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Background Many studies have revealed that mucosal healing improves the long-term prognosis of ulcerative colitis. Frequent colonoscopy is difficult because of its invasiveness and cost. Therefore, in diagnosing and treating ulcerative colitis, noninvasive, low-cost methods for predicting mucosal healing using useful biomarkers are required in the clinical setting. This study aimed to evaluate whether serum amyloid A is a better serum biomarker than C-reactive protein in predicting mucosal healing in ulcerative colitis patients in clinical remission. Methods Ulcerative colitis patients whose C-reactive protein and serum amyloid A were measured within 1 month before and after colonoscopy were included in this retrospective study, and the relationship between the C-reactive protein and serum amyloid A values and the mucosal condition was analyzed. Mucosal condition was assessed using the Mayo Endoscopic Score, with score 0 or 1 indicating mucosal healing. Results A total of 199 colonoscopic examinations were conducted in 108 ulcerative colitis patients who underwent C-reactive protein and serum amyloid A blood tests. In clinical remission patients, serum amyloid A showed a strong correlation with mucosal inflammation compared to C-reactive protein and had excellent sensitivity and specificity rates with significant statistical significance. Conclusions Serum amyloid A is a more useful marker compared to C-reactive protein in predicting mucosal inflammation in ulcerative colitis patients in clinical remission.

Background We report the case of a patient with smoking‐induced radiation laryngeal necrosis (RLN) after undergoing definitive radiotherapy (RT) alone for T1a glottic squamous cell carcinoma. Case The patient was a 63‐year‐old man who had a history of heavy smoking. He quit smoking when he was diagnosed with glottic squamous cell carcinoma. The RT dose was 63 Gy, delivered in 28 fractions with the three‐dimensional conventional RT technique for the larynx. After RT completion, the initial treatment response was complete response. He then underwent follow‐up examinations. At 13 months after RT, the patient resumed smoking. At 2 months after resuming smoking, he had severe sore throat and hoarseness. Laryngoscopy revealed a large tumor in the glottis. Surgical excision was performed, and the patient was histologically diagnosed with RLN, as late toxicity without cancer recurrence. At 3 weeks postoperatively, the patient had dyspnea, and laryngoscopy revealed total laryngeal paralysis. Thus, he underwent an emergent tracheostomy. The administration of steroids affected RLN, and laryngeal paralysis gradually improved. Conclusions This case suggests that smoking may have the potential to induce RLN after RT. Moreover, continuing smoking cessation is significantly important for patients with glottic cancer who receive RT. Rather than leaving smoking cessation up to the patient, it would be necessary for clinicians to actively intervene to help patients continue their effort to quit smoking.

The aim of the present study was to evaluate the prognostic significance of serum markers that reflect tumor progression, liver function, or liver fibrosis in patients with hepatocellular carcinoma (HCC), focusing on how their impact changes over time after diagnosis. Alpha‐fetoprotein (AFP), des‐gamma‐carboxy prothrombin (DCP), albumin‐bilirubin (ALBI) score, aspartate aminotransferase to platelet ratio index (APRI), and FIB‐4 index were measured at the time of initial non‐recurrent HCC diagnosis in 1669 patients between 1997 and 2016. Survival rates after diagnosis were compared after stratifying patients by these markers. Time‐dependent receiver‐operating characteristics (ROC) analysis was carried out to assess how these markers predict patient survival or death. Serum AFP and DCP levels, ALBI score, and APRI and FIB‐4 index were strongly correlated with HCC progression, liver function, and degree of liver fibrosis, respectively. Survival rates after diagnosis were significantly different when patients were stratified by these markers. In the time‐dependent ROC analysis, AFP and DCP had a high prognostic impact within 3 years of diagnosis but the impact decreased thereafter. In contrast, APRI and FIB‐4 index had higher prognostic impact 10 years after diagnosis. ALBI score had a high prognostic impact throughout the study period. Time‐dependent ROC analysis clearly showed changes in the prognostic importance of serum markers based on the duration after diagnosis. Whereas the prognostic impact of tumor progression markers was strong in the short term, liver fibrosis markers had higher prognostic impact long after diagnosis. Liver function had constant prognostic impact on patient survival after diagnosis. Although tumor progression, liver function, and the degree of liver fibrosis significantly predict the survivals of patients with hepatocellular carcinoma, respectively, the impacts of these factors on patient prognosis are different over time.

BackgroundEven though both interferon (IFN)-based and direct-acting antiviral (DAA) therapies against hepatitis C virus (HCV) reduce the risk of hepatocellular carcinoma (HCC), post-sustained virological response (SVR) patients remain at elevated risk of HCC.MethodsA total of 4620 patients who achieved SVR were enrolled in this retrospective cohort study. After excluding patients who had a history of HCC or developed HCC within 1 year and whose follow-up period was less than 1 year and who were positive for HBsAg, we investigated the association between clinical characteristics and HCC development after SVR in the remaining 3771 patients.ResultsMedian observation period was 41 months. We confirmed known risk factors. In addition, we found that PNPLA3 and HLA-DQB1 polymorphisms were associated with HCC after SVR. Finally, we propose an estimation model for the incidence of HCC after SVR. Based on gender, FIB-4 index, AFP, and PNPLA3 polymorphism, about 18% of all patients were classified as having high risk, with a cumulative incidence rate (CIR) at 5 years of 16.5%. Another 17% were classified as having moderate risk with a CIR of 7.6%. The remaining 65% showed a CIR of 0.5%. The effect of PNPLA3 polymorphism might be more pronounced in patients with lower body mass index (BMI) and without diabetes mellitus compared to those with higher BMI and diabetes mellitus.ConclusionsWe demonstrated that PNPLA3 and HLA-DQB1 polymorphisms were associated with HCC after SVR. These findings might be useful to inform risk stratification for HCC surveillance after SVR.

Background Fatty liver is frequently found in a general population, and it is critical to detect advanced fibrosis. FIB-4 index is considered a useful marker for evaluating liver fibrosis but the distribution of FIB-4 index in the general population remains unknown. Methods This cross-sectional study included residents who underwent ultrasonography at health checkups in Hiroshima or Iwate prefectures. The distribution of FIB-4 index in the total study population (N = 75,666) as well as in non-alcoholic fatty liver disease (NAFLD) populations (N = 17,968) and non-drinkers without fatty liver populations (N = 47,222) was evaluated. The distribution of aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT) levels was also evaluated. Results The mean FIB-4 index in the total study population was 1.20 ± 0.63. FIB-4 index ≥ 2.67, which indicates a high risk of liver fibrosis, was found in 16.4% of those aged ≥ 70 years. In the NAFLD population, 58.1% of those in their 60 s and 88.1% of those ≥ 70 years met the criteria for referral to hepatologists by using the recommended FIB-4 index cutoff value (≥ 1.3). The mean FIB-4 index in the NAFLD population (1.12 ± 0.58) was significantly lower than in the non-drinkers without fatty liver (1.23 ± 0.63, p  < 0.0001). The non-drinkers without fatty liver tended to have higher AST relative to ALT levels (60.0% with AST/ALT > 1.0), whereas the results in the NAFLD population were opposite (14.8% with AST/ALT > 1.0). AST > ALT resulted in a higher FIB-4 index in non-drinkers without fatty liver due to the nature of FIB-4 index formula. Conclusions The cutoff value of FIB-4 index (≥ 1.3) for triaging the elderly people with fatty liver for referral to hepatologists should be reconsidered to avoid over-referral. Due to the impact of age and characteristics of AST/ALT ratios, there is no prospect of using FIB-4 index for primary screening for liver fibrosis in a general population of unknown presence or absence of liver disease, even though it can be easily calculated using routine clinical indices. It is desired to develop a non-invasive method for picking up cases with advanced fibrosis latent in the general population.

Background: Background liver function in patients with hepatocellular carcinoma (HCC) has improved remarkably with advances in various treatments. Recently, the Child-Pugh classification (CPC) system has been recognized as limited in its ability to assess patients with good hepatic reserve. We compared the albumin-bilirubin (ALBI) grade, which is suitable for a more detailed evaluation of patients with good liver function, with CPC over a 30-year period. Methods: A total of 2,347 patients were analyzed. Patients were stratified by year of diagnosis into 6 groups: Group A (1990–1994, n = 376), Group B (1995–1999, n = 434), Group C (2000–2004, n = 438), Group D (2005–2009, n = 444), Group E (2010–2014, n = 392), and Group F (2015–2018, n = 263). We compared ALBI grade and CPC across the groups. Results: The prevalence of patients with CPC A at diagnosis increased throughout the study period, reaching nearly 80% in Groups E and F (p < 0.001). By contrast, the percentage of patients with ALBI grade 1 disease remained approximately 50% in Groups E and F (p < 0.001). Modified ALBI (mALBI) grade 2a corresponds to patients with CPC A who have poor hepatic function. There were significant survival differences between patients with mALBI grade 1 versus 2a, 1 versus 2b, and 2a versus 2b disease, respectively (p < 0.0001), in patients with CPC A. Conclusions: CPC is not suitable for assessing patients with recently diagnosed HCC and good remnant hepatic function. In such patients with HCC, the prognosis can be stratified by ALBI grade rather than CPC.

Background Prognosis of patients with hepatocellular carcinoma (HCC) remains poor because HCC is frequently diagnosed late. Therefore, regular surveillance has been recommended to detect HCC at the early stage when curative treatments can be applied. HCC biomarkers, including Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), are widely used for surveillance in Japan. A newly developed immunoassay system measures AFP-L3 % with high sensitivity. This retrospective study aimed to evaluate clinical utility of high-sensitivity AFP-L3 (hs-AFP-L3) as a predictor of early stage HCC in surveillance at a single site. Methods Of consecutive 2830 patients in the surveillance between 2000 and 2009, 104 HCC-developed and 104 non-HCC patients were selected by eligibility criteria and propensity score matching. Samples were obtained from the HCC patients who had blood drawn annually for 3 years prior to HCC diagnosis. Results In the present study, hs-AFP-L3 was elevated 1 year prior to diagnosis in 34.3 % of patients. The survival rate of patients with the hs-AFP-L3 ≥ 7 % at 1 year prior to diagnosis was significantly lower than that of patients with hs-AFP-L3 < 7 %. Conclusions Elevation of hs-AFP-L3 was early predictive of development of HCC even at low AFP levels and in absence of ultrasound findings of suspicious HCC. The hs-AFP-L3 should be added to surveillance programs with US because elevated hs-AFP-L3 may be a trigger to perform enhanced imaging modalities for confirmation of HCC.

miRNAs circulating in the blood in a cell-free form have been acknowledged for their potential as readily accessible disease markers. Presently, histological examination is the golden standard for diagnosing and grading liver disease, therefore non-invasive options are desirable. Here, we investigated if miRNA expression profile in exosome rich fractionated serum could be useful for determining the disease parameters in patients with chronic hepatitis C (CHC). Exosome rich fractionated RNA was extracted from the serum of 64 CHC and 24 controls with normal liver (NL). Extracted RNA was subjected to miRNA profiling by microarray and real-time qPCR analysis. The miRNA expression profiles from 4 chronic hepatitis B (CHB) and 12 non alcoholic steatohepatitis (NASH) patients were also established. The resulting miRNA expression was compared to the stage or grade of CHC determined by blood examination and histological inspection. miRNAs implicated in chronic liver disease and inflammation showed expression profiles that differed from those in NL and varied among the types and grades of liver diseases. Using the expression patterns of nine miRNAs, we classified CHC and NL with 96.59% accuracy. Additionally, we could link miRNA expression pattern with liver fibrosis stage and grade of liver inflammation in CHC. In particular, the miRNA expression pattern for early fibrotic stage differed greatly from that observed in high inflammation grades. We demonstrated that miRNA expression pattern in exosome rich fractionated serum shows a high potential as a biomarker for diagnosing the grade and stage of liver diseases.

BackgroundThe relationship between the hepatitis B e antigen (HBeAg) seroconversion and the long-term natural history of liver disease has not been sufficiently investigated.MethodsA total of 408 [4352 person-year (PY) units] patients with chronic hepatitis B virus (HBV) without antiviral therapy were enrolled. The study patients were divided into three groups, as follows: Group A (2666 PY units), seroconverted of HBeAg at age < 40; Group B (413 PY units), seroconverted of HBeAg at age ≥ 40; Group C (1273 PY units), persistently HBeAg positive. Yearly transition probabilities from each liver state [chronic HBV infection, chronic hepatitis B, cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) negativity] were calculated using the Markov chain model.ResultsIn the analysis of 1 year liver disease state transition probabilities, the liver states remained almost the same in Group A. In Groups B and C, each liver state tended to progress to a worse state. Assuming a chronic hepatitis B state at age 40 as the starting condition for simulation over the next 40 years, the chronic hepatitis B state accounted for approximately 60% of males aged ≥ 50 and approximately 40% of females aged ≥ 60 in Group A, and the HBsAg-negative state accounted for approximately 30–40% of males and females aged ≥ 60. In Groups B and C, the probabilities of patients with cirrhosis and HCC gradually increased with age.ConclusionsNot only patients with persistent HBeAg positive, but also patients with delayed HBeAg seroconversion showed poor prognosis of liver-related natural history.

Purpose: This study prospectively compared the diagnostic accuracy of vibration-controlled transient elastography (VCTE) and point shear wave elastography (pSWE) in the assessment of liver fibrosis, versus a reference standard of magnetic resonance elastography (MRE).Methods: This study prospectively enrolled patients with chronic liver disease, who underwent pSWE, VCTE, and MRE. Fibrosis was staged based on liver stiffness (LS) values measured using MRE: F0 (<2.61 kPa), F1 (≥2.61 to <2.97 kPa), F2 (≥2.97 to <3.62 kPa), F3 (≥3.62 to <4.69 kPa), and F4 (≥4.69 kPa). Each modality was performed independently, and the results were blinded to minimize bias. Diagnostic performance was assessed using the Pearson correlation coefficient (CC), Lin concordance correlation coefficient (CCC), area under the receiver operating characteristic curve (AUROC), Obuchowski index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI).Results: In total, 251 patients (median age, 64 years; 97 women) were evaluated. Both pSWE (CC, 0.838; CCC, 0.825) and VCTE (CC, 0.803; CCC, 0.784) demonstrated strong correlations with MRE, with no statistically significant differences. AUROC values for diagnosing fibrosis stage were comparable between pSWE and VCTE. Based on the Obuchowski index, pSWE provided closer agreement with MRE in detecting ≥F1, ≥F2, and ≥F4. Analyses of IDI and NRI also displayed significantly better agreement between pSWE and MRE in detecting ≥F1, ≥F2, and ≥F4 (NRI: P<0.001; IDI: F1 and F2, P<0.001; F4, P=0.002).Conclusion: pSWE demonstrated closer alignment than VCTE with LS values measured by MRE, suggesting the potential of pSWE for noninvasively assessing liver fibrosis.