ABSTRACT
The regulation of the circadian clock plays an important role in influencing physiological conditions. While it is reported that the timing and quantity of energy intake impact circadian regulation, the underlying mechanisms remain unclear. This study investigated the impact of dietary protein intake on peripheral clocks. Firstly, transcriptomic analysis was conducted to investigate molecular targets of low-protein intake. Secondly, mPer2::Luc knock-in mice, fed with either a low-protein, normal, or high-protein diet for 6 weeks, were analyzed for the oscillation of PER2 expression in peripheral tissues and for the expression profiles of circadian and metabolic genes. Lastly, the candidate pathway identified by the in vivo analysis was validated using AML12 cells. As a result, using transcriptomic analysis, we found that the low-protein diet hardly altered the circadian rhythm in the central clock. In animal experiments, expression levels and period lengths of PER2 were different in peripheral tissues depending on dietary protein intake; moreover, mRNA levels of clock-controlled genes and endoplasmic reticulum (ER) stress genes were affected by dietary protein intake. Induction of ER stress in AML12 cells caused an increased amplitude of Clock and Bmal1 and an advanced peak phase of Per2. This result shows that the intake of different dietary protein ratios causes an alteration of the circadian rhythm, especially in the peripheral clock of mice. Dietary protein intake modifies the oscillation of ER stress genes, which may play key roles in the regulation of the circadian clock.
Subject(s)
Circadian Rhythm , Dietary Proteins , Period Circadian Proteins , Animals , Mice , Circadian Rhythm/genetics , Period Circadian Proteins/genetics , Period Circadian Proteins/metabolism , Dietary Proteins/administration & dosage , Endoplasmic Reticulum Stress , Circadian Clocks/genetics , Male , Mice, Inbred C57BL , Gene Expression Regulation/drug effects , CLOCK Proteins/genetics , CLOCK Proteins/metabolism , ARNTL Transcription Factors/genetics , ARNTL Transcription Factors/metabolism , Gene Expression Profiling , Cell Line , TranscriptomeABSTRACT
The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.
Subject(s)
Leonurus , Plant Extracts , Probiotics , Humans , Double-Blind Method , Male , Female , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Middle Aged , Leonurus/chemistry , Probiotics/administration & dosage , Lactobacillus plantarum , Aged , Treatment Outcome , Gastrointestinal Microbiome/drug effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/microbiology , AdultABSTRACT
BACKGROUND: Myringotomy with tympanostomy tube insertion (MTI) is a superficial surgical procedure used to prevent hearing loss in children with serous otitis media. Intravenous anesthesia, often ketamine, is preferred for this procedure because of its ability to induce sedation without compromising airway reflexes. However, ketamine alone may be insufficient and potentially lead to spontaneous movement during surgery. This study evaluated the effectiveness of midazolam and fentanyl as adjuvants to ketamine in reducing spontaneous movement during MTI and enhancing the quality of recovery. METHODS: This study involved two groups of 30 patients each: one group received intravenous ketamine (1.5 mg/kg) with an equal volume of normal saline (K group), while the other received a combination of midazolam, fentanyl, and ketamine (0.05 mg/kg, 1 µg/kg, and 1.5 mg/kg, respectively; MFK group). We assessed side effects, intraoperative patient movement, surgeon satisfaction, and emergence agitation scores. RESULTS: The MFK group exhibited significantly lower scores for patient movement (p<0.01) and emergence agitation (p<0.01) and markedly higher surgeon satisfaction scores (p<0.01) than the K group. CONCLUSION: Administering a midazolam-fentanyl-ketamine combination effectively reduced spontaneous movement during surgery and emergence agitation during recovery without prolonging discharge times in children undergoing MTI.
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Nicotinamide Adenine Dinucleotide (NAD) is an endogenous substance in redox reactions and regulates various functions in metabolism. NAD and its precursors are known for their anti-ageing and anti-obesity properties and are mainly active in the liver and muscle. Boosting NAD+ through supplementation with the precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), enhances insulin sensitivity and circadian rhythm in the liver, and improves mitochondrial function in the muscle. Recent evidence has revealed that the adipose tissue could be another direct target of NAD supplementation by attenuating inflammation and fat accumulation. Moreover, murine studies with genetically modified models demonstrated that nicotinamide phosphoribosyltransferase (NAMPT), a NAD regulatory enzyme that synthesizes NMN, played a critical role in lipogenesis and lipolysis in an adipocyte-specific manner. The tissue-specific effects of NAD+ metabolic pathways indicate a potential of the NAD precursors to control metabolic stress particularly via focusing on adipose tissue. Therefore, this narrative review raises an importance of NAD metabolism in white adipose tissue (WAT) through a variety of studies using different mouse models.
Subject(s)
NAD , Nicotinamide Mononucleotide , Mice , Animals , NAD/metabolism , Nicotinamide Mononucleotide/metabolism , Nicotinamide Mononucleotide/pharmacology , Adipose Tissue/metabolism , Liver/metabolism , ObesityABSTRACT
The role of the muscle circadian clock in regulating oxidative metabolism exerts a significant influence on whole-body energy metabolism; however, research on the connection between the muscle circadian clock and obesity is limited. Moreover, there is a lack of studies demonstrating the regulatory effects of dietary butyrate on muscle circadian clock and the resulting antiobesity effects. This study aimed to investigate the impacts of dietary butyrate on metabolic and microbiome alterations and muscle circadian clock in a diet-induced obesity model. Male Sprague-Dawley rats were fed a high-fat diet with or without butyrate. Gut microbiota and serum metabolome were analyzed, and molecular changes were examined using tissues and a cell line. Further correlation analysis was performed on butyrate-induced results. Butyrate supplementation reduced weight gain, even with increased food intake. Gut microbiome analysis revealed an increased abundance of Firmicutes in butyrate group. Serum metabolite profile in butyrate group exhibited reduced amino acid and increased fatty acid content. Muscle circadian clock genes were upregulated, resulting in increased transcription of fatty acid oxidation-related genes. In myoblast cells, butyrate also enhanced pan-histone acetylation via histone deacetylase inhibition, particularly modulating acetylation at the promoter of circadian clock genes. Correlation analysis revealed potential links between Firmicutes phylum, including certain genera within it, and butyrate-induced molecular changes in muscle as well as phenotypic alterations. The butyrate-driven effects on diet-induced obesity were associated with alterations in gut microbiota and a muscle-specific increase in histone acetylation, leading to the transcriptional activation of circadian clock genes and their controlled genes.
Subject(s)
Circadian Clocks , Gastrointestinal Microbiome , Animals , Rats , Male , Circadian Clocks/genetics , Butyrates/pharmacology , Butyrates/metabolism , Histones/metabolism , Epigenesis, Genetic , Rats, Sprague-Dawley , Obesity/metabolism , Diet, High-Fat/adverse effects , Fatty Acids/metabolismABSTRACT
BACKGROUND/AIMS: The model for end-stage liver disease (MELD) serves as an indicator for short-term mortality among patients diagnosed with liver cirrhosis (LC) and is used to prioritize patients for liver transplantation. In 2021, the updated version of MELD, MELD-3.0, was introduced to improve the accuracy of the mortality prediction of MELD. Therefore, this study aimed to compare the efficacy of MELD 3.0 and MELD-Na in predicting mortality among Korean patients with LC. METHODS: A retrospective review was conducted using the medical records of patients diagnosed with LC who were admitted to Konkuk University Hospital From 2011 to 2021. The study calculated the predictive values of MELD-Na and MELD-3.0 for 3- and 6-months mortality using the area under the receiver operating curve (AUROC) and compared the results using the DeLong test. RESULTS: Of the 3,034 patients enrolled in the study, 339 (11.2%) died within 3 months and 421 (14.4%) died within 6 months. The AUROCs values for predicting 3 months mortality were 0.846 for MELD-Na and 0.851 for MELD-3.0. The corresponding AUROC values for predicting 6 months mortality were 0.843 for MELD-Na and 0.848 for MELD-3.0. MELD-3.0 exhibited better discrimination ability than MELD-Na for both 3 (p = 0.03) and 6 months mortality (p = 0.01). CONCLUSION: Our study found a significant difference between the performance of MELD-3.0 and MELD-Na in Korean patients with LC.
Subject(s)
End Stage Liver Disease , Humans , End Stage Liver Disease/diagnosis , Prognosis , Sodium , Predictive Value of Tests , Severity of Illness Index , Liver Cirrhosis/diagnosis , Retrospective Studies , Republic of Korea/epidemiology , ROC CurveABSTRACT
Background and Objectives: The Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) are classical systems for predicting mortality in patients with liver cirrhosis (LC). The MELD-GFR assessment in liver disease-sodium (MELD-GRAIL-Na) was designed to better reflect renal function and, therefore, provide better mortality predictions. This study aimed to compare the prediction accuracy of MELD-GRAIL-Na compared to CP and MELD in predicting short-term (1- and 3-month) mortality in Korean patients. Materials and Methods: Medical records of patients with LC admitted to the Konkuk University Hospital from 2015 to 2020 were retrospectively reviewed. Predictive values of the CP, MELD, and MELD-GRAIL-Na for 1-month and 3-month mortality were calculated using the area under the receiver operating curve (AUROC) and were compared using DeLong's test. Results: In total, 1249 patients were enrolled; 102 died within 1 month, and 146 within 3 months. AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.831, 0.847, and 0.857 for 1-month mortality and 0.837, 0.827, and 0.835 for 3-month mortality, respectively, indicating no statistical significance. For patients with CP classes B and C, AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.782, 0.809, and 0.825 for 1-month mortality and 0.775, 0.769, and 0.786 for 3-month mortality, respectively. There was a significant difference between CP and MELD-GRAIL-Na in predicting 1-month mortality (p = 0.0428) and between MELD and MELD-GRAIL-Na in predicting 1-month (p = 0.0493) and 3-month mortality (p = 0.0225). Conclusions: Compared to CP and MELD, MELD-GRAIL-Na was found to be a better and more useful system for evaluating short-term (1- and 3-month) mortality in Korean patients with cirrhosis, especially those with advanced cirrhosis (CP class B and C).
Subject(s)
End Stage Liver Disease , Liver Cirrhosis , Humans , End Stage Liver Disease/mortality , Liver Cirrhosis/mortality , Predictive Value of Tests , Prognosis , Republic of Korea/epidemiology , Retrospective Studies , ROC Curve , Severity of Illness Index , Sodium , East Asian PeopleABSTRACT
RATIONALE: Piriformis syndrome (PS) is neuromuscular disorder caused by sciatic nerve compression by piriformis muscle and related to sciatic-type pain. When the conservative care fails, local injection or surgery can be also performed into piriformis. In recent years, botulinum toxin (BoNT) has also been considered as a new therapeutic option of piriformis syndrome. PATIENT CONCERNS: A man in his late 40s came to pain clinic for left low back pain. The symptom was aggravated with sitting position. DIAGNOSIS: Piriformis syndrome. INTERVENTIONS: The patient underwent BoNT injection with 100 IU with 2 mL into piriformis muscle for piriformis syndrome treatment, and his pain was relieved. However, it recurred 8 months later. BoNT injection was repeated with 100 IU with 5 mL. OUTCOMES: At the time of this writing, his pain was reduced for 2 years without any medication. LESSONS: We report a case of treating relapsed piriformis syndrome with BoNT injection of different dilution volume, suggesting that the higher the dilution volume, the more effective for therapeutic effect of BoNT.
Subject(s)
Botulinum Toxins , Low Back Pain , Piriformis Muscle Syndrome , Sciatic Neuropathy , Male , Humans , Piriformis Muscle Syndrome/drug therapy , Sciatic Nerve , Botulinum Toxins/therapeutic use , Low Back Pain/drug therapyABSTRACT
Patients with chronic hepatitis B (CHB) who were administered tenofovir disoproxil fumarate (TDF)-based combination therapy after receiving multiple drugs are frequently switched to TDF monotherapy in South Korea. We evaluated the efficacy and safety of switching to TDF monotherapy from TDF-based combination therapy over 5 years. This was a retrospective study of multidrug-experienced CHB patients who switched from TDF-based combination therapy to TDF monotherapy after achieving a virologic response (VR; <20 IU/mL) at Konkuk University Hospital and Sanggye Paik Hospital. The biochemical response was defined as a normalized serum ALT level during follow-up. Each patient was assessed from the date of switching to TDF monotherapy to the date of the last follow-up over 5 years. A total of 39 patients who received at least one antiviral therapy before TDF-based combination therapy were analyzed. The median duration of VR before switching to TDF monotherapy was 18 months and the median duration of TDF monotherapy was 55 months. In this study, except for one patient who had poor compliance, all patients maintained a VR. Three patients had a temporarily increased HBV DNA level and 91.2% of the patients showed a biochemical response. Switching multidrug-experienced patients to TDF monotherapy is generally safe and effective.
Subject(s)
Hepatitis B, Chronic , Antiviral Agents , DNA, Viral , Drug Resistance, Viral , Drug Therapy, Combination , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Humans , Retrospective Studies , Tenofovir , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: It remains unknown whether tenofovir alafenamide (TAF) could replace tenofovir disoproxil fumarate (TDF) in patients with drug-resistant hepatitis B virus (HBV). METHODS: In this multicenter randomized non-inferiority trial, 174 patients with HBV resistant to multiple drugs (lamivudine, entecavir, and/or adefovir) under TDF monotherapy for ≥96 weeks were randomized 1:1 to switch to TAF (n = 87) or continue TDF (n = 87) for 48 weeks. The primary endpoint was proportion of patients with HBV DNA <60 IU/mL at week 48. RESULTS: At baseline, 84 and 80 patients had HBV DNA <60 IU/mL in the TAF and TDF groups, respectively. At week 48, the proportion of patients with HBV DNA <60 IU/mL was 98.9% (86/87) in TAF group, showing non-inferiority to TDF group (97.7%, 85/87; difference, 1.1%; 95% confidence interval, -2.7% to 5.0%). Changes in median alanine aminotransferase at week 48 from baseline were statistically different between TAF and TDF groups (-3 IU/L vs +2 IU/L; P = .02). TAF group showed a statistically greater increase in bone mineral density at spine (+1.84% vs +0.08%; P = .01) and numerically higher increase in mean estimated glomerular filtration rate (+8.2% vs +4.5%; P = .06) compared with TDF group. Compared with TDF group, TAF group showed significantly greater increases in mean body weight (0.71 vs -0.37 kg; P = .01) and total, low-density lipoprotein, and high-density lipoprotein cholesterol levels (P < .001 for all) at week 48 from baseline. CONCLUSIONS: TAF could be substituted for TDF in patients with multidrug-resistant HBV for improved bone and renal safety without a loss of efficacy. However, increases in body weight and cholesterol levels with TAF treatment would be a concern. ClinicalTrials.gov no.: NCT03241641.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Hepatitis B/drug therapy , Hepatitis B, Chronic/drug therapy , Humans , Tenofovir/analogs & derivatives , Tenofovir/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Holmium laser enucleation of the prostate (HoLEP) has become an important treatment modality for benign prostate hypertrophy. The aim of the present study was to compare regional anesthesia methods for HoLEP operation and to determine the optimal technique. METHODS: Sixty patients with American Society of Anesthesiologists scores of I-III were randomly allocated into 3 groups. Patients in group E received an epidural block with 75âmg of bupivacaine plus 50âµg of fentanyl. In group S, 15âmg of bupivacaine and 50âµg fentanyl were used for spinal anesthesia. In group SA, patients received saddle block with 15âmg of bupivacaine and 50âµg of fentanyl. RESULTS: Time to T10 dermatome block and to maximal level block were longest in group E (Pâ<â.05), and maximal sensorial block level was higher in group E than group SA (Pâ<â.05). There was a significant difference in postoperative motor block, but no difference in systolic blood pressure and heart rate. CONCLUSION: Among 3 techniques, saddle block might be preferable in HoLEP because an adequate sensorial level was achieved with lower motor block and stable hemodynamics.
Subject(s)
Anesthesia, Epidural/methods , Anesthesia, Spinal/methods , Laser Therapy/methods , Lasers, Solid-State/therapeutic use , Prostatectomy/methods , Prostatic Hyperplasia/surgery , Adjuvants, Anesthesia/administration & dosage , Aged , Aged, 80 and over , Anesthetics, Local/administration & dosage , Body Mass Index , Bupivacaine/administration & dosage , Fentanyl/administration & dosage , Humans , Male , Middle Aged , Prospective Studies , Time FactorsABSTRACT
Backgrounds/Aims: The HBsAg levels have been used to monitor the chronic hepatitis B (CHB) treatment response to antiviral therapy. On the other hand, it is unclear if the HBsAg quantification levels at each treatment point differ according to the HBeAg status and drug in CHB patients. This study compared the changes in HBsAg in CHB patients according to the HBeAg status and treatment drugs. Methods: CHB patients with at least 1 year of follow-up treatment with one drug, either entecavir (ETV) or tenofovir (TDF), were enrolled in this study. The mean HBsAg levels were measured annually for up to 6 years. A linear mixed model was used to compare the HBsAg quantification levels during the follow-up period. An independent samples t-test was used to analyze the differences in the HBsAg quantification levels at each treatment time point. Results: Ninety-seven patients were enrolled in this study; 59 among them were HBeAg-positive. Two patients in the TDF group achieved HBsAg seroconversion. The HBsAg level decreased during the follow-up in the ETV and TDF groups. The HBsAg level was lower in the TDF group than the ETV group during the follow-up. On the other hand, subgroup analysis showed that this trend was the same only in the HBeAg-negative patients, not in the HBeAg-positive patients. In the HBeAg-negative patients, HBsAg level in the TDF group was significantly lower than that in the ETV group at 36, 48, and 72 months. The change in HBsAg level from the baseline increased at a decreasing rate during the follow-up in both groups. Furthermore, the change in the HBsAg level in the TDF group was significantly larger than that of the ETV group at 36 months in the HBeAg-negative patients. Conclusions: Although TDF might be more efficient than ETV in reducing the HBsAg level in HBeAg-negative patients in a few years, HBsAg seroconversion occurred very rarely. A further large-scale, long-term study will be needed to confirm the antiviral effects on the HBsAg level.
Subject(s)
Hepatitis B, Chronic , Antiviral Agents/therapeutic use , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Nucleosides , Nucleotides , Pharmaceutical Preparations , Tenofovir/therapeutic use , Treatment OutcomeABSTRACT
Craniofacial hyperhidrosis causes sweating of the face and scalp due to excessive action of the sweat glands and manifests when patients become tense/nervous or develop an elevated body temperature. If noninvasive treatments are ineffective, invasive treatments such as a sympathetic block and resection are considered. A 32-year-old woman with no specific medical history was referred for uncontrolled craniofacial hyperhidrosis that included excessive sweating and hot flushing. Physical examination showed profuse sweating, and infrared thermography showed higher temperature in the neck and face than in the trunk. The patient underwent several stellate ganglion blocks, and her symptoms improved; however, the treatment effect was temporary. Botulinum toxin was then injected into the stellate ganglion. At the time of this writing, her sweating had been reduced for about 6 months and she was continuing to undergo follow-up. Craniofacial hyperhidrosis is a clinical condition in which patients experience excessive sweating of their faces and heads. It is less common than palmar and plantar hyperhidrosis. Botulinum toxin injection into the stellate ganglion is simple and safe and produces longer-lasting effects than other treatments, such as endoscopic sympathectomy and a single nerve block.
Subject(s)
Botulinum Toxins, Type A , Hyperhidrosis , Adult , Botulinum Toxins, Type A/therapeutic use , Female , Humans , Hyperhidrosis/drug therapy , Hyperhidrosis/surgery , Stellate Ganglion , Sweating , Sympathectomy , Treatment OutcomeABSTRACT
BACKGROUND: The efficacy of endoscopic ultrasonography for the follow-up of gastric varices treated with endoscopic variceal ligation (EVL) has not been established. AIM: To evaluate the diagnostic correlation of esophagogastroduodenoscopy (EGD) and high-frequency intraluminal ultrasound (HFIUS) for type 1 gastric varices (GOV1) after EVL and to identify the predictability for rebleeding of EGD and HFIUS. METHODS: In liver cirrhosis patients with GOV1, we performed endoscopic follow-up using EGD and HFIUS synchronously after EVL for hemorrhage from GOV1. Endoscopic grading and red color signs were analyzed using EGD, and the largest variceal cross-sectional areas were measured using HFIUS. In addition, 1-year follow-up was performed. Variceal rebleeding was defined as the presence of hematemesis, hematochezia, or melena without other evidence of bleeding on endoscopic follow-up. RESULTS: In 26 patients with GOV1, variceal cross-sectional areas on HFIUS of GOV1 was poorly correlated with EGD grading of GOV1 (r = 0.36). In 17 patients who completed the 1-year follow-up, variceal cross-sectional areas on HFIUS was a good predictor of subsequent rebleeding, whereas EGD grading was not a predictor of subsequent rebleeding. CONCLUSION: HFIUS measurement is more predictive of GOV1 rebleeding than EGD grading, so HFIUS measurement may be necessary for endoscopic follow-up after EVL in patients with GOV1.
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Background/Aims: Because hepatitis B virus (HBV) replication has been known to play an important role in cancer recurrence after curative treatment of HBV-related hepatocellular carcinoma (HCC), we examined whether treatment based on nucleos(t)ide analogues (NAs) might decrease the recurrence rate and improve patient survival. Methods: The retrospective cohort study enrolled 73 patients with chronic hepatitis B who were treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) with curative intent for HCC. Among those, 30 and 43 patients were treated with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), respectively. Results: Of the 73 patients, 51 experienced HCC recurrence, and 14 patients were dead during a follow-up of 73±34 months. Multivariate analyses showed that tumor size (hazard ratio [HR], 1.590; 95% confidence-interval [CI], 1.106-2.285; P=0.012) and Child-Pugh class B (vs. class A/non cirrhosis; HR, 5.794; 95% CI, 2.311-14.523; P=0.001) was significantly associated with HCC recurrence, and Child-Pugh class B (HR, 7.357; 95% CI, 2.100-25.777; P=0.002) was an independent unfavorable prognostic factor for survival. During NAs therapy, TDF was superior to ETV for complete viral response at 1 year after the date of combination of TACE and RFA (P=0.016). However, the risks of HCC recurrence and survival were not significantly different between those treated with TDF versus ETV. Conclusions: TDF was superior to ETV for achieving complete viral response. However, the recurrence and mortality after TACE and RFA for HBV-related HCC were not significantly different between patients treated with TDF versus ETV.
ABSTRACT
BACKGROUND/AIMS: Chronic hepatitis C (CHC) treatment has dramatically improved since direct-acting antiviral (DAA) therapy was introduced. However, the use of DAA therapy in CHC patients with hepatocellular carcinoma (HCC) remains controversial. We investigated the DAA treatment response in CHC patients with HCC. METHODS: We retrospectively analyzed CHC patients treated with DAA from 2016 to 2018. Patients were divided into two groups based on their HCC-history before DAA therapy. Baseline characteristics, sustained virologic response at 12 weeks (SVR 12), and HCC recurrence after DAA therapy were evaluated. We also used propensity score matching (PSM) in a 2:1 ratio to reduce confounding variables. RESULTS: A total of 192 patients were enrolled; 78.1% were treatment-naïve, and 34.9% had liver cirrhosis (LC). Among these patients, 168 did not have HCC, and 24 had HCC. The HCC group was older (57.0 years vs. 72.0 years, p < 0.001), had a higher incidence of LC (26.2% vs. 95.8%, p < 0.001), fibrosis-4 index (2.6 vs. 9.2, p < 0.001), liver stiffness measurement (7.0 kPa vs. 17.4 kPa, p = 0.012), and α-fetoprotein (4.4 ng/mL vs. 8.2 ng/mL, p ≤ 0.001). The SVR 12 rate was 97.0% in the non- HCC group and 91.7% in the HCC group (p = 0.213). HCC recurrence was observed in 14 patients (58.3%) in the HCC group. CONCLUSION: DAA treatment efficacy in CHC patients with or those without HCC were not significantly different, and HCC recurrence was relatively common.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Liver Neoplasms , Antiviral Agents/adverse effects , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/etiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Humans , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local , Retrospective StudiesABSTRACT
INTRODUCTION: Because nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of chronic liver disease, noninvasive evaluations of its severity are immediately needed. This prospective cross-sectional study evaluated the effectiveness of noninvasive assessments of hepatic steatosis, fibrosis, and steatohepatitis. METHODS: Patients underwent laboratory tests, liver biopsy, transient elastography, and MRI. Multiparametric MR was used to measure MRI proton density fat fraction, MR spectroscopy, T1 mapping, and MR elastography (MRE). RESULTS: We enrolled 130 patients between October 2016 and July 2019. For the diagnosis of moderate-to-severe steatosis (grade ≥ 2), the area under the receiver operating characteristic curve (AUROC) was lower in controlled attenuation parameter (0.69; 95% confidence interval [CI], 0.60-0.76) than MRI proton density fat fraction (0.82; 95% CI, 0.75-0.89; P = 0.008) and MR spectroscopy (0.83; 95% CI, 0.75-0.89; P = 0.006). For the diagnosis of advanced fibrosis (stage ≥ 3), the AUROC of MRE (0.89; 95% CI, 0.83-0.94) was superior compared with those of the Fibrosis-4 index (0.77; 95% CI, 0.69-0.84; P = 0.010), NAFLD fibrosis score (0.81; 95% CI, 0.73-0.87; P = 0.043), and transient elastography (0.82; 95% CI, 0.74-0.88; P = 0.062). For detecting advanced fibrosis or nonalcoholic steatohepatitis, the AUROC of MRE (0.86; 95% CI, 0.79-0.91) was higher than that of TE (0.76; 95% CI, 0.68-0.83) with statistical significance (P = 0.018). DISCUSSION: Multiparametric MR accurately identified a severe form of NAFLD. Multiparametric MR can be a valuable noninvasive method for evaluating the severity of NAFLD.
Subject(s)
Liver Cirrhosis/diagnosis , Liver/diagnostic imaging , Multiparametric Magnetic Resonance Imaging , Non-alcoholic Fatty Liver Disease/diagnosis , Severity of Illness Index , Adult , Cross-Sectional Studies , Elasticity Imaging Techniques/methods , Feasibility Studies , Female , Humans , Liver/pathology , Liver Cirrhosis/pathology , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/pathology , Prospective Studies , ROC CurveABSTRACT
Background/Aims: A switch to systemic therapy, such as sorafenib, should be considered for hepatocellular carcinoma (HCC) patients refractory to transarterial chemoembolization (TACE). On the other hand, treatment changes are difficult if the liver function worsens to Child-Pugh B or C. Therefore, predicting the risk factors for non-responsiveness to TACE and deteriorating liver function may be helpful. Methods: Newly diagnosed Child-Pugh A HCC patients who underwent TACE from January 2012 to June 2018 were included. After 1 year, this study evaluated whether there was a treatment response to TACE and whether the Child-Pugh class had worsened. Results: Among 121 patients, 65 were refractory and 56 responded to TACE. In multivariable logistic regression analysis, the tumor size, tumor number, and albumin at the time of the diagnosis of HCC were significant prognostic factors for the treatment response to TACE. Among 65 patients who presented TACE-refractoriness, 27 showed liver function deterioration from Child-Pugh class A to class B or C after TACE. In multivariable logistic regression analysis, bilirubin at the diagnosis of HCC was a significant prognostic factor for liver function deterioration. A predictive algorithm based on the regression equations revealed a sensitivity, specificity, positive predictive value, and negative predictive value of 74.1%, 74.5%, 45.5%, and 90.9%, respectively, for TACE-refractoriness and liver function deterioration. Conclusions: The prognostic model incorporating the tumor size, tumor number, albumin, and bilirubin at the diagnosis of HCC may help identify patients who show a poor response to TACE and aggravation of liver function after TACE, who may benefit from early switching into systemic therapy before liver function aggravation.
Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/adverse effects , Liver Neoplasms/therapy , Liver/physiopathology , Aged , Area Under Curve , Bilirubin/analysis , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Logistic Models , Male , Middle Aged , Neoplasm Staging , Prognosis , ROC Curve , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy, arising from the peripheral intrahepatic bile duct epithelium. Hepatitis B virus (HBV) or hepatitis C virus (HCV) may be involved in the development of ICC. We explored the prognostic value of hepatitis virus infection, as well as other prognostic factors affecting survival in patients with ICC. METHODS: A retrospective chart review was performed for patients diagnosed with ICC between August 2005 and December 2018 at Konkuk University Medical Center. We identified a total of 131 patients with ICC. Overall survival rates of patients with and without hepatitis were determined. Univariate and multivariate analyses were used to estimate factors influencing survival outcomes. RESULTS: A total of 17.6% (23/131) of patients were positive for HBV or HCV. Hepatitis B positive ICC patients were significantly younger with higher albumin and higher α-fetoprotein than those without hepatitis viral infections. The median survival of hepatitis-positive and hepatitis-negative groups was 280 and 213 days, respectively. Survival rates were not significantly different between the two groups (p = 0.279). Multivariate analyses indicated that lower serum carbohydrate antigen 19-9 (CA 19-9) (p < 0.001), lower T stage (p = 0.042), the absence of lymph-node metastasis (p = 0.043), and receiving curative surgery (p = 0.033) were independent predictors of better outcomes. CONCLUSION: While hepatitis influenced a number of clinical features in ICC patients, it did not affect survival rate. Prognostic factors influencing survival outcomes with ICC were CA 19-9 level, T stage, the presence of lymph node metastasis, and curative surgery.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Hepatitis B , Liver Neoplasms , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic , Hepatitis B/diagnosis , Humans , Prognosis , Retrospective StudiesABSTRACT
Alpha fetoprotein (AFP) has been used as a serologic indicator of hepatocellular carcinoma (HCC). We aimed to identify an HCC-specific serum biomarker for diagnosis using a multiplexed proteomic technique in HCC patients with normal AFP levels. A total of 152 patients were included from Guro Hospital, Korea University. Among 267 identified proteins, 28 and 86 proteins showed at least a two-fold elevation or reduction in expression, respectively. Multiple reaction monitoring (MRM) analysis of 41 proteins revealed 10 proteins were differentially expressed in patients with liver cirrhosis and HCC patients with normal AFP. A combination of tripartite motif22 (Trim22), seprase, and bone morphogenetic protein1 had an area under receiver operating characteristic of 0.957 for HCC diagnosis. Real-time PCR and western blot analysis of the paired tumor/non-tumor liver tissue in HCC revealed a reduced expression of Trim22 in the tumor tissue. Also, serum levels of Trim22 were significantly reduced in HCC patients with normal AFP compared to those with liver cirrhosis (p = 0.032). Inhibition of Trim22 increased cellular proliferation in human hepatoma cell lines, whereas overexpression of Trim22 decreased cellular proliferation in hepatoma cell lines. In conclusion, the combination of three serum markers improved the chance of diagnosing HCC. MRM-based quantification of the serum protein in patients with normal AFP provides the potential for early diagnosis of HCC.