Evaluation of Renessans (Iodine Complex Molecule) Safety in Human Beings: An Open-Labeled Clinical Study.

Extensive studies on evaluation of effectiveness/toxicity of different oral doses of iodine have not been explored yet. An open-labeled phase I clinical studies were conducted using iodine complex based research compound called Renessans. Study groups were observed for development of any adverse/serious adverse events and alteration in laboratory values of vital organs, TSH and T4 hormones before and after the administration of the products. Out of 31 consented individuals, 24 healthy individuals participated in the study. Rate of occurrence of mild Adverse Events (AEs) in group A was 8.3% while in Group B it was 33.33% but these Adverse Events were self-resolving. After completion of study treatment blood serum iodine was reported to 3522.88 µg/l while mean urine iodine concentration (MUIC) was greater than 2000 µg/l. Hormonal and vital organ's testing revealed that all parameters of TSH and T4, LFT, CBC, RFT remained unaltered except from ALT-SGPT (P-value = .006) and AST-SGOT (P-value = .02). From all of these findings, it can be inferred that the use of Renessans formulations did not pose any sort of risk to human body and can be considered safe through this pilot study.

PNPLA3 and TM6SF2 genetic variants and hepatic fibrosis and cirrhosis in Pakistani chronic hepatitis C patients: a genetic association study.

BACKGROUND: The present study investigates if common missense functional variants p.I148M and p.E167K in PNPLA3 and TM6SF2 genes, respectively, associate with development of hepatic fibrosis and cirrhosis in a geographically novel cohort of Pakistani chronic hepatitis C (CHC) patients. METHODS: In total, 502 Pakistani CHC patients [242 males, median age 40 years, 220 with significant hepatic fibrosis, including 114 with cirrhosis] were genotyped for PNPLA3 and TM6SF2 variants using TaqMan genotyping assays. Associations between genotypes, biochemical and clinical parameters were evaluated. RESULTS: Genotypic distributions for PNPLA3 and TM6SF2 polymorphisms conformed to Hardy-Weinberg equilibrium and did not associate with fibrosis grades ≥ F2 or cirrhosis in any of the genetic models tested (all p = > 0.05). PNPLA3 and TM6SF2 variants did not modulate baseline characteristics and serum markers of liver injury in CHC patients. Similarly, increasing number of risk alleles of PNPLA3 and TM6SF2 polymorphisms had no trend effect on serum liver enzyme activities or proportion of CHC patients with significant or advanced fibrosis or cirrhosis (p = > 0.05). The same trend of no association with hepatic fibrosis or cirrhosis persisted in the multivariate logistic regression models adjusting for age, gender, body mass index and HCV viral load (p = > 0.05). CONCLUSIONS: PNPLA3 and TM6SF2 variants do not appear to modulate development of hepatic fibrosis or cirrhosis in present CHC patients of Pakistani origin, and may be of more relevance in liver pathology involving abnormalities in hepatic fat accumulation. These results also reflect the divergent associations observed for different genetic modifiers of hepatic fibrosis and cirrhosis in distinct ethnicities.

Phylogenetic analysis and antimicrobial susceptibility profile of uropathogens.

The uropathogens is the main cause of urinary tract infection (UTI). The aim of the study was to isolate bacteria from urine samples of UTI patients and find out the susceptibility of isolated bacteria. Bacteria were identified using both conventional and molecular methods. Sanger sequence procedure used for 16S ribosomal RNA and phylogenetic analysis was performed using Molecular Evolutionary Genetics Analysis (MEGA-7) software. In this study, Escherichia coli, Klebsiella pneumonia, Staphylococcus were reported as 58, 28 and 14.0% respectively. Phylogenetic tree revealed that 99% of sample No. Ai (05) is closely related to E. coli to (NR 114042.1 E. coli strain NBRC 102203). Aii (23) is 99% similar to K. pneumoniae to (NR 117686.1 K. pneumonia strain DSM 30104) and 90% Bi (48) is closely linked to S. aureus to (NR 113956.1 S. aureus strain NBRC 100910). The antibiotic susceptibility of E. coli recorded highest resistance towards ampicillin (90%) and least resistant to ofloxacin (14%). Some of the other antibiotics such amoxicillin, ciprofloxacin, gentamicin, ceftazidime, cefuroxime and nitrofurantoin resistance were observed 86, 62, 24, 55, 48 and 35% respectively. The cefuroxime showed the highest antibiotic resistance against K. pneumoniae with 85% followed by amoxicillin, ciprofloxacin, gentamicin, ceftazidime, ampicillin and nitrofurantoin resulted in 60, 45, 67, 70, 75 and 30% respectively. The resistance of S. aureus against erythromycin, cefuroxime and ampicillin were found with 72%. The resistance against amoxicillin, gentamicin, ceftazidime and ceftriaxone found 57, 43, 43 and 15% respectively. Phylogenetic analysis shows that sequences are closely related with the reference sequences and E. coli is the dominant bacteria among UTI patients and is resistant to the commercially available antibiotics.

Hepatocellular carcinoma occurs frequently and early after treatment in HCV genotype 3 infected persons treated with DAA regimens.

BACKGROUND: There are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after direct-acting antiviral agent (DAA) treatment. Risk of HCC in HCV genotype-3 infected persons after DAA therapy is not well known. METHODS: We prospectively studied HCV infected persons initiated on a DAA regimen between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. HCC was confirmed based on characteristic CT scan findings. Patients were followed for 12 months after the completion of therapy. RESULTS: A total of 662 persons initiated treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic, 91% were genotype 3 and 91.9% attained SVR. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCV), 10.6%; SOF/DCV, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the 12-month period after treatment completion and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85). In Kaplan-Meier plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCV, or SOF/DCV regimens had a shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen. CONCLUSION: In a predominantly genotype 3 cohort, incident HCC occurred frequently and early after treatment completion, and exclusively in those with pre-treatment cirrhosis. SVR reduced the risk of HCC. Treating HCV infected persons before development of cirrhosis may reduce risk of HCC.

Liver Cancer-Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma.

INTRODUCTION: Liver cancer-secreted serine protease inhibitor Kazal (LC-SPIK) is a protein that is specifically elevated in cases of hepatocellular carcinoma (HCC). We assessed the performance of LC-SPIK in detecting HCC, including its early stages, in patients with cirrhosis, hepatitis B virus (HBV), and hepatitis C virus (HCV). METHODS: We enrolled 488 patients, including 164 HCC patients (81 early HCC) and 324 controls in a blinded, prospective, case-control study. Serum LC-SPIK levels were determined by an enzyme-linked immunosorbent assay-based assay. The performance of serum LC-SPIK and α-fetoprotein (AFP), including area under the curve (AUC), sensitivity, and specificity, are compared. The performance of LC-SPIK was evaluated in an independent validation cohort with 102 patients. RESULTS: In distinguishing all HCC patients from those with cirrhosis and chronic HBV/HCV, LC-SPIK had an AUC of 0.87, with 80% sensitivity and 90% specificity using a cutoff of 21.5 ng/mL. This is significantly higher than AFP, which had an AUC of 0.70 and 52% sensitivity and 86% specificity using a standard cutoff value of 20.0 ng/mL. For early-stage HCC (Barcelona Clinic Liver Cancer stage 0 and A), LC-SPIK had an AUC of 0.85, with 72% sensitivity and 90% specificity, compared with AFP, which had an AUC of 0.61, with 42% sensitivity and 86% specificity. In addition, LC-SPIK accurately detected the presence of HCC in more than 70% of HCC patients with false-negative AFP results. DISCUSSION: The study provided strong evidence that LC-SPIK detects HCC, including early-stage HCC, with high sensitivity and specificity, and might be useful for surveillance in cirrhotic and chronic HBV/HCV patients, who are at an elevated risk of developing HCC.

Correction: Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0203149.].

Streptococcal toxic shock syndrome with primary group A streptococcus peritonitis in a healthy female.

A 47-year-old female with a history of chronic alcoholism presented with nausea, vomiting and mild epigastric tenderness. She reported subjective fever, abdominal fullness and loose, watery stools and had stable vitals on arrival. Examination was positive for mild epigastric tenderness with hepatic enlargement. Computed tomography of the abdomen showed circumferential thickening of the stomach wall, lower esophagus and the first part of the duodenum in addition to peritoneal ascites. She was admitted for alcohol-related gastritis, acute alcoholic hepatitis, and acute kidney injury. She was started on fluid resuscitation and supportive management. After 8-hours, the patient became hemodynamically unstable with subsequent intubation and fluid resuscitation. She was started on empiric antibiotics. Blood and ascitic fluid cultures were obtained showing group A beta-hemolytic streptococci (GAS). The patient was diagnosed with primary GAS peritonitis along with diffuse gastritis and streptococcal toxic shock syndrome. No cutaneous source of Streptococcus pyogenes was identified, and there was no personal or family history of streptococcal pharyngitis. Antibiotics were switched to IV ampicillin and clindamycin. However, the patient continued to deteriorate and succumbed to death within 2-days.

Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.

BACKGROUND: We previously developed a logistic regression algorithm that uses AFP, age, gender, ALK and ALT levels to improve the detection of hepatocellular carcinoma (HCC). In 3,158 patients from 5 independent sites, this algorithm, referred to as the "Doylestown" algorithm, increased the AUROC of AFP 4% to 12% and had equal benefit regardless of tumor size or the etiology of liver disease. AIMS: Analysis of the Doylestown algorithm using samples from individuals taken before their diagnosis of HCC. METHODS: Here, the algorithm was tested using samples at multiple time points from (a) patients with established chronic liver disease, without HCC (120 patients) and (b) 116 patients with HCC diagnosis (85 patients with early stage HCC and 31 patients with recurrent HCC), taken at the time of, and up to 12 months prior to cancer diagnosis. RESULTS: Among patients who developed HCC, comparing the Doylestown algorithm at a fixed cut-off to AFP at 20 ng/mL, the Doylestown algorithm increased the True Positive Rate (TPR) in identification of HCC from 36 to 50%, at a time point of 12 months prior to the conventional HCC detection. Similar results were obtained in those patients with recurrent HCC, where the Doylestown algorithm increased TPR in detection of HCC from 18% to 59%, at 12 months prior to detection of recurrence. CONCLUSIONS: This algorithm significantly improves the prediction of HCC by AFP alone and may have value in the early detection of HCC.

Correlation of biochemical markers and HCV RNA titers with fibrosis stages and grades in chronic HCV-3a patients.

INTRODUCTION: Hepatitis C virus (HCV) is one of the most important causes of chronic liver diseases, which include inflammation, fibrosis, cirrhosis and hepatocellular carcinoma. Several factors have been proposed to determine the clinical outcome of HCV infection. The accurate mechanism by which HCV damages the liver remains poorly understood. In chronic hepatitis C patients, the relation between serum biochemical markers, HCV RNA titers and histological liver injury remain controversial. OBJECTIVES: The aim of this study was to investigate the relation between serum biochemical markers, HCV RNA titers and the degree of liver damage in patients with chronic HCV. MATERIALS AND METHODS: Liver biopsies were performed on 79 of a total of 100 enrolled patients. The histological activity was evaluated by the METAVER scoring system. HCV RNA quantification was performed by quantitative real-time PCR, and HCV genotyping was performed by nested PCR. Biochemical markers were measured with biochemical instruments. RESULTS: HCV RNA titers were significantly correlated with aspartate aminotransferase (AST) (P=0.004), alkaline phosphatase (ALP) (P=0.001) and total bilirubin (P=0.012) levels. HCV RNA titers were also significantly correlated with a progression of the fibrosis stage (P=0.000), but no correlation was observed with the change in inflammatory grades. It was observed that bilirubin levels were higher in later fibrosis stages as compared with the initial stage (P=0.000). Results revealed that in different fibrosis stages, the levels of AST (P=0.000), ALP (P=0.000) and alanine aminotransferase (ALT) (P=0.008), the age at diagnosis (P=0.000), the present age (P=0.000) and the BMI (P=0.009) were statistically significant. In the case of the inflammatory grade, levels of bilirubin (P=0.000), ALP (P=0.000), AST (P=0.016) and ALT (P=0.000) were statistically different between the inflammatory grades. CONCLUSION: Serum HCV RNA titers were correlated with AST, ALP and total bilirubin. Levels of ALT, AST, ALP and bilirubin had significant relation with the liver fibrosis stage and the inflammatory grade in genotype 3a. Hence, our study suggests that AST, ALP and ALT may correlate with liver damage.