Outcomes of immune checkpoint inhibitor‐induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team

Outcomes of immune checkpoint inhibitor-induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team

This study demonstrated a hepatologist consultation system in an immune-related adverse events-focused multidisciplinary toxicity team significantly increases the rate of consultation to hepatologists from the primary physician across the department and accelerates the improvement of liver toxicity. The evaluation of liver toxicity by a hepatologist can assist in identifying severe immune checkpoint inhibitor-induced liver toxicity, such as immune-related cholangitis, and in establishing appropriate treatment strategies.


Abstract

Aim

To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity.

Methods

To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023).

Results

The median follow-up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n = 22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period.

Conclusion

A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity.

Epidemiological assessment of hepatitis E virus infection among 1565 pregnant women in Siem Reap, Cambodia using an in‐house double antigen sandwich ELISA

Abstract

Aim

This study investigated hepatitis E virus (HEV) prevalence among pregnant women in Siem Reap, Cambodia, by developing a cost-effective, user-friendly in-house enzyme-linked immunosorbent assay (ELISA) for detecting total anti-HEV immunoglobulins (Ig).

Methods

The in-house ELISA was designed for large-scale screening in resource-limited settings. Its performance was benchmarked against two commercial tests: the Anti-HEV IgG EIA (Institute of Immunology, Co. Ltd) and the Anti-HEV IgG RecomLine LIA (Mikrogen). The in-house ELISA demonstrated a sensitivity of 76% and 71.4%, and a specificity of 94.1% and 98.6%, against the two commercial tests, respectively, with overall agreement rates of 92.4% and 94.3%.

Results

Among 1565 tested pregnant women, 11.6% were anti-HEV positive. Prevalence increased with age, particularly in women aged 35–40 years and over 40 years. No significant associations were found with education, number of children, family size, or history of blood transfusion and surgery, except for the occupation of the family head as a public officer. Of the total anti-HEV positive women, 22.7% had anti-HEV IgM, indicating recent or ongoing infection.

Conclusion

The study concluded that the in-house ELISA is a viable option for HEV screening in regions with limited resources due to its high accuracy and cost-effectiveness. It is particularly suitable for large-scale studies and public health interventions in areas where HEV is endemic and poses a significant risk to pregnant women.

A new criterion including the aspartate aminotransferase‐to‐platelet ratio index and liver and spleen stiffness to rule out varices needing treatment in children with biliary atresia: Modification of the Baveno VII criteria

A new criterion including the aspartate aminotransferase-to-platelet ratio index and liver and spleen stiffness to rule out varices needing treatment in children with biliary atresia: Modification of the Baveno VII criteria

The usefulness of the Baveno VII criteria to exclude varices needing treatment (VNT) in the pediatric population has not been evaluated. Using the Baveno VII criteria with platelet count, liver stiffness, and splenic stiffness, about 20% of VNT were missed, indicating poor diagnostic accuracy. Endoscopy for the screening of VNT can be omitted in children and adolescents with biliary atresia who meet our new criteria using AST-to-platelet ratio, and liver and spleen stiffness.


Abstract

Aims

Biliary atresia (BA) is a congestive biliary disease that develops in the neonatal period or early infancy. It may present with portal hypertension and varices needing treatment (VNT) even after successful Kasai portoenterostomy. This study aimed to stratify the risk of VNT in children and adolescents with BA.

Methods

In this prospective cross-sectional study, we measured liver stiffness (LS) and spleen stiffness (SS) by two-dimensional shear wave elastography and checked for VNT endoscopically in 53 patients with BA who attended for follow-up between July 2018 and September 2022. Varices needing treatment were defined as large esophageal varices, esophageal varices of any size with red color signs, and/or gastric varices along the cardia.

Results

Twenty-five patients (aged 0–18 years) had VNT. Eighteen patients met the Baveno VI criteria (LS <20 kPa; platelet count >150 000/L) and were deemed to be at low risk of VNT (spared endoscopies) while three had missed VNT (16.7%). Applying the Baveno VII criteria, which combines the SS cut-off value of 40 kPa with the Baveno VI criteria, resulted in five missed VNTs among 22 spared endoscopies (22.7%). A modification of the Baveno VII criteria using the aspartate aminotransferase-to-platelet ratio index (APRI) instead of the platelet count with cut-off values of 25 kPa, 30 kPa, and 1.04 for LS, SS, and APRI, respectively, missed only one VNT (5.0%) among 20 spared endoscopies.

Conclusions

A novel diagnostic criterion that combines LS, SS, and APRI reduced the risk of missing VNT to 5% in children and adolescents with BA.

Impact of post‐progression survival in second‐line treatment with molecular target agents for unresectable hepatocellular carcinoma

Abstract

Aim

Sequential therapies are essential to extend overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). Several second-line treatments with molecular target agents have shown survival benefits. However, the significance of post-progression survival (PPS) in extending OS in patients with HCC given such treatments remains uncertain.

Methods

Through a systematic review of the literature in the PubMed database, this study investigated the correlation between PPS and OS and that between progression-free survival (PFS) and OS in patients with HCC given second-line treatments.

Results

In total, 3935 patients who had received second-line treatment with regorafenib, ramucirumab, or cabozantinib, which are approved molecular target agents, were identified. In the patients treated with regorafenib, PPS showed a strong correlation with OS (R 2 = 0.729, R = 0.854, p < 0.001) whereas PFS showed a weak correlation (R 2 = 0.218, R = 0.467, p = 0.021). In the patients treated with ramucirumab, PPS showed a strong correlation with OS (R 2 = 0.800, R = 0.894, p = 0.016) whereas PFS showed a negligible correlation (R 2 = 0.020, R = 0.140, p = 0.791). In the patients treated with cabozantinib, PPS showed a strong correlation with OS (R 2 = 0.856, R = 0.925, p = 0.003) as did PFS (R 2 = 0.946, R = 0.973, p < 0.001).

Conclusions

PPS plays a more significant role than PFS in extending OS in patients given second-line treatment for unresectable HCC. Sequential therapies after disease progression in second-line treatment are essential to acquire good OS. Maintenance of hepatic reserve function and the patient's general condition is essential during systemic treatments for unresectable HCC.

Liver abscess after drug‐eluting bead transarterial chemoembolization for hepatic malignant tumors: Clinical features, pathogenesis, and management

Abstract

Aim

The study aimed to investigate the clinical features, incidence, pathogenesis, and management of liver abscess after drug-eluting bead transarterial chemoembolization (DEB-TACE) for primary and metastatic hepatic malignant tumors.

Methods

From June 2019 to June 2021, patients with liver abscess after DEB-TACE for primary and metastatic hepatic malignant tumors were reviewed and evaluated at our hospital. Demographic and clinical data, radiological findings, management approaches, and prognosis were retrospectively analyzed.

Results

In total, 419 DEB-TACE procedures were carried out in 314 patients with primary and metastatic liver tumors at our medical center. Twelve patients were confirmed to have liver abscesses after DEB-TACE through clinical manifestations, laboratory investigations, and imaging. In this study, the incidence of liver abscess was 3.82% per patient and 2.86% per DEB-TACE procedure. After percutaneous drainage and anti-inflammatory treatments, 10 patients recovered, and the remaining 2 patients died due to direct complications of liver abscess, such as sepsis and multiple organ failure. The mortality rate of liver abscesses after DEB-TACE was 16.7% (2/12).

Conclusion

The incidence of liver abscess after DEB-TACE is relatively high and can have serious consequences, including death. Potential risk factors could include large tumor size, history of bile duct or tumor resection, history of diabetes, small DEB size (100–300 μm). Sensitive antibiotics therapy and percutaneous abscess aspiration/drainage are effective treatments for liver abscess after DEB-TACE.

Effects of weight loss on metabolic dysfunction‐associated fatty liver disease in Japanese people: Non‐alcoholic fatty liver disease in the Gifu area, longitudinal analysis study

Effects of weight loss on metabolic dysfunction-associated fatty liver disease in Japanese people: Non-alcoholic fatty liver disease in the Gifu area, longitudinal analysis study

Patients with non-alcoholic fatty liver disease could achieve remission with weight loss, although the link between weight loss and metabolic dysfunction-associated fatty liver disease (MAFLD) remission is unclear. Our study shows that weight loss is associated with MAFLD remission regardless of the type of metabolic dysfunction in MAFLD. The cutoff values for MAFLD remission were a loss of 1.9 kg, 3.0 kg, 1.9 kg, and 0.8 kg for all participants, participants with type diabetes, overweight participants, and non-overweight patients with metabolic dysfunctions, respectively.


Abstract

Aim

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major health concern. This cohort study aimed to evaluate the association between weight loss and remission of MAFLD in the Japanese population to aid the development of efficient treatment strategies.

Methods

This retrospective cohort study was conducted at a Japanese health screening center. Participants included 3309 individuals diagnosed with baseline MAFLD between 2004 and 2016. Logistic regression analysis was used to assess the association between MAFLD remission from baseline to 5 years and weight change.

Results

After 5 years, 671 participants achieved MAFLD remission. Weight loss was associated with MAFLD remission for every 1 kg of weight loss over 5 years; the odds ratio for MAFLD remission was 1.24 (95% CI 1.15–1.34) for participants with type 2 diabetes, 1.40 (95% CI 1.35–1.45) for overweight participants, and 1.51 (95% CI 1.33–1.72) for non-overweight participants with metabolic dysfunctions. The cutoff values for weight loss for MAFLD remission were 1.9 kg for all participants, 3.0 kg for participants with type 2 diabetes, 1.9 kg for overweight participants, and 0.8 kg for non-overweight participants with metabolic dysfunctions.

Conclusions

Among participants diagnosed with MAFLD, weight loss was associated with MAFLD remission regardless of the type of metabolic dysfunction in MAFLD. The results of this study may contribute to the development of novel approaches to achieve MAFLD remission.

Metabolic management after sustained virologic response in elderly patients with hepatitis C virus: A multicenter study

Metabolic management after sustained virologic response in elderly patients with hepatitis C virus: A multicenter study

Metabolic dysfunction-associated steatotic liver disease at 24 weeks of sustained virological response is a risk factor for hepatocellular carcinoma development in elderly patients with hepatitis C virus eradication. No significant difference was observed in the cumulative incidence of hepatocellular carcinoma between patients with alpha-fetoprotein ≥7 ng/mL and patients with alpha-fetoprotein <7 ng/mL and metabolic dysfunction-associated steatotic liver disease.


Abstract

Aims

Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct-acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication.

Methods

We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α-fetoprotein (AFP), Fibrosis-4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication.

Results

A total of 86 patients (6.7%) developed HCC during the follow-up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04–1.11, P = 0.0008), Fibrosis-4 index (HR 1.17, CI 1.08–1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40–6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis-4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD.

Conclusion

MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL.