Introduction

The number of individuals who will be treated for and cured from HCV infection world-wide is expected to exceed 1 million per year for the next decade. In those with compensated advanced chronic liver disease (cACLD), the risks of de-novo hepatocellular carcinoma (HCC) and hepatic decompensation are decreased but not completely abolished by HCV-cure. Thus, risk stratification is key to decrease resource utilization by individualizing post-treatment management. We evaluated whether the incidences of HCC and hepatic decompensation decrease with time after HCV-cure and whether the discriminatory ability of a one-time post-treatment assessment is maintained during long-term follow-up.

Aims & Methods

We retrospectively analyzed cACLD patients with paired liver stiffness measurement (LSM) & platelet count (PLT) before and after HCV-cure by interferon-free therapies from 7 European regions. Cumulative incidence curves were used to estimate the incidence of hepatic decompensation/HCC over time in the overall group and throughout previously defined risk strata: Baveno VII criteria for clinically significant portal hypertension after HCV-cure (CSPH excluded: FU-LSM <12kPa & FU-PLT >150G/L; CSPH ruled-in: FU-LSM ≥25kPa), and Semmler et al., J Hepatol 2022 (algorithm based on age, LSM, albumin and alcohol consumption) for HCC.

Results

2347 patients (mean age 60±12 years, 60% male, 21% obese, 21% diabetes) with a median LSM of 16.3kPa (IQR: 12.1-24.5, 25% ≥25kPa) before HCV-cure were followed for a median of 6.0 years after treatment. Interestingly, the incidence of first hepatic decompensation was strictly linear with 65 patients (2.8%) developing hepatic decompensation before eventually being diagnosed with HCC (incidence rate 0.57/100 patient years, incidence at 6 years: 3.1%). Similarly, incidence of HCC was also linear with 184 patients (7.8%) developing HCC (incidence rate 1.60/100 patient years, incidence at 6 years: 8.3%). Stratifying the risks for hepatic decompensation according to Baveno VII identified patients with a distinct prognosis during long-term follow-up (incidence at 6 years: 0.3% [CSPH excluded] vs. 2.1% [Gray-zone] vs. 15.6% [CSPH ruled-in]). Similarly, cumulative HCC incidence at 6 years was 15.8% in the high-risk group vs. 5.4% in the low-risk group according to Semmler et al. Results were similar when limiting prediction to events occurring >3 years after HCV-cure.

Conclusion

In patients with cACLD, the risks of hepatic decompensation, and more importantly, HCC remain constant after HCV-cure, even in the long-term (>3 years). A one-time post-treatment risk stratification based on non-invasive criteria confers important prognostic information that is maintained during long-time follow-up, as the hazards over time remain proportional.

Introduction

Recent research from the Netherlands, the United States, and Korea suggests that individuals who receive a positive result on the fecal immunochemical test (FIT) may be at a higher risk of developing gastroesophageal cancer (GEC) within the following 36 months. However, the associations reported in these studies may be biased due to differences in age and sex between the FIT-positive and FIT-negative groups and other confounding factors.

Aims & Methods

We aimed to evaluate the association between FIT results and the risk of GEC in a matched cohort by age and sex. Additionally, we assessed the cost-effectiveness of a one-time Esophago-Gastro-Duodenoscopy (EGD) for individuals with positive FIT results.. We created a matched cohort of individuals aged 50 to 75 who underwent FIT testing at Clalit Health in Israel between June 2016 and June 2019. For each FIT-positive individual, we matched three FIT-negative individuals based on age, sex, and H. pylori status. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized to evaluate the association between a positive FIT result and the risk of GEC within 36 months. We calculated the incremental cost-effectiveness ratio (ICER) for a one-time EGD at $400 in individuals who tested positive for FIT. Screening is considered cost-effective if the ICER is below $50,000.

Results

The primary cohort included 483,710 individuals, while the matched cohort comprised 151,500 individuals (47.6% female, median age 62.5 years). During the follow-up period, 202 cases of GEC occurred: 0.2% (64/38,575) among FIT-positive individuals and 0.1% (138/112,925) among FIT-negative individuals, adjusted HR 1.39 (95% CI 1.03-1.87). Age, male sex, H. pylori exposure, country of birth, proton-pump inhibitor usage, smoking status, and anemia were all significantly associated with an increased risk of gastric cancer. A one-time EGD has been determined to be a cost-effective option in a range of ages and rates of localized disease at the time of EGD.

Conclusion

This matched cohort study suggests that individuals with a positive FIT may have an increased risk of GEC, which occurs at an overall rate of 0.2% within 36 months. A one-time EGD priced at $400 can be cost-effective in many scenarios.

Disclosure

NONE

Introduction

Lynch syndrome (LS) is a heritable autosomal dominant genetic condition caused by mutations in several DNA mismatch repair (MMR) genes, MLH1, MSH2, MSH6, PMS2 and EPCAM. Affected individuals have an increased life-long risk of developing cancers especially colorectal cancer (CRC) and endometrial cancer (EC). LS accounts for approximately up to 3% of all CRC. Traditionally, diagnosis was based on clinical criteria (Amsterdam II, Bethesda and revised Bethesda), which have proven to be of limited applicability in clinical practice. In recent years tumor testing via immunohistochemistry (IHC) of all CRCs for the expression of MMR proteins has successfully integrated into clinical care. Universal screening through IHC of CRC tumor samples is cost-effective and recommended by major guidelines, which also recommend its application to endometrial cancers.

Aims & Methods

Our aim was to assess the main differences between LS families where the first individual received a genetic diagnosis after IHC on tumor sample and LS families where the first individual received a genetic diagnosis due to meeting the Amsterdam II or revised Bethesda criteria. We obtained data (year of genetic test confirmation, first tumor diagnosis, family tree) of all our single center’s LS patients who undergo surveillance in our Institute (n = 101 patients). Accordingly, we grouped patients by family and identified each family’s index case-defined as the first individual to receive a genetic diagnosis - and relatives of index cases. Therefore, we divided the cohort into two groups: families whose the index case was identified after IHC on tumor sample and families whose the index case was identified due to meeting the Amsterdam II or revised Bethesda criteria. We subsequently evaluatedwhether patients identified through IHC would have also met the revised Bethesda or Amsterdam II criteria for genetic testing.

Results

We found that index cases identified through IHC (n =16; of which 8 on CRC tissue, 7 on EC tissue and 1 on lung cancer tissue) had a mean age of 57.93 years at the time of genetic diagnosis, whereas those identified through clinical criteria (n = 20) had a mean age of 46.35 years. As for the relatives, those whose index case was identified via IHC (n = 11) had a mean age of 45.72 years, while relatives of individuals diagnosed based on clinical criteria (n= 54) had a mean age of 37.96 years. Patients carrying pathogenic variants in MSH6 and PMS2 (leading to lower penetrance and a late onset of LS related cancers) were 8 out of 16 (50 %) in the IHC group and 1 out of 20 (5 %) in the clinical criteria group. Furthermore 8 out of 16 (50%) index patients diagnosed through IHC did not meet the Amsterdam II criteria.

Conclusion

The mean age of index cases diagnosed due to clinical criteria is lower than that of cases identified through IHC, probably because of the early onset of LS related cancers in these patients and since the clinical criteria require at least one case to be diagnosed at a young age (<50 years old). In contrast, universal immunohistochemistry (IHC) screening enables the detection of all patients with mismatch repair-deficient tumors, including those diagnosed later in life and those without an evident family history of cancer or carrying pathogenic variants in genes such as MSH6 and PMS2 with a lower penetrance. Our data strengthen the important role of IHC screening for MMR proteins loss of expression both in CRC and EC to find LS families that would not be possible to identify with clinical criteria only.