Seroprevalence and incidence of hepatitis E virus infection in the general population of Iwate prefecture, Japan: A retrospective cohort study.

AIM: Hepatitis E virus (HEV) causes subclinical or acute self-limiting hepatitis. We surveyed the current seroprevalence and incidence of HEV infection among the general population in Iwate Prefecture, Japan, where the endemic infection is presumed to be low. METHODS: Between 2014 and 2016, we recruited individuals from Iwate Prefecture, Japan, who visited a general medical work-up program. Serum anti-HEV antibody and HEV RNA were measured twice, with an interval of 2 years. Anti-HEV antibody was measured with enzyme-linked immunosorbent assay and HEV RNA with reverse transcription-polymerase chain reaction. RESULTS: Study participants comprised 1284 Japanese (650 men and 634 women) with age ranging 20-89 years. A total of 90 participants were found to be positive for anti-HEV immunoglobulin G on the first visit, with a prevalence of 7.0% (95% confidence interval [CI] 5.6%-8.4%). Seroprevalence was higher in men than in women (10.1% vs. 3.7%, p < 0.001), and in those aged in their 50s-80s than in those aged in their 20s-40s (p = 0.006). Positive seroconversion indicating new HEV infection was found in seven of 1194 seronegative participants (0.59%; 95% CI 0.15%-1.0%), indicating the incidence of HEV infection to be 272 per 100 000 person-years (95% CI 109-561). CONCLUSIONS: Our observations suggest that the incidence of HEV infection is high and that it is a leading cause of hepatitis virus infection in Iwate Prefecture, Japan.

Low liver reserve is a risk factor for acute pancreatitis in patients with acute liver failure.

AIM: Acute pancreatitis is a complication of acute liver failure (ALF). This study aimed to investigate the prevalence of and clinical features associated with acute pancreatitis in patients with ALF. METHODS: We retrospectively analyzed a cohort of ALF patients without hepatic encephalopathy diagnosed during a period 2011-2018, and compared clinical features between patients with acute pancreatitis and those without. Acute pancreatitis was diagnosed according to the Acute Pancreatitis Clinical Practice Guidelines 2021. A multivariate analysis was carried out to identify factors associated with acute pancreatitis. RESULTS: There were 83 ALF patients without hepatic encephalopathy (34 men; 11 deaths; 6 liver transplants; median age, 63 years). Acute pancreatitis occurred in nine patients (10.8%). The median time duration from ALF to the onset of acute pancreatitis was 8 days. The survival rate was lower in patients with than those without acute pancreatitis (22% vs. 86%). The model for end-stage liver disease score (hazard ratio 1.10, 95% confidence interval 1.03-1.18) was found to be a significant factor associated with acute pancreatitis, whereas triglyceride, age, and sex were not. CONCLUSIONS: A high model for end-stage liver disease score may be a marker to stratify patients with ALF at a risk of acute pancreatitis.

Grip strength complements performance status in assessing general condition in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

AIM: An accurate assessment of the general condition of patients with hepatocellular carcinoma (HCC) is essential. We evaluated the impact of grip strength (GS) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) on the clinical outcomes of patients with unresectable HCC (u-HCC) treated with atezolizumab plus bevacizumab. METHODS: This observational cohort study analyzed 89 patients with u-HCC treated with atezolizumab plus bevacizumab between October, 2020 and October, 2023. A Cox proportional hazards model and Kaplan-Meier curve were used to identify the prognostic factors associated with survival outcomes. RESULTS: There were 33 patients who had low GS and 16 had an ECOG-PS ≥1. The frequency of patients with low GS increased as the ECOG-PS score increased. The overall survival of the normal GS group was significantly higher than that of the low GS group (p < 0.01). There was no significant difference in progression-free survival between the normal GS group and low-GS group (p = 0.28). Among the patients in the ECOG-PS 0 groups, the overall survival in the normal GS group was significantly higher than that in the low GS group (p < 0.01). A multivariate analysis revealed that modified albumin-bilirubin 2b (HR 2.24; 95% confidence interval [CI] 1.06-4.73), α-fetoprotein ≥100 ng/mL (HR 2.35; 95% CI 1.20-4.58), and low GS (HR 2.87; 95% CI 1.31-6.27) were independently associated with a poor overall survival. CONCLUSIONS: The present study demonstrated that GS is a sensitive marker for detecting a subclinical decline in the general condition and is therefore a potential predictor of the outcome of u-HCC patients treated with atezolizumab plus bevacizumab.

Positive impact of obesity on the prognosis of liver cirrhosis.

BACKGROUND AND AIM: The study aims to determine the prognostic impact of obesity, sarcopenic obesity, and dynapenic obesity in patients with chronic liver disease. METHODS: This retrospective observational study enrolled patients with chronic hepatitis (n = 746) and liver cirrhosis (n = 434) without hepatocellular carcinoma at entry. The patients were evaluated for sarcopenia and obesity between April 2016 and April 2022. Obesity was defined as a body mass index of ≥ 25 kg/m2. Sarcopenic obesity was defined as low skeletal muscle mass (pre-sarcopenia) with obesity and dynapenic obesity was defined as low muscle strength (dynapenia) with obesity. The effects of obesity on survival were evaluated retrospectively. RESULTS: The mean observation period was 2.5 years. Obesity, sarcopenic obesity, and dynapenic obesity were found in 271 (45.5%), 17 (2.9%), and 21 (3.5%) men, and 261 (44.7%), 59 (10.1%), and 53 (9.1%) women, respectively. A multivariate Cox proportional hazards model revealed that Child-Pugh class, dynapenia (hazard ratio [HR] 3.89), elderly (≥ 65 years old) (HR 2.11), and obesity (HR 0.58) were independently associated with overall survival (OS). However, neither sarcopenic nor dynapenic obesity were associated with OS. In patients with cirrhosis, the OS of the obese group was significantly higher than that of the non-obese group. The effect of obesity on OS was significant in elderly patients, but not in younger patients. CONCLUSIONS: Sarcopenic and dynapenic obesity seem unrelated to the prognosis of patients with chronic liver disease. Obesity has a positive effect on the prognosis of elderly patients with cirrhosis.

Coincidental items in the definition of metabolic dysfunction-associated fatty liver are useful in identifying patients having significant fibrosis with fatty liver.

AIM: We aimed to establish a method that will identify patients at a high risk for progressive phenotype of fatty liver. METHODS: Patients with fatty liver who underwent liver biopsy between July 2008 and November 2019 were included as cohort 1, and those who underwent abdominal ultrasound screening examination by general physicians between August 2020 and May 2022 served as cohort 2. According to the definition of metabolic dysfunction-associated fatty liver (MAFLD), the subjects were classified by body mass index of ≥23, diabetes mellitus, and coexistence of two or more metabolic risk items. The progressive phenotype of MAFLD is defined by significant fibrosis complicated with either nonalcoholic fatty liver disease activity score ≥4 (BpMAFLD) or steatosis grade ≥2 by ultrasound examination (UpMAFLD). RESULTS: One hundred sixty-eight patients and 233 patients were enrolled in cohorts 1 and 2, respectively. In cohort 1, the prevalence of BpMAFLD was 0% in patients without a complicating factor (n = 10), 13% in those with one complicating factor (n = 67), 32% in those with two (n = 73), and 44% in those with all three complicating factors (n = 36). A logistic regression analysis revealed that factors in the MAFLD definition were significantly associated with BpMAFLD. In cohort 2, a criterion of two or more positive MAFLD definitions was found to have a 97.4% negative predictive value for the diagnosis of UpMAFLD. CONCLUSION: Patients with two or more complicating factors in the MAFLD definition should have further evaluation for liver fibrosis.

Clinical characteristics and efficacy of pioglitazone in a Japanese patient with familial partial lipodystrophy due to peroxisome proliferator-activated receptor γ gene mutation.

Familial partial lipodystrophy (FPLD) 3 is a rare genetic disorder caused by peroxisome proliferator-activated receptor γ gene (PPARG) mutations. Most cases have been reported in Western patients. Here, we describe a first pedigree of FPLD 3 in Japanese. The proband was a 51-year-old woman. She was diagnosed with fatty liver at age 32 years, dyslipidemia at age 37 years, and diabetes mellitus at age 41 years. Her body mass index was 18.5 kg/m2, and body fat percentage was 19.2%. On physical examination, she had less subcutaneous fat in the upper limbs than in other sites. On magnetic resonance imaging, atrophy of subcutaneous adipose tissue was seen in the upper limbs and lower legs. Fasting serum C-peptide immunoreactivity was high (3.4 ng/mL), and the plasma glucose disappearance rate was low (2.07%/min) on an insulin tolerance test, both suggesting apparent insulin resistance. The serum total adiponectin level was low (2.3 µg/mL). Mild fatty liver was seen on abdominal computed tomography. On genetic analysis, a P495L mutation in PPARG was identified. The same mutation was also seen in her father, who had non-obese diabetes mellitus, and FPLD 3 was diagnosed. Modest increases in body fat and serum total adiponectin were seen with pioglitazone treatment. Attention should be paid to avoid overlooking lipodystrophy syndromes even in non-obese diabetic patients if they show features of insulin resistance.

Calf and arm circumference as simple markers for screening sarcopenia in patients with chronic liver disease.

AIM: To prevent the progression of sarcopenia, early identification is important. We investigated the usefulness of sarcopenia screening tests using the arm and calf circumferences in patients with chronic liver disease. METHODS: This was a single-center cross-sectional study based on data collected from a university hospital. We analyzed simple anthropometric data and sarcopenia-related chemical data or imaging data between April and December 2019. Sarcopenia was defined according to the Japan Society of Hepatology guidelines. RESULTS: In total, 661 patients participated. Low muscle mass and low muscle strength were found in 245 (37.1%) and 153 (23.1%) patients, respectively. Ultimately, 90 (13.6%) patients were diagnosed with sarcopenia. The sarcopenia group was significantly older and had a higher cirrhosis ratio and poorer liver function than the non-sarcopenia group. The sarcopenia group had a significantly lower body mass index, arm circumferences and calf circumferences than the non-sarcopenia group. A receiver operating characteristics analysis for diagnosing sarcopenia by arm and calf circumferences showed respective areas under the curve of 0.89 and 0.91 for men and 0.84 and 0.89 for women. The optimal cut-off values of arm and calf circumferences were respectively determined to be 25.0 and 32.6 cm for men (sensitivity 88.4% and 83.7%; specificity 74.0% and 84.7%) and 22.7 and 32.1 cm for women (sensitivity 66.0% and 85.1%; specificity 90.0% and 81.3%). CONCLUSIONS: The arm and calf circumferences seem useful as simple surrogate markers for screening sarcopenia in patients with chronic liver disease.

Two hepatectomy cases for initially unresectable hepatocellular carcinoma after achieving a radiological complete response to sequential therapy with lenvatinib and transcatheter arterial chemoembolization.

We herein report two cases of locally advanced unresectable hepatocellular carcinoma (u-HCC) that were resected after achieving a radiological complete response to initially administered lenvatinib followed by transcatheter arterial chemoembolization (LEN-TACE sequential therapy). A 78-year-old woman and an 80-year-old man with HCC of Barcelona Clinic Liver Cancer classification stage C were treated for 15 and 14 months with lenvatinib, respectively. Both patients were subsequently treated with TACE, resulting in complete remission on imaging. The α-fetoprotein level in the woman and man decreased markedly from 9370 ng/ml to 46 ng/ml and from 6380 ng/ml to 3 ng/ml, respectively, leading to hepatectomy. A histopathological examination showed coagulative necrosis of the entire HCC in one case, while the other showed a small population of viable HCC cells. The results showed that LEN-TACE sequential therapy has a synergic effect and could be a promising option for locally advanced u-HCC.

Sustained virologic response by direct-acting antivirals suppresses skeletal muscle loss in hepatitis C virus infection.

BACKGROUND AND AIM: Although chronic liver disease is associated with secondary sarcopenia, the effect of primary disease treatment (hepatitis C virus elimination) on the skeletal muscle is unclear. This study aimed to determine the effect of a sustained virologic response at 24 weeks following direct-acting antiviral therapy on the skeletal muscle in hepatitis C virus-infected patients. METHODS: Hepatitis C virus-infected patients treated with direct-acting antivirals between 2014 and 2017 in our hospital were included. We evaluated the skeletal muscle index and intramuscular adipose tissue content at the third lumbar vertebra on abdominal computed tomography and compared the rate of change in the skeletal muscle index per year and intramuscular adipose tissue content per year before and after direct-acting antiviral treatment. RESULTS: Ninety-two patients participated. At sustained virologic response at 24 weeks, liver test results, including fibrosis marker levels, were significantly improved compared to those before direct-acting antiviral treatment. Skeletal muscle index measured before direct-acting antiviral treatment initiation was significantly lower than that at the first computed tomography scan. However, no significant change was found between the skeletal muscle index at the second computed tomography scan and final follow up. The rate of change in skeletal muscle index measured after direct-acting antiviral treatment was significantly higher than that before direct-acting antiviral treatment (-0.07 vs -0.99% per year). There was no significant difference between the change in intramuscular adipose tissue content before and after direct-acting antiviral treatment. CONCLUSIONS: Viral eradication by direct-acting antiviral treatment improved the liver function and suppressed skeletal muscle loss in hepatitis C virus-infected patients.

Association of ghrelin dynamics with beta cell function in Japanese subjects with normal glucose tolerance.

BACKGROUND: Ghrelin is involved in feeding regulation and energy metabolism and is also known to inhibit insulin secretion (ß). However, few clinical studies have demonstrated the relationship between ß and ghrelin dynamics. This study tested the hypothesis that, in oral glucose tolerance tests (OGTT), ghrelin dynamics are associated with ß. METHODS: Subjects were 1145 healthy individuals <40 years old who tested normal on the 75-g OGTT. The following indicators and the ghrelin suppression ratio (GSR) during OGTT were calculated: insulin sensitivity (SI) [1/homoeostasis model assessment of insulin resistance, insulin sensitivity index-Matsuda and 1/fasting insulin (1/FIRI)]; and ß [Stumvoll first-phase index (Stumvoll-1), Stumvoll second-phase index and insulinogenic index]. From nine combinations of SI and ß, combinations that produce hyperbolic relationships were identified. RESULTS: Stumvoll-1 and 1/FIRI showed a hyperbolic relationship in nonobese subjects, and the product of Stumvoll-1 and 1/FIRI was used as the disposition index (DI). When analyzed by BMI quartiles, post-loading glucose and insulin levels at each time point increased from Q1 (low BMI) through Q4 (high BMI), whereas the DI, ghrelin levels at each time point, and GSR decreased from Q1 to Q4. On multivariate and bivariate analysis, GSR and DI were positive and independent, and fasting ghrelin and FIRI were negatively and independently correlated. CONCLUSIONS: Ghrelin dynamics were associated with beta cell function in subjects with normal glucose tolerance. Glucose intolerance in obesity may be due not only to insulin resistance but also to impaired beta cell function associated with abnormalities of ghrelin dynamics.

The impact of portal vein thrombosis on the prognosis and liver function of nonmalignant cirrhotic patients.

OBJECTIVES: The clinical impact of portal vein thrombosis (PVT) in cirrhotic patients remains unclear. The aim of the study is whether recanalization of acute PVT in nonmalignant cirrhotic patients is associated with their prognosis. MATERIALS AND METHODS: We identified subject with PVT in cirrhotic patients from institutional database. Patients with ≥50% reduction in thrombus size were classified into the improved group and those with ≤49% reduction in thrombus size, or thrombus development in other branches were classified into the deteriorated group. We compared the cumulative survival rate, event-free survival rate (EFS), and liver function (albumin-to-bilirubin (ALBI) and model for end-stage liver disease XI (MELD-XI) between the two groups. RESULTS: Twenty-seven patients were enrolled in this retrospective study. Sixteen patients were classified into the improved group, and 11 were classified into the deteriorated group. In the improved group, the ALBI grade and MELD-XI measured before the onset of PVT and at one year after the onset of PVT were not significantly different. In contrast, MELD-XI was significantly aggravated in deteriorated group (MELD-XI [p = .02]). The cumulative survival of the two groups did not differ significantly; however, the EFS of the deteriorated group was significantly lower (p = .049). CONCLUSIONS: Residual thrombosis of PVT in cirrhotic patients increased the incidence of liver-related events and was associated with the deterioration of the liver function.

Efficacy of combination therapy with transcatheter arterial chemoembolization and radiofrequency ablation for intermediate-stage hepatocellular carcinoma.

OBJECTIVES: Transcatheter arterial chemoembolization (TACE) is the standard therapy for patients with intermediate-stage hepatocellular carcinoma (HCC). This study aimed to determine whether combination therapy with radiofrequency ablation (RFA) and TACE was superior to TACE monotherapy for intermediate-stage HCC and identify cases in which this technique was the most effective. MATERIALS AND METHODS: We selected patients with intermediate HCC who met the following eligibility criteria: (1) ≥ 20 years of age, (2) receiving initial therapy, (3) ≤7 tumors, and (4) maximum tumor diameter <5 cm. We performed propensity score matching (PSM) using potential confounding factors. We retrospectively compared the cumulative overall survival rate and recurrence-free survival rate between the TACE + RFA and TACE groups. Additionally, a sub-group analysis was performed for preoperative factors. RESULTS: Among the 103 patients, 92 were selected using PSM. The cumulative overall survival rates at 1, 3, and 5 years for the TACE + RFA group were 97.4%, 70.4%, and 60.4%, respectively, which were significantly higher than those for the TACE group (92.7%, 55.7%, and 22.8%, respectively, p = .045). The recurrence-free survival rates at 0.5, 1, and 2 years for the TACE + RFA group were 80.0%, 58.6%, and 33.3%, respectively, which were significantly higher than those for the TACE group (34.5%, 8.8%, and 2.9%, respectively, p < .01). For the sub-group with α-fetoprotein (AFP) <100 ng/mL, the TACE + RFA group demonstrated a significantly improved prognosis than the TACE group (p = .036). CONCLUSIONS: The addition of RFA to TACE improved cumulative overall and recurrence-free survival in patients with intermediate-stage HCC, especially in patients with AFP <100.

A case of pheochromocytoma with a marked decrease in catecholamine levels after rupture in which a good outcome was achieved by elective surgery.

Changes in imaging findings and hormone levels before and after pheochromocytoma rupture, as well as detailed histopathology of resected tumors, have rarely been reported. A 52-year-old woman developed hypertension and diabetes mellitus in 2014, but despite treatment with antihypertensive and hypoglycemic drugs, good control was not achieved. On April 2, 2016, the patient started to have headaches and palpitations, and on April 6, she visited our hospital. Plain computed tomography (CT) of the abdomen showed a 4-cm, isodense mass in the left adrenal gland, and the patient was hospitalized for further examination. Because the patient had hypertension, tachycardia, and hyperglycemia on admission, therapies for those were started. Catecholamine levels were markedly elevated. However, after the patient developed left flank pain on Day 4, antihypertensive and insulin therapies were no longer required. Plain CT then showed heterogeneous high density areas in the left adrenal mass. On Day 7, 3 meta-iodobenzylguanidine scintigraphy showed no abnormal uptake. On Day 8, contrast CT showed low density areas within the left adrenal tumor and contrast enhancement of the tumor margins, and catecholamine levels were markedly decreased. Elective left adrenal tumor resection was performed on Day 49. The capsule of the resected tumor was ruptured. Histopathology showed widespread hemorrhagic necrosis and viable cell components in the tumor margins. Positive chromogranin A staining of the tumor cells confirmed a diagnosis of pheochromocytoma. This patient displayed remarkable changes in imaging findings and hormone levels before and after pheochromocytoma rupture. Pheochromocytoma rupture and hemorrhagic necrosis were confirmed histopathologically.

The characteristics of osteoporotic patients in Graves' disease patients newly diagnosed after menopause: a prospective observational study.

Overt hyperthyroidism is associated with reduced bone density. The extent of restoration of reduced bone density caused by hyperthyroidism in postmenopausal Graves' disease (GD) patients has not fully been investigated. We examined 85 newly diagnosed postmenopausal GD patients, and we measured their serum thyroid hormone levels as well as their bone turnover marker levels and the bone mineral density (BMD) of their lumbar spine (LS), both femoral necks (FN), and left distal radius (DR). We prospectively observed the patients for changes in BMD and bone turnover marker levels during a 24-month period after euthyroidism had been established by ATD treatment. The median age of the subjects was 57 years old (range: 50 to 79). 46 (54.1%) patients had osteoporosis. 42 of the 46 osteoporosis patients had low BMD in the DR. The patients with osteoporosis were significantly older, had a significantly lower BMI, and had significantly higher bone turnover marker levels compared to the normal BMD patients. The best predictor of the BMD in the DR was BMD in the FN (ß = 0.40, p < 0.0001). A total of 42 patients were followed up for 24 months after attainment of euthyroidism, and 19 of them were osteoporosis at the first visit. The BMD of the 19 osteoporotic patients had increased by 4.9% in the LS, 11.9% in the FN, and 9.3% in the DR at 24 months. After maintaining a euthyroid state for 24 months by means of ATD treatment, 26% of the osteoporotic patients had recovered from osteoporosis.

Alpha-fetoprotein: A biomarker for the recruitment of progenitor cells in the liver in patients with acute liver injury or failure.

AIM: The optimal conditions for hepatocyte proliferation should be clarified in an attempt to improve the impaired liver regeneration observed in patients with acute liver failure (ALF). In order to evaluate the significance of the serum α-fetoprotein (AFP). level and prothrombin time international normalized ratio (PT-INR) as possible biomarkers of the proliferation of liver stem/progenitor cells (LPC) and mature hepatocytes (MH), respectively, we focused on donors of living donor liver transplantation (LDLT) and patients with acute liver injury (ALI), including ALF. METHODS: Seventy-three patients with ALI/ALF and 11 donors for LDLT were evaluated. LPC induction was histologically evaluated using cytokeratin (CK)-7 staining in 45 ALI/ALF patients. RESULTS: The AFP level was not apparently elevated during the observation period in any of the LDLT donors, whereas the serum AFP levels were substantially increased in the patients with ALI/ALF and significantly correlated with the number of CK-7 positive LPC in the liver, except for very severe damaged liver. All patients exhibiting an early peak in the AFP level prior to PT-INR elevation died. CONCLUSION: The serum AFP level may reflect the induction of LPC in ALI/ALF patients. The substantial and persistent induction of LPC until sufficient regeneration of MH may be needed for a recovery from ALF. We herein demonstrate that the serum AFP level may be a serum marker of LPC in patients with ALI/ALF. A comparison of the serial changes in the AFP levels and PT-INR in our study patients showed impaired proliferation of LPC and delayed recovery of MH in the patients who died.

Quantitative and simultaneous translational control of distinct mammalian mRNAs.

The introduction of multiple genes into cells is increasingly required for understanding and engineering biological systems. Small-molecule-responsive transcriptional regulation has been widely used to control transgene expression. In contrast, methods for specific and simultaneous regulation of multiple genes with a single regulatory protein remain undeveloped. In this report, we describe a method for quantitatively tuning the expression of multiple transgenes with a translational regulatory protein. A protein that binds a specific RNA motif inserted in the 5'-untranslated region (UTR) of an mRNA modulates the translation of that message in mammalian cells. We provide two independent mechanisms by which to rationally fine-tune the output: the efficiency of translation correlates well with the distance between the inserted motif and the 5' terminus of the mRNA and is further modulated by the tandem insertion of multiple RNA motifs. The combination of these two approaches allowed us to fine-tune the translational efficiency of target mRNAs over a wide dynamic range. Moreover, we controlled the expression of two transgenes simultaneously and specifically by engineering each cis-regulatory 5'-UTR. The approach provides a useful alternative regulatory layer for controlling gene expression in biological research and engineering.

Immune checkpoint inhibitor-associated colitis in unresectable hepatocellular carcinoma: two cases of early onset after treatment with durvalumab plus tremelimumab.

The HIMALAYA trial is the first chemotherapeutic trial to demonstrate the efficacy of combined immune checkpoint inhibitors (ICIs) for unresectable hepatocellular carcinoma (u-HCC). The STRIDE regimen used in this trial consists of a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor and programmed cell death ligand 1 (PD-L1) inhibitor. Herein, we report two cases of ICI-colitis that occurred immediately after the initiation of the STRIDE regimen for u-HCC. A 73-year-old man and 75-year-old man with u-HCC were treated with the STRIDE regimen. Both patients developed grade 3 diarrhea (Common Terminology Criteria for Adverse Events, ver. 5.0) within 10 days of treatment initiation. Colonoscopy revealed aphthous erosions and erythema extending from the terminal ileum to the rectum in one case, while the other showed aphthous ulcers in the terminal ileum and shallow ulcers in the colorectum. Histopathological examination of a biopsy specimen revealed epithelial cell apoptosis and neutrophil infiltration bodies, consistent with ICI-colitis. Prednisolone (0.5 mg/kg) was effective in both patients. Our experience suggests the need for both careful monitoring and early endoscopic examination of ICI colitis in patients with unresectable HCC treated with the STRIDE regimen.

Cardio-ankle vascular index relates to left ventricular ejection fraction in patients with heart failure. A retrospective study.

The cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive marker of arterial stiffness independent of blood pressure. Arterial stiffness is closely related to afterload, and elevated afterload aggravates heart failure. We hypothesized that CAVI is a potential marker of afterload in patients with heart failure. Thirty patients who were admitted because of acute heart failure were identified retrospectively from a review of clinical records. Plasma brain natriuretic peptide (BNP) levels, CAVI, cardiothoracic ratio (CTR), and echocardiographic parameters obtained during acute and chronic phases of heart failure were analyzed. Left ventricular ejection fraction (LVEF) increased significantly and CTR, BNP and CAVI decreased significantly after treatment of heart failure. A significant negative correlation was observed between the change in CAVI and change in LVEF in all subjects (r = -0.3272, P < 0.05). To examine the relationship between CAVI and LVEF, we divided the patients into two subgroups (∆CAVI < -0.5; CAVI decrease group, ∆CAVI ≥ -0.5; CAVI non-decrease group). CAVI was significantly improved after heart failure treatment only in the CAVI decrease group. LVEF decreased significantly in both groups, but the P value was smaller in the CAVI decrease group than in the CAVI non-decrease group. The change in LVEF correlated significantly with the change in CAVI in the CAVI decrease group (r = -0.4201, P < 0.05), whereas no significant correlation was found in the CAVI non-decrease group. CAVI correlates inversely with LVEF after heart failure treatment. Our results suggest that CAVI might partially reflect the afterload in patients with heart failure.

Systematic genetic identification of functional domains on collided di-ribosomes responsible for rescue pathways upon translation arrest in Saccharomyces cerevisiae.

Translation elongation becomes arrested when various obstacles arise, such as a series of inefficient rare codons or stable RNA secondary structures, thus causing ribosomal stalling along the mRNA. Certain wasteful and persistent stalling states are resolved by ribosome rescue pathways. For instance, collisions between stalled and subsequent ribosomes are thought to induce ubiquitination of ribosomal S20 protein by the E3 ubiquitin ligase Hel2, which triggers subsequent rescue reactions. Although structural studies have revealed specific contact sites between collided ribosomes, the ribosomal regions crucial for the rescue reaction remain uncharacterized. In this study, we performed a systematic genetic analysis to identify the molecular regions required for ribosome rescue in Saccharomyces cerevisiae. A series of dominant negative mutations capable of abolishing the rescue reaction were isolated in ribosomal proteins S20 and Asc1. Moreover, mutations in both proteins clustered on the surface of ribosomes between the collided ribosome interfaces, aligned in such a way that they seemingly faced each other. Further analysis via the application of the split-TRP1 protein assay revealed that the mutation of either protein distinctively affected the functional interaction between Hel2 and Asc1, suggesting the development of differential functionality at the interface between collided ribosomes. Our results provide novel and complementary insights into the detailed molecular mechanisms of ribosomal rescue pathways.

Annual changes in grip strength and skeletal muscle mass in chronic liver disease: observational study.

Sarcopenia is a common complication in patients with chronic liver disease (CLD); however, the progression of sarcopenia over the course of CLD is unclear. The present study therefore determined the natural course of the progression of sarcopenia in patients with CLD and the effect of liver cirrhosis (LC) on this progression. This observational study analyzed patients with chronic hepatitis (CH) (n = 536) and LC (n = 320) who underwent evaluations of the grip strength and skeletal muscle mass of the arms, trunk, and legs for sarcopenia between 2016 and 2021. A bioelectrical impedance analysis was used to evaluate skeletal muscle mass. The annual rate of change (%/year) in two tests were compared between patients with CH and LC. The annual rates of change in grip strength and skeletal muscle of arms, trunk, and legs of patients with CH and LC were - 0.84% vs. - 2.93%, - 0.54% vs. - 1.71%, - 0.43% vs. - 1.02%, and - 0.76% vs. - 1.70% for men and - 0.12% vs. - 1.71%, - 0.66% vs. - 1.71%, - 0.49% vs. - 1.31%, and - 0.76% vs. - 1.54% for women, respectively. The progression of sarcopenia was greater in LC patients than in CH patients and that the decrease in grip strength was most prominent in the progression of sarcopenia in patients with LC.