Nucleos(t)ide analog-treated chronic hepatitis B patients with a higher Fibrosis-4 index (≥1.58) at year 1 after the therapy showed a higher incidence of hepatocellular carcinoma. A fibrosis and alanine aminotransferase-1 (FAL-1) score that can be calculated simply with the Fibrosis-4 index and alanine aminotransferase at year 1 of nucleos(t)ide analog might be useful to predict hepatocellular carcinoma development in the clinical settings.

Abstract

Aim

Nucleos(t)ide analogs do not completely prevent hepatocellular carcinoma (HCC) in chronic hepatitis B virus infection. This study aimed to evaluate the dynamics of a non-invasive liver fibrosis marker, the Fibrosis-4 (FIB-4) index, for predicting HCC development.

Methods

Among a total of 882 chronically hepatitis B virus infection-infected patients who were treated with nucleos(t)ide analogs, 472 patients without HCC history whose FIB-4 at baseline and 1 year of treatment was obtained were evaluated for the incidence of HCC.

Results

The median FIB-4 was 2.00 at baseline and was significantly reduced to 1.58 at 1 year (P < 0.001), but the reduction was small at 2 years or later. When a receiver operating characteristic analysis of FIB-4 was performed to predict HCC within 5 years, the area under the curve of FIB-4 at 1 year was higher than that at baseline (0.676 vs. 0.599). The HCC incidence was significantly higher in patients with FIB-4 ≥1.58 than in those with FIB-4 <1.58 (14.8% vs. 3.6% at 10 years, P < 0.001). Additionally, an abnormal alanine aminotransferase (≥31 U/L) at 1 year was an independent risk for HCC. When a fibrosis and alanine aminotransferase-1 (FAL-1) score was evaluated as an applicable number of FIB-4 ≥1.58, and alanine aminotransferase ≥31 as 0, 1, and 2, the HCC risk in patients with score 2 was significantly higher than in those with score 1 or score 0 (24.1% vs. 9.8% vs. 0.7% at 10 years, P < 0.001).

Conclusions

FIB-4 ≥1.58 and alanine aminotransferase ≥31 at 1 year of nucleos(t)ide analog was an independent risk factor for HCC development, and a score using these factors stratified the risk of HCC.

Abstract

Aim

It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitis C virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10 kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy.

Methods

The study participants were recruited from a historical cohort of 116 chronically hepatitis C virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2 years after the end of treatment (EOT) as the regression (n = 71) and non-regression (n = 45) groups, respectively.

Results

Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24 weeks after the EOT, and serum IP-10 change from baseline to 24 weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline.

Conclusions

Serum IP-10 change from baseline to 24 weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.

Abstract

Aims

To investigate the impact of endovascular (EV) treatment on liver cirrhosis in Chinese patients with Budd–Chiari syndrome (BCS).

Methods

From September 2011 to March 2022, 97 patients from four hospitals in China who were diagnosed with primary BCS complicated with liver cirrhosis and received EV treatment were retrospectively enrolled in this study for clinical analysis. In addition, liver tissues for basic research were acquired from 25 patients between June 2022 and March 2023, including six with benign liver tumors, 11 with BCS before EV treatment, and eight with EV-treated BCS. Liver cirrhosis was assessed by clinical outcomes, histological studies, and the expression of related genes at the mRNA and protein levels.

Results

The patients with BCS had better liver function after EV treatment, evidenced by an increased albumin level and reduced total bilirubin, ALT, and AST. The imaging findings suggested an amelioration of liver cirrhosis and portal hypertension, including increased portal vein velocity (13.52 ± 8.89 cm/s vs. 17.51 ± 6.67 cm/s, p < 0.001) and decreased liver stiffness (30.37 ± 6.39 kPa vs. 23.70 ± 7.99 kPa, p < 0.001), portal vein diameter (14.97 ± 3.42 mm vs. 13.36 ± 2.89 mm, p < 0.001), and spleen volume (870.00 ± 355.61 cm³ vs. 771.36 ± 277.45 cm³, p < 0.001). Furthermore, histological studies revealed that EV treatment resulted in a restoration of liver architecture with reduced extracellular matrix deposition. Meanwhile, hepatic angiogenesis and inflammation, which have a close relationship with cirrhosis, were also inhibited. In addition, the state of hepatocytes switches from apoptosis to proliferation after EV treatment.

Conclusions

BCS-induced liver cirrhosis could be reversed by EV treatment from macroscopic to microscopic dimensions. Our study may provide further insights into understanding BCS and treating cirrhosis.

Malnutrition defined by the modified Global Leadership Initiative on Malnutrition (GLIM) criteria using both handgrip strength and skeletal muscle area can more accurately predict short- and long-term outcomes compared to malnutrition defined by the GLIM criteria. Nutritional and exercise therapy could become more important in patients with malnutrition and poor liver function.

Abstract

Aim

A recent study reported the utility of the definition of malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) criteria in many types of cancers and chronic inflammatory disease. The present retrospective study aimed to investigate the significance of malnutrition defined with GLIM criteria in patients with hepatic resection for hepatocellular carcinoma (HCC) and also to compare malnutrition using handgrip strength.

Methods

We retrospectively reviewed data from 174 patients who had undergone curative hepatic resection for HCC including both skeletal muscle area and handgrip strength. Patients were divided according to malnutrition defined by GLIM or modified GLIM and clinicopathologic and short- and long-term outcomes were analyzed. The modified GLIM criteria was defined using both handgrip strength and skeletal muscle area.

Results

Malnutrition defined by GLIM criteria was diagnosed in 47 patients (26.7%) and malnutrition defined by modified GLIM criteria was diagnosed in 21 patients (11.9%). Malnutrition defined by GLIM or modified GLIM criteria was associated with poorer liver function and malignant tumor behavior, but modified GLIM criteria predicted the postoperative complication and recurrence-free survival outcome independently. In patients with poor liver function, malnutrition defined by modified GLIM criteria predicted postoperative complication and overall and recurrence-free survival.

Conclusions

Malnutrition defined by modified GLIM criteria using both handgrip strength and skeletal muscle area can more accurately predict short- and long-term outcomes compared to malnutrition defined by the GLIM criteria. Nutritional and exercise therapy could become more important in patients with malnutrition and poor liver function.

A total of 71 254 participants from 13 health centers in Japan were analyzed, with an overall prevalence of NAFLD of 25.8%. A total of 14% of NAFLD patients had diabetes, 31% had hypertension, and 48% had dyslipidemia. The estimated prevalence of NAFLD with advanced fibrosis was 1%–2%.

Abstract

Aim

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. The aim of this study was to determine the recent prevalence and clinical characteristics of NAFLD in Japan.

Methods

This study initially included 410 061 retrospectively enrolled adults from the medical health checkup registry for metabolic syndrome, chronic kidney disease, and fatty liver in Japan (MIRACLE-J; UMIN-CTR no. UMIN000049419), who were evaluated between 2014 and 2018 at 13 health centers in Japan. Individuals consuming >20 g of alcohol/day or with chronic liver disease were excluded. Fatty liver was diagnosed by ultrasonography. The probability of NAFLD with advanced fibrosis was estimated based on the fibrosis-4 index and NAFLD fibrosis score.

Results

A total of 71 254 participants were included in the final analysis. The overall prevalence of NAFLD was 25.8%. There was a significant, twofold difference in NAFLD prevalence between men (37.4%) and women (18.1%). Nonalcoholic fatty liver disease prevalence increased linearly with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even in the absence of obesity. Among patients with NAFLD, 14% had diabetes mellitus, 31% had hypertension, and 48% had dyslipidemia. The estimated prevalence of NAFLD with advanced fibrosis was 1.7% and 1.0% according to the fibrosis-4 index and NAFLD fibrosis score, respectively.

Conclusions

The prevalence of NAFLD was approximately one-quarter of the general population in Japan. There was a linear relationship between NAFLD prevalence and various metabolic parameters, even in nonobese participants. The prevalence of NAFLD with advanced fibrosis was estimated to be 1%–2%.

Abstract

Aim

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitis B virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population.

Method

A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitis B envelope antigen (HBeAg) negative chronic hepatitis B (n = 255), with HBeAg positive chronic hepatitis B (n = 99) and with HBeAg negative HBV infection (n = 228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n = 195) and in healthy controls (n = 160).

Results

In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR = 1.75, 95% CI 1.04–2.94, p = 0.034), with an increased likelihood of HBeAg negative chronic infection (OR = 1.93, 95% CI 1.05–3.54, p = 0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07–3.39, p = 0.029) in male patients.

Conclusion

The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.

Abstract

Aim

The prognosis of patients with resected intrahepatic cholangiocarcinoma (ICC) is still unsatisfactory, with a high recurrence rate. We aimed to evaluate risks of recurrence changing over time and the survival benefit of resection for recurrent ICC.

Methods

This study included patients who underwent hepatectomy for ICC during 1995–2020. Risk factors for recurrence-free survival (RFS) in patients undergoing initial resection and overall survival (OS) in patients who developed recurrence after initial resection were analyzed. Conditional cumulative incidence of recurrence was assessed.

Results

A total of 169 patients were included in the study and 114 patients (67.5%) developed recurrence. Cumulative analyses showed that the 5-year recurrence rate was 69.3% at the time of initial resection but decreased to 24.8% in patients free from recurrence at 2 years after initial resection and 2.6% in patients free from recurrence at 4 years. Re-resection was carried out in 26 (22.8%) of 114 patients who developed recurrence. Multivariable Cox proportional hazards model analysis indicated re-resection (hazard ratio [HR] 0.19; 95% confidence interval [CI] 0.11–0.40, p < 0.001), microvascular invasion (MVI) (HR 2.39; 95% CI 1.05–5.40, p = 0.037), and disease-free interval (months) (HR 0.97; 95% CI 0.95–1.00, p = 0.067) were significantly associated with longer OS after recurrence.

Conclusions

Although the rate of recurrence remains high, conditional cumulative recurrence rate analysis showed that the rate of recurrence decreased by disease-free interval. Resection of recurrent ICC was associated with improved OS, particularly among patients with longer disease-free interval and absence of MVI after initial hepatectomy.

Although a low-calorie diet with lipid restriction is recommended in clinical practice guidelines for nonalcoholic fatty liver disease, both compliance and adherence are poor. The present study aimed to evaluate the compliance, adherence, and effectiveness of a moderate-carbohydrate diet without caloric or lipid restrictions. In conclusion, compliance and adherence to our moderate-carbohydrate diet was high, and therapy appeared easy to maintain. Sustained correction of excessive carbohydrate intake would lead to not only reductions in body weight, visceral fat, and liver steatosis, but also improvements in pathophysiological states of nonalcoholic fatty liver disease such as chronic hepatitis, liver fibrosis, abnormal metabolisms, and low-grade systemic inflammation.

Abstract

Aim

Although a low-calorie diet with lipid restriction is recommended in clinical practice guidelines for nonalcoholic fatty liver disease (NAFLD), both compliance and adherence are poor. The present study aimed to evaluate the compliance, adherence, and effectiveness of a moderate-carbohydrate diet without caloric or lipid restrictions.

Methods

Participants comprised 300 patients with NAFLD with elevated ALT levels who received counseling in carbohydrate restriction (150–200 g/day). Complete response (CR) was defined as ALT normalization and partial response as a ≥30% reduction in ALT from baseline without CR.

Results

Dropout rates were 3% (10 of 300) after 6 months and 8% (23 of 300) after 12 months. Achievement rates of carbohydrate intake ≤200 g/day after 1, 3, 6, and 12 months were 80%, 81%, 80%, and 73%, respectively. CR and partial response rates were 60% and 31% after 6 months, and 65% and 25% after 12 months, respectively. Rates of achieving a ≥7% weight reduction after 6 and 12 months were 51% and 49%, respectively. Significant reductions in percentage body fat and visceral fat area were obtained, along with a significant increase in liver/spleen attenuation ratio. Serum lipids, uric acid, homeostatic model assessment for insulin resistance, hemoglobin A1c, C-reactive protein, ferritin, immunoglobulin, blood cell, shear wave velocity in the liver, and Mac-2-binding protein glycosylated isomers all decreased significantly.

Conclusions

Compliance and adherence to a moderate-carbohydrate diet without caloric or lipid restriction is high. The sustained high effectiveness of this therapy would improve the pathophysiological state of NAFLD.

Abstract

Aim

There are few reports on the prognosis of liver-related events in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We undertook an observational study to compare the prognosis between fibrotic and nonfibrotic groups in Japanese NAFLD patients.

Methods

Prognosis in 393 NAFLD patients who underwent liver biopsy between April 2013 and April 2015 at multiple centers were investigated. The time to onset of liver-related events, cardiovascular events, development of extrahepatic cancers, and death were compared between the pathologically fibrotic nonalcoholic steatohepatitis (NASH) group and nonalcoholic fatty liver (NAFL) + nonfibrotic NASH group. A similar analysis was carried out based on the fibrotic classification diagnosed using four noninvasive fibrosis prediction models.

Results

The mean age and body mass index at the time of liver biopsy was 55.7 years old and 28.04 kg/m², respectively The cumulative incidence of liver-related events at 1080 days after liver biopsy was 5.79% in the pathologically fibrotic NASH group and 0% in the NAFL + nonfibrotic NASH group, with a significant difference (p = 0.0334). The cumulative incidence of liver-related events was significantly higher in the positive group for the prediction model than in the negative group in all four models (all p values were <0.0001). There was no significant difference between the pathologically fibrotic NASH group and NAFL + nonfibrotic NASH group in terms of cumulative incidence of cardiovascular events, development of extrahepatic cancers, and death.

Conclusions

The incidence of liver-related events was significantly higher in the fibrotic NASH group than that of the NAFL + nonfibrotic NASH group in Japanese NAFLD patients.