accordingly, ADAPT score increased from median 5.3 to 6.1 (p = 0.019). The other NITs did not significantly change over 12 months. Conclusions: The ADAPT score shows the best performance among non-invasive scores for the identification of advanced fibrosis, not different from LS. Collagen-derived biomarker PRO-C3 and the derivative score ADAPT display significant changes over time, and may be useful tools for monitoring the progression of liver disease or assessing responses to treatments.

Expression of SARS-Cov-2 Entry Factors in Patients with Chronic Hepatitis.

Chronic hepatitis (CH) of dysmetabolic or viral etiology has been associated with poor prognosis in patients who experienced the severe acute respiratory coronavirus virus-2 (SARS-Cov-2) infection. We aimed to explore the impact of SARS-Cov-2 infection on disease severity in a group of patients with CH. Forty-two patients with CH of different etiology were enrolled (median age, 56 years; male gender, 59%). ACE2 and TMPRSS2 were measured in plasma samples of all patients by ELISA and in the liver tissue of a subgroup of 15 patients by Western blot. Overall, 13 patients (31%) experienced SARS-Cov-2 infection: 2/15 (15%) had CHB, 5/12 (39%) had CHC, and 6/15 (46%) had non-alcoholic fatty liver disease (NAFLD). Compared to viral CH patients, NAFLD subjects showed higher circulating ACE2 levels (p = 0.0019). Similarly, hepatic expression of ACE2 was higher in subjects who underwent SARS-Cov-2 infection compared to the counterpart, (3.24 ± 1.49 vs. 1.49 ± 1.32, p = 0.032). Conversely, hepatic TMPRSS2 was significantly lower in patients who experienced symptomatic COVID-19 disease compared to asymptomatic patients (p = 0.0038). Further studies are necessary to understand the impact of COVID-19 in patients with pre-existing liver diseases.

Predictive Factors of Surgical Recurrence in Patients with Crohn's Disease on Long-Term Follow-Up: A Focus on Histology.

In patients with Crohn's disease (CD) that underwent surgery, predictive factors of surgical recurrence have been only partially identified. The aim of our study was to identify potential factors associated with an increased risk of surgical recurrence. A monocentric retrospective observational study was conducted including patients diagnosed with CD, according to ECCO criteria who received their first ileocolic resection. Overall, 162 patients were enrolled in our study; 54 of them were excluded due to a lack of sufficient data. The median follow-up was 136.5 months, IQR 91.5−176.5, and the surgical recurrence rate after the median follow-up was 21.3%. In the multivariate analysis, an age ≤ 28 years at the first surgical resection (aHR = 16.44, p < 0.001), current smoking (aHR = 15.84, p < 0.001), female sex (aHR = 7.58, p < 0.001), presence of granulomas at local lymph nodes (aHR = 12.19, p < 0.001), and treatment with systemic corticosteroids after the first surgical resection (aHR = 7.52, p = 0.002) were factors significantly associated with a risk of surgical recurrence, while cryptitis resulted in a protective factor (aHR = 0.02, p < 0.001). In conclusion, the heterogeneous spectrum of factors associated to the risk of surgical recurrence in patients with CD that underwent ileocolic resection supports the need of a personalized follow-up taking into account different clinical, surgical, and histologic features.

Changes in Liver Stiffness and Markers of Liver Synthesis and Portal Hypertension following Hepatitis C Virus Eradication in Cirrhotic Individuals.

The advent of direct antiviral agents (DAAs) has radically changed the natural history of hepatitis C virus (HCV) chronic liver disease. Even patients with cirrhosis may display improvements in liver function or features of portal hypertension following viral eradication. The aim of this study was to assess whether a HCV cure would lead to improvements in cirrhotic patients using simple, readily available tools in clinical practice, together with liver stiffness (LS) measurement. This is a retrospective study of cirrhotic patients with cured HCV infection, with or without previous decompensation. Clinical and biochemical parameters as well as LS measurements were collected before antiviral treatment with DAAs and after 6 months following sustained virological response. Hepatic synthesis was assessed by serum albumin levels. Portal hypertension was indirectly assessed by platelet count. Liver function was determined by the CHILD score. A total of 373 cirrhotic patients with successful HCV eradication were retrospectively included. After 6 months of follow-up, a significantly higher proportion of patients showed improved liver function, shifting from the CHILD B/C to CHILD A group, (71.4%, p < 0.001). Similarly, LS improved from a median of 19.3 kPa (14.7−27) at the baseline vs. a median of 11.6 (7.7−16.8 kPa) at follow-up (p < 0.001). The proportion of patients who showed improved hepatic synthesis was 66.0%, which was statistically different when compared to that of patients who had a worsened condition (0.3%) (p < 0.001). Moreover, when classifying the cohort according to the RESIST-HCV score, we found that a significant proportion of patients shifted into the "low risk" group following DAA treatment (52% baseline vs. 45.6% at follow-up, p = 0.004). Even in the decompensated patients, LS improved from 1.6 to 2-fold from the baseline. Antiviral treatment is effective in improving indirect signs of hepatic synthesis and portal hypertension. Similarly, the LS values displayed significant improvements, even in decompensated patients.

Liver Cancer-Specific Isoform of Serine Protease Inhibitor Kazal for the Detection of Hepatocellular Carcinoma: Results from a Pilot Study in Patients with Dysmetabolic Liver Disease.

Reliable non-invasive biomarkers for the surveillance of patients at risk of hepatocellular carcinoma (HCC) development represent an unmet medical need. Recently, the liver-cancer-specific isoform of serine protease inhibitor Kazal (LC-SPIK) has been proposed as a valuable biomarker for the detection of HCC in patients with chronic liver disease of viral etiology. In the present study, we assessed the diagnostic accuracy of LC-SPIK, alone or in combination with standard serologic biomarkers (i.e., alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II, PIVKA-II), for the detection of HCC among patients with dysmetabolic liver disease. A total of 120 patients with non-alcoholic fatty liver disease (NAFLD), including 62 patients with a diagnosis of HCC and 58 with cirrhosis but without tumor, were retrospectively analyzed. The serum levels of LC-SPIK were measured by enzyme-linked immunosorbent assay (ImCare Biotech, Doylestown, PA). The serum LC-SPIK values were significantly different between patients with HCC (24.3, 17.6−39.8 ng/mL) and those with cirrhosis but without tumor (11.7, 8.7−18.2 ng/mL) (p < 0.001). By receiver operating characteristic curve analysis, we observed an area under the curve (AUC) of 0.841 for the detection of HCC; the combination with PIVKA-II further increased the accuracy to AUC = 0.926 (cross-validation). The promising results observed in the present pilot study foster additional research to investigate the usefulness of LC-SPIK for the stratification of the risk of HCC development in patients with NAFLD and advanced liver disease.