Peripheral lymphocyte fluctuation as an indicator of severe immune-related adverse events in patients treated with immune checkpoint inhibitors.

AIM: Immune checkpoint inhibitors (ICIs) have proven to be effective treatments for various cancers, but can also elicit immune-related adverse events (irAEs). Given that severe irAEs can be life-threatening, biomarkers that can predict the occurrence of irAEs are of paramount importance. ICIs affect the dynamics of lymphocytes, and alterations in these dynamics may play a role in the development and severity of irAEs. The aim of this study was to investigate the correlation between irAEs and changes in lymphocyte counts. METHODS: Information on irAEs was collected from 226 ICI cases from 2014 to 2020. We compared lymphocyte counts before treatment and at the onset of irAE and investigated the association between lymphocyte count fluctuations and the presence and severity of irAE, the course after steroid treatment, and overall survival. RESULTS: Of the 226 cases, 27 patients developed grade 3 or higher irAE. Compared to the other groups, the lymphocyte count in this group was significantly decreased at the time of irAE (p < 0.01). There was a trend toward a rapid increase in lymphocyte count in the steroid responder group compared to the non-responder group. Regarding overall survival, patients with irAE had significantly longer survival than those without irAE (p = 0.0025). However, there was no association between changes in lymphocyte count and survival in patients with irAE. CONCLUSION: The percentage change in lymphocyte count was found to correlate with the incidence of severe irAEs. Close monitoring of the patient's condition is crucial when the lymphocyte count decreases during ICI treatment.

Assessment of the association between dysphagia and sarcopenia among elderly patients with cirrhosis: Usefulness of the finger-ring test.

AIM: Sarcopenic dysphagia has become an urgent matter of debate in our aging society. However, little is known about the relationship between sarcopenia and dysphagia in patients with liver cirrhosis. Our aim was to assess sarcopenia and dysphagia among elderly patients with cirrhosis using two easy-to-use screening tests, i.e., the eating assessment tool-10 and the finger-ring test. METHODS: The eating assessment tool-10, handgrip strength, skeletal muscle mass index, computed tomography, and the finger-ring test were included in our analysis. One hundred patients with cirrhosis and without a history of aspiration pneumonia were divided into the elderly (≥75 years) and non-elderly (<75 years) groups. RESULTS: In the elderly group, sarcopenia was identified in 56.5% of the patients; of these, 30.4% and 13.0% had eating assessment tool-10 scores of ≥2 and ≥3, respectively. Sarcopenia-related factors correlated significantly with the eating assessment tool-10 scores (p<0.01). Multivariate regression analysis revealed that sarcopenia was significantly associated with dysphagia (p=0.028; odds ratio, 7.27). Among the elderly patients, the calf size of the non-dominant lower limb was less than the finger-ring circumference in 37.0% of the patients. This group had a significantly higher proportion of patients with an eating assessment tool-10 score of ≥2 than those with a greater calf than finger-ring circumference (p<0.01). CONCLUSIONS: Sarcopenia, rather than the hepatic reserve function, is associated with dysphagia among elderly patients with cirrhosis. The finger-ring test might be useful in screening for dysphagia.

Changes in serum LDL, PCSK9 and microRNA-122 in patients with chronic HCV infection receiving Daclatasvir/Asunaprevir.

The present study evaluated the changes in lipid profile, and the associations between serum protein convertase subtilisin/kexin 9 (PCSK9), microRNA (miR)122 and low-density lipoprotein variation following treatment of hepatitis C virus (HCV) genotype 1b infection with Daclatasvir/Asunaprevir. A total of 39 patients with HCV genotype 1b infection with chronic hepatitis received a 24-week treatment regimen of Daclatasvir/Asunaprevir. Laboratory data were obtained for each subject every 4 weeks during treatment and every 12 weeks after treatment. Serum miR122 and PCSK9 were measured at the start of treatment (week 0), end of treatment (week 24), 4 weeks after the end of treatment (week 28), 12 weeks after the end of treatment (week 36) and 28 weeks after the end of treatment (week 52). LDL was increased at week 4 after the start of treatment to week 52. The increased LDL/HDL ratio at week 52 compared with week 4 was also associated with relative miR122 at week 52. At week 4, PCSK9-active form (A) was lower than that at other time points, and PCSK9-inactive form (I) exhibited the greatest increase. At week 52, PCSK9-A was higher than that during treatment, but PCSK9-I level at week 52 did not markedly differ from that any time point except for week 4. Relative miR122 at week 4 was associated with increased PCSK9-A at weeks 36 and 52 from the start of DAA. In summary, treatment of HCV with Daclatasvir/Asunaprevir resulted in elevated LDL, and relative miR122 and PCSK9-A levels in serum appeared to have some association with LDL increase.

Carotid Intima-media Thickness and Small Dense Low-density Lipoprotein Cholesterol Increase after One Year of Treatment with Direct-acting Antivirals in Patients with Hepatitis C Virus Infection.

Objective Direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV) infection exert a significantly high sustained viral response (SVR), and patients experience a rebound increase in low-density lipoprotein cholesterol (LDL) and total cholesterol levels. Carotid intima-media thickness (IMT) is a highly reproducible and non-invasive parameter for assessing the atherosclerotic process, and the small dense (sd) LDL level is useful for clinically evaluating the atherogenic risk. Methods A total of 48 patients with chronic HCV infection were treated with DAAs. All patients exhibited an SVR 24 weeks later. We compared the metabolic profiles of the patients, including the sdLDL and IMT values, at the start of DAA treatment with those after one year of treatment. We verified whether the HCV clearance after the administration of DAAs is associated with the development of atherosclerosis. Results The sdLDL, %sdLDL (sdLDL/LDL), and LDL values were exacerbated after a year of treatment; however, the triglyceride level, glycated hemoglobin level, insulin resistance, and body weight remained unaltered. The max-IMT was increased after a year compared to that at the start of treatment. Differences in the max-IMT (dmax-IMT) were greater in men than in women; however, no correlation was observed between the dmax-IMT and genotype, fibrosis, hypertension, hyperlipidemia, diabetes, obesity, and dialysis status. The %sdLDL at the start and a year later was positively correlated with the dmax-IMT. No correlation was observed among various factors including the LDL, triglyceride, body mass index, insulin resistance and dmax-IMT. In uni- and multivariate analyses, a significant correlation was observed between %sdLDL≥16% at the start of treatment and the sex and dmax-IMT. Conclusion Because the sdLDL and IMT values were exacerbated after a year of DAA treatment, atherosclerosis must be evaluated in patients achieving an SVR.

Hepatitis C virus-related symptoms, but not quality of life, were improved by treatment with direct-acting antivirals.

AIM: Direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection have a significantly high sustained virologic response rate after a short treatment course and do not have any severe adverse effects. Patient-reported outcomes (PROs) have become increasingly important to assess the total impact of a chronic disease. We aimed to evaluate the changes in symptoms of patients with HCV infection treated with DAAs by using PROs. METHODS: A total of 107 patients with chronic HCV infection were treated with DAAs. Daclatasvir/asunaprevir or sofosbuvir/ledipasvir was used for HCV 1B infection, and sofosbuvir/ribavirin for HCV 2A/2B infection. The PROs measured at the start of treatment and 1 year after the start of treatment were cirrhosis-related symptom score (CSS), presence of restless legs syndrome (RLS), Epworth sleepiness scale (ESS), Pittsburg sleep quality index (PSQI), Kessler 6 score (K-6), and the SF-36 to measure quality of life (QOL). All patients had a sustained virologic response rate of 24. RESULTS: The CSS, PSQI, K-6, and RLS scores were improved 1 year after beginning treatment. However, QOL had not recovered. Changes in total CSS were correlated with HCV genotype, sex, hypertensive drug use, serum low-density lipoprotein, and ESS at the start of treatment and RLS 1 year after the start of treatment. The factors that contributed to worsening of CSS were HCV genotype 2B and RLS 1 year after the start of treatment. CONCLUSION: Treatment with DAAs eliminated HCV-RNA and improved most symptoms, but QOL did not recover.