Impact of metabolic dysfunction‐associated fatty liver disease on the incidence of Helicobacter pylori‐negative gastric cancer

Posted on 20 January 2024 by

Metabolic dysfunction-associated fatty liver disease (MAFLD) was an independent risk factor for Helicobacter pylori-negative gastric cancer (HPNGC), along with age and smoking. Data mining analyses identified MAFLD as the most influential independent factor associated with HPNGC.

Abstract

Aim

The incidence of Helicobacter pylori-negative gastric cancer (HPNGC) is increasing worldwide. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been reported to be associated with various cancers, but its association with HPNGC has not been reported. We aimed to identify important independent factors associated with HPNGC, including MAFLD.

Methods

This multicenter observational cohort study enrolled patients with gastric cancer (n = 1078) and health checkup examinees (n = 17 408). We analyzed patients with HPNGC (n = 26) and healthy participants with no H. pylori infection or any abnormal findings on upper gastrointestinal endoscopy (n = 1130). A logistic regression model was used to identify independent factors associated with HPNGC. The priority of the factors associated with HPNGC was evaluated using a decision-tree algorithm and random forest analysis.

Results

Among all patients with gastric cancer, 2.4% (26/1078) were diagnosed with HPNGC (mean age, 64 years; male/female, 13/13). In the logistic regression analysis, age, smoking, and MAFLD (odds ratio, 6.5359; 95% confidence interval, 2.5451–16.7841; p < 0.0001) were identified as independent factors associated with HPNGC. Metabolic dysfunction-associated fatty liver disease was also identified as the most important classifier for the presence of HPNGC in decision-tree analyses. Helicobacter pylori-negative gastric cancer was observed in 5.2% of patients with MAFLD and 0.8% of patients without MAFLD. In the random forest analysis of the HPNGC, MAFLD was identified as the distinguishing factor with the highest variable importance (0.32).

Conclusions

Metabolic dysfunction-associated fatty liver disease was the most influential independent factor associated with HPNGC. These findings suggest that fatty liver and metabolic dysfunction could be involved in the pathogenesis of HPNGC.

Development and validation of a prognostic model for 90‐day survival in patients with alcohol‐associated cirrhosis and acute decompensation

Posted on 19 January 2024 by

We established a nomogram to identify the 90-day mortality risk of alcoholic cirrhosis and acute decompensation and validated the model's high reliability and better diagnostic performance in both cohorts.

Abstract

Background/purpose

Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression.

Methods

We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90-day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C-index, area under the receiver operating curve, calibration curve, and decision curve analysis.

Results

Total bilirubin >10 upper limit of normal, high-density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90-day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C-index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high- and low-risk groups. Mortality was significantly higher in the high-risk group than in the low-risk group (p < 0.0001).

Conclusion

The nomogram could accurately predict the 90-day mortality risk in patients with alcohol-associated cirrhosis and acute decompensation, helping to identify high-risk patients and personalize treatment at their first admission.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real‐world study

Posted on 19 January 2024 by

Hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) showed considerable antitumor effects and low systemic toxicity in hepatocellular carcinoma (HCC) patients after systemic treatment failure. HAIC-FOLFOX treatment potentially could serve as second-line therapy for treating HCC patients who failed systemic treatments, even in patients with Child–Pugh B liver function.

Abstract

Aim

The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents.

Methods

Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed.

Results

The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1–12.9) and 6.0 months (95% CI, 5.1–6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin–bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05–2.34; p = 0.028), tumor number (>3 vs. 1–3, HR 2.18; 95% CI, 1.10–4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06–2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37–0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17–0.53; p < 0.001). Grade 3–4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed.

Conclusions

Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Concordance between metabolic dysfunction‐associated steatotic liver disease and nonalcoholic fatty liver disease

Posted on 17 January 2024 by

The concordance rate between nonalcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease in Japanese patients was 96.7% using the original waist circumference criteria and 96.2% using the Japanese metabolic syndrome criteria. Therefore, NAFLD could be considered MASLD using the original MASLD criteria, and insights from NAFLD research could be applied to MASLD.

Abstract

Aim

A multisociety consensus group proposed a new nomenclature for metabolic dysfunction-associated steatotic liver disease (MASLD). Although patients with nonalcoholic fatty liver disease (NAFLD) are expected to be reclassified as patients with MASLD under the new nomenclature, the concordance between MASLD and NAFLD remains unclear. Moreover, waist circumference could be adjusted by ethnicity for diagnosing MASLD; however, there are limited data on the optimal waist circumference in the Japanese population.

Methods

This cross-sectional study was conducted on 3709 Japanese patients with NAFLD. The primary endpoint was the prevalence of MASLD in patients with NAFLD. The difference between the original waist circumference criteria (>94 cm for men and >80 cm for women) and the Japanese metabolic syndrome criteria (≥85 cm for men and ≥90 cm for women) for concordance between NAFLD and MASLD was also investigated.

Results

According to the original criteria, the prevalence of MASLD in patients with NAFLD was 96.7%. Similarly, according to the Japanese waist circumference criteria, 96.2% of patients with NAFLD could be reclassified as those with MASLD. The concordance rate was significantly higher in the original criteria than in the Japanese criteria (p = 0.02).

Conclusions

NAFLD could be considered MASLD using the original MASLD criteria in the Japanese population, and insights from NAFLD research could be applied to MASLD.

Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease

Posted on 16 January 2024 by

The analysis of peripheral memory T lymphocyte frequencies can noninvasively sensitively detect nonalcoholic fatty liver disease (NAFLD) severity in addition to existing biomarkers. We should focus on CD8⁺ terminally differentiated effector memory T cells as a predictor of severe fibrosis and also on CD8⁺ effector memory T cells, and CD4⁺ and Th17 central memory T cells as indicators of the pathological progression of NAFLD.

Abstract

Aim

Differential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers.

Methods

We assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7⁺ CD45RA⁺ naïve T, CCR7⁺ CD45RA^– central memory T cells (TCM), CCR7^– CD45RA^– effector memory T, and CCR7^– CD45RA⁺ terminally differentiated effector memory T (TEMRA) cells in CD4⁺ and CD8⁺ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS).

Results

Several significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8⁺ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4⁺ TCM: lobular inflammation, and CD8⁺ TEMRA and effector memory T cells: hepatocellular ballooning).

Conclusions

Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD.

Prognostic significance of C‐reactive protein in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab

Posted on 11 January 2024 by

CRP levels ≥1 mg/dL were associated with higher baseline ALBI score and AFP levels, lower disease control rate, and shorter overall survival in patients (n = 213) who received atezolizumab plus bevacizumab for advanced HCC. This study highlighted the importance of considering the treatment line when evaluating CRP as a prognostic factor.

Abstract

Aim

C-reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC).

Methods

A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C-reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score.

Results

Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin–bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313–5.107; log-rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin–bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1-year survival prediction after first-line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively.

Conclusions

CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy.

The change in Fibrosis‐4 index in Japanese patients with type 2 diabetes treated by a fixed‐ratio combination therapy of insulin degludec and liraglutide: A retrospective observational study

Posted on 9 January 2024 by

The efficacy of a combination preparation of insulin degludec and liraglutide in patients with type 2 diabetes, focusing particularly on the change in the FIB-4, was investigated. Fixed-ratio combination therapy using insulin degludec and liraglutide is useful for liver protection, improving blood glucose levels, and preventing an increase in bodyweight.

Abstract

Aim

The efficacy of titratable fixed-ratio combination therapy by a combination preparation of insulin degludec and liraglutide (IDegLira) in Japanese patients with type 2 diabetes, focusing particularly on the change in Fibrosis-4 index (FIB-4), a noninvasive method for the evaluation of liver fibrosis, was investigated.

Methods

As the full analysis set, 113 patients were treated with IDegLira. The patients were categorized into two groups according to the absence (GLP-1RA-naïve group, n = 72) or presence (GLP-1RA-treated group, n = 41) of glucagon-like peptide-1 receptor agonist (GLP-1RA) use before starting IDegLira. The clinical parameters were retrospectively determined over 6 months.

Results

The glycated hemoglobin value was significantly reduced in both groups. The bodyweight significantly decreased from 67.4 ± 11.0 kg at baseline to 66.4 ± 11.6 kg at 6 months in the GLP-1RA-naïve group, although it slightly increased in the GLP-1RA-treated group. FIB-4 significantly decreased from 1.60 ± 0.84 at baseline to 1.49 ± 0.74 at 6 months in the GLP-1RA-naïve group. Although FIB-4 significantly increased in the GLP-1RA-treated group, it remained within the low-risk level for liver fibrosis.

Conclusion

Fixed-ratio combination therapy using IDegLira for the treatment of type 2 diabetes is useful for glycemic control and weight management. In particular, IDegLira may be more effective for lowering FIB-4 than adding unused oral antidiabetic agents or increasing the dose of insulin in GLP-1RA-naïve patients.

A new imaging classification for safer radial access visceral intervention of the liver and optimal case selection: A preliminary report

Posted on 8 January 2024 by

This study reported a new classification for a safer transradial approach during hepatic interventional radiology, based on preoperative evaluation of the location of the left subclavian artery bifurcation in the aortic arch. From the anatomical characteristics and the direction of blood flow, this classification may be useful for preventing procedure-related cerebral complications.

Abstract

Aim

The aim of this study was to evaluate the use of a new classification for safer transradial access hepatic interventional radiology, based on preoperative evaluation of the location of the left subclavian artery bifurcation in the aortic arch.

Methods

A total of 38 consecutive patients with hepatocellular carcinoma and 74 sessions of radial access for visceral intervention (R.A.V.I.) were reviewed. We classified the location of the left subclavian artery bifurcation in the aortic arch in three areas using an oblique view computed tomography image matched with the curve of the aortic arches according to a new criteria Three Areas Criteria For R.A.V.I. (named “TAC-F-R”), and measured the required time from initial left radial artery arteriography to celiac artery or superior mesenteric artery arteriography.

Results

The median time required for left radial artery arteriography to the celiac artery or superior mesenteric artery arteriography in each of the three areas were: area A, 0:11:10 (h, min, s); area B, 0:14:44; and area C, 0:31:51. There were significant differences between each area after Bonferroni correction (p < 0.01; A vs. B, p = 0.086; A vs. C, p = 0.001; and B vs. C, p = 0.045), with areas A and B requiring a significantly shorter time. Finally, no patients showed neurogenic disfunction within 1 week after the R.A.V.I. procedure.

Conclusions

The new classification, “TAC-F-R,” for safer transradial access hepatic interventional radiology is effective for avoiding difficult cases, and selects more suitable patients with hepatocellular carcinoma for the R.A.V.I. procedure.

Potential role of Fibrosis‐4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study

Posted on 6 January 2024 by

More than 21% of hepatocellular carcinoma cases were identified in patients with cardiometabolic risk factors with or without hepatic steatosis on ultrasound. However, screening for hepatocellular carcinoma in individuals without cirrhosis or viral hepatitis has limited effectiveness and may lead to unnecessary tests. The Fibrosis-4 score, a non-invasive index, may have a potential role in hepatocellular carcinoma screening by identifying high-risk groups with metabolic risk factors or hepatic steatosis.

Abstract

Aim

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD.

Methods

Korean adults (n = 340 825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods.

Results

In 93 HCC cases, 71 were identified in G4, whereas 20 cases (21.5%) in G2 and G3 combined where ultrasound and Fibrosis-4 performed similarly to alpha-fetoprotein and ultrasound. In G2, Fibrosis-4 and ultrasound had the highest area under the receiver operating characteristic curve (0.93 [0.87–0.99]), whereas in G3, the combined screening methods had the highest area under the receiver operating characteristic curve (0.98 [0.95–1.00]). The positive predictive value was lower in G2 and G3 than in G4, but was >5% when restricted to a high Fibrosis-4 score.

Conclusions

More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the Fibrosis-4 score in identifying individuals at high risk of HCC.

A case of A20 haploinsufficiency complicated by autoimmune hepatitis

Posted on 6 January 2024 by

Abstract

Aim

A20 haploinsufficiency (HA20) is a recently described autoinflammatory disease that manifests symptoms similar to those of Behçet's disease. However, little is known about the involvement of the liver in HA20. Here, we report a case of HA20 complicated by autoimmune hepatitis (AIH).

Case presentation

A 33-year-old woman was previously diagnosed with HA20 and chronic thyroiditis, and was treated with prednisolone (PSL; 7.5 mg/day) and levothyroxine sodium hydrate (125 μg/day). She experienced general malaise and jaundice, and biochemical evaluation revealed elevated liver function with an aspartate aminotransferase level of 817 U/L, an alanine aminotransferase level of 833 U/L, and a total bilirubin of 8.3 mg/dL. Pathological evaluation of the liver biopsy revealed interface hepatitis and the patient was diagnosed with acute exacerbation of AIH. Upon increasing the PSL dose to 60 mg/day, the liver enzyme levels rapidly decreased. During tapering of PSL, azathioprine 50 mg/day was added, and there was no relapse of AIH with combination therapy of PSL 7 mg/day and azathioprine 50 mg/day.

Conclusion

This is the first report of biopsy-proven AIH in an Asian patient with HA20. This case has significant implications for the pathogenesis and treatment of AIH in patients with HA20.