Project description:Background and aimsHCV genotype (GT) 3 is associated with rapid liver disease progression. However, the liver disease progression and its risk factors in patients with HCV GT 3 infection after sustained virological response (SVR) following direct-acting antivirals (DAAs) remain unclear. Therefore, we aimed to investigate the liver disease progression of patients with GT 3 after SVR.MethodsThis was a retrospective cohort study of patients with HCV infection who achieved SVR by DAAs. The clinical outcome was overall liver disease progression (OLDP), defined as newly diagnosed compensated liver cirrhosis, decompensated liver cirrhosis, or hepatocellular carcinoma. The incidence of OLDP was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the risk factors for OLDP.ResultsA total of 409 patients (46.9% GT3) were followed for 43.7 (32.9, 58.7) months. The incidence of OLDP was higher in patients with GT 3 (4.63/100PY) than non-GT 3 (0.60/100PY; P < 0.001). According to Cox multivariate analysis, GT 3 was significantly associated with OLDP (HR 6.41, 95% CI 1.82 - 22.56; P=0.004). The predictors of OLDP in patients with GT 3 were HCV recurrence (HR 12.15, 95% CI 3.18 - 46.46; P < 0.001) and FIB-4 > 3.25 (HR 16.40, 95% CI 1.03 - 39.81; P = 0.046) at baseline.ConclusionHCV GT 3-infected patients remain at a higher risk of OLDP even after achieving SVR by DAAs, especially patients with advanced liver fibrosis and at high risk for reinfection or virological late relapse.
Project description:UnlabelledHigher coffee consumption has been associated inversely with the incidence of chronic liver disease in population studies. We examined the relationship of coffee consumption with liver disease progression in individuals with advanced hepatitis C-related liver disease. Baseline coffee and tea intake were assessed in 766 participants of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C-related bridging fibrosis or cirrhosis on liver biopsy and failed to achieve a sustained virological response to peginterferon plus ribavirin treatment. Participants were followed for 3.8 years for clinical outcomes and, for those without cirrhosis, a 2-point increase in Ishak fibrosis score on protocol biopsies. At baseline, higher coffee consumption was associated with less severe steatosis on biopsy, lower serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, alpha-fetoprotein, insulin, and homeostatic model assessment (HOMA2) score, and higher albumin (P < 0.05 for all). Two hundred thirty patients had outcomes. Outcome rates declined with increasing coffee intake: 11.1/100 person-years for none, 12.1 for less than 1 cup/day, 8.2 for 1 to fewer than 3 cups/day, and 6.3 for 3 or more cups/day (P-trend = 0.0011). Relative risks (95% confidence intervals) were 1.11 (0.76-1.61) for less than 1 cup/day; 0.70 (0.48-1.02) for 1 to fewer than 3 cups/day; and 0.47 (0.27-0.85) for 3 or more cups/day (P-trend = 0.0003) versus not drinking. Risk estimates did not vary by treatment assignment or cirrhosis status at baseline. Tea intake was not associated with outcomes.ConclusionIn a large prospective study of participants with advanced hepatitis C-related liver disease, regular coffee consumption was associated with lower rates of disease progression.
Project description:Background/aimsUndetectable HCV RNA 12 weeks after the end of treatment (SVR12) has been the valid efficacy endpoint in the era of direct-acting antivirals (DAAs). Its concordance with SVR4 and SVR24 and long-term durability is unknown in Taiwanese chronic hepatitis C (CHC) patients.MethodsA total of 1080 CHC patients who received all-oral DAAs and an achieved end-of-treatment virological response (EOTVR), defined as undetectable HCV RNA at the end of therapy, were consecutively enrolled. HCV RNA was monitored 4, 12, and 24 weeks after EOT. Patients who achieved SVR24, defined as undetectable HCV RNA 24 weeks after EOT, were followed annually for assessing SVR durability.ResultsEleven (1.02%) patients experienced HCV RNA reappearance after EOT. The most frequent timing of RNA reappearance was observed at SVR4 (n = 7), followed by SVR12 (n = 3) and SVR 24 (n = 1). The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 in predicting SVR12 were 99.7% and 100%, respectively, whereas the PPV and NPV of SVR12 in predicting SVR24 were 99.9% and 100%, respectively. Pyrosequencing confirmed delayed relapse rather than reinfection for the patient who had detectable HCV RNA at SVR24. Among 978 patients who achieved SVR24, after a median follow-up period of 17.3±8.2 months, the SVR durability is 100% up to a 4-year follow-up.ConclusionAchievement of SVR12 provides excellent durability of HCV seroclearance after DAA therapy. On-demand HCV RNA beyond SVR12 should be recommended for patients with unexplainable abnormal liver function or high-risk behaviors.
Project description:Background & aimsChronic HCV infection is an important cause of hepatocellular carcinoma (HCC) and liver failure in the US but limited data are available in China. We compared the incidence of clinical outcomes among adults with chronic HCV infection in the US and China and examined factors associated with outcomes.MethodsA parallel prospective study of 2 cohorts of patients with HCV RNA+ recruited in 1 site in the US (UMHS) and 3 sites (PUHSC) in China between September 2011 and July 2015 was carried out. Composite liver outcomes (liver-related deaths, HCC, liver transplantation or liver decompensation), were analysed using competing-risk Cox proportional hazards model to determine incidence and associated factors.ResultsA total of 795 UMHS and 854 PUHSC patients were followed for a median of 3.06 and 3.99 years, respectively. At enrolment, a significantly higher percentage of UMHS patients had cirrhosis (45.4% vs. 16.2%). The 5-year cumulative incidence of composite liver outcomes was significantly higher in UMHS than in PUHSC patients (25.3% vs. 6.6%, p <0.0001). Stratification by stage of liver disease at enrolment showed this difference persisted only in the subgroup without cirrhosis due to higher aspartate aminotransferase to platelet ratio index (APRI) in the UMHS cohort. A total of 493 UMHS and 502 PUHSC patients received HCV treatment, and sustained virologic response (SVR) was achieved in 88.0% UMHS and 86.8% PUHSC treated-patients. SVR as time-dependent variable was associated with 80% lower risk of composite liver outcomes among patients with decompensated cirrhosis but not the overall cohorts.ConclusionsWhen accounting for disease severity at entry, the incidence of composite liver outcomes was similar in patients with HCV in the US and China. Achievement of SVR had the greatest short-term impact on patients with decompensated cirrhosis.Lay summaryPatients with chronic hepatitis C virus infection were recruited from centres in the United States and China. During follow-up, a higher percentage of the American patients had clinical outcomes: liver failure, liver cancer, liver transplant or liver-related deaths than the Chinese patients, mainly because more American patients had cirrhosis at enrolment. Older age and more advanced liver disease were associated with higher incidence of outcomes overall and viral clearance after hepatitis C treatment was associated with a lower incidence of outcomes in patients with advanced cirrhosis. Our findings highlight the importance of improving diagnosis and treatment of hepatitis C before advanced liver disease develops.
Project description:BackgroundMost existing predictive models of hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) are built on data collected at baseline and therefore have limited accuracy. The current study aimed to construct an accurate predictive model incorporating longitudinal data using a novel modeling strategy. The predictive performance of the longitudinal model was also compared with a baseline model.MethodsA total of 400 patients with HCV-related cirrhosis who achieved SVR with direct-acting antivirals (DAA) were enrolled in the study. Patients were randomly divided into a training set (70%) and a validation set (30%). Informative features were extracted from the longitudinal variables and then put into the random survival forest (RSF) to develop the longitudinal model. A baseline model including the same variables was built for comparison.ResultsDuring a median follow-up time of approximately 5 years, 25 patients (8.9%) in the training set and 11 patients (9.2%) in the validation set developed HCC. The areas under the receiver-operating characteristics curves (AUROC) for the longitudinal model were 0.9507 (0.8838-0.9997), 0.8767 (0.6972,0.9918), and 0.8307 (0.6941,0.9993) for 1-, 2- and 3-year risk prediction, respectively. The brier scores of the longitudinal model were also relatively low for the 1-, 2- and 3-year risk prediction (0.0283, 0.0561, and 0.0501, respectively). In contrast, the baseline model only achieved mediocre AUROCs of around 0.6 (0.6113, 0.6213, and 0.6480, respectively).ConclusionsOur longitudinal model yielded accurate predictions of HCC risk in patients with HCV-relate cirrhosis, outperforming the baseline model. Our model can provide patients with valuable prognosis information and guide the intensity of surveillance in clinical practice.
Project description:Background and aimTo investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis.MethodFrom January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded.ResultsSeven patients were HBsAg+ (7.2%), 64 were HBsAg-/HBcAb+ (65.9%), and 26 were HBsAg-/HBcAb- (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg-/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 107 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up.ConclusionsTocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, strict monitoring is necessary.
Project description:We evaluated the relationship of daily coffee intake with endothelial function assessed by flow-mediated vasodilation and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation in patients with hypertension. A total of 462 patients with hypertension were enrolled in this cross-sectional study. First, we divided the subjects into two groups based on information on daily coffee intake: no coffee group and coffee group. The median coffee intake was two cups per day in the coffee group. There were significant differences in both flow-mediated vasodilation (2.6 ± 2.8% in the no coffee group vs. 3.3 ± 2.9% in the coffee group, p = 0.04) and nitroglycerine-induced vasodilation (9.6 ± 5.5% in the no coffee group vs. 11.3 ± 5.4% in the coffee group, p = 0.02) between the two groups. After adjustment for confounding factors, the odds ratio for endothelial dysfunction (OR: 0.55, 95% CI: 0.32-0.95) and the odds ratio for vascular smooth muscle dysfunction (OR: 0.50, 95% CI: 0.28-0.89) were significantly lower in the coffee group than in the no coffee group. Next, we assessed the relationship of the amount of daily coffee intake with vascular function. Cubic spline curves revealed that patients with hypertension who drank half a cup to 2.5 cups of coffee per day had lower odds ratios for endothelial dysfunction assessed by flow-mediated vasodilation and vascular smooth muscle dysfunction assessed by nitroglycerine-induced vasodilation. Appropriate daily coffee intake might have beneficial effects on endothelial function and vascular smooth muscle function in patients with hypertension.
Project description:Coffee beverage consumption is well-known to exert various health benefits; however, the effects of coffee aroma are rarely explored. This study aimed to investigate the calming effect of inhaling coffee aroma while the patients underwent dental procedures (probing and scaling). Salivary α-amylase (sAA) and cortisol (sCort) levels were measured as proxies of sympathetic nervous system and hypothalamic-pituitary-adrenal axis responses to stress respectively. Blood pressures and pulse rates were recorded. The results showed that undergoing dental procedures could increase sAA and sCort levels of the patients inhaling sham aroma while those inhaling coffee aroma had significantly decreased sAA and sCort levels (40% and 25% differences, respectively). The pulse rates of those inhaling coffee aroma were also lower. Subjective assessment using visual analog scale was in line with objective measures as well. The preference for coffee aroma or the frequency of coffee drinking had no effect on the sAA and sCort responses. This is the first study to provide evidence on the effect of coffee aroma on sAA and sCort levels in patients undergoing dental procedures.
Project description:Background & aimsHCV subtypes which are unusual in Europe are more prevalent in the African region, but little is known of their response to direct-acting antivirals (DAAs). These include non-1a/1b/ non-subtypeable genotype 1 (G1) or non-4a/4d (G4). In this report we aimed to describe the genotype distribution and treatment outcome in a south London cohort of African patients.MethodsWe identified all patients born in Africa who attended our clinic from 2010-2018. Information on HCV genotype, treatment regimen and outcome were obtained. Non-subtypeable samples were analysed using Glasgow NimbleGen next-generation sequencing (NGS). Phylogenetic analysis was carried out by generating an uncorrected nucleotide p-distance tree from the complete coding regions of our sequences.ResultsOf 91 African patients, 47 (52%) were infected with an unusual subtype. Fourteen novel, as yet undesignated subtypes (G1*), were identified by NGS. Three individuals were infected with the same subtype, now designated as subtype 1p. Baseline sequences were available for 22 patients; 18/22 (82%) had baseline NS5A resistance-associated substitutions (RASs). Sustained virological response (SVR) was achieved in 56/63 (89%) overall, yet only in 21/28 (75%) of those with unusual G1 subtypes, with failure in 3/16 G1*, 1/2 G1p and 3/3 in G1l. Six treatment failures occurred with sofosbuvir/ledipasvir compared to 1 failure on a PI-based regimen. The SVR rate for all other genotypes and subtypes was 35/35 (100%).ConclusionsMost individuals in an unselected cohort of African patients were infected with an unusual genotype, including novel subtype 1p. The SVR rate of those with unusual G1 subtypes was 75%, raising concern about expansion of DAAs across Africa. Depending on the regimen used, higher failure rates in African cohorts could jeopardise HCV elimination.Lay summaryDirect-acting antiviral medications are able to cure hepatitis C in the majority of patients. The most common genotype of hepatitis C in Europe and the United States is genotype 1a or 1b and most clinical trials focused on these genotypes. We report that in a group of African patients, most of them had unusual (non-1a/1b) genotype 1 subtypes, and that the cure rate in these unusual genotypes was lower than in genotypes 1a and 1b.
Project description:ObjectiveThis study summarises nutritional intake among patients with tuberculosis (TB) along the Myanmar-Thailand border according to the local diet.SettingTB clinic along the Myanmar-Thailand border.ParticipantsCross-sectional surveys of 24-hour food recall were conducted with participants receiving anti-TB treatment. Participants were purposively selected to reflect proportion of age, sex and HIV co-infection based on historical patient records. Out of a total of 28 participants, 20 (71.4%) were men and 5 (17.9%) were co-infected with HIV.Primary and secondary outcome measuresThe primary outcome compared actual recorded intake to recommended intake. Secondary outcomes compared weight gain and body mass index (BMI) from diagnosis to time of survey.ResultsThere were no significant differences in macronutrient or micronutrient intake by sex or for patients supplementing their rations. Mean treatment length at time of survey was 20.7 weeks (95% CI: 16.5 to 24.8). A significantly higher proportion of women (8/8, 100%) met caloric requirements compared with men (9/20, 45.0%, p=0.010), but few participants met other macronutrient or micronutrient requirements, with no significant differences by sex or for patients supplementing their rations. From diagnosis to the time of the survey, participants averaged significant weight gain of 6.48 kg (95% CI: 3.87 to 9.10) and increased BMI of 2.47 kg/m2 (95% CI: 1.45 to 3.49; p=0.0001 for both). However, 50% (14/28) still had mild or more severe forms of malnutrition.ConclusionsThis cross-sectional survey of nutritional intake in patients undergoing TB treatment in a sanatorium setting demonstrates the difficulty in sufficiently meeting nutritional demands, even when providing nutritional support.