Treatment of Hepatitis C Virus Infection with Direct-acting Antiviral Agents Elevates the Serum Small-dense Low-density Lipoprotein Cholesterol Level.

Objective The low-density lipoprotein cholesterol (LDL) level is known to increase following the treatment of hepatitis C virus (HCV) infection using direct-acting antiviral agents (DAAs). This study aimed to investigate the changes in the lipid profiles, including small-dense LDL cholesterol (sdLDL), in HCV patients treated with DAAs. Patients We retrospectively assessed 67 HCV patients who achieved sustained virological response with DAA administration and were observed for more than 2 years, of whom 32 were on daclatasvir/asunaprevir, 14 were on sofosbuvir/ledipasvir, and 21 were on sofosbuvir/ribavirin. Methods We evaluated the lipid profiles, including sdLDL, every 6 months until 2 years after the start of treatment and analyzed the factors related to changes in the sdLDL level. Results The median sdLDL value at baseline was 12.8 mg/dL, which increased to 19.5 mg/dL at 6 months (p<0.001) and remained elevated at 25.4 mg/dL at 2 years later (p<0.001). The Kaplan-Meier curve indicated that patients with high values of LDL, albumin, muscle attenuation and visceral to subcutaneous adipose tissue area ratio were at increased risk for elevation of sdLDL over 35 mg/dL (log-rank test: p<0.001; p=0.008, p=0.002 and p=0.042, respectively). A multivariate analysis performed on the factors contributing to elevation of sdLDL 2 years after DAA treatment (≥35.0 mg/dL) revealed pretreatment LDL (≥91.0 mg/dL) and muscle attenuation (≥33.7 HU) as significant factors (p=0.007 and p=0.032, respectively). Conclusion SdLDL increased continuously after DAA treatment, and high LDL levels and low intramuscular fat deposition before treatment contributed to elevated sdLDL levels after treatment.

Indices calculated by serum creatinine and cystatin C as predictors of liver damage, muscle strength and sarcopenia in liver disease.

Serum creatinine (Cr)-based glomerular filtration rate (CrGFR) is overestimated in liver disease. The present study evaluated whether the difference in CrGFR and cystatin C (CysC) GFR (dGFR) is significant in liver disease. The Cr-to-CysC ratio and sarcopenia index (SI) have been reported to correlate with muscle volume. An estimated total body muscle mass with Cr, CysC and calculated body muscle mass (CBMM) has also been reported to correlate with muscle mass. The applicability of dGFR, SI and CBMM for liver disease were evaluated. A total of 313 patients with liver damage were evaluated for Child-Pugh score, albumin-bilirubin (ALBI) score, model for end-stage liver disease, fibrosis-4, Cr, CysC, Cr-based estimated GFR (CreGFR), CysCGFR and grip strength. Of the 313 patients, 199 were evaluated using cross-sectional computed tomography (CT) of the third lumbar vertebra to determine the skeletal muscle (SM) mass. dGFR, CBMM and SI were compared to liver damage, muscle strength and muscle mass. In the 313 patients, dGFR was correlated with age, ALBI and grip strength; CBMM was correlated with body mass index (BMI) and grip strength; and SI was correlated with BMI and grip strength. In patients evaluated with CT, the correlation coefficients for CBMM and SI with SM were 0.804 and 0.293, respectively. Thus, CBMM and SI were associated with sarcopenia. The relationship between dGFR and ALBI does not differ with different grades of CrGFR-based chronic kidney disease (CKD). dGFR is a marker of liver damage and muscle strength regardless of CKD. CBMM and SI are markers for sarcopenia in liver disease.

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.

Relationship of tooth grinding pattern during sleep bruxism and dental status.

Tooth grinding during sleep is thought to be one of the important factors causing oral diseases. However, no evidence is available regarding the relationship between the dental status and tooth contact during sleep bruxism. The purpose of this clinical study was to investigate the relationship between oral diseases and tooth grinding patterns during sleep bruxism. Fifty subjects (21 men and 29 women) were selected. The clinical attachment level, tooth mobility, noncarious cervical lesion (NCL) and hypersensitivity were examined in each tooth. Subjects wore a bruxism-recording device to visualize the grinding pattern during sleep bruxism. The grinding pattern was categorized into laterotrusive grinding (LG) and mediotrusive side grinding (MG). Furthermore, LG was divided into three types: incisor-canine (IC), incisor-canine-premolar (ICP), and incisor-canine-premolar-molar (ICPM) types. The average attachment level and tooth mobility of the ICPM and ICPM+MG types were much more aggravating than those of the IC or ICP types. The NCL encountered in the ICPM type was more aggravating than the other types. The average NCL of the ICPM type was significantly larger than that of the IC (p = 0.01), the ICP (p = 0.05), the ICP+MG (p = 0.05) and the ICPM+MG (p = 0.05) types and MG (p = 0.01). The average hypersensitivity of the ICP type was significantly greater than that of the IC type (p = 0.05). There was a moderate correlation between the attachment level and mobility. It was concluded that grinding patterns during sleep bruxism should be considered as a probable causative factor in the development of dental problems related to clinical attachment level, tooth mobility, NCL, and hypersensitivity, especially the ICPM type and mediotrusive grinding that seems to be the pattern that could more easily deteriorate the dental condition.

Relationship of tooth grinding pattern during sleep bruxism and temporomandibular joint status.

The purpose of this study was to investigate the relationship between tooth grinding pattern during sleep bruxism and temporomandibular joint (TMJ) status based on condylar movement. Fifty subjects (21 males and 29 females) wore a bruxism recording device, BruxChecker, to record their grinding pattern during sleep bruxism. The grinding pattern was categorized into laterotrusive grinding (LG) and mediotrusive side grinding (MG). Furthermore, LG was divided into three types; incisor-canine (IC), incisor-canine-premolar (ICP) and incisor-canine-premolar-molar (ICPM) type. Condylar movements were also recorded using computer-aided axiograph to evaluate the signs of TMJ hypermobility. The average maximum separation distance of excursion and incursion and the average maximum condylar lateral deviation during protrusion/retrusion and open/close movements in the ICPM type and the ICPM+MG type were larger than those of the IC and ICP types. While reconstructing the occlusion, it is important to take into consideration the presence of bruxing patterns of the ICPM type and mediotrusive side grinding.

An atypical case of "Takotsubo cardiomyopathy" during alcohol withdrawal: abnormality in the transient left ventricular wall motion and a remarkable elevation in the ST segment.

A 64-year-old man was admitted due to hypokalemia-related myopathy. He was heavy drinker. He felt the stress of alcohol withdrawal during his hospitalization. The patient suffered a cardiopulmonary arrest lasting approximately 5 minutes on the fifth hospital day. One day later, ST-segment elevation was observed in leads I, aV(L), and V(2-6). Emergent cardiac catheterization was performed for suspicion of acute myocardial infarction. Normal coronary arteries with anterior akinesis of the left ventricle were revealed during the procedure. The present case may be an atypical form of "Takotsubo cardiomyopathy" in which the left ventricular contraction is due to focal anterior wall motion abnormalities.