Treatment of chronic hepatitis D patients with pegylated interferon: a real-world experience

Background: Published experience of treating chronic hepatitis D patients with pegylated interferon (PEG-IFN)-alpha is limited. The aim of this study was to determine the efficacy of 48 weeks of treatment with PEG-IFN in naive patients outside the clinical trial setting, in the real world. Methods: Patients with chronic hepatitis D were treated with PEG-IFN. The primary end points were sustained clearance of HDV RNA and normal alanine aminotransferase (ALT) at 24 weeks post-treatment. Results: The total number of patients treated with PEG-IFN was 104; 91 males, mean age ±SD 30.1 ±10.0 years (range 15-55). Cirrhosis was present in 41 patients. With an intention-to-treat analysis, end of treatment virological response (ETR) was achieved in 44 (42.3%), normalization of ALT in 38 (35%) and a combined response in 23 (22.1%) patients. Sustained virological response (SVR) at 24 weeks post-treatment was seen in 24 (23.1%) patients each for the virological and biochemical responses and in 13 (12.5%) as combined response. Both ETR and SVR were associated with a negative HDV RNA at 24 weeks of treatment (P=0.001 and P=0.000, respectively). Detectable HDV RNA at this point had a positive predictive value of 0.95 (range 0.85-0.99) for detectable RNA at 6 months post-treatment. End of treatment biological response, that is, normal ALT at the end of treatment was also a predictor of ETR and SVR (P=0.004 and P=0.041, respectively). Conclusion:: Treatment with PEG-IFN for hepatitis D is of limited efficacy. Detectable HDV RNA at 24 weeks of treatment is a predictor for a failed SVR

Interferon lambda-3 rs12979860 variants and response to pegylated interferon in chronic hepatitis-c genotype-3

Objective: To assess the role of single nucleotide polymorphisms (SNPs) near the interferon lambda-3 (IFNλ3) (formal IL-28B) gene rs12979860 in predicting sustained virologic response (SVR) in hepatitis-C virus genotype-3 (HCV-3). Study Design: Descriptive, analytical study. Place and Duration of Study: Department of Medicine, The Aga Khan University Hospital, Karachi, from July 2012 to June 2014. Methodology: Patients with HCV-3 were classified as sustained virologic response (SVR), relapsers and non-responders. SNP rs12979860 was determined by PCR-RFLP protocol. Differences between categorical variables were assessed by chi-square or Fisher\u27s exact test, while those between continuous variables were evaluated using the Mann-Whitney U-test. Binary logistic regression analysis by forward conditional method was performed by using significant variables with p-values less than 0.05 as the criteria for model inclusion. Results: Out of 115 patients, rs12979860 genotype-CC, CT, TT was found in 37 (32.2%), 70 (60.9%), and 8 (7%) patients. 72 patients were male with median age of 45 years. Cirrhosis was present in 32 patients. Patients with response failures (no response and relapse, n=36 and 29, respectively) had higher baseline gamma glutamyl transferase (GGT) level (p \u3c 0.001), higher alanine aminotransferase (p=0.027) and cirrhosis (p=0.001) than patients with SVR. Genotype-CC was present in 16/65 in response failures compared to 21/50 who achieved SVR (p=0.048). Rapid virologic response (RVR) (p \u3c 0.001), low GGT (p=0.001) and absence of cirrhosis (p=0.039) were the independent predictive factors for SVR. In patients who could not achieve RVR and in patients with cirrhosis, SVR was seen more in with genotype-CC (p=0.007 and 0.038). Conclusion: In patients infected with HCV-3, IFNλ3 rs12979860, SNP has less impact on SVR

Aflatoxins and Hepatitis B, C Viral Associated Hepatocarcinogenesis

Hepatocellular carcinoma is a serious human disease with fatal consequences. The most distressing aspect of hepatocellular carcinoma is the limited improvement in mortality (mortality rate of more than 90%). At present, the underlying molecular mechanisms are not well understood and treatment options are often of limited efficacy. This review presents our current understanding of the burden of hepatocellular carcinoma on human health, pathogenesis and pathophysiology, and molecular mechanisms associated with the disease, as well as our knowledge of the physical barriers, cellular mechanisms and molecular elements that may be targets for therapeutic interventions and/ or the development of preventative measures. As the proposed findings present a major risk to public health, it is hoped that robust intervention measures will be introduced for aflatoxins monitoring and reduction in diet

Substitution reactions of cis-dichloro(2,2′-biquinoline)palladium(II) with amino acids

AbstractThe substitution reactions of the 2,2′-biquinoline (biq) complex cis-[Pd(biq)Cl2] with different amino acids, namely, glycine (glyH), l-serine (serH), l-tyrosine (tyrH), l-phenylalanine (pheH) and l-alanine (alaH) have been investigated. The new complexes [Pd(biq)(gly)]Cl, [Pd(biq)(ser)]PF6·0.5H2O, [Pd(biq)(tyr)2], [Pd(biq)(tyr)]PF6·H2O, [Pd(biq)(phe)2]·2.5H2O, [Pd(biq)(phe)]PF6·H2O and [Pd(biq)(ala)]Cl.1·5H2O have been characterized by elemental analysis, conductivity measurements, IR, electronic absorption and 1H and 13C NMR spectra. Based on these data all amino acid anions are found to act as bidentates except tyrosinate and phenylalanilate which behave also as monodentates

The effect of Cd substitution in PbS thin film on the optical properties

Abstract:Thin films of Cd‌x‌Pb‌1-x S were prepared by chemical spray pyrolysis with ( x=0.6 , 0.7 , 0.8 , 0.9 , 1 ) .The optical properties of prepared thin films were studied by UV-VIS spectrophotomer . From the measurement of absorption and transmission , the optical parameters and the optical energy gap (Eg) were calculated .The optical energy gap (Eg) was increased with increasing the value of Cd from 1.2 eV when x=0.6 to 2.4 eV when x=1 . The maximum value of refractive index (n) is equal to 2.5 and the maximum value of extinction coefficient is varied between 0.2 to 0.45 depending on the value of x . The film with x=0.7 was doped by Ag in the ratio 1% ,3% and 5% . The film after dopping have a direct energy gap also and the value of Eg were increased with increasing (Ag) ratio , these values increased from 1.2 eV for absent Ag to 1.74 eV for 5% Ag

Candida esophagitis: Risk factors in non-HIV population in Pakistan

AIM: Candida esophagitis is a frequent infection in immunocompromised patients. This study was designed to determine its characteristics in non- human immune deficiency virus (HIV) infected patients attending a teaching hospital. METHODS: Clinical records of all patients coded by international classification of diseases 9th revision with clinical modifications\u27 (ICD-9-CM), with candida esophagitis diagnosed by esophagogastroduodenoscopy (EGD) and histopathology over a period of 5 years were studied. RESULTS: Fifty-one patients (27 males, 24 females, range 21-77 years old and mean age 52.9 years) fulfilled the criteria (0.34% of the EGD). The common predisposing factors were carcinoma (OR 3.87, CI 1.00-14.99) and diabetes mellitus (OR 4.39, CI 1.34-14.42). The frequent clinical symptoms were retrosternal discomfort, dysphagia and epigastric abdominal pain with endoscopic appearance of scattered mucosal plaques. Another endoscopic lesion was associated with candida esophagitis in 15% patients. CONCLUSION: Carcinomas, diabetes mellitus, corticosteroid and antibiotic therapy are major risk factors for candida esophagitis in Pakistan. It is an easily managed complication that responds to treatment with nystatin

Yield of esophagogastroduodenoscopy and colonoscopy in cancer of unknown primary

Objectives: Carcinoma of unknown primary origin (CUP) is heterogeneous group of cancers. Role of gastrointestinal (GI) endoscopy in this entity is under investigated. Aim of this study was to evaluate yield of Colonoscopy and Esophagogastroduodenoscopy (EGD) in localizing primary tumor in patients with CUP. METHODOLOGY: Patients with histopathologically proven CUP who underwent colonoscopy / EGD to find the primary tumor from December 2009 to December 2011 were included in the study. Abdominal symptoms and cytokeratin (CK) 7 and 20 markers were correlated with presence of primary in GI tract. Results: After giving informed consent 86 patients were included in final analysis. All patients underwent colonoscopy while 60(70%) got EGD along with colonoscopy. Mean age was 55.10 +/-11.94 years with 52(60%) male. Abdominal symptoms were present in 50%. CK7+/CK20- in 34(40%); CK7-/CK20+ in 2(2%) while CK7+/20+ in 7(8%) of metastatic tumor samples. Liver was metastatic site in 47(55%), Lymph node 12(14%) and Ascites in 8(9%). Endoscopy detected primary in 6 (7%) patients with 3 each in stomach and colon. No association of abdominal symptoms and cytokeratin markers was found with presence of GI primary site. CONCLUSION: Yield of localizing primary lesion in the GI tract by pan-endoscopy was limited. Abdominal symptoms and cytokeratin markers do not predict presence of gastrointestinal malignancies

Acute-on-chronic liver failure: Consensus recommendations of the Asian pacific association for the study of the liver (APASL): An update

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the APASL ACLF Research Consortium (AARC) was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the \u27Golden Therapeutic Window\u27, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here