Introduction

HNF1A gene variants have been reported to be involved in developing mature onset diabetes mellitus (DM). Many studies reported the role of DM as a risk factor for hepatocellular carcinoma (HCC) development. To date, it has not been reported whether HNF1A gene variants are associated with the risk of DM in cirrhotic patients and their subsequent HCC.

Aims & Methods

Aim: To evaluate the HNF1A (the hepatocyte nuclear factor 1 homeobox A) genetic variants as a cofactor with DM for HCC development in HCV-infected patients.
Methods: This study was conducted on 140 subjects; 30 had HCC without DM, 30 HCC with DM, and 40 patients had DM with no HCV infection or had HCC; in addition, 80 healthy volunteers with matched ages and genders were enrolled in the study as a control group. Liver function tests, hepatitis viral markers, alpha-fetoprotein (AFP), fasting sugar and HBA1c and HNF1A (rs2464196 and rs1169310) using real-time polymerase chain reaction (PCR) were done for all participants.

Results

The frequency of HNF1A rs2464196 (AA) genotype in patient groups (DM, HCC, HCC+DM) was significantly higher compared to the control group (P=0.006, P=0.018, P<0.001respectively). The combined dominant model (AA + GA) of rs 2464196 was significantly higher than the (GG) genotype in patient groups (DM, HCC, HCC+DM) than the control group. In addition, the frequency of the AA genotype is more prevalent in HCC+DM (73%) compared to the group of DM or HCC patients. In contrast, the HNF1A rs 1169310 (TT, TC or CC genotypes) showed no significant difference among the four studied groups and their T or C allele distributions.

Table 1: Comparison between the studied groups according to HNF SNP2 (rs1169310) genotypes and allele frequencies

Conclusion

This finding suggested that the HNF1A rs2464196 (AA) genotype could be associated with DM and may raise the possibility of HCC development among HCV-infected patients who harbour this genotype more than (GG). On the contrary, the HNF1A rs 1169310 polymorphism was of no significance as a risk factor in the current study. Large scale studies are recommended on other variants of HNF1A to clarify the role of this gene in HCC development.

Introduction

HCC is the sixth most common malignancy worldwide and a major cause of death in patients with CLD and cirrhosis. it accounts for 90% of primary liver cancer.
it is important to detect patient with high risk to develop HCC. Liver fibrosis (LF) is a major risk factor regardless of its etiology.
Using of liver biopsy is limited by its invasiveness, poor acceptance, cost, intra and interobserver errors. TE for liver can rapidly measure liver stiffness and also can predict the absence or presence of significant fibrosis as well as advanced cirrhosis.

Aims & Methods

To assess the ability of TE for detection of LF and HCC in patients with CLD. we searched MEDLINE, Cochrane, EMBASE database until 2019, using the following search items: TE, fibroscan, HCC and hepatoma. Each title and abstract was reviewed to make sure it is relevant. The full text was studied if the abstract indicated that the paper reported HCC risk by fibroscan. sensitivity analysis and assessment of publication bias were performed.

Results

Forty-six studies were included, 18 studies evaluated the role of LSM in predicting HCC in CLDs patients, 6 studies evaluated the role of LSM in predicting hepatic decompensation, 1 study reported a composite outcome of HCC and hepatic decompensation, and 4 studies evaluated the role of LSM in predicting mortality.

Conclusion

HCC is associated with increased LS. Each unit increase in LSM was associated with an 11% higher risk of HCC. LSM may be a useful method to identify patients with CLD at risk for HCC.

Introduction

Transplantation techniques and immunosuppression treatments have been increasing notably in the past years, particularly when considering liver transplant (LT). LT is the preferred treatment for early-stage hepatocellular carcinoma (HCC). Despite the use of the Milan criteria, recurrence remains a major concern, with an estimated incidence ranging from 5% to 20%. Therefore, our objective is to assess potential risk factors, including clinical, laboratory and pathological parameters, as well as prognosis of HCC recurrence in LT recipients.

Aims & Methods

Retrospective evaluation of medical records from a Brazilian tertiary hospital, including adults who were submitted to LT due to HCC, during the period of 01/01/2002 up to 31/12/2021. Patients who had a LT for other causes, who presented a follow-up less than 1 year or with incidental detection of HCC in the liver explants were excluded. Data collection included demographic information, immunosuppressive treatments, clinical, radiological and histhopathological findings related to the HCC, as well as characteristics associated with the post-transplant follow-up and tumoral recurrence, including death. Primary outcome was recurrence of HCC, whereas secondary outcomes were survival and adopted treatments after cancer recurrence, as well as time elapsed until HCC recrudescence.

Results

150 patients were included (males 95 [63.3%], median age 60 years-old [IQR 56-66]), 130 (86.6%) were classified as Milan-in. The main cirrhosis etiologies were viral (88%) and metALD (10%). Half of patients presented an A CHILD score (50%) and a median MELDNa score of 12 (IQR 9-14). Main locoregional therapies included transarterial chemoembolization (TACE) and percutaneous ethanol injection (PEI), accounting for 48 (32%) and 45 (30%) respectively. 47 (31.33%) patients underwent two or more locoregional therapy modalities, and downstaging was achieved in 20 patients (13.3%). Explant analysis with microvascular invasion and Milan-out were detected in 18 (12%) and 30 (20.1%) individuals, respectively. HCC recurrence occurred in 21/150 patients (14%), while non-HCC neoplasias in 27/150 (18.1%) after LT. The median time to recurrence was 30 months (IQR 20-43), and systemic therapy to HCC with sorafenib was used in 12/21 patients (57.14%). Among those who presented recurrence, 19/21 died (90.4%), and prognosis after recurrence was dismal (median survival of 14.5 months, IQR 3.25-33.5). Evaluation of possible associations between HCC recurrence and clinical, laboratorial, imaging and histopathological parameters was performed, but none showed impact on HCC recurrence after LT. However, there was a trend to an association between recurrence and CHILD score (p = 0.06) and smoking (p = 0.08). Also, when evaluating patients who presented early recurrence (less than 24 months after LT), a trend of an association with the number of involved liver segments was found (p = 0.07).

Conclusion

Identifying patients at risk of HCC recurrence after LT remains as a great challenge. There are some parameters previously suggested as possible predictors, but, in accordance to literature findings, our study didn't identify significant associations. Nonetheless, the possible association between early recurrence and the number of affected liver segments hasn't been studied yet, and this is the first study that suggests an association. Thus, evaluating the number of liver segments affected by HCC might help physicians to identify patients with higher risk of recurrence, as well as giving another possible parameter to investigate in further studies.

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common cancer in incidence and the third in mortality worldwide. Its incidence is variable worldwide. Seventy-two percent of cases occur in Asia. It is more common in males. Alpha-Feto protein is negative in only 30% of patients with HCC. 60-months survival of HCC ranges from 70% (for early stages) to 20% (for advanced stages). The overall median survival of metastatic HCC is 11 months. Patients with negative AFP usually have better survival than those with positive AFP. The effect of AFP negativity on metastatic HCC survival duration and the factors affecting survival of this subgroup of patients is not well studied.

Aims & Methods

This study aims to identify the factors affecting the overall survival of patients with AFP negative metastatic HCC and their survival duration. A total of 1146 patients with AFP-negative metastatic HCC diagnosed between 1975 to 2020 were extracted from the U.S. Surveillance, Epidemiology and End-results (SEER) program databases. Univariable and Multivariable Cox regression were performed, associated hazards ratio (HR) and Kaplan Meier curves/statistics were generated for overall survival analysis.

Results

Most patients were males (78.8%). Their mean age was 65.6. Most patients were of white race (74.9%) and of non-Spanish-Hispainc-Latino origin (79.8%). Most patients lived in metropolitan areas (87.6%) and earned $75,000+ (37.3%). Most patients were married (48.1%). The mean tumor size was 9.93 cm with 75.1% > 2cm in size. Most patients had T0/T1 stage (41.1%) followed by T3 (32.7%). Most patients had N0/Nx stage (72.7%). Most patients didn’t receive chemotherapy (62.1%).
The median survival of the cohort was 5 months (95% confidence interval: 5-6 months). The survival of the cohort was 99%, 28.3%, 8.5%, 3.8% at 1,12, 36 and 60 months respectively. Univariable Cox regression was statistically significant for age (HR 1.01), grade III (HR 1.55), grade IV (2.75), receiving chemotherapy (HR 0.48), black race (HR 0.80). Univariable Cox regression was non-statistically significant for sex, T stage, N stage, origin, rurality, marital status. Grade wasn’t included in multivariable cox regression due to missing data (71.9%). Multivariable cox regression model was only statistically significant for receiving chemotherapy (HR 0.49).

Conclusion

The overall survival of AFP-negative metastatic HCC is very poor. Chemotherapy may be associated with better survival. However, the chemotherapy variable in SEER is limited by data incompleteness and possible unmeasured causes for receiving or not receiving chemotherapy. It is unclear if patients with negative AFP metastatic HCC survive longer than those with positive AFP metastatic HCC. More studies are needed to study the effect of different biomarkers on the survival of HCC patients.

References

McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021;73 Suppl 1(Suppl 1):4-13. doi:10.1002/hep.31288

Introduction

Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide, affecting more than 65% of patients with Type 2 Diabetes Mellitus (T2DM). The aim of our study was to determine the prevalence of MASLD among T2DM patients, with or without coexisting significant fibrosis, to assess its association with diabetic complications, and to identify the factors linked to MASLD in our population.

Aims & Methods

We conducted a retrospective, descriptive, and analytical study including T2DM patients admitted to the Endocrinology Department in 2019. MASLD diagnosis was based on the presence of hepatic steatosis detected by abdominal ultrasound or a Hepatic Steatosis Index (HSI) >36. Fibrosis was assessed using the Fibrosis-4 (FIB-4) index (with a threshold of ≥1.3 or <1.3). Chronic Kidney Disease (CKD) associated with T2DM was defined by an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² and/or dipstick-positive proteinuria (>1+). Diabetic Peripheral Neuropathic Pain (DPNP) was assessed using the Douleur Neuropathique 4 (DN4) questionnaire, and Diabetic Retinopathy was diagnosed via dilated eye examination.

Results

Among the 202 patients included, the median age was 57 years (±12 years) with a marked female predominance (sex ratio = 2.6). Regarding comorbidities, 58.4% of patients had hypertension and 34.2% had dyslipidemia. The median Body Mass Index (BMI) was 27 kg/m² (±5.62), with overweight or obesity present in 61.4% of the cohort. The median duration of diabetes was 10 years (±7.8 years). Impaired renal function (eGFR <60 ml/min/1.73 m²) was found in 9.9% of patients, and proteinuria in 6.9%. Diabetic neuropathy (DN4 score ≥4) was present in 7.9% of patients, while diabetic retinopathy was diagnosed in 37.6% of cases.
The prevalence of MASLD in our cohort was 73.3%. The median FIB-4 score was 0.91 (±0.63), with 25.7% of patients presenting a FIB-4 >1.3. Statistical analysis identified several factors significantly associated with the presence of MASLD: female sex (p=0.004), dyslipidemia (p=0.004), BMI (p<0.001), alanine aminotransferase (ALT) levels (p<0.001), low-density lipoprotein cholesterol (LDL-C) levels (p=0.006), and triglyceride levels (p=0.013). In particular, higher BMI was strongly associated with MASLD (Odds Ratio [OR] = 1.970; 95% Confidence Interval [CI]: 1.580–2.460; p<0.001), as were elevated ALT levels (OR = 1.115; 95% CI: 1.053–1.18; p<0.001).
However, after adjustment, LDL-C levels (p=0.163), triglycerides (p=0.402), dyslipidemia (p=0.329), and sex (p=0.360) were no longer significantly associated with MASLD. Finally, a significantly higher proportion of CKD was observed in patients with MASLD (22.3%) compared to those without MASLD (9.2%, p=0.036), although this association was not maintained in the subgroup with advanced fibrosis (FIB-4 >1.3).

Conclusion

Our study confirmed the high prevalence of MASLD among patients with T2DM. Early screening is therefore essential, particularly in female patients and in those presenting with chronic kidney disease or other associated cardiometabolic risk factors such as obesity and dyslipidemia.

References

Younossi ZM, Golabi P, Price JK, Owrangi S, Gundu-Rao N, Satchi R, Paik JM. The Global Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among Patients With Type 2 Diabetes. Clin Gastroenterol Hepatol. 2024 Oct;22(10):1999-2010.e8. doi: 10.1016/j.cgh.2024.03.006. Epub 2024 Mar 21. PMID: 38521116.

Introduction

Several studies have suggested a possible association between hepatic steatosis and colonic adenomas, positioning hepatic steatosis on the list of potential risk factors.

Aims & Methods

Our study aims to investigate the relationship between hepatic steatosis and the development of colonic adenomas. This is an observational study, with both a retrospective and a prospective arm, spamming from 2017 till 2023. Selected patients are those who underwent a Fibroscan and a colonoscopy during the same year. We collected demographic data, medical history, medication intake, and results of both Fibroscan and colonoscopy. Our population was divided in two: population A with a Controlled Attenuation Parameter (CAP)<258 and population B with a CAP³258. The main outcome was the presence of adenomas on colonoscopy.

Results

In total, our analysis included 232 patients. A ROC curve was obtained, determining that a CAP³258 was associated with the presence of adenomas on a colonoscopy with an AUC of 0.630 with a sensitivity and specificity of 65% and 64% respectively. From these 232, 125 patients had a CAP≥258 (53.8%) and 107 patients had a CAP<258 (46.2%). Patients with a CAP³258 more frequently exhibited: hypertension (54% vs 35.7%, p=0.016), diabetes (36% vs 10.7%, p<0.001), and dyslipidemia (70.6% vs 29.8%, p<0.001) compared to those with a CAP<258. The BMI was higher (29.2 vs 26.7, p=0.001) in the group (CAP³258). Finally, adenomas were more frequent (46.4% vs 33.6%, p=0.025) in this same group.
A multivariate analysis was done. The presence of CAP³258 (OR 2.58, p=0.017), diabetes (OR=3.71, p=0.02), and older age (OR=1.04, p=0.017) are associated with the presence of adenomas on colonoscopy.

Conclusion

Hepatic steatosis is independently associated with the presence of adenomas with an OR of 2.58. Therefore, early screening for colorectal cancer might be warranted in patients with hepatic steatosis. Further studies are required to establish hepatic steatosis as a risk factor of colonic adenomas.