Long-term Favorable Efficacy of Regular and Repeated Hospitalizations with a Personalized Diet and Exercise Treatment for Steatotic Liver Disease.

Objective The long-term impact of personalized diet and exercise programs for steatotic liver disease (SLD) remains unclear. Materials The subjects of this retrospective cohort study included 104 consecutive Japanese patients with SLD. The long-term treatment efficacy of personalized diet and exercise treatment was evaluated two years after the start of observation. Regular and repeated hospitalizations every 6 months (RRH group, n=23) indicated the 4 times of the number of hospitalizations, and irregular hospitalizations (IH group, n=56) showed the 1 to three times. The group without hospitalization was defined as the no hospitalization group (NH group, n=25). To balance confounding biases, the difference in treatment efficacy between the RRH and IH groups was evaluated using propensity score (PS)-matched analysis. A diet of 25 to 30 kcal/kg multiplied by ideal body weight (BW) daily, and aerobic and resistance exercise (exercise intensity of 4 to 5 metabolic equivalents daily, respectively) was performed for 6 days. Results At 2 years compared to baseline, the decrease rates of liver function tests, HbA1c, and physical findings in the RRH group were significantly higher than those in the NH or IH groups by multiple comparisons. According to the liver function tests and physical findings, the rate of decrease in the RRH group (17 cases) was significantly higher than that in the IH group (17 cases) using a PS-matched analysis. Conclusion The present study indicated the long-term favorable efficacy of personalized diet and exercise programs for SLD. In particular, this RRH program was effective in improving the findings of liver function tests and might help to sustain diet and exercise.

Impact of the COVID-19 Pandemic on Health Check-ups in 2021 and 2022: A Nationwide Follow-up Survey of Healthcare Facilities in Japan Society of Ningen Dock.

Introduction: Preventive programs, including screenings for cancer and diabetes, were disrupted globally due to the coronavirus disease 2019 (COVID-19) pandemic in 2020. We previously conducted a nationwide survey to investigate the initial impact of the pandemic on health check-ups; however, the impact in the second and third years of the pandemic has not yet been elucidated. Here, we conducted a follow-up survey targeting healthcare facilities to evaluate the impact of the pandemic until the end of 2022. Methods: A questionnaire survey was conducted between December 15, 2022, and February 10, 2023, targeting member facilities of Japan Society of Ningen Dock. The survey consisted of two parts. Part I comprised a web-based questionnaire, in which the facilities were asked about their commitment to COVID-19-related care, precautions against COVID-19, and whether the pandemic had a negative financial impact on the management of health check-ups. In Part II, the facilities were asked about the number of examinees who underwent health check-ups between 2019 and 2022, the proportion of those who needed and adhered to follow-up visits, and the number of cancer cases found between 2019 and 2021. Results: Of the 1,343 eligible facilities, 885 participated (response rate: 65.9%). The observation that the number of people undergoing mandatory check-ups increased while those undergoing nonmandatory check-ups (e.g., cancer screenings by local governments) decreased in 2021, compared with that of 2019, persisted into 2022. Approximately 60% of the facilities reported a negative financial impact on the management of health check-ups, even in 2022. Conclusions: In 2022, the pandemic's detrimental effects on health check-ups persisted.

Impact of genetic polymorphism on personalized diet and exercise program for steatotic liver disease.

AIMS: The effects of genetic polymorphism on a personalized diet and exercise program for steatotic liver disease (SLD) are still unclear. METHODS: Participants of this retrospective cohort study were 203 Japanese patients with SLD diagnosed by abdominal ultrasonography. All of them were introduced the personalized diet and exercise treatment. A diet of 25-30 kcal/kg multiplied by ideal body weight (BW) daily and aerobic and resistance exercise (exercise intensity of 4-5 metabolic equivalents daily, respectively) were performed for 6 days. Treatment efficacy was evaluated in terms of the rate of decrease of liver function tests, glycolipid metabolism markers, physical findings, image findings, and cardiovascular disease (CVD) risk score at 6 months compared with baseline. Furthermore, the impact of genetic polymorphism was also investigated. RESULTS: At 6 months compared with baseline, liver function tests (AST, ALT, γGTP), glycolipid metabolism markers (hemoglobin A1c, triglycerides [TG], low-density lipoprotein cholesterol), physical findings (BW, body mass index), image finding (liver stiffness measurement), and CVD risk score (Suita score) improved significantly. There was no significant difference in treatment efficacy, except for the rates of decrease of TG, according to genotype PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs6834314. The rates of decrease of TG with TM6SF2 CT were significantly higher than those with CC or TT, and the rates of TG with HSD17B13 AA were significantly higher than those with AG by multiple comparisons. CONCLUSION: Personalized diet and exercise program for SLD improved liver function tests, physical findings, glycolipid metabolism markers, and CVD risk score. Genetic polymorphism might partially affect treatment efficacy. Further studies should be performed to develop an individualized program for SLD, considering genetic polymorphism.

Clinical outcome after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients who achieved HBsAg seroclearance.

BACKGROUND: We determined the long-term clinical outcome and the durability of treatment cessation after HBsAg seroclearance following nucleos(t)ide analog (NA) therapy in patients with chronic hepatitis B (CHB). METHODS: We analyzed virological relapse (VR), HBsAg reversion, clinical relapse, and changes in HBsAg and HBcrAg levels by iTACT assay after treatment cessation of 90 CHB patients who achieved HBsAg seroclearance by NA treatment. RESULTS: Median age of patients at treatment cessation was 57 years. Median duration of NA treatment and follow-up from cessation of NA were 9.25 and 5.2 years, respectively. Although VR occurred in 19 of 90 (21.1%) patients, HBV DNA levels of 18 patients had temporal elevations and sustained levels under the detection level thereafter. HBsAg reversion using Architect HBsAg QT assay occurred in six patients (6.7%) after cessation of NA. Five patients had temporal HBsAg level elevations and sustained levels under the detection level thereafter. One patient had virological and clinical relapse at 6 months after cessation of NA, and received NA re-treatment. HBsAg levels by iTACT assay from end of treatment (EOT) gradually decreased and in 18 of 28 (64%) patients reached an undetectable level at 5 years after EOT. In contrast, HBcrAg levels by iTACT assay slowly decreased, and in 8 of 29 patients (28%) reached an undetectable level at 5 years after EOT. CONCLUSIONS: Patients receiving NA treatment who achieved HBsAg seroclearance as determined by HBsAg QT assay rarely experienced virological or clinical relapse after the cessation of treatment.

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

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. 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.

Impact of the COVID-19 Pandemic on Health Check-ups: A Nationwide Questionnaire Survey in 639 Healthcare Facilities in Japan Society of Ningen Dock.

Introduction: Health check-ups have been disrupted worldwide by the COVID-19 pandemic, especially at its beginning. In Japan, undergoing annual check-ups is mandatory for full-time employees of all ages, while those other than full-time employees are entitled to undergo nonmandatory cancer screenings and specific health check-ups. To evaluate the impact of the COVID-19 pandemic on health check-ups, we conducted a nationwide questionnaire survey targeting healthcare facilities. Methods: A questionnaire survey was conducted between December 10, 2021, and January 28, 2022. Healthcare facilities were eligible if they were members of Japan Society of Ningen Dock and could respond via email. The monthly and yearly numbers of examinees undergoing mandatory or nonmandatory check-ups in 2020 and 2021 were compared with those in 2019. The proportions of examinees requiring follow-up visits and adhering to follow-up visits were compared between 2020 and 2019. Precautions taken against COVID-19 were also investigated. Results: Of the 1,299 eligible facilities, 639 participated (response rate, 49.2%). Health check-up services were suspended in 484 (75.7%) facilities for a median duration of 5 (interquartile range [IQR]: 4-8) weeks. A total of 19,861,230 and 21,748,125 examinees underwent health check-ups in 591 facilities in 2020 and 2021, respectively, 10.0% and 1.4% less than the numbers in 2019. The number of examinees undergoing health check-ups decreased by a median of 8.3% (IQR: -14.6 to -3.1) in 2020 compared to that in 2019, with the largest decrease of 70.3% (IQR -87.9 to -48.5) in May. Although the number of examinees undergoing mandatory check-ups increased in 2021 compared with that in 2019, the number of those undergoing nonmandatory check-ups remained low. Conclusions: While people eligible for mandatory check-ups were adherent to check-ups in 2021, those ineligible for mandatory check-ups seemed less adherent. Public health efforts to encourage these people to adhere to check-ups during the pandemic are required.

Favorable Impact of Serum TERT C228T for Prognosis after Surgical Resection for Liver Cancer.

INTRODUCTION: Personalized medicine and molecular therapies with the diagnosis of somatic genetic alterations are expected to be developed for liver cancer. Nevertheless, it is unknown whether a mutation in the telomere reverse transcriptase promoter (TERT C228T) in serum cfDNA might be useful for making prognostic predictions after surgical resection for primary liver cancer. METHODS: This cohort study retrospectively investigated 111 patients who had undergone surgical resection of liver cancer for the first time. We investigated the differences between clinicopathological features and prognosis according to classification of three tumor markers, including AFP, PIVKAII, and TERT C228T. RESULTS: Multivariate analysis identified etiology (fatty liver disease vs. HBV odds ratio [OR] 6.853) and fibrosis stage (2-4, OR: 0.137) as determinants of TERT C228T-positive liver cancer with normal levels of AFP and PIVKAII (TERT single positive liver cancer). TERT single positive (Yes, OR: 0.301), fibrosis (FIB)-4 index (≥3.25, OR: 2.038), Child-Pugh classification (B, OR: 4.975), and number of tumors (≥2, OR: 4.098) were identified as determinants of the recurrence of liver cancer. TERT single positive (Yes, OR: 3.311), FIB-4 index (≥3.25, OR: 0.433), and number of tumors (≥2, OR: 0.262) were identified as determinants of disease-free survival. CONCLUSIONS: Our results highlight the impact of classification of prognostic tumor markers. TERT single positive is one predictor of favorable prognosis after surgical resection for liver cancer.

Efficacy of the Combination of Systemic Sequential Therapy and Locoregional Therapy in the Long-Term Survival of Patients with BCLC Stage C Hepatocellular Carcinoma.

BACKGROUND: The aim of this study was to evaluate the clinical impact of a combination of systemic sequential therapy and locoregional therapy on the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). METHODS: Sixty-four consecutive patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The clinical impact of the combined use of systemic sequential therapy and locoregional therapy was evaluated by determining overall survival (OS). The combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while only systemic sequential therapy and repeated locoregional-treatment was defined as a single treatment procedure (STP). RESULTS: R0 resection, MCT, and STP resulted in significantly better OS compared with no additional treatment (median OS, not reached vs. 18.2 months and 12.6 vs. 8.1 months, respectively; p = 0.002). Multivariate analysis confirmed that the use of R0 resection and MCT were associated with better OS (hazard ratio [HR]; 0.053, p = 0.006 and 0.189, p < 0.001, respectively) compared with that for STP (HR; 0.279, p = 0.003). CONCLUSIONS: MCT is may effective in patients with BCLC stage C HCC and intrahepatic target nodules who have previously received systemic therapy-based treatment.

Retrospective cohort study to examine the association between serum amylase and the incidence of type 2 diabetes mellitus, Toranomon Hospital Health Management Center Study 23 (TOPICS 23).

INTRODUCTION: Low serum amylase values are cross-sectionally associated with the prevalence of type 2 diabetes mellitus (T2DM) but have not been shown to be longitudinally associated with its incidence. This retrospective cohort (ie, historical cohort) study aimed to examine the association of previously lowered levels of serum amylase with incident T2DM. RESEARCH DESIGN AND METHODS: Examined were 8316 individuals who had annual health examinations for 6 years (ie, 7 times) at the Toranomon Hospital Health Management Center. The trajectory of serum amylase as the study exposure was classified into two elements: (1) serum amylase level at entry and (2) change in serum amylase, which was expressed as the annual change rate. The annual change rate was calculated by dividing the change in the amylase values according to follow-up periods. Regression analyses were performed to examine the association between low and decreased levels of serum amylase and the incidence of T2DM. RESULTS: Analyzed were 6917 individuals who had not developed T2DM within 1 year after cohort entry. T2DM thereafter occurred in 1021 patients. Cox regression indicated that the adjusted HR (95% CI) for incident T2DM for amylase ≤57 IU/L (quintile (Q) 1) was 0.97 (0.84 to 1.13) compared with amylase ≥58 IU/L (Q2-Q5). Logistic regression indicated that the adjusted OR (95% CI) for an annual change rate of amylase ≤-2.0% (Q1) vs ≥-1.9% (Q2-Q5) was 3.53 (3.00 to 4.16). The adjusted ORs were consistently significant throughout sensitivity analyses according to baseline amylase and the combination of age, body mass index, and hemoglobin A1c. CONCLUSIONS: Results showed that not low but previously decreased serum amylase was a risk factor for T2DM, suggesting the significance of periodic examinations of serum amylase values to detect individuals at high risk of T2DM.

Treatment efficacy of diet and exercise program for fatty liver and pretreatment predictors.

AIMS: Both diet and exercise counseling are recommended for patients with fatty liver, including nonalcoholic fatty liver disease (NAFLD), to achieve weight loss goals. However, data evaluating treatment efficacy are limited. METHODS: The subjects of this retrospective cohort study were 186 consecutive Japanese cases with fatty liver diagnosed by abdominal ultrasonography. Treatment efficacy and predictive factors of "Hospitalization Program for Improvement Purpose for Fatty Liver" as a combined diet and aerobic and resistance exercise program were evaluated according to the hospitalization group (153 cases) or the no hospitalization group (33 cases). To balance the confounding biases, treatment efficacy was evaluated using propensity score-matched analysis. In the hospitalization group, a diet of 25-30 kcal/kg multiplied by ideal body weight (BW) daily and aerobic and resistance exercise (exercise intensity of 4-5 metabolic equivalents daily, respectively) were performed for 6 days. RESULTS: In liver function tests and BW at 6 months compared with baseline, the rates of decrease of the hospitalization group (24 cases) were significantly higher than those of the no hospitalization group (24 cases), using propensity score-matched analysis. In markers of glycolipid metabolism and ferritin levels, the rates of the hospitalization group were not different from those of the no hospitalization group. In the hospitalization group (153 cases), multivariate regression analysis identified the etiology of non-NAFLD, the presence of diabetes mellitus, and large waist circumference as independent predictors of decreased rates of hemoglobin A1c levels. CONCLUSION: The diet and exercise program for fatty liver improved liver function tests and BW. Further study should be performed to develop a feasible and suitable program.

Association between Hypokalemia and Albuminuria in a Japanese General Population.

INTRODUCTION: Hypokalemia is associated with an increased risk of chronic kidney disease (CKD) and is a risk factor for mortality. Albuminuria is an early manifestation of CKD. We investigated the association between hypokalemia and the prevalence of albuminuria in a Japanese general population. METHODS: We analyzed the data of 18,289 subjects who underwent annual health checkups in 2018. We categorized them into four groups according to their concentration of serum potassium (sK) and performed a multivariate logistic regression analysis to determine the association between hypokalemia and the prevalence of albuminuria in this population. Hypokalemia was defined as having an sK = 3.1-3.5 mEq/L. After dividing the subjects into those with/without renal dysfunction, those with/without hypertension, and those with/without hyperglycemia, we examined the association between hypokalemia and albuminuria in each group. RESULTS: Compared to the subjects with sK = 4.1-4.5 mEq/L, the subjects with hypokalemia had a significantly high prevalence of albuminuria: multivariable-adjusted odds ratio (OR) = 2.70 (95% confidence interval [CI] 1.84-3.96). The subgroup analyses showed the following multivariable-adjusted ORs (95% CIs) of the subjects: without renal dysfunction, 3.08 (2.00-4.73); with renal dysfunction, 2.05 (0.89-4.69); without hypertension, 2.89 (1.36-6.16); with hypertension, 2.60 (1.67-4.04); without hyperglycemia, 2.49 (1.62-3.84); and with hyperglycemia, 3.55 (1.43-8.79). CONCLUSIONS: Hypokalemia was significantly associated with the high prevalence of albuminuria in general population. Regardless of the presence/absence of renal dysfunction, hypertension, or hyperglycemia, hypokalemia was positively associated with the prevalence of albuminuria, and the associations were significant except for the subjects with renal dysfunction.

Simple Predictive Markers and Clinicopathological Features of Primary Liver Cancer following HCV Clearance with Direct-Acting Antivirals.

INTRODUCTION: Simple predictive markers enabling even nonspecialized medical doctors and clinicopathological features of primary liver cancer (PLC) following HCV clearance with direct-acting antivirals (DAAs) are unclear. METHODS: The subjects of this retrospective study were 2,476 patients following HCV clearance with DAAs. All patients were confirmed to be PLC-free before and during DAAs. RESULTS: PLC was diagnosed in 73 patients during the follow-up, with an incidence rate per 1 000 person-years of 5.9. The annual rate of PLC during the first 6 years was 0.6%. Multivariate analysis identified gender, GGT, and FIB-4 index as the significant determinants of PLC. According to a combination of these risk factors, the cumulative PLC incidence rates were significantly different among the five subgroups based on the number of PLC risk scores. In 73 patients with PLC, the rates of abnormal AFP, PIVKAII, and serum TERT C228T positive were 37.0, 32.4, and 22.2%. PIVKAII levels in BCLC stage A and B were significantly higher than those in stage 0. In 41 patients, who underwent surgical resection for PLC, maximum tumor diameters of abnormal PIVKAII were significantly larger than those of normal PIVKAII. PLC of abnormal PIVKAII significantly indicated presence of vp more than that of normal PIVKAII, and did not contain well-differentiated HCC. CONCLUSIONS: Combination of simple markers, enabling even nonspecialized medical doctors, is useful for the evaluation of PLC risk following HCV clearance with DAAs. However, imaging studies are regularly recommended for the early detection of PLC.

Well-preserved liver function enhances the clinical impact of curative-intent subsequent treatment during lenvatinib treatment for unresectable hepatocellular carcinoma.

BACKGROUND: The aims of this study were to evaluate the clinical impact of curative-intent subsequent treatment on overall prognosis in lenvatinib-treated hepatocellular carcinoma (HCC) patients. METHODS: Eighty-three consecutive patients with intrahepatic target nodules who received lenvatinib were reviewed. The clinical impact of curative-intent subsequent treatments was investigated through analysis of overall survival (OS) according to pathological deterioration stratified by mALBI grade. RESULTS: In patients with mALBI grade 1 and 2a liver function, R0 resection and lenvatinib-transarterial chemoembolization (lenvatinib-TACE) sequential therapy resulted in significantly better OS compared with other, non-curative-intent subsequent therapy and lack of additional treatment (median OS, 37.6 vs 29.0 months and 17.1 vs 8.9 months, respectively; P < 0.001). Multivariate analysis confirmed that use of R0 resection and lenvatinib-TACE sequential therapy were associated with better OS (hazard ratio [HR], 0.021; P < 0.001 and 0.108; P < 0.001) compared with other, non-curative-intent subsequent treatment (HR 0.256; P = 0.010). In contrast, in patients with mALBI grade 2b liver function, multivariate analysis confirmed higher treatment efficacy for non-curative-intent subsequent treatment with respect to OS (HR 0.041; P < 0.001) compared with R0 resection and lenvatinib-TACE sequential therapy (HR 0.057; P = 0.027 and 0.063; P = 0.001). CONCLUSION: Curative-intent subsequent treatment is more useful for HCC patients with better liver function (mALBI grade 1 and 2a) and intrahepatic target nodules who have received lenvatini b-based treatment.

The Impact of Lenvatinib on Tumor Blood Vessel Shrinkage of Hepatocellular Carcinoma during Treatment: An Imaging-Based Analysis.

INTRODUCTION: When lenvatinib is administered to people with hepatocellular carcinoma (HCC), tumor blood flow is reduced due to the inhibition of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR). Few studies have examined the decrease in tumor blood flow with respect to changes in tumor blood vessels (TBVs) in clinical practice. We investigated the mechanism of tumor blood flow control by investigating changes in the diameter of relatively large TBVs in large-sized lesions with high blood flow. METHODS: From January 2011 to October 2021, patients receiving lenvatinib for unresectable intrahepatic HCC at Toranomon Hospital, Tokyo, Japan, were considered for inclusion. We investigated the TBV diameter in the arterial phase of dynamic computed tomography before treatment and its change over time (2-12 weeks after lenvatinib initiation). The relationship between changes in TBV diameter and prognosis was also examined. RESULTS: Of 114 patients treated with lenvatinib for HCC, 26 patients who had intrahepatic lesions with a tumor diameter of 30 mm or more enrolled in the study. The median tumor and TBV diameters before treatment were 58 mm and 2.55 mm, respectively. Twenty-five patients (96%) had a shrinkage in TBV diameter 2-12 weeks after lenvatinib administration. The maximum TBV diameter shrinkage of 20% or more was observed in 19 patients (73%), and progression-free survival was prolonged in these patients compared to the group with less than 20% TBV diameter shrinkage (p = 0.039). DISCUSSION/CONCLUSION: Due to the antiangiogenic effect of lenvatinib, a shrinkage in the TBV diameter of HCC was observed. The shrinkage of TBV may be regarded as a process of normalization of TBVs. The shrinkage of TBVs in imaging analysis may be associated with improved prognosis; however, additional studies are still required.

A case of drug-induced acute liver failure caused by corticosteroids.

We report a 61-year-old man treated with betamethasone for sudden-onset deafness. Several days later, he had a temperature > 38 °C. He sought care at another hospital and was admitted based on abnormal liver function tests (aspartate aminotransferase [AST], 866 IU/L [normal < 31 IU/L] and alanine aminotransferase [ALT] 1524 IU/L [normal < 31 IU/L]). Liver function improved daily and the patient was discharged from the hospital after 5 days. Two days after discharge, he had a recurrent fever and liver dysfunction. After admission to our hospital, liver function improved spontaneously. A liver biopsy was performed, but a diagnosis was not established; however, a tentative diagnosis of antinuclear antibody-negative autoimmune hepatitis was made and the patient was started on prednisolone (30 mg). Two days later, he developed a fever and persistent liver dysfunction, thus the prednisolone was discontinued. The next day, the AST and ALT increased significantly (18,000 and 12,000 U/L, respectively). Because the level of consciousness was altered, plasma exchange was started for acute liver failure. After discontinuing the prednisolone, the hospital course was uneventful. Drug-induced liver injury due to corticosteroids is rare. Herein, we report a patient with acute liver failure who survived with timely treatment.

Favorable impact of long-term SGLT2 inhibitor for NAFLD complicated by diabetes mellitus: A 5-year follow-up study.

The aim of this study was to determine the impact at 5 years of sodium-glucose cotransporter 2 inhibitor (SGLT2i) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes mellitus (T2DM) on liver histopathology and clinical features. In this retrospective study, the histological impacts at 5 years after the start of SGLT2i in NAFLD with T2DM were investigated. Six patients with NAFLD and T2DM were treated for the long term with canagliflozin of SGLT2i, and liver biopsies were obtained at the points of the pretreatment, 24 weeks, 3 years, and 5 years after the start of treatment. The primary outcome was liver histopathological changes at 5 years (defined as decrease in NAFLD activity score of one point or more without worsening in fibrosis stage, compared with the pretreatment). The additional treatment of glucagon-like peptide 1 receptor agonist (GLP-1RA) was performed in 2 patients after the point of 3 years, and evaluated as histological worsening. As the primary outcome, histological improvement, no change, and worsening were 50%, 17%, and 33% at 5 years, respectively. Overall, the scores of steatosis, lobular inflammation, ballooning, and fibrosis stage decreased at 5 years in 67%, 33%, 0%, and 33%, respectively. As the secondary outcomes, homeostasis model assessment of insulin resistance and serum ferritin decreased significantly at 5 years. None developed 3-point major adverse cardiovascular events. Two patients with the addition of GLP-1RA on SGLT2i did not show the worsening of steatosis, ballooning, and fibrosis stage at 5 years compared with 3 years. Conclusion: A 5-year follow-up study with SGLT2i indicated the favorable histological impact on NAFLD with T2DM.

Serum TERT C228T is an important predictor of non-viral liver cancer with fatty liver disease.

BACKGROUND: Molecular therapies and precision medicine are expected to be developed for liver cancer based on the diagnosis of DNA somatic alterations. However, it remains unclear whether TERT promoter mutation (TERT C228T) in serum cfDNA is useful for the diagnosis of liver cancer with non-viral fatty liver disease (FLD). METHODS: This retrospective cohort study examined 258 Japanese patients who had a confirmed diagnosis of primary liver cancer. We investigated the factors associated with TERT C228T and abnormal levels of liver cancer-specific tumor markers (AFP and PIVKAII) in serum samples. RESULTS: Multivariate analysis identified the etiology of FLD, vascular invasion, and non-cirrhosis as determinants of TERT C228T-positive liver cancer. Rates of positive TERT C228T in FLD were significantly higher than those of HBV and HCV. Conversely, rates of abnormal AFP in FLD were significantly lower than those of HBV and HCV. Viral suppression of HBV/HCV and alcohol intake did not affect TERT C228T, but AFP was significantly reduced by viral suppression. The rates of positive TERT C228T were significantly lower in HCV patients with viral clearance than those of FLD patients. CONCLUSION: Our results highlight the importance of serum TERT C228T for the detection of non-viral FLD-related liver cancer. TERT C228T is a tumor marker that might not be influenced by inflammation.

The useful predictors of zinc deficiency for the management of chronic liver disease.

BACKGROUND: Zinc deficiency is likely to occur in chronic liver disease. The aim of this study was to determine the prevalence of zinc deficiency in different types of chronic liver disease and to identify the factors that predicted low serum zinc levels. METHODS: The study was an observational single-center design. We obtained the medical records of 666 patients with chronic liver disease whose serum zinc levels had been measured. The cutoff value for zinc deficiency was a serum level < 70 µg/dL. RESULTS: Serum zinc levels in the alcoholic liver disease (ALD) group were significantly lower than in the other groups (hepatitis C virus [HCV], hepatitis B virus [HBV], and other cause) (P < 0.01). The CONUT and ALBI score (r = 0.527, P < 0.01), serum zinc level and ALBI score (r = - 0.607, P < 0.01), and serum zinc level and CONUT score (r = - 0.465, P < 0.01) correlated with each other. The prevalence of zinc deficiency were 44.8%, 63.2%, 86.7%, 97.1%, and 100% in the mALBI grade 1-CONUT normal, CONUT undernutrition, and mALBI grade 2a, 2b, and 3 groups, respectively. Multivariate analysis identified ALD, CONUT score, aspartate aminotransferase, and hemoglobin as significant, independent predictors of zinc deficiency (P < 0.05). CONCLUSIONS: This study identified ALD, CONUT score, aspartate aminotransferase, and hemoglobin as predictors of zinc deficiency in chronic liver disease. The rate of zinc deficiency is high even in patients classified as mALBI grade 1, especially in ALD, while caution may be required in those classified as mALBI grade 1-CONUT undernutrition.

Pretreatment Positron Emission Tomography with 18F-Fluorodeoxyglucose May Be a Useful New Predictor of Early Progressive Disease following Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND AND AIMS: The aim of this study was to identify the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a predictor of early progressive disease (e-PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atezo/Bev). METHODS: Twenty consecutive patients with measurable intrahepatic target nodules who received Atezo/Bev treatment were reviewed. The oncological aggressiveness of tumors estimated by 18F-FDG-PET/CT was analyzed using the rate of e-PD within 12 weeks and early progression-free survival (e-PFS) and overall survival (OS). Multivariate analysis was used to identify potential confounders for PD during Atezo/Bev therapy. RESULTS: Using the Response Evaluation Criteria in Solid Tumors version 1.1, a tumor-to-normal liver ratio (TLR) ≥2, indicating higher oncological aggressiveness in HCCs, was associated with lower objective response rates compared with TLR values <2 (18% vs. 33%, respectively). Moreover, TLR values ≥2 were significantly associated with higher e-PD rates compared with TLR values <2 (64% vs. 11%, respectively) and worse e-PFS (p = 0.021). In multivariate analysis, TLR ≥2 showed marginal significance as a predictor of e-PD (p = 0.053), and utility as a predictor for worse e-PFS (hazard ratio, 7.153; 95% confidence interval, 1.258-40.689; p = 0.027). In contrast, no significant differences in OS with/without e-PD were observed during the treatment course. In this study, 8 patients experienced e-PD and almost 40% of patients experienced acceptable disease control following subsequent lenvatinib treatment. CONCLUSION: Pretreatment 18F-FDG-PET/CT may be a useful new predictor of e-PD and may enable early decision-making based on early treatment changes following Atezo/Bev treatment of HCC.