Introduction

Direct-acting antivirals (DAA) have revolutionized the treatment landscape for chronic hepatitis C (CHC), yielding notably high sustained virological response (SVR) rates. While SVR is associated with reduced hepatocellular carcinoma (HCC) risk, recent studies emphasize the importance of ongoing surveillance, particularly in patients with advanced fibrosis (F3-F4), mainly within the initial three years post-SVR.

Aims & Methods

The aim of this study was to assess the risk of hepatocellular carcinoma over a five-year period following DAA-induced SVR in a real-life cohort of F3-F4 patients.
Data were retrospectively collected from CHC F3-F4 patients initiating DAA treatment between February 2015 and January 2017 at a tertiary center. Statistical analysis was performed with SPSS 29.0 (significance level ≤0.05).

Results

Out of 239 patients included (69.5% male; median age: 58 years), a SVR at 12 weeks rate of 96.6% was achieved. Among those with SVR and continued follow-up (n=229), 5.2% (n=12) developed HCC over the five-year period, with 50% occurring more than three years post-SVR.
The annual HCC incidence rate was 1.1 cases/100 person-years (33.3% HCC-related mortality rate). Most HCC cases occurred in males (75%) and cirrhotic patients (75%, Child-Pugh A: 77.8%). The mean alpha-fetoprotein level at HCC diagnosis was 156.1 ng/mL. Additionally, 75% of patients who developed HCC had other co-factors for liver disease, mainly metabolic. Comparing the presence of other liver disease co-factors, no statistically significant difference was found between those who developed HCC and those who did not during the five-year follow-up period (p-value 0.267).

Conclusion

The incidence rate of HCC post- SVR has been reported to be 0.9-2.96/100 person-years for DAA therapy, consistent with the findings of this investigation. Nevertheless, our study underscores that the risk of HCC persists for at least five years following SVR, warranting long-term surveillance. Contrary to previous research, there is insufficient evidence to support the involvement of other co-factors in HCC development.

Disclosure

Hsu CC, Gopalakrishna H, Mironova M, Lee MH, Chen CJ, Yang HI, Wiese M, Chang KM, Wright EC, Abijo T, Feld JJ, Kaplan DE. Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review. Clin Infect Dis. 2023 Aug 14;77(Suppl 3):S245-S256. doi: 10.1093/cid/ciad380. PMID: 37579210; PMCID: PMC10425144.
Li M, Li Y, Zhang Y, Wang X, Lin C. Five-year follow-up of sustained virological response with hepatitis C infection after direct-acting antiviral therapy: A single-center retrospective study. Medicine (Baltimore). 2024 Feb 16;103(7):e37212. doi: 10.1097/MD.0000000000037212. PMID: 38363923; PMCID: PMC10869073.

Introduction

Upadacitinib, a selective JAK inhibitor, is approved for moderate-to-severe Crohn’s disease (CD). However, real-world data on its effectiveness and safety, particularly in highly refractory populations, remain scarce. The UPITA-Crohn registry was established to evaluate the outcomes of upadacitinib in clinical practice across multiple centers in Andalusia, Spain.

Aims & Methods

This ambispective, multicenter registry included 142 patients with refractory CD treated with upadacitinib in 12 Andalusian hospitals. Clinical and biochemical data were collected at baseline, weeks 12 and 16, and at 6 months. Clinical remission (CR) was defined as a Harvey-Bradshaw Index (HBI) <5; clinical-biochemical remission (CBR) as HBI <5, CRP <5 mg/L, and fecal calprotectin <250 μg/g; and steroid-free remission (SFR) as HBI <5 without corticosteroids from week 12. Outcomes were also analyzed overall and according to prior exposure to advanced therapies.

Results

The UPITA-Crohn registry cohort included 142 patients with refractory Crohn’s disease. The mean age was 40.8 years (range 18–76), with 40% male. The mean disease duration at the time of upadacitinib initiation was 13.3 years (range 1–42), with a mean of 2.7 failed advanced therapies, highlighting a population with longstanding and complex disease. Most patients had ileocolonic involvement (50%), 22% had perianal disease, and 32% had previously undergone resective surgery.
The majority (74.4%) received induction with upadacitinib 45 mg for 12 weeks. At week 12, clinical remission was achieved by 54% of patients, with 15% reaching clinical-biochemical remission. At 6 months, among those still on treatment, 48.3% maintained clinical remission, 16.1% achieved clinical-biochemical remission, and 18.4% achieved steroid-free remission (Table 1).
When stratified by prior therapy, 6-month clinical remission was similar between patients with ≥2 prior advanced therapies (48.5%) and those with only 1 prior therapy (47.4%), with no significant difference. Steroid-free and clinical-biochemical remission rates were also slightly higher among less refractory patients, but differences were modest.
A total of 31 patients (21.8%) discontinued upadacitinib before 6 months, mainly due to primary non-response (70.9%). Adverse events were reported in 21.1% of patients, most commonly infections (9 cases), acne (7), transient transaminase elevation (5), and herpes zoster (2). Seven discontinuations were due to serious adverse events, including thrombosis, stroke, myocardial infarction, fever, and severe infections.

Table 1: Effectiveness Outcomes

Conclusion

Upadacitinib demonstrated meaningful effectiveness and a manageable safety profile in a real-world cohort of refractory Crohn’s disease patients. Notably, clinical remission rates remained stable even in those with multiple prior advanced therapies, suggesting upadacitinib may be a valuable option for patients with limited alternatives.

Introduction

The recommended treatment for severe complications of portal hypertension (PH) is transjugular intrahepatic portosystemic shunt (TIPS) implantation. Despite alcohol-related liver disease (ALD) representing the most frequent cause of advanced chronic liver disease (ACLD) and PH, literature on the effects of ongoing alcohol use (AU) after TIPS placement currently remains scarce.

Aims & Methods

The study population consisted of patients with ALD-related ACLD who had undergone TIPS implantation at two Viennese tertiary care centers (pooled cohort from the prospective AUTIPS study, NCT03409263: 01/2017-11/2022; and a retrospective cohort: 09/2000-09/2019). Through the electronic patient management system, individual demographic, laboratory, and clinical data were retrieved. AU after TIPS placement was investigated according to clinical documentation, serum ethanol quantification if available, and patients' reporting.

Results

Overall, the study population consisted of 276 patients (median follow-up 29 [IQR 54] months), 196 (71.0%) of which had received TIPS for refractory ascites while in 80 (29.0%) the indication for TIPS implantation had been variceal hemorrhage. The median age was 56 (IQR 13) years and 215 (77.9%) of the patients were men. At the time of the TIPS insertion, the median MELD was 11 (IQR 9) and 38 (13.8%) individuals were classified as Child-Pugh C. AU after TIPS placement was documented in 85 (30.8%) study participants. Baseline characteristics at TIPS implantation were similar in patients with and without post-TIPS AU, specifically regarding the prevalence of ascites (p=0.51), variceal hemorrhage (p=0.87), and hepatic encephalopathy (p=0.87).
Bacterial infections were more frequently detected among patients with ongoing AU (log-rank p=0.002). Importantly, patients with ongoing AU showed a higher incidence of acute-on-chronic liver failure (ACLF; log-rank p<0.001) and higher overall mortality (log-rank p=0.005; including liver-related death [log-rank p<0.001]).
Furthermore, cumulative incidence of ACLF (p=0.014) and liver-related death (p=0.004) were significantly higher in patients with ongoing AU. Of note, ongoing AU was independently associated with ACLF (asHR: 1.66; 95%CI: 1.13-2.44; p=0.010) and liver-related death (asHR: 2.09; 95%CI: 1.32-3.33; p=0.002) in multivariable competing risks regression analysis adjusted for age, MELD, and portal pressure gradient after TIPS implantation.

Conclusion

AU represents an independent risk factor for outcome deterioration after TIPS placement. These findings emphasize the paramount role of psychiatric care and harm reduction measures in addition to hepatological optimization after TIPS implantation.

Disclosure

C.S. received travel support from Gilead, Abbvie, Galapagos and Gebro; speaking honoraria from Abbvie and Gilead; and payments for consulting from Gilead.
M.S. received travel support from MSD, Sandoz, BMS, Abbvie and Gilead; and speaking honoraria from BMS.
M.J. received speaking honoraria from Abbvie and Gilead.
T.R. received grant support from Abbvie, Boehringer- Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from Boehringer-Ingelheim, Gilead, and Roche.
M.M. served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Collective Acumen, Gilead, and W. L. Gore & Associates and received travel support from AbbVie, Bristol-Myers Squibb, and Gilead.
B.S. received travel support from AbbVie and Gilead.

Introduction

Inflammatory Bowel Diseases (IBD) can lead to various complications, with Acute Severe Colitis (ASC) being among the most critical. ASC is a medical and surgical emergency that poses a significant risk to life, necessitating prompt and effective diagnosis and management. The first-line treatment typically involves intravenous corticosteroids. However, some cases are resistant to corticosteroids and require second-line medical therapy or immediate surgical intervention.

Aims & Methods

The objective was to identify factors associated with the failure of first-line medical treatment in patients with ASC. A retrospective descriptive and analytical study was conducted over ten years (January 2014 to March 2024) in the gastroenterology department of Charles Nicolle Hospital. The study included patients with IBD complicated by ASC, defined by the Truelove and Witts criteria and a Lichtiger score greater than 10.Patients with bacterial superinfection were not included.

Results

Forty-five patients over 18 years old were included, with a mean age of 37.87 years (range: 18–74 years). There was a slight female predominance (53%), with a male-to-female ratio of 0.87. In 31% of cases, ASC was the initial presentation of the disease. Endoscopic signs of severity at admission were observed in 49% of patients. All patients received intravenous corticosteroid therapy with hydrocortisone hemisuccinate as the first-line treatment. The response rate to first-line treatment was 64.5%. Second-line medical therapy was administered to 24.4% of patients, consisting of cyclosporine in 11.1% and infliximab in 13.3%. Five patients (11.1%) underwent subtotal colectomy due to corticosteroid failure.
In univariate analysis, factors associated with corticosteroid failure included male gender (p=0.011), absence of extraintestinal manifestations (p=0.017), higher average number of stools on the first day (p=0.013), Lichtiger score >10 on the third (p=0.011) and fifth day (p<0.001), hemoglobin levels >11 g/dL on the first day (p<0.001), >10 g/dL on the third day (p=0.009), >9 g/dL on the seventh day (p=0.013), white blood cell count >10,000/mm³ on the first day (p=0.008), >12,000/mm³ on the third (p=0.001) and seventh day (p=0.004), C-reactive protein (CRP) level >30 mg/L on the seventh day (p=0.005), and persistent endoscopic signs of severity after three to five days of corticosteroid therapy (p=0.001).
Multivariate Analysis showed that only the presence of severe endoscopic signs on follow-up endoscopy after three to five days of corticosteroid therapy was predictive of corticosteroid failure (Odds Ratio = 42.2; p=0.028).

Conclusion

Acute Severe Colitis is a potentially life-threatening complication. The presence of severe endoscopic signs after five days of corticosteroid therapy should prompt the initiation of second-line therapy. Understanding the predictive factors for corticosteroid failure is essential for individualized management to improve both immediate and long-term outcomes.

Disclosure

The authors declare no conflicts of interest.

Introduction

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a disease that complements Nonalcoholic Fatty Liver Disease (NAFLD) and is newly defined in 2020. It is defined based on metabolic abnormalities, regardless of the presence of liver disease caused by other causes such as alcohol consumption. Regarding the newly defined MAFLD, there has not been many studies related to the prevalence and risk factors in Korea, and no studies were found targeting soldiers, especially pilots.

Aims & Methods

The purpose of this study is to identify prevalence and risk factors for MAFLD in Korean air force army inclusive of pilots. The subjects are 1044 soldiers who underwent health checkups in Korean Air Force Aerospace medical center from January 2020 to December 2022. The data was retrospectively collected including age, height, weight, body mass index, waist circumference, blood pressure, smoking, drinking, exercise intensity, various blood test results, presence of fatty liver, and degree of fatty liver. Risk factors were analyzed using logistic regression.

Results

There were 667 pilots (64%) in our study, of whom 477 (72%) were high-performing pilots. The prevalence of MAFLD was 316 (30%) in all soldier. There was difference in the prevalence of MAFLD between pilot and non-pilot group (pilot group: 185 (28%), non-pilot group: 131 (35%) p-value=0.018). According to the multivariate analysis, body mass index (BMI), diabetes, systolic blood pressure, triglycerides (TG), uric acid (UA), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT) were a risk factor associated with MAFLD among the entire soldiers. When categorized into pilot and non-pilot group, risk factors were associated with BMI, diabetes, alcohol consumption, and ALT in the non-pilot group. In the pilot group, they were statistically associated with age, BMI, dyslipidemia, TG, UA, HDL and ALT. Among them, UA showed the largest difference between the non-pilot group and the test group (non-pilot group: 1.14 (95% CI: 0.80-1.62), pilot group: 1.80 (95% CI: 1.38-2.36)).

Conclusion

There was a difference in the prevalence of MAFLD between pilot and non-pilot group. In particular, UA could be used to predict MAFLD as a specific risk factor in pilots comparing with non-pilots.

Introduction

Upadacitinib has shown to be more effective than placebo for treating extraintestinal manifestations (EIM) in post-hoc analyses. However, real-world data on the effectiveness of upadacitinib in patients with inflammatory bowel disease (IBD) and EIMs are lacking.

Aims & Methods

A multicenter, retrospective and observational study was conducted at 19 Spanish hospitals. Patients with IBD and active EIMs when initiating upadacitinib were eligible. The primary outcome was EIM improvement at weeks 8-12. The EIM assessment was based on the physician's subjective evaluation and categorized into clinical remission, partial response, nonresponse and worsening. EIM improvement was defined as either clinical remission or partial response. Axial arthropathy, peripheral arthropathy, pyoderma gangrenosum, erythema nodosum, sweet syndrome, aphthous stomatitis, uveitis, episcleritis, primary sclerosing cholangitis and bronchiectasis were considered. In patient experiencing >1 EIM, all had to be resolved or improved to be considered. If not, the worst outcome was recorded. Patients’ visits were scheduled at weeks 0, 8-12, and 6 months. Multivariate analysis was performed to find factors associated with EIM improvement at w8-12.

Results

A total of 160 patients were included, 120 patients with Crohn’s Disease (75.6%), 90 females (56.3%) with a median age of 46.6 years (IQR 37.9-56.7). Upadacitinib was initiated in one hundred twenty-six (78.8%) patients due to EIMs and luminal activity and 35 patients (21.3%) exclusively due to EIMs. All patients were bio-experienced with 84 patients previously treated with ≥3 biologics (52.5%). Baseline EIMs assessment was for at least 1 EIM in 107 patients (66.9%), 42 patients presented 2 EIMs (26.3%) while 11 patients (6.9%) experienced ≥ 3 EIMs.
At w8-12, 99 patients (61.9%) achieved EIM improvement, 40 patients (25 %) clinical remission, 58 patients (36.9%) partial response, 58 patients (36.5 %) nonresponse and worsening in 3 patients. Patients initiating Upadacitinib due to exclusively active EIMs was associated with EIM improvement at weeks 8-12 (OR 2.99 95% CI 1.06-8.42; p=0.04). IBD clinical remission at w8-12 was achieved in 75 patients (61%).
Evaluation at 6 months was available for 103 patients, 73 patients (70.9%) presented EIM improvement, 41 patients (39.8%) clinical remission, 32 patients (31.1%) partial response, 20 patients (19.4%) nonresponse and 10 patients (9.7%) worsening. IBD clinical remission at 6 months was achieved in 51 patients (62.2%).
During the follow-up, Upadacitinib was ceased in 27 patients (16.9%). Adverse events were detected in 39 patients (24.3%) and 7 patients (4.4%) experienced worsening of previous inactive EIMs.

Conclusion

Upadacitinib was highly effective in the short term for treating bio-experienced patients with active EIMs, particularly for patients without luminal activity

Disclosure

No conflict