Hepatology Research最新文献

Background: Alcohol consumption in patients with steatotic liver disease (SLD) with metabolic dysfunction (MD) increases the risk of liver fibrosis and mortality. However, whether these risks vary by age remains poorly understood.

Methods: Data from NHANES-III were used, including participants with data on SLD, alcohol consumption, and mortality. SLD was determined using ultrasonography, MD was defined according to the guidelines as ≥ 1 metabolic risk factor, and mild-to-moderate alcohol consumption as 10-50 g/day (females) or 20-60 g/day (males). Mortality data were obtained from the National Death Index until December 31, 2015. The impact of SLD with MD and alcohol consumption on mortality was evaluated using multivariable Cox regression, including age (categorized as 20-< 40, 40-< 60, and 60-< 80 years) as an interaction term, and adjusted for demographic and cardiometabolic factors. The risk of fibrosis was determined using two distinct, validated, non-invasive tests: the Metabolic Dysfunction Associated Fibrosis-5 (MAF-5) score and the Fibrotic NASH Index (FNI).

Results: We included 13,062 participants (aged 20-< 40: 3097; 40-< 60: 3960; 60-< 80: 3008). SLD with MD was present in 31% (20-< 40: 23%; 40-< 60: 28%; 60-< 80: 41%), and 11% reported mild-to-moderate alcohol use (mean intake: 5.4 g/day, 6.2 g/day, and 3.7 g/day, respectively). Over a median follow-up of 23 years, 30% of participants died. Both SLD with MD (aHR: 1.29, 95% CI: 1.01-1.65) and alcohol consumption (aHR: 1.63, 95% CI: 1.21-2.19) were associated with increased all-cause mortality. Significant interactions with age were observed for SLD with MD (p = 0.037) and alcohol use (p < 0.001), with younger adults experiencing highest relative mortality risks. A similar age-dependence was seen for fibrosis risk.

Conclusions: Young adults face the highest fibrosis and mortality risk associated with SLD with MD and alcohol consumption, likely reflecting years lived with these risk factors. Our findings highlight the need to prioritize lifestyle interventions in younger adults to prevent fibrosis and premature mortality.

Aim: Liver stiffness measurement is a noninvasive liver disease assessment (NILDA) for hepatic fibrosis and is covered by health insurance in Japan. This study aimed to examine nationwide trends in liver stiffness measurement in Japan by analyzing data from the National Database of Health Insurance Claims (NDB).

Methods: We analyzed NDB open data from 2016 to 2020. In the NDB, liver stiffness measurement (Medical Fee Schedule Code: D215-2) includes both imaging techniques (transient elastography) and biochemical examinations (mac-2 binding protein glycosylation isomer). The claim number was counted across all 47 Prefectures in Japan.

Results: The annual number of liver stiffness measurements all over Japan was 76,183 in 2016. The number increased to 124,584 in 2020, representing a 1.64-fold increase during this period. The annual number of liver stiffness measurements adjusted by population size (1000 population) was 0.60 in 2016. The numbers were 0.64, 0.53, 0.89, and 0.99 in 2017, 2018, 2019, and 2020, respectively. There was a 1.67-fold increase during the period. We carried out statistical analysis using Poisson regression, which confirmed that the observed increases in liver stiffness measurement uptake were statistically significant (p < 0.0001). In almost all Prefectures, the population-adjusted number of liver stiffness measurements showed an increasing trend. Notably, Saga Prefecture had the highest prevalence of liver stiffness measurements (4.10) during the period. This was followed by Kagawa (3.19), Miyazaki (2.70), and Wakayama (2.44) Prefectures.

Conclusions: The number of liver stiffness measurements has increased from 2016 to 2020 throughout Japan. Liver stiffness has been increasingly measured nationwide and is expected to become a valuable NILDA for identifying at-risk patients and evaluating treatment efficacy in steatotic liver disease.

Alanine aminotransferase (ALT) is a commonly used indicator of hepatocellular injury in clinical liver disease practice. While a variety of factors influence serum ALT levels, we focus here on the effect of alcohol consumption on ALT levels in the context of the common East Asian aldehyde dehydrogenase 2 (ALDH2) dysfunctional polymorphism, ALDH2*2 (or rs671 E504K missense variant). ALDH2 plays a key role in the detoxification of alcohol-derived metabolite, acetaldehyde. Four of the five studies identified from a literature search showed that individuals with the ALDH2*1/*2 heterozygous genotypes had ALT levels below the normal range if they consume alcoholic beverages despite having only 10%–38% of the normal ALDH2 activity. This effect is consistent and more pronounced in men in studies from different East Asian populations. It is noteworthy that one large study showed that low ALT levels of ALDH2*1/*2 were also observed with excessive alcohol consumption, which is a common risk factor for alcohol-related liver disease (42 g ethanol per day in men). It is unclear if these lower-than-normal ALT levels indicate a hepatoprotective effect or if it is a missed clinical indicator of hepatic injury. As ALT levels in the general practice are used to diagnose potential liver disease, it is therefore necessary to determine whether alcohol-induced decline in ALT may mask the diagnosis of liver disease in an estimated 540 million carriers of the ALDH2*1/*2 genotypes in the East Asian ancestry group in clinical practice.

Background: The recent reclassification of nonalcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease reflects the central role of metabolic dysfunction in its pathogenesis. Obesity underlies metabolic perturbations; however, liver health risks are not exclusive to individuals with a higher BMI and some individuals with obesity have favorable metabolic health (MH). Thus far, there has been limited examination of liver health indicators among metabolically healthy and unhealthy phenotypes, which is the aim of this study.

Methods: A cross-sectional sample of 2040 middle- to older-aged adults were classified as metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy nonobese (MHNO), and metabolically unhealthy nonobese (MUNO), according to three MH definitions (MeigsA, MeigsB, and Wildman). Liver biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured, and the fatty liver index (FLI) was calculated. Crude and adjusted logistic regression models examined associations between liver function indicators and MH phenotypes.

Results: In fully adjusted models, higher FLI scores were consistently associated with lower likelihood of MHO and MHNO (odds ratios and 95% confidence intervals for MHO: 0.947 (0.934, 0.961) [MeigsA], 0.952 (0.938, 0.966) [MeigsB] and 0.945 (0.931, 0.959) [Wildman] and for MHNO: 0.957 (0.950, 0.964) [MeigsA], 0.950 (0.942, 0.958) [MeigsB] and 0.961 (0.955, 0.968) [Wildman] (all p < 0.001)). Higher ALT and GGT concentrations were inversely associated with MHO, and AST additionally with MHNO, in all models across the three definitions.

Conclusions: Liver function indicators are linked with MH status in middle- to older-aged adults.

Aims: Understanding the molecular characteristics and genotype distribution of hepatitis B virus (HBV) is essential to elucidate intra and inter community transmission routes, identify cluster cases, and assess clinical implications based on genotype-specific virulence. This study aimed to investigate HBV genotype distribution in a geographically isolated Japanese islands with high HBV endemicity.

Methods: From 1977 to 2008, all 34,136 residents of the Kamigoto area in the Goto Islands were screened for HBsAg, identifying 1474 positive cases (4.3%). Among them, 916 stocked serum samples with sufficient volume were randomly selected. HBV DNA levels were quantified using real-time PCR. Genotyping was carried out through nested PCR targeting the overlapping surface-polymerase or surface gene, followed by phylogenetic analysis. Full genome sequencing was conducted on 23 randomly selected samples to identify sub-genotypes.

Results: HBV DNA was detected in 82.9% of participants. Genotyping was successful in 81.8%, revealing predominant genotype C (96.5%), followed by genotypes B (3.1%) and A (0.4%). Phylogenetic analysis identified multiple genotype C clusters, suggesting intra-community transmission. Full genome sequencing confirmed sub-genotypes C2 and B1, closely related to Japanese reference strains. HBV DNA levels were significantly higher in younger age groups (p < 0.0001), with no sex difference.

Conclusion: This study presents rare population-based molecular evidence of sustained HBV genotype C2 endemicity and intra-community transmission within a defined setting. The findings underscore clinical significance of implementing targeted area- and population-specific strategies including early detection through screening, linkage to care, vaccination, and long-term surveillance, as an effective model for HBV micro-elimination in high-burden communities.

Aim: Excessive fructose ingestion causes fat accumulation and can lead to fatty liver, obesity, and related diseases. Eucalyptus leaf extract (ELE) contains oenothein B, which inhibits fructose absorption in the intestine. In this study, we evaluated the effects of ELE on fat accumulation caused by sugar-sweetened beverage intake in adult Japanese men with a body mass index of ≥ 23 and < 30 kg/m².

Methods: In this randomized, placebo-controlled, double-blind, and parallel-group pilot study, participants consumed test capsules containing oenothein B (3.38 mg/day), along with a beverage containing free sugars (22.5 g/day), as a loading diet for 12 weeks. The abdominal visceral fat area (VFA) and controlled attenuation parameter (CAP), which is an indicator of hepatic fat levels, were measured and compared to those in the placebo group.

Results: Twenty participants were included in the analysis of the placebo and intervention groups. After 12 weeks, VFA and CAP increased significantly from baseline (p = 9.81 × 10^-3 and 1.59 × 10^-2) in the placebo group, whereas no significant increase was observed in the intervention group. Sensitivity analysis after unblinding revealed that the CAP was significantly lower in the intervention group (p = 4.84 × 10^-2) than that in the placebo group after 12 weeks.

Conclusion: ELE ingestion suppressed visceral and hepatic fat accumulation. Thus, oenothein B-containing ELE may be a useful antiobesity agent. This is the first report showing that the consecutive ingestion of dietary free sugars results in hepatic and visceral fat accumulation in adult Japanese men.

Trial registration: UMIN000037428; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000042668.

Background and aims: Direct oral anticoagulants (DOACs) are increasingly used in various thrombotic disorders. However, data on the use of DOACs in patients with Budd-Chiari syndrome (BCS) remain limited. We aimed to assess the efficacy and safety of DOACs in patients with BCS after percutaneous recanalization.

Methods: We carried out a single-center retrospective analysis of patients with primary BCS who received DOACs or vitamin K antagonists (VKAs) after percutaneous recanalization. The primary endpoints were the cumulative primary and secondary patency rates. Secondary endpoints included bleeding events and death.

Results: A total of 236 patients were included, with 133 receiving DOACs (rivaroxaban, n = 59; dabigatran, n = 74) and 103 receiving VKAs. The median duration of anticoagulation was 18.8 months (IQR: 6.3-28.6) in the DOAC group (median follow-up: 22.8 months, IQR: 12.6-31.8) and 32.2 months (IQR: 6.0-73.5) in the VKA group (median follow-up: 70.6 months, IQR: 39.0-85.6). The 1-, 2-, and 3-year cumulative primary patency rates were 79.3%, 70.0%, and 62.9% in the DOAC group, compared to 83.5%, 78.2%, and 73.8% in the VKA group (p = 0.269). Furthermore, no significant differences were observed between the DOAC and VKA groups in major bleeding rates (DOAC: 1.8 per 100 person-years; VKA: 2.8 per 100 person-years; incidence rate ratio [IRR]: 1.6, 95% CI: 0.4-5.9; p = 0.436).

Conclusion: DOACs may be an effective and safe alternative to VKAs for patients with BCS after percutaneous recanalization. Further prospective studies are needed to confirm these findings.

Aim: Tamoxifen is a widely used endocrine treatment for breast cancer, also responsible for drug-induced steatotic liver diseases. This study aimed to investigate the frequency, clinical course and risk factors for tamoxifen-induced liver injury in patients with breast cancer.

Methods: We conducted a retrospective analysis of 192 patients with breast cancer who initiated tamoxifen therapy between January 2008 and December 2017, undergoing blood tests and abdominal ultrasonography after receiving tamoxifen for at least 1 year. Liver injury was defined as alanine transaminase and/or alkaline phosphatase levels exceeding twice the upper limit of the normal range. We explored the risk factors for CTCAE grade ≥ 2 tamoxifen-induced liver injury and validated the results with a cohort of additional 166 patients.

Results: Among the 192 patients, 30 (15.6%) experienced tamoxifen-induced liver injury, including 13 patients with grade ≥ 2 liver injury. Although most patients with grade 1 liver injury experienced spontaneous resolution, several patients with grade ≥ 2 liver injury required treatment interruption/discontinuation or developed persistent liver injury. Progression to cirrhosis was suspected in two (1.0%) patients. High body mass index (BMI), diabetes, dyslipidemia and pre-existing liver steatosis were significantly associated with an increased risk of grade ≥ 2 liver injury.

Conclusions: Tamoxifen-induced liver injury was observed in 15.6% of the patients. Metabolic factors, such as high BMI, diabetes, dyslipidemia and pre-existing liver steatosis, were considered potential predictors of CTCAE grade ≥ 2 liver injury. Collaboration with gastroenterologists should be encouraged in patients with grade ≥ 2 liver injuries, where spontaneous remission is uncommon.