Our study investigated whether switching to tenofovir alafenamide affects hepatocellular carcinoma recurrence in patients previously treated with tenofovir disoproxil fumarate or entecavir. Comprehensive analyses indicate that switching to tenofovir alafenamide does not increase the risk of hepatocellular carcinoma recurrence, making it a suitable option due to its fewer side-effects and lower potential for resistance development compared with other nucleos(t)ide analogs.

Abstract

Aim

Antiviral treatment reduces the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. However, there is a lack of high-quality evidence regarding the preventive effects of tenofovir alafenamide (TAF) on HCC. We evaluated the impact of TAF use after curative treatment on HCC recurrence.

Methods

Patients who underwent surgery or radiofrequency ablation as a curative treatment for HCC were selected. Those patients who continued antiviral treatment with nucleos(t)ide analogs (NAs; entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) or switched to TAF were included. The primary outcome was HCC recurrence, and the time-varying effect of NA use on HCC recurrence was analyzed using various statistical methods.

Results

Among 2794 consecutive patients with chronic hepatitis B who received curative treatment for HCC, 199 subsequently switched from ETV or TDF to TAF. After a median of 3.0 years, 1303 patients (46.6%) experienced HCC recurrence. After propensity score matching (ratio 1:10), switching to TAF was not associated with an increased HCC recurrence (HR 1.00, 95% CI 0.68–1.47; p = 1.00) by time-varying Cox analysis. Switching to TAF was not associated with HCC recurrence in subgroups of NA (HR 1.06, 95% CI 0.67–1.67; p = 0.81 for TDF, and HR 1.09, 95% CI 0.51–2.33; p = 0.82 for ETV). Kaplan–Meier analysis showed comparable HCC recurrence-free survival between patients who switched to TAF and those who continued with their NA (p = 0.08). Time-varying Cox analyses in various subgroups confirmed the primary findings.

Conclusions

TAF is as effective as TDF and ETV in preventing HCC recurrence after curative treatment.

Among 528 Japanese patients with intractable hepatobiliary diseases (220 AIH, 251 PBC, 6 AIH–PBC/PSC overlap, 39 PSC, 4 BCS, 5 IPH, and 3 EHO) who received SARS-CoV-2 vaccines, post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

Abstract

Aim

There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease.

Methods

Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd–Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected.

Results

The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH– primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd–Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination.

Conclusion

SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

This study aimed to investigate independent factors and profiles associated with significant hepatic fibrosis, including alanine aminotransferase (ALT) levels >30 U/L in health check-up examinees. Of the patients aged ≥65 years, 35% had significant hepatic fibrosis, moreover, of the patients aged ≥65 years with ALT levels >30 U/L, 52% had significant hepatic fibrosis. ALT levels >30 U/L may be involved in the pathogenesis of significant hepatic fibrosis in patients ≥65 years.

Abstract

Aim

In patients with steatotic liver disease (SLD), significant hepatic fibrosis is a prognostic factor with various etiologies, including inflammation and metabolic dysfunction. This study aimed to investigate independent factors and profiles associated with significant hepatic fibrosis, including alanine aminotransferase (ALT) levels >30 U/L and metabolic dysfunction-associated SLD (MASLD), in health check-up examinees.

Methods

This single-center, retrospective, observational cohort study enrolled 1378 consecutive health checkup examinees from April 2018 to September 2022. Shear wave elastography (SWE) was performed during a routine ultrasound examination, and patients with liver stiffness ≥6.60 kPa were defined as having significant hepatic fibrosis. Patients were classified into nonsignificant hepatic fibrosis (n = 1220) or a significant hepatic fibrosis (n = 158) group according to this definition.

Results

In multivariate analysis, the independent factor for significant hepatic fibrosis was aging (≥65 years; OR 9.637, 95% CI 6.704–13.852, p < 0.0001). According to decision tree analysis, the initial classifier was aging (≥65 years). After aging, an ALT level >30 U/L was the second relevant factor for significant hepatic fibrosis, regardless of age. An undirected graphical model showed that an ALT level of >30 U/L was directly associated with significant hepatic fibrosis. In patients aged ≥65 years with an ALT level >30 U/L, significant hepatic fibrosis was observed in 52% of the patients. Meanwhile, in patients aged ≥65 years with an ALT level ≤30 U/L, MASLD was the third classifier, with significant hepatic fibrosis observed in 38% of patients.

Conclusions

ALT levels >30 U/L and MASLD may be involved in the pathogenesis of significant hepatic fibrosis in patients aged ≥65 years.

Improved algorithm of attenuation measurement showed the strong correlation with magnetic resonance imaging-derived proton density fat fraction. An area under the receiver operating characteristic curve of 0.926 was used for discriminating grade ≥1 steatosis. Improved algorithm of attenuation measurement is an accurate and simple method for quantifying hepatic steatosis and is expected to be used clinically in the future.

Abstract

Aim

This study aimed to evaluate the diagnostic performance of attenuation measurement (ATT; dual-frequency method) and improved algorithm of ATT (iATT; reference method) for the assessment of hepatic steatosis using magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) as the reference standard.

Methods

We prospectively analyzed 427 patients with chronic liver disease who underwent ATT, iATT, or MRI-derived PDFF. Correlation coefficients were analyzed, and diagnostic values were evaluated by area under the receiver operating characteristic curve (AUROC). The steatosis grade was categorized as S0 (<5.2%), S1 (≥5.2%, <11.3%), S2 (≥11.3%, <17.1%), and S3 (≥17.1%) according to MRI-derived PDFF values.

Results

The median ATT and iATT values were 0.61 dB/cm/MHz (interquartile range 0.55–0.67 dB/cm/MHz) and 0.66 dB/cm/MHz (interquartile range 0.57–0.77 dB/cm/MHz). ATT and iATT values increased significantly as the steatosis grade increased in the order S0, S1, S2, and S3 (p < 0.001). The correlation coefficients between ATT or iATT values and MRI-derived PDFF values were 0.533 (95% confidence interval [CI] 0.477–0.610) and 0.803 (95% CI 0.766–0.834), with a significant difference between them (p < 0.001). For the detection of hepatic steatosis of ≥S1, ≥S2, and ≥S3, iATT yielded AUROCs of 0.926 (95% CI 0.901–0.951), 0.913 (95% CI 0.885–0.941), and 0.902 (95% CI 0.869–0.935), with significantly higher AUROC values than for ATT (p < 0.001, p < 0.001, p = 0.001).

Conclusion

iATT showed excellent diagnostic performance for hepatic steatosis, and was strongly correlated with MRI-derived PDFF, with AUROCs of ≥0.900.

Neoadjuvant transcatheter arterial chemoembolization plus surgery was compared with surgery alone for hepatocellular carcinoma >5 cm in this exploratory, multicenter, randomized phase II study. Neoadjuvant transcatheter arterial chemoembolization allowed delay of surgical treatment without increased morbidity and cancer progress.

Abstract

Aim

Neoadjuvant transcatheter arterial chemoembolization (TACE) for large tumors is controversial, especially in the minimally invasive surgery era. The aim of this study was to compare features between groups treated with neoadjuvant TACE followed by surgery (TACE + surgery) or upfront surgery for hepatocellular carcinoma >5 cm.

Methods

In this exploratory, multicenter, randomized phase I study, the primary measure was 2-year disease-free survival (DFS). Secondary measures were resection rate, necrosis rate by TACE, 2-year overall survival, and site of recurrence. A total of 30 patients were randomly allocated to each arm.

Results

The two arms did not differ in patient characteristics. The median time to surgery from randomization was 48 days for TACE + surgery and 29 for surgery only (p < 0.001). Postoperative morbidities did not differ between arms. The 2-year DFS, overall survival, and resection rates were 56.7%, 80.0%, and 93.3%, respectively, in the TACE + surgery arm, and 56.1%, 89.9%, and 90.0% in the upfront surgery arm. Minimally invasive surgery was carried out in 35.7% in the TACE + surgery arm and in 29.6% in the upfront surgery arm. The median necrosis rate by TACE was 90.0%. In resected specimens, invasion to the hepatic vein was less with TACE + surgery (3.6% vs. 22.2%, p = 0.0380). In cases of 100% necrosis with TACE, 2-year DFS was 100%. Site of recurrence did not differ between groups.

Conclusion

Neoadjuvant TACE did not improve 2-year DFS, and neoadjuvant TACE allowed delay of surgical treatment without increased morbidity and cancer progress.

Clinical trial registration

UMIN: 000005241.

Abstract

Aim

Tumor Ki-67 expression reflects prognosis and cancer grade, and biopsy-based preoperative assessment of Ki-67 expression is key to treatment. Apparent diffusion coefficient (ADC) values obtained with this imaging may noninvasively predict Ki-67 by reflecting tumor cell density and limited water molecule movement from irregular alignment. This study aimed to investigate the ability of ADC values to predict Ki-67 expression in intrahepatic cholangiocarcinoma (ICC).

Method

We retrospectively analyzed 39 cases of ICC confirmed by surgical pathology. All patients had undergone magnetic resonance imaging, and ADC values (mean, minimum, and maximum) were calculated. Ki-67 expression was assessed by immunohistochemistry, and patients were divided into groups of high (n = 18) and low (n = 21) Ki-67 expression. To assess the diagnostic performance of the ADC values for Ki-67 expression, we used the receiver operating characteristic curve and compared the areas under the curve (AUC).

Results

The mean and minimum ADC values were significantly lower in the group with high Ki-67 expression. For predicting high Ki-67 expression, the AUC values were 0.701 for mean ADC, 0.818 for minimum ADC, and 0.571 for maximum ADC. The diagnostic sensitivity and specificity of the minimum ADC values were 88.9% and 76.2%, respectively. In addition, with ADC values combined, the AUC increased to 0.831. Apparent diffusion coefficient is a useful predictor of Ki-67 expression level in ICC.

Conclusion

Apparent diffusion coefficient values, especially minimum ADC values, can noninvasively predict ICC associated with high Ki-67 expression.