Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

A Single Nucleotide Polymorphism rs1010816 Predicts Sorafenib Therapeutic Outcomes in Advanced Hepatocellular Carcinoma.

Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 × 10-7) was associated with sorafenib therapeutic response in aHCC patients. Kaplan-Meier analysis indicated that the "TT" genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 "TT" genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 "TT" genotype.

Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS. CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.

Blood lead level: an overlooked risk of carpal tunnel syndrome in hemodialysis patients.

Introduction: Carpal tunnel syndrome (CTS) is a severe complication observed in long-term maintenance hemodialysis (MHD) patients. The most common cause of CTS is dialysis-related ß2-microglobulin amyloidosis, which is associated with inflammation and oxidative stress in dialysis patients. Patients on MHD have higher blood lead levels (BLLs) than the general population. Lead (Pb) exposure in chronic dialysis patients has been noted to induce oxidative stress and inflammation. Therefore, lead-related inflammation and oxidative stress might contribute to CTS. Methods: The medical records of 866 MHD patients were reviewed. Two hundred and thirty-four patients with symptoms of CTS were surveyed by senior neurologists via physical examinations and nerve conduction studies. Patients in this study were stratified into groups with low-normal (<10 µg/dL), high-normal (10 to 20 µg/dL), and abnormal (>20 µg/dL) BLLs. The associations between CTS and BLLs and the clinical data were analyzed. Results: Multivariate logistic regression analyses showed that Log BLL (OR: 54.810, 95% CI: 13.622-220.54, p < .001), high-normal BLLs (OR: 4.839, 95% CI: 2.262-10.351, p < .001) with low-normal BLL as a reference, high BLLs (OR: 12.952, 95% CI: 5.391-31.119, p < .001) with low-normal BLL as a reference, and a BLL >12.3 µg/dL (OR: 6.827, 95% CI: 3.737-12.472, p < .001) were positively associated with CTS according to three different analyses. Discussion: In conclusion, blood lead levels were positively associated with CTS in patients on MHD. Dialysis patients should pay more attention to their environmental exposure to Pb. Avoidance of environmental Pb may reduce the incidence of CTS in MHD patients. Future studies will address the role of Pb in the pathophysiology of CTS in this patient population.

Uremic Pruritus is Associated with Two-Year Cardiovascular Mortality in Long Term Hemodialysis Patients.

BACKGROUND/AIMS: Uremic pruritus (UP) is an unpleasant complication in patients undergoing maintenance dialysis. Cardiovascular and infection related deaths are the major causes of mortality in patients undergoing dialysis. Studies on the correlation between cardiovascular or infection related mortality and UP are limited. METHODS: We analyze 866 maintenance hemodialysis (MHD) patients in our hemodialysis centers. Clinical parameters and 24-month cardiovascular and infection-related mortality are recorded. RESULTS: The associations between all-cause, cardiovascular and infection related mortality with clinical data including UP are analyzed. Multivariate Cox regression demonstrated that UP is a significantly predictor for 24-month cardiovascular mortality in the MHD patients (Hazard ratio: 3.164; 95% confidence interval, 1.743-5.744; p < 0.001). CONCLUSION: Uremic pruritus is one of the predictor of 24-month cardiovascular mortality in MHD patients.

Association Between Environmental Particulate Matter and Carpal Tunnel Syndrome in Patients Undergoing Hemodialysis.

BACKGROUND/AIMS: The deposition of ß2-microglobulin induced by reactive inflammation causing carpal tunnel syndrome (CTS) is one of the complications of dialysis-related amyloidosis in maintenance hemodialysis (MHD) patients. Air pollution levels, especially particulate matter with an aerodynamic diameter of <2.5 mm (PM2.5), have significantly been associated with the elevation of systemic inflammatory markers. There is no previous research on possible associations between CTS and PM2.5. METHODS: This study enrolled 866 MHD patients treated at the outpatient HD centers. Senior neurologists diagnosed the presence of CTS. Air pollution levels were recorded by a network of 27 monitoring stations near or in the patients' living areas throughout Taiwan. The 12- and 24-month average concentrations of PM with an aerodynamic diameter of <10 and <2.5 mm (PM10 and PM2.5, respectively), sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone were included. RESULTS: Multivariate logistic regression analyses showed that HD duration, the normalized protein catabolic rate (nPCR), hypoalbuminemia (albumin < 4 g/dl), and the mean previous 12-month environmental PM2.5 were positively associated with CTS; HD duration, nPCR, hypoalbuminemia (albumin < 4 g/dl), and the mean previous 24-month environmental PM2.5 were positively associated with CTS; HD duration, hypoalbuminemia (albumin < 4 g/dl), and previous 12-month PM2.5 excess days were positively associated with CTS; and HD duration, nPCR, hypoalbuminemia (albumin < 4 g/dl), and previous 24-month PM2.5 excess days were positively associated with CTS. CONCLUSION: PM2.5 levels and PM2.5 excessing days were positively correlated with CTS.

Carbon dioxide insufflation during colonoscopy can significantly decrease post-interventional abdominal discomfort in deeply sedated patients: A prospective, randomized, double-blinded, controlled trial.

BACKGROUND AND AIM: CO2 has been reported to be absorbed from the bowel more rapidly than air, resulting in a discomfort reduction after colonoscopy. Its role in deeply sedated patients is limited. This study was designed to investigate the efficacy and safety of CO2 insufflation during colonoscopy in patients deeply sedated with propofol. METHODS: A total of 125 continuous patients were randomly assigned to receive either CO2 (n = 63) or air (n = 62) insufflation during propofol-sedated colonoscopy. Postcolonoscopy abdominal pain, distention, and satisfaction were assessed at 1, 3, and 24 h after the procedure, and the proportions of pain-free and distention-free patients were compared. Residual bowel gas in the colon and small bowel was evaluated at 1 h after colonoscopy. End-tidal CO2 and O2 saturation was measured for safety analysis. RESULTS: There was a significant difference between the two groups regarding the postcolonoscopy abdominal pain, distention, and subjective satisfaction at 1 h (P < 0.001) and 3 h (P < 0.01) after the procedure. Patients' pain and distention at 1 and 3 h after the procedure were significantly lower in the CO2 group (P < 0.01). Residual bowel gas in the colon and small bowel was significantly less in the CO2 group (P < 0.001). There was no significant difference in end-tidal CO2 levels between two groups before, during, and after the procedure. CONCLUSIONS: Compared with air, CO2 insufflation during colonoscopy reduced postcolonoscopy abdominal discomfort and improved patients' satisfaction. It was safe to use CO2 insufflation in deeply sedated colonoscopy.

Transient Elastography for Spleen Stiffness Measurement in Patients With Cirrhosis: Role in Degree of Thrombocytopenia.

OBJECTIVES: The purpose of our study was to evaluate the relationship between spleen stiffness measured by transient elastography and the degree of thrombocytopenia in patients with liver cirrhosis. METHODS: A total of 67 patients with liver cirrhosis were prospectively enrolled in the study. All patients underwent single-day hematologic and biochemical tests, sonography, and transient elastography of the liver and spleen. Thrombocytopenia was categorized as mild (platelet count, 75,000-150,000/µL), moderate (50,000-75,000/µL), and severe (<50,000/µL). RESULTS: The degree of thrombocytopenia was significantly correlated with spleen stiffness (P = .001) and spleen size (P = .002) but not with liver stiffness (P = .086). In patients without splenomegaly, spleen stiffness values were significantly higher in patients with thrombocytopenia than in those without thrombocytopenia (P = .035). In patients with splenomegaly, spleen stiffness values were significantly higher in patients with moderate to severe thrombocytopenia than in those with a normal platelet count or mild thrombocytopenia (P = .007). Compared to liver stiffness, spleen stiffness showed a better and statistically significant correlation with platelet count and spleen size in patients with cirrhosis. CONCLUSIONS: The degree of thrombocytopenia was directly correlated with spleen stiffness, irrespective of the presence of splenomegaly. The clinical phenomenon of unexpected thrombocytopenia may be explained by a subtle or irreversible change in spleen stiffness.

Interleukin-28B gene non-TT allele strongly predicts treatment failure for genotype 1 infected chronic hepatitis C patients with advanced fibrosis: a case control study.

BACKGROUND: The role of single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B in predicting therapeutic response of pegylated interferon (peg-IFN) plus ribavirin (PR) for genotype 1 infected chronic hepatitis C patients with advanced fibrosis (AF) is limited. The aim of this study is to assess its role in predicting sustained virologic responses (SVR) to treatment. METHODS: Forty-two patients with biopsy proven hepatitis C virus (HCV) related AF (group A; Ishak fibrosis score, ≥4) and 126 sex- and HCV genotype-matched patients without AF (group B; Ishak fibrosis score, ≤3) were recruited into study. All patients received PR therapy for 24 weeks. Baseline and on-treatment clinical, virological and host factors were evaluated for treatment efficacy. RESULTS: The SVR rate was significantly lower in group A than group B patients with genotype 1 infection (24% vs. 53.3%; p=0.011). However, it was similar in those with genotype non-1 infection (76.5% vs. 76.5%; p=1.0). IL-28B rs8099917 genotype TT is the strongest predictor for SVR in genotype 1 infection. Patients who had TT genotype and achieved RVR in group A had similar SVR rates with those in group B (44.4% vs. 53.3%; p=0.614). One third of patients in group A developed hematological adverse effects and had required modified doses during antiviral therapy. CONCLUSIONS: In HCV genotype 1 infected AF receiving 24 weeks of PR treatment, patients with IL28B rs8099917 genotype TT, achieving RVR had similar SVR rate with those without AF. In contrast, patients with IL-28B rs8099917 non-TT genotype without achieving RVR are suggested to stop therapy.

Association between environmental particulate matter and arterial stiffness in patients undergoing hemodialysis.

BACKGROUND: Aortic pulse wave velocity (PWV) has been shown to be an independent predictor of cardiovascular mortality in patients with end-stage renal disease and the general population. Atmospheric particulate- matter (PM) concentrations and their effects on cardiovascular system by affecting arterial stiffness and central hemodynamic parameters had been noted. The purpose of this study was to access the correlation of air pollution variables and PWV in patients undergoing hemodialysis (HD). METHODS: This study analyzed 127 HD patients treated at the outpatient HD center. Brachial-ankle pulse wave velocity (baPWV) was measured by using a Vascular Profiler 1000 (VP-1000). Air pollution levels were recorded by a network of 27 monitoring stations near or in the patients' living areas throughout Taiwan. The 12-month average concentrations of PM with an aerodynamic diameter of <10 and <2.5 mm (PM10 and PM2.5, respectively), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide(CO), and ozone (O3) were included. RESULTS AND DISCUSSION: Multivariate linear regression analyses indicated that systolic blood pressure (SBP) (ß = 0.589, P < 0.025), age (ß = 0.316, P < 0.001), serum aluminum level (Al) (ß = 0.149, P = 0.020), and PM10 (ß = 0.133, P = 0.036) were positively correlated with baPWV. CONCLUSION: This cross-sectional study shows that in HD patients, the environmental PM10 level is associated with the baPWV.

Patients with Non-Alcoholic Fatty Liver Disease and Alcohol Dehydrogenase 1B/Aldehyde Dehydrogenase 2 Mutant Gene Have Higher Values of Serum Alanine Transaminase.

Patients with non-alcoholic fatty liver disease (NAFLD) share similar pathophysiologies to those of patients with alcohol liver disease. Alcoholic metabolic enzyme-related genes (alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2)) may be associated with pathophysiology in NAFLD patients. In this study, the association between ADH1B/ALDH2 gene polymorphism and serum metabolic factors, body statures, and hepatic steatosis/fibrosis status was evaluated in patients with NAFLD. Using biochemistry data, abdominal ultrasonography, fibrosis evaluation (Kpa), and steatosis evaluation (CAP), ADH1B gene SNP rs1229984 and ALDH2 gene SNP rs671 polymorphism were analyzed in sixty-six patients from 1 January 2022 to 31 December 2022. The percentage of the mutant type (GA + AA) was 87.9% (58/66) in the ADH1B allele and 45.5% (30/66) in the ALDH2 allele. Patients with the mutant-type ADH1B/ALDH2 allele had higher values of alanine aminotransferase (ALT) than the wild type (ß = 0.273, p = 0.04). No association was observed between body mass index, serum metabolic factors (sugar and lipid profile), CAP, kPa, and ADH1B/ALDH2. A high proportion of the mutant-type ADH1B allele (87.9%) and ALDH2 allele (45.5%) was observed in patients with NAFLD. No association was observed between ADH1B/ALDH2 allele, BMI, and hepatic steatosis/fibrosis. Patients with the mutant-type ADH1B/ALDH2 allele had higher values of ALT than those with the wild type.

Assessing Cross-Sectional Association of Uremic Pruritus with Serum Heavy Metal Levels: A Single-Center Study.

(1) Background: Uremic pruritus (UP) is a common and taxing symptom in patients on maintenance hemodialysis (MHD). We have previously shown that blood lead levels (BLLs) and blood aluminum levels (BALs) were separately positively associated with UP in MHD patients. We also found that blood cadmium levels (BCLs) were positively associated with all-cause mortality and cardiovascular-related mortality in MHD patients. We wondered whether there is any correlation between BCLs and UP after adjusting for BLLs and BALs. (2) Methods: Patients enrolled in this study were all from three hemodialysis (HD) centers at Chang Gung Memorial Hospital, Lin-Kou Medical Center, including both the Taipei and Taoyuan branches. Correlations between UP and BLLs, BALs, BCLs, and other clinical data were analyzed. (3) Results: Eight hundred and fifty-three patients were recruited. Univariate logistic regressions showed that diabetes mellitus, hepatitis B virus infection, hepatitis C virus infection, HD duration, hemodiafiltration, dialysis clearance of urea, normalized protein catabolic rate, non-anuria, serum albumin levels, log (intact-parathyroid hormone levels), total serum cholesterol levels, serum low-density lipoprotein levels, log (blood aluminum levels), and log (blood lead levels) were associated with UP. Although log BCLs were not significantly associated with UP (p = 0.136) in univariate analysis, we still included log BCLs in multivariate logistic regression to verify their effect on UP given that our aim in this study was to verify associations between serum heavy metals and UP. Multivariate logistic regressions showed that log BLLs (OR: 27.556, 95% CI: 10.912-69.587, p < 0.001) and log BALs (OR: 5.485, 95% CI: 2.985-10.079, p < 0.001) were positively associated with UP. The other logistic regression, which stratified BLLs and BALs into high and low BLLs and BALs, respectively, showed that high BLLs or high BALs (low BLLs and low BALs as reference) (OR: 3.760, 95% CI: 2.554-5.535, p < 0.001) and high BLLs and high BALs combined (low BLLs and low BALs as reference) (OR: 10.838, 95% CI: 5.381-21.828, p < 0.001) were positively correlated with UP. (4) Conclusions: BLLs and BALs were positively correlated with UP. BCLs were not correlated with UP. Clinicians should pay more attention to the environmental sources of lead and aluminum to prevent UP.

An artificial intelligence algorithm for analyzing globus pallidus necrosis after carbon monoxide intoxication.

Globus pallidus necrosis (GPN) is one of typical neurological imaging features in patients with carbon monoxide (CO) poisoning. Current clinical guideline recommends neurological imaging examination for CO-intoxicated patients with conscious disturbance rather than routine screening, which may lead to undiagnosed GPN. We aimed to develop an artificial intelligence algorithm for predicting GPN in CO intoxication patients. We included CO intoxication patients with neurological images between 2000 and 2019 in Chang Gung Memorial Hospital. We collected 41 clinical and laboratory parameters on the first day of admission for algorithm development. We used fivefold cross validation and applied several machine learning algorithms. Random forest classifier (RFC) provided the best predictive performance in our cohort. Among the 261 patients with CO intoxication, 52 patients presented with GPN. The artificial intelligence algorithm using the RFC-based AI model achieved an accuracy = 79.2 ± 2.6%, sensitivity = 77.7%, precision score = 81.9 ± 3.4%, and F1 score = 73.2 ± 1.8%. The area under receiver operating characteristic was approximately 0.64. Top five weighted variables were Platelet count, carboxyhemoglobin, Glasgow Coma scale, creatinine, and hemoglobin. Our RFC-based algorithm is the first to predict GPN in patients with CO intoxication and provides fair predictive ability. Further studies are needed to validate our findings.

Waist-to-height ratio for the prediction of gallstone disease among different obesity indicators.

Background: Factors of metabolic syndrome such as obesity are well-known risk factors for gallstone disease (GSD). There are different indicators of obesity, including weight, body mass index, waist circumference, and waist-to-height ratio. The predictive ability of different obesity indicators for GSD remains unclear. Objective: To explore the most efficient predictor of GSD among the different anthropometric indicators of obesity. Methods: This population-based cross-sectional study included 2263 participants who completed a questionnaire detailing their demographics, medical history, and lifestyle between 2014 and 2017 in Taiwan. Blood samples were collected and physical examinations, including anthropometric measurements, were performed. Gallstone disease was ascertained using ultrasonography. Multivariate analyses were performed to identify independent risk factors for GSD. Results: The overall prevalence of GSD was 8.8%. According to the multivariate analysis, individuals with a waist-to-height ratio ≥0.5 (odds ratio|odds ratios (OR) = 1.65, 95% confidence interval (CI) = 1.10-2.48, p = 0.017) had an increased risk of GSD. Diabetes was the main risk factor for GSD in men (OR = 2.06, 95% CI = 1.17-3.65, p = 0.013). Among women, waist-to-height ratio >0.5 (OR = 1.76, 95% CI = 1.03-3.02, p = 0.040) and current hormone drug use (OR = 2.73, 95% CI = 1.09-6.84, p = 0.033) were significant risk factors for gallstones. Conclusion: GSD was independently associated with central obesity and exogenous hormone intake in women. Among the anthropometric indicators used to assess central obesity, waist-to-height ratio was the most accurate predictor of GSD.

Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Receiving Finite Periods of Antiviral Therapy.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most severe complications in chronic hepatitis B virus (HBV) infection. HCC can still develop in patients with chronic HBV (CHB) infection undergoing antiviral therapy. Several effective scoring systems for the prediction of HCC risk in CHB patients have been established. However, very few of them are designed for CHB patients receiving nucleos(t)ide analogues (NAs) therapy. Furthermore, none are available for HCC risk prediction in CHB patients receiving finite periods of antiviral therapy. METHODS: This study enrolled 790 consecutive treatment-naïve patients with CHB infection who had visited our liver clinics from 2008 to 2012 for pretreatment assessment before receiving antiviral therapies. The treatments were provided at finite periods according to the National Health Insurance Policy in Taiwan. The last follow-up date was 31 December 2021. We analyzed the virological and clinical factors in these 790 CHB patients receiving finite periods of NA treatments and identified the most significant risk factors for HCC to establish a novel predictive scoring system. By using stepwise selection in a multivariate Cox proportional hazards model, we divided the patients into three risk groups. RESULTS: Our predictive scoring system included five independent variables: genotype C (adjusted HR [aHR] = 2.23), NA-withdraw-related hepatitis relapse (aHR = 6.96), male (aHR = 4.19), liver cirrhosis (aHR = 11.14), and T1768A core promoter mutation (aHR = 3.21). This model revealed significant differences in HCC incidence among the three risk groups. The 5-year cumulative HCC risk significantly differed among the three risk groups (low risk: 1.33%, moderate risk: 4.99%, and high risk: 17.46%), with log-rank test p < 0.001. CONCLUSION: Our predictive scoring system is a promising tool for the prediction of HCC in CHB patients receiving finite NA treatments. Genotype C, NA-withdraw-related hepatitis relapse, male gender, liver cirrhosis, and the T1768A HBV core promoter mutation were significant independent risk factors.

Identification of hepatitis B virus rtS117F substitution as a compensatory mutation for rtM204I during lamivudine therapy.

OBJECTIVES: The replication defect of hepatitis B virus (HBV) lamivudine-resistant mutants can be restored by the development of compensatory mutations. Such mutations have long been recognized for the rtM204V mutant, while little is known about any compensatory mutation specific to the rtM204I mutant. The aim of this study was to search for previously unrecognized compensatory mutations following development of lamivudine-resistant mutants. METHODS: Of 83 lamivudine-resistant patients, 49 and 34 patients harboured the rtM204I and rtM204V mutations, respectively. Serial serum samples obtained during the therapeutic course were submitted to sequence analysis. Site-directed mutagenesis experiments were performed to examine the functions of the identified associated mutations. RESULTS: Of the 49 patients carrying the rtM204I mutation, 5 subsequently developed an rtS117F substitution during the follow-up, whereas 4 harboured an rtN124D substitution prior to the development of the rtM204I mutation. Emergence of the rtS117F mutation was associated with an increase in hepatitis activity, whereas prior existence of the rtN124D mutation was associated with decompensated liver function upon development of the rtM204I mutation. Site-directed mutagenesis experiments showed that the rtS117F mutation by itself did not confer lamivudine resistance but it compensated for replication deficiency of the rtM204I mutant in HepG2 and Mahlavu cells. Additionally, virion and hepatitis B surface antigen secretion of the rtS117F mutant was significantly impaired. CONCLUSIONS: The rtS117F substitution served as a compensatory mutation for rtM204I. Emergence of the rtS117F mutation in lamivudine-resistant patients carrying rtM204I was associated with increased hepatitis activities. Prior existence of the rtN124D substitution was associated with liver decompensation upon development of the rtM204I mutation.

Predictors of changes in hemoglobin levels in patients with chronic hepatitis C treated with ribavirin plus pegylated interferon-α.

BACKGROUND: Combination therapy with pegylated interferon (pegIFN)-α and ribavirin (RBV) for chronic hepatitis C virus (HCV) infection is associated with reduction in hemoglobin (Hb) concentrations and anemia. The aim of this study was to evaluate the magnitude and frequency of change in Hb and determine the predictive risk factors for Hb decrease during this therapy. METHODS: We enrolled 308 patients with chronic HCV infection who were receiving weekly subcutaneous pegIFN injection in combination with body weight-based oral RBV for 24 weeks. Clinical and virological characteristics were used for studying the predictors of decrease in Hb. RESULTS: The majority (95%) of patients showed reduction in Hb concentration of at least 1 g/dL during pegIFN and RBV combination therapy. The mean and median maximal decrease in Hb level of the study patients was 3.9 g/dL (range -0.3 to 8.2 g/dL; interquartile range 2.8-5.0 g/dL). Of all patients, 49.4% showed a reduction in Hb level of more than 4 g/dL; a higher number of male patients than female patients showed an Hb decrease of >4 g/dL. Multivariate analysis of our data showed that older age, high baseline Hb concentration, high HCV RNA viral load, low estimated glomerular filtration rate (eGFR), and low platelet count were independent predictors of significant decline in Hb levels. CONCLUSIONS: Patients with low eGFR before antiviral therapy may have an increased risk of RBV-related anemia and should be closely monitored. Clinician should consider the potential risk of significant reduction in Hb level according to eGFR while deciding the RBV dose.

Predictors of acquired perforating dermatosis in uremic patients on hemodialysis: a case-control study.

OBJECTIVES: The purpose of this study was to identify the predictors of acquired perforating dermatosis (APD) in patients on maintenance hemodialysis (HD). METHODS: A case-control study was performed at our outpatient HD center between January 1, 2000 and March 31, 2011. Patients on HD with APD were matched (1 : 2) for gender and age with controls on HD. Conditional logistic regression was used to identify factors associated with APD. RESULTS: A total of 19 patients with APD and 38 age and gender matched patients were enrolled in the study. Univariate logistic regression showed that APD was significantly associated with diabetes mellitus (DM), reduced levels of intact parathyroid hormone (iPTH) and albumin (Alb), reduced dialysis adequacy (Kt/V) and urea reduction rate (URR), and elevated levels of high-sensitivity C-reactive protein (hsCRP). Multivariate logistic regression identified reduced iPTH (hazard ratio (HR): 0.983; P = 0.026) and Alb (HR: 0.099; P = 0.047) and elevated hsCRP (HR: 1.210, P = 0.024) as risk factors for APD. CONCLUSIONS: iPTH, hsCRP, and Alb are predictors for APD in HD patients.

Serum Uric Acid but Not Ferritin Level Is Associated with Hepatic Fibrosis in Lean Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease: A Community-Based Study.

Elevated serum ferritin and uric acid levels are common in patients with fatty liver disease. This study assessed the association between serum ferritin and uric acid levels and liver fibrosis in subjects with lean metabolic dysfunction-associated fatty liver disease (MAFLD). This cross-sectional study used data from a community screening examination for metabolic syndrome from December 2018 to September 2019 at Keelung Chang Gung Memorial Hospital. Subjects with lean MAFLD were defined as those with a body mass index (BMI) < 23 kg/m2 and hepatic steatosis according to the MAFLD criteria. A total of 182 lean subjects were included and were divided into lean MAFLD and lean healthy groups. Serum ferritin and uric acid concentrations were positively correlated with liver fibrosis, regardless of whether FIB-4, APRI, or NFS were used as references. Univariate logistic regression analysis showed that age and uric acid were associated with advanced liver fibrosis. After adjusting for potential confounders, only uric acid level was statistically significant in predicting the advanced liver fibrosis (OR = 6.907 (1.111−42.94), p = 0.038) in the lean MAFLD group. We found that an elevated serum uric acid level is an independent factor associated with advanced liver fibrosis in lean MAFLD subjects by noninvasive fibrosis scores.

Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan.

PURPOSE: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both recommended as first-line treatments for patients with chronic hepatitis B virus (CHB) infection according to international HBV treatment guidelines. However, recent studies reported conflicting results regarding the preferred antiviral in the prevention of hepatocellular carcinoma (HCC). This cohort study aimed to investigate this issue by using Taiwan's National Health Insurance Research Database, wherein a "finite" but not life-long treatment policy was applied. METHODS: From January 2008 to December 2013, a total of 12,388 consecutive adult patients with CHB who received a finite course of TDF treatment (n = 1250) or ETV treatment (n = 11,138) were analyzed through screening for study eligibility followed by the 1:4 propensity score matching method. FINDINGS: In the entire cohort, the annual incidence and survival between the ETV and TDF groups were not significantly different regarding HCC occurrence (2.05 vs 2.74 per 100 patient-years [PY]; P = 0.055; hazard ratio [HR], 0.975; log-rank, P = 0.966), cirrhosis-related complications (1.9 vs 2.4 per 100 PY; P = 0.149; HR, 0.869; log-rank, P = 0.388), or all-cause mortality (2.16 vs 1.6 per 100 PY; P = 0.119; HR, 0.831; log-rank, P = 0.342), respectively. Propensity score matching analyses yielded similar results regarding HCC occurrence, cirrhosis-related complications, and all-cause mortality. In addition, these findings were consistently reproduced in the subgroups of patients with chronic hepatitis and cirrhosis that developed before antiviral treatment. IMPLICATIONS: ETV and TDF did not significantly differ in prevention of HCC occurrence or reduction of cirrhosis-related complications and all-cause mortality in patients with CHB receiving a finite period of treatment.