ABSTRACT
OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.
ABSTRACT
Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors (PEComas) because PEComas are mainly benign tumors and may not require surgical intervention. By analyzing the causes, properties and clinical manifestations of PEComas, we summarize the challenges and solutions in the diagnosis of PEComas.
Subject(s)
Liver Neoplasms , Perivascular Epithelioid Cell Neoplasms , Humans , Perivascular Epithelioid Cell Neoplasms/surgery , Perivascular Epithelioid Cell Neoplasms/pathology , Perivascular Epithelioid Cell Neoplasms/diagnosis , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Liver Neoplasms/diagnosis , Hepatectomy , Preoperative Care/methods , Biomarkers, Tumor/analysis , Diagnosis, Differential , Liver/pathology , Liver/surgery , Liver/diagnostic imagingABSTRACT
BACKGROUND: Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear. AIM: To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients. METHODS: In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents. RESULTS: A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity. CONCLUSION: In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.
ABSTRACT
Mitochondrial dynamics, including mitochondrial fission and fusion, are critical for maintaining mitochondrial functions. Evidence shows that TANK-binding kinase 1 (TBK1) regulates mitochondrial fusion and fission and then mitophagy. Since a previous study demonstrates a strong correlation between mitophagy and osteoarthritis (OA), we herein investigated the potential role of TBK1 in OA process and mitochondrial functions. We demonstrated a strong correlation between TBK1 and OA, evidenced by significantly downregulated expression of TBK1 in cartilage tissue samples of OA patients and in the chondrocytes of aged mice, as well as TNF-α-stimulated phosphorylation of TBK1 in primary mouse chondrocytes. TBK1 overexpression significantly attenuated TNF-α-induced apoptosis and abnormal mitochondrial function in primary mouse chondrocytes. Furthermore, TBK1 overexpression induced remodeling of mitochondrial morphology by directly phosphorylating dynamin-related protein 1 (DRP1) at Ser637, abolishing the fission of DRP1 and preventing its fragmentation function. Moreover, TBK1 recruitment and DRP1 phosphorylation at Ser637 was necessary for engulfing damaged mitochondria by autophagosomal membranes during mitophagy. Moreover, we demonstrated that APMK/ULK1 signaling contributed to TBK1 activation. In OA mouse models established by surgical destabilization of the medial meniscus, intraarticular injection of lentivirus-TBK1 significantly ameliorated cartilage degradation via regulation of autophagy and alleviation of cell apoptosis. In conclusion, our results suggest that the TBK1/DRP1 pathway is involved in OA and pharmacological targeting of the TBK1-DRP1 cascade provides prospective therapeutic benefits for the treatment of OA.
Subject(s)
Mitochondrial Dynamics , Tumor Necrosis Factor-alpha , Mice , Animals , Phosphorylation , Tumor Necrosis Factor-alpha/metabolism , Autophagy/physiology , Dynamins/metabolism , Protein Serine-Threonine Kinases/metabolismABSTRACT
OBJECTIVE: To evaluate the clinical characteristics, biochemical parameters and the distribution of HLA-DQ genotypes among adult patients with celiac disease (CD) in Northwest China. METHODS: This cross-sectional study retrospectively collected clinical, biochemical, and HLA-DQ genotype of patients with CD from a tertiary hospital in Xinjiang Uygur Autonomous Region, China between March 2016 and December 2021. Small intestinal biopsy and serum-specific antibodies were used to diagnose CD. RESULTS: Of the 102 CD patients, 63.7% were women (female: male = 1.76:1), and the mean age was 47.3 ± 14.7 years at diagnosis. Common gastrointestinal symptoms included abdominal pain (50.0%), diarrhea (39.2%), and abdominal distension (24.5%). While common extraintestinal manifestations were anemia (48.0%), osteopenia or osteoporosis (36.3%), and fatigue (35.3%). Approximately 34.3% of patients with CD had comorbidities, with the most common being thyroid diseases (18.6%). Biochemical profiles showed lower hemoglobin, higher platelet count, and 25-hydroxyvitamin D (25[OH]D) deficiency. HLA-DQ2/DQ8 was detected among all 53 patients who underwent genotype testing; the frequency of the HLA-DQ2.5, DQ2.2, and DQ8 haplotypes was 71.7%, 24.5%, and 3.8%, respectively. CONCLUSIONS: CD was more common among women. Clinical manifestations include primarily gastrointestinal symptoms, but extraintestinal manifestations were not uncommon. Lower hemoglobin level, higher platelet count, and 25[OH]D deficiency are the main biochemical manifestations. The HLA-DQ2.5 and DQ2.2 haplotypes are the most common genotypes in CD.
Subject(s)
Celiac Disease , Adult , Female , Humans , Male , Middle Aged , Celiac Disease/complications , Celiac Disease/diagnosis , Celiac Disease/genetics , Haplotypes , Cross-Sectional Studies , Retrospective Studies , HLA-DQ Antigens/genetics , Genotype , Genetic Predisposition to DiseaseABSTRACT
Background: In December 2019, the cases of pneumonia of unknown etiology emerged in Wuhan, China, and rapidly spread throughout the country. The disease was later designated by the World Health Organization (WHO) as Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Few studies have assessed the clinical characteristics of COVID-19 and control strategies used to mitigate disease spread in high-altitude plateau regions of China. Study Objective: To assess the impact of real-world strategies to control COVID-19 spread in remote plateau regions. Methods: A retrospective study was performed to assess the epidemiology of COVID-19 and strategies used to control disease spread in the high-altitude plateau of Sichuan, China from 24 January 2020 to 19 March 2020. Results: COVID-19 spread and outbreaks in Sichuan were attributed to mass gatherings. A total of 70 patients and 20 asymptomatic individuals were found in the hypoxic plateau region of Sichuan. Twelve patients were admitted after the onset of symptoms, while 58 patients and 20 asymptomatic individuals were found by active screening. The symptomatic patients included those with uncomplicated illness (16/70, 22.9%), mild pneumonia (44/70, 62.9%), and severe pneumonia (10/70, 14.3%). Most patients in the study area showed relatively mild and atypical symptoms such as low or no fever and dyspnea. The incidence of severe pneumonia, fever, dyspnea, and interstitial abnormalities identified by chest CT were all significantly lower in screened patients than those admitted after symptom onset (P < 0.05). Severe pneumonia was noted in patients with chronic conditions like hypertension, diabetes etc. as compared to less severe pneumonia in healthy subjects (P <0.05). No patients died and all were eventually discharged. Conclusion: Mass gatherings increased risk of spread of SARS-CoV-2 responsible for COVID-19. Active screening and early management have collectively contributed to reduced incidence of severe pneumonia and satisfactory prognoses of infections with COVID-19 in this hypoxic plateau region.
ABSTRACT
BACKGROUND: Research on celiac disease (CD) in northwest China is still in its infancy. At present, large-sample data on the epidemiological, clinical, and pathological characteristics of CD are limited. AIM: To investigate the epidemiological, clinical, and pathological characteristics of CD in northwest China. METHODS: The clinical data of 2884 patients with gastrointestinal (GI) symptoms were retrospectively analyzed. Total immunoglobulin A (IgA) and anti-tissue transglutaminase (tTG) IgA levels were examined in all patients. Gastroscopy and colonoscopy were performed in patients with positive anti-tTG IgA and deficient total IgA levels. Atrophy of the duodenal and ileal villi was examined and histopathological examinations were performed. The modified Marsh-Oberhuber classification system was used to grade villous atrophy in the duodenum or distal ileum. The patients' Helicobacter pylori (H. pylori) infection status was compared in terms of clinical presentation and Marsh grade. Statistical analyses were performed using the t-test or chi-square test. RESULTS: Among the 2884 patients, 73 were positive for serum anti-tTG IgA, and 50 were diagnosed with CD. The CD detection rate was significantly higher in Kazakhs (4.39%) than in Uyghurs (2.19%), Huis (0.71%), and Hans (0.55%). The main symptoms of CD were chronic diarrhea, anorexia, anemia, fatigue, weight loss, sleep disorders, osteopenia, and osteoporosis. The body mass index of patients with CD was significantly lower than that of patients without CD. A total of 69 patients with positive serum anti-tTG IgA and two patients with deficient total IgA levels underwent GI endoscopy. Endoscopy revealed crypt hyperplasia and/or duodenal villous atrophy, mainly manifested as nodular mucosal atrophy, grooves, and fissures. The difference in H. pylori infection rates was not statistically significant between CD and non-CD patients but was significantly different among CD patients with different Marsh grades. CONCLUSION: Among the patients with GI symptoms in northwestern China, the prevalence of CD was more in the Uyghur and Kazakh populations. H. pylori infection may be associated with CD severity.
Subject(s)
Celiac Disease , Helicobacter Infections , Atrophy/epidemiology , Atrophy/pathology , Autoantibodies , Celiac Disease/complications , Celiac Disease/diagnosis , Celiac Disease/epidemiology , Duodenum/pathology , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter Infections/epidemiology , Humans , Immunoglobulin A , Retrospective Studies , TransglutaminasesABSTRACT
OBJECTIVES: Whether patent foramen ovale (PFO) closure is effective on migraine is controversial. This article was aimed at assessing the efficacy of PFO closure on migraine based on randomized controlled trials (RCTs) and observational studies. METHODS: We searched PubMed, Embase, and Cochrane databases up to October 2020 evaluating PFO closure versus control in patients with migraine, then conducted a meta-analysis of all RCTs and observational studies, respectively. The main outcomes were (1) respond rate: complete cessation of migraine; (2) reduction in the frequency of migraine attacks per month; and (3) reduction in migraine days per month. RESULTS: Seven studies (3 RCTs and 4 observational studies), containing 887 migraine patients, were identified. (1) The respond rate of PFO closure on migraine was significantly higher than control group both in RCT subgroup and observational studies subgroup (OR 3.86, 95% CI 1.35-11.04, P = 0.01 in RCTs; OR 8.28, 95% CI 2.31-29.67, P = 0.001 in observational studies). (2) Reduction in frequency of migraine attacks was higher in PFO closure group compared with control group in the RCT subgroup analysis (mean difference (MD) = 0.57, 95% CI 0.23-0.90, P = 0.0009). (3) Reduction in migraine days was also higher in PFO closure group compared with control group in the RCT subgroup analysis (MD = 1.33, 95% CI 0.35-2.31, P = 0.008). CONCLUSIONS: PFO closure might be suitable for migraine patients, especially for migraine with aura, by cessation of migraine headaches or reducing migraine attacks and migraine days.
Subject(s)
Cardiac Catheterization , Foramen Ovale, Patent , Migraine with Aura , Septal Occluder Device , Foramen Ovale, Patent/complications , Foramen Ovale, Patent/physiopathology , Foramen Ovale, Patent/surgery , Humans , Migraine with Aura/etiology , Migraine with Aura/physiopathology , Migraine with Aura/surgery , Observational Studies as Topic , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Ulcerative colitis (UC) is one of the main subtypes of inflammatory bowel disease (IBD). The incidence of UC in the Xinjiang region is relatively high in China and the manifestations of UC in Uyghur and Han patients are usually differential. This study aimed to identify potential biomarkers of UC. METHODS: All miRNA and mRNA were extracted from the tissue samples obtained from participants in Xinjiang. Differential expression analysis was performed on all mRNAs and miRNAs. The target genes of miRNAs were predicted via three databases. The clusterProfiler package was used for GO and KEGG pathway enrichment analysis. RESULTS: Preliminarily, four miRNAs and 15 genes were associated with the differential manifestations of UC in Uyghur and Han patients. Through the co-expression network construction and further screening in more samples, two miRNAs (hsa-miR-141-5p and hsa-miR-378a-5p) and three genes (ARNTL2, CLDN1 and SLC6A14) were found to be more crucial. These 15 genes were enriched in tight junction, NF-κB, and several other pathways. CONCLUSION: Two miRNAs (hsa-miR-141-5p and hsa-miR-378a-5p) and three genes (ARNTL2, CLDN1, and SLC6A14) associated with the differential manifestations of UC in Uyghur and Han population were identified, which were potential biomarkers.
ABSTRACT
BACKGROUND: Gastric Helicobacter pylori (H. pylori) infection is related to chronic gastritis, gastroduodenal ulcer, and gastric malignancies; whether this infection is related to colorectal polyps and colorectal cancer (CRC), remains debatable. AIM: To investigate the relationship between gastric H. pylori infection and the risk of colorectal polyps and CRC. METHODS: We retrospectively analyzed 3872 patients with colorectal polyps who underwent colonoscopy and pathological diagnosis. We also analyzed 304 patients with primary CRC. The characteristics of these patients were compared with those of the control group, which included 2362 patients with the normal intestinal mucosa. All subjects completed a 14C-urea breath test, bidirectional gastrointestinal endoscopy, and a biopsy on the same day. Data on the number, size, location, and pathology of the polyps, the location, and pathology of the CRC, the detection of H. pylori, and the incidence of H. pylori-associated atrophic gastritis or intestinal metaplasia were obtained. A logistic regression model was used to analyze the relationship between gastric infection due to H. pylori, and the incidence of colorectal polyps and CRC. RESULTS: The prevalence of H. pylori infection was higher in the multiple polyps group than in the solitary polyp group and the control group [95% confidence interval (CI) = 1.02-1.31, P = 0.03; 95%CI: 2.12-2.74, P < 0.001]. The patients with adenomatous polyps had a higher incidence of H. pylori infection than patients with non-adenomatous polyps [59.95% vs 51.75%, adjusted odds ratio (OR) = 1.41, 95%CI: 1.24-1.60, P < 0.01]. Patients with H. pylori-associated atrophic gastritis or intestinal metaplasia were at high risk of CRC (adjusted OR = 3.46, 95%CI: 2.63-4.55, P < 0.01; adjusted OR = 4.86, 95%CI: 3.22-7.34, P < 0.01, respectively). The size and location of the polyps, the histopathological characteristics and the location of CRC were not related to H. pylori infection. CONCLUSION: Our study demonstrates that the incidence of gastric H. pylori infection and H. pylori-associated atrophic gastritis or intestinal metaplasia elevates the risk of colorectal polyps and CRC.
ABSTRACT
BACKGROUND: Colorectal cancer is a common malignant tumor of the digestive tract. The relationship between sentinel polyps (rectal polyps with proximal colon cancer) and proximal colon cancer has received extensive attention in recent years. However, there is still no clear conclusion regarding the relationship. AIM: To investigate the clinical characteristics of sentinel polyps and their correlation with proximal colon cancer. METHODS: A retrospective analysis of 2587 patients with rectal polyps from January 2006 to December 2017 was performed. According to whether or not proximal colon cancer was diagnosed, the patients were divided into either a sentinel polyp group (192 patients) or a pure rectal polyp group (2395 patients). The endoscopic features, clinicopathological features, therapeutic effects, and short-term prognosis were analyzed and compared between the two groups. RESULTS: The mean age of patients in the sentinel polyp group was generally higher than that of the pure rectal polyp group, and the positivity rates of anemia, stool occult blood, and tumor markers of the sentinel polyp group were also significantly higher than those in the rectal polyp group (χ 2 = 90.56, P < 0.01; χ 2 = 70.30, P < 0.01; χ 2 = 92.80, P < 0.01). The majority of the patients in the sentinel polyp group had multiple polyps, large polyps, adenomatous polyps, or sessile polyps (χ 2 = 195.96, P < 0.01; χ 2 = 460.46, P < 0.01; χ 2 = 94.69, P < 0.01; χ 2 = 48.01, P < 0.01). Most of the proximal colon cancers were Duke's A and B stages in the sentinel polyp group. In the pure rectal polyp group, 2203 patients underwent endoscopic treatment, and all of the patients were cured and discharged. In the sentinel polyp group, 65 patients underwent radical operation, and 61 patients received endoscopic submucosal dissection or endoscopic mucosal resection. Additionally, 21 patients were lost to follow-up after 6-12 mo, and the loss rate was 10.94%. A total of 63.16% of patients experienced remission without tumor recurrence or metastasis, 33.33% of patients experienced tumors regression or improved symptoms, and the other 3.51% of the patients died. CONCLUSION: If there are multiple, sessile, and adenomatous rectal polyps with a maximum diameter > 1 cm, the possibility of the carcinogenesis of the polyps or of the proximal colon should be monitored closely. These patients should be followed in the short-term and should undergo a whole-colon examination.
ABSTRACT
High-flow oxygen inhalation is one of the most effective acute treatments for cluster headache. The therapy was first described for the treatment of cluster headache in 1952 by Horton, and has exhibited some advantages and efficacy compared to other acute medicines. The mechanism is not very clear, but some evidence has demonstrated its relationship to the trigeminovascular system and neuroinflammation. High-flow oxygen inhalation via a non-rebreather mask during cluster headache attacks has been widely recommended. Patients with frequent attacks and/or intolerance to drugs may prefer the oxygen treatment.
Subject(s)
Cluster Headache/therapy , Hyperbaric Oxygenation , Cluster Headache/pathology , Humans , Hypothalamus/metabolism , Oxygen/metabolism , Tryptamines/therapeutic useABSTRACT
OBJECTIVE: We aimed to study the association between HLA-DRB1 alleles and anti-neutrophil cytoplasmic antibodies (ANCA) among Uyghur and Han patients with ulcerative colitis (UC) in China. METHODS: Altogether 160 UC patients and 466 healthy controls of Uyghur and Han groups residing in the Xinjiang Uyghur Autonomous Region of China were included. HLA-DRB1 variants were identified from genomic DNA using polymerase chain reaction and gene sequencing. Serum ANCA were determined by indirect immunofluorescence assay. RESULTS: Among the Uyghur populations, the HLA-DRB1*08 gene frequency was lower in the UC patients than in the control group (P = 0.012, OR 0.12, 95% CI 0.02-0.91); however, that of HLA-DRB1*13 was much higher in the UC patients than in the controls (P = 0.001, OR 4.32, 95% CI 1.92-9.74). In Han patients with UC, there was no significant difference in HLA-DRB1 frequency between UC patients and healthy controls. The positive rate of ANCA in Uyghur patients with UC was significantly higher than in Han UC patients (P = 0.026), and ANCA positivity was associated with an increased frequency of HLA-DRB1*13 in Uyghur UC patients, but no such difference was observed in the Han patients. CONCLUSIONS: Genetic polymorphisms of the HLA-DRB1*08 and *13 may contribute to the clinical heterogeneity of UC between Uyghur and Han UC patients in China. In Uyghur UC patients, HLA-DRB1*13 may be correlated with ANCA positivity.
Subject(s)
Antibodies, Antineutrophil Cytoplasmic/blood , Colitis, Ulcerative/genetics , HLA-DRB1 Chains/genetics , Adult , Alleles , Asian People/genetics , Case-Control Studies , China/epidemiology , Colitis, Ulcerative/ethnology , Colitis, Ulcerative/immunology , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymorphism, GeneticABSTRACT
OBJECTIVE: To investigate the effect of human concentration nucleoside transporters 1 (hCNT1/ SLC28A1) and multi-drug resistance protein 4 (MRP4/ABCC4) gene polymorphism on the response of chronic hepatitis B patients to nucleoside analogues treatment. METHODS: There were 136 patients of chronic hepatitis B treated with entecavir (68) or telbivudine (68). The allele and gene frequency distributing of the four loci of hCNT1/SLC28A1 and MRP4/ABCC4 as well as the polymorphisms were detected in all patients by multiplex snapshot single base extension method. Based on the treatment response, the patients were divided into primary partial response (PPR) group and complete viral response (CVR) group, hCNTI/SLC28A1 and MRP4/ABCC4 gene polymorphism between these two groups were analyzed. RESULTS: The rates of PPR and CVR were 56. 6%00 (77 136) and 43. 4% (59/136) respectively. There was no statistical difference in baseline HBV DNA value, hepatitis B virus genotype and HBeAg status between PPR and CVR groups (P=0.148, P= 0. 622,P=0. 071) . The distribution of allelotype rs2290272 C/T and rs11568658 G/G in PPR group were higher than those in CVR group (P=0.043. P=0.049). Haplotype of C/A/T/C and C/C/G/G in CVR group were higher than those in PPR group (P=0. 024,P=0. 005). CONCLUSION: The single nucleotide polymorphisms (SNPs) of two candidate genes, including rs2290272 C/T of hCNT1/SLC28A1 and rs11568658 G/G of MRP4/ABCC4, may weak the response of chronic hepatitis B to nucleoside analogues treatment, as well as haplotype of C/A/T/C and C/C/G/G may enhance the response.
Subject(s)
Antiviral Agents/pharmacology , Drug Resistance, Multiple, Viral , Hepatitis B, Chronic/genetics , Membrane Transport Proteins/genetics , Multidrug Resistance-Associated Proteins/genetics , Guanine/analogs & derivatives , Guanine/pharmacology , Hepatitis B e Antigens , Humans , Polymorphism, Single Nucleotide , Telbivudine , Thymidine/analogs & derivatives , Thymidine/pharmacologyABSTRACT
To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Adult , Autoantibodies/blood , Drug Therapy, Combination , Female , Hepatitis C, Chronic/blood , Humans , Male , Recombinant Proteins/therapeutic use , Treatment OutcomeABSTRACT
The objective of this study was to compare the efficacy and safety of two rescue strategies for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with resistance to adefovir dipivoxil (ADV). This prospective study included 58 HBeAg-positive CHB patients with resistance to ADV; 30 patients underwent telbivudine (LdT) plus ADV combination therapy and 28 patients switched to entecavir (ETV) monotherapy. After 48 weeks of treatment, the rates of hepatitis B virus (HBV) DNA <3 log10 copies/mL in the LdT plus ADV group and the ETV group were not significantly different (73.3% vs 57.1%, P = 0.195). Six patients receiving LdT plus ADV had HBeAg seroconversion, while none of the patients receiving ETV alone had HBeAg seroconversion (20% vs 0%, P = 0.039). During the 48-week treatment period, two patients in the ETV monotherapy group had viral breakthrough and the strains were confirmed to be of a variant associated with ETV resistance (rtM204V+ rtL180M+ rtT184G), while one patient receiving LdT plus ADV had viral breakthrough and an LdT-associated resistance mutation (rtM204I) was detected. For the majority of the patients, both LdT plus ADV combination treatment or ETV monotherapy were generally well tolerated, and no serious side effects were observed. Both LdT plus ADV combination therapy and ETV monotherapy led to significant decreases in serum HBV DNA in HBeAg-positive CHB patients with resistance to ADV, and LdT plus ADV combination therapy exhibited a significantly higher rate of HBeAg seroconversion compared with ETV monotherapy.
Subject(s)
Adenine/analogs & derivatives , Antiviral Agents , Drug Resistance, Viral , Guanine/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Organophosphonates , Thymidine/analogs & derivatives , Adenine/adverse effects , Adenine/pharmacology , Adenine/therapeutic use , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , China , DNA, Viral/blood , DNA, Viral/genetics , Drug Therapy, Combination , Female , Guanine/adverse effects , Guanine/pharmacology , Guanine/therapeutic use , Hepatitis B e Antigens/blood , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Humans , Male , Organophosphonates/adverse effects , Organophosphonates/pharmacology , Organophosphonates/therapeutic use , Prospective Studies , Telbivudine , Thymidine/adverse effects , Thymidine/pharmacology , Thymidine/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: A functional interferon regulatory element (IRE) has been found in the EnhI/X promoter region of hepatitis B virus (HBV) genome. The purpose of this study is to compare the gene order of responder and non-responder to interferon therapy in patients with chronic hepatitis B (CHB), so as to evaluate the relationship between IRE mutation and the response to interferon treatment for CHB patients. RESULTS: Synthetic therapeutic effect is divided into complete response (CR), partial response (PR) and non-response (NR). Among the 62 cases included in this study, 40 cases (64.5%) were in the response group (CR and PR) and 22 (35.5%) cases were in the NR group. Wild type sequence of HBV IRE TTTCACTTTC were found in 35 cases (56.5%), and five different IRE gene sequences. included TTTtACTTTC, TTTCAtTTTC, TTTtAtTTTC, TTTtACTTTt and cTTtACcTTC, were found in 22 cases (35.5%), 1 case (1.6%), 1 case (1.6%), 2 cases (3.2%) and 1 case (1.6%) respectively. There were 41.9%cases (26/62) with forth base CâT mutation, consisted of 32.5% (13/40) cases in response group and 59.1% (13/22) cases in NR group. Among the 35 cases with IRE sequences, there were 67.5% (27/40) cases in response group and 36.4% (8/22) in NR group, and the difference in IRE sequences between two groups was statistic significantly (P = 0.027). The result suggested that there is likely relationship between the forth base mutation (CâT) of IRE region and the response of HBV to Interferon therapy, and this mutation may partially decrease the inhibition effect of interferon on HBV. CONCLUSION: The forth base CâT mutation in IRE element of HBV may partially influence the response of Interferon treatment in CHB patients.
Subject(s)
Antiviral Agents/administration & dosage , Biological Products/administration & dosage , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Interferons/administration & dosage , Mutation , Adolescent , Adult , Child , Child, Preschool , DNA Mutational Analysis , DNA, Viral/genetics , Female , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , Humans , Interferons/immunology , Male , Middle Aged , Promoter Regions, Genetic , Sequence Analysis, DNA , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Hemoperitoneum is associated with several emergency conditions and is especially evident when it occurs in patients with liver cirrhosis. This study aimed to assess the clinical characteristics of cirrhotic patients who did not have abdominal trauma or tumor but who developed hemoperitoneum. METHODS: We reviewed the clinical records of 1276 consecutive cirrhotic patients with hemoperitoneum at our center between January 2007 and December 2009. Hemoperitoneum was confirmed by abdominal paracentesis. RESULTS: Of the 1276 cirrhotic patients, 19 were found to have hemoperitoneum, but only 6 did not have abdominal trauma or tumor. The occurrence of spontaneous hemoperitoneum in the cirrhotic patients was therefore 0.5%. Hemoperitoneum can occur spontaneously in severely decompensated cirrhotic patients with intra-abdominal collateral vessels and high scores on the model for end-stage liver disease and Child-Pugh-Turcotte test. Most patients presented with abdominal distension, abdominal pain, increased abdominal girth and hemodynamic instability with a significant drop in the hemoglobin level. Three patients died of hemorrhagic shock within 24 hours, and the other 3 died of hepatic encephalopathy or spontaneous bacterial peritonitis after 5 to 10 days because of further decompensation of the liver. CONCLUSIONS: Hemoperitoneum can occur in cirrhotic patients who do not have abdominal trauma or tumor. It mainly occurs in severely decompensated end-stage cirrhotic patients. Cirrhotic patients with hemoperitoneum have a poor prognosis.
Subject(s)
Hemoperitoneum/etiology , Liver Cirrhosis/complications , Paracentesis/methods , Abdominal Injuries , Abdominal Neoplasms , Adult , China/epidemiology , Diagnosis, Differential , Female , Follow-Up Studies , Hemoperitoneum/diagnosis , Hemoperitoneum/epidemiology , Humans , Incidence , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Male , Portal Pressure , Prevalence , Prognosis , Retrospective Studies , Severity of Illness IndexABSTRACT
BACKGROUND/AIMS: This study reports our preliminary experience of living donor liver transplantation (LDLT) for patients with acute-on-chronic liver failure (AoCLF) caused by hepatitis B. METHODOLOGY: 47 patients who demonstrated Ao- CLF caused by hepatitis B with mean (±SD) Model for End-Stage Liver Disease scores of 39.2±5.1 were divided by the transplantation group (n=19) and the non-transplantation group (n=28) according to whether or not undergoing LDLT. At the same time, 30 hepatitis B cirrhosis recipients who underwent LDLT and did not reach the criteria of AoCLF were selected as the control group (n=30). In the transplantation group, veno-venous bypass, molecular adsorbent recirculating system (MARS) and continuous renal replacement therapy (CRRT) were introduced. The intraoperative data, post-transplant complications and mortality were analyzed retrospectively. RESULTS: There were no significant differences in survival rates of 1, 6 and 12 months and the postoperative complications except for pneumonia and diabetes, between the control group and the transplantation group (p>0.05). Recurrence of hepatitis B was not found in the recipients of the control group and the transplantation group. CONCLUSIONS: Right-lobe LDLT may be an effective therapeutic option for patients with acute-on-chronic hepatitis B liver failure.