Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients

This study aimed to characterize the genetic subtypes of HCV-GT4 and identify the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT4 patients was analyzed. Sequence analysis of NS3, NS5A and NS5B regions was performed by direct sequencing. In addition, phylogenetic analysis was used to determine genetic subtypes, RAS and polymorphisms. Nine patients were infected by a GT4a, one with GT4o, 3 with GT4d. The remaining four patients were infected with a recombinant virus (GT4a+GT4o in three patients, GT4c+GT4d in a patient). Natural RASs were found in six patients (35%), including three infected by GT4a, two by GT4a+GT4o and one patient infected by GT4c+GT4d. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M+M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about a third of patients, but only one of them showed a treatment failure.

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Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients

Viruses ◽

10.3390/v13091832 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1832

Author(s):

Mariantonietta Di Stefano ◽

Mona H. Ismail ◽

Thomas Leitner ◽

Giuseppina Faleo ◽

Saada A. Elmnan Adem ◽

...

Keyword(s):

Saudi Arabia ◽

Direct Sequencing ◽

Phylogenetic Analyses ◽

Natural Resistance ◽

Resistance Mutations ◽

Hepatitis C Infection ◽

Genotype 4 ◽

Genetic Subtypes ◽

Small Cohort ◽

Lost To Follow Up

This study aimed to characterize the HCV genetic subtypes variability and the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT patients were analyzed. Sequence analysis of NS3, NS5A, and NS5B regions was performed by direct sequencing, and phylogenetic analyses were used to determine genetic subtypes, RAS, and polymorphisms. Nine patients were infected by GT 4a, two with GT 4o and three with GT 4d. Two patients were infected with apparent recombinant virus (4a/4o/4a in NS3/NS5A/NS5B), and one patient was infected with a previously unknown, unclassifiable, virus of GT 4. Natural RASs were found in six patients (35%), including three infected by GT 4a, two by GT 4a/GT 4o/GT 4a, and one patient infected by an unknown, unclassifiable, virus of GT 4. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M + M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up, whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT 4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about one-third of patients, but only one of them showed a treatment failure.

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Imatinib Mesylate and Hyper-CVAD (IM-HCVAD) for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL).

Blood ◽

10.1182/blood.v114.22.4103.4103 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4103-4103

Author(s):

Martha Arellano ◽

Disni Muringampurath-John ◽

Pareen J. Shenoy ◽

Elliott F. Winton ◽

Beverly Bryan ◽

...

Keyword(s):

Residual Disease ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Allogeneic Transplantation ◽

Newly Diagnosed ◽

Small Cohort ◽

Cytogenetic Remission ◽

Lost To Follow Up ◽

Disease Free

Abstract Abstract 4103 Introduction The addition of IM to hyper-CVAD led to higher rates and longer duration of complete remissions in Ph+ ALL. The purpose of this study is to report single institution experience with IM-HCVAD followed by maintenance IM or allogeneic transplantation in newly diagnosed adult Ph+ ALL treated between 10/02 and 08/08. Methods IRB-approved retrospective analysis of the institutional hematological database. Results Thirty-three patients, median age 51 (22-72), with 8 (24%) older than 60, presented with a median WBC of 24,000/mm3 (range, 2-200) and LDH of 2.6 ULN (1.3-11). Four (12%) had extra-medullary/CSF leukemia. Patients received a median of 7 (range, 1-8) cycles of IM-HCVAD followed by maintenance IM +/- POMP as tolerated (Blood 2004;103:4396-4407). After 2 cycles, 1 patient had primary refractory disease and expired, and 32 (97%) achieved complete hematological and cytogenetic remission. Twenty-four of 32 (75%) subsequently achieved complete molecular remission (CMR). Among those who achieved CMR, 6/24 relapsed with preceding loss of CMR in 4. Four of 8 who did not achieve CMR relapsed. One patient in CR was lost to follow-up after induction. Thirteen (39%) were allografted in CR1 using TBI-based myeloablative (9) or non-myeloablative (4) conditioning and 18 received maintenance IM-based therapy. With a median follow-up of 18.3 months (range, 4.4-76), 10 patients (32%) relapsed (1 post-transplant and 9 during IM maintenance) and received salvage therapy leading to CR2 in 4, of which 1 was successfully allografted, and 3 remain in CR2 with a follow-up of 20, 36, and 60 months. Eleven patients died (6 from GVHD/infection, and 5 from relapsed refractory leukemia). For the 13 allograft recipients in CR1 disease-free (DFS) and overall survival (OS) were 15, and 18 months; and 15 months and 20 months for the 18 IM maintenance patients, respectively (Figure). WBC > 30,000/mm3 and residual disease detected by flow cytometry after 2 cycles were associated with decreased OS (p < 0.03). A trend for lower survival was noted among African American patients (p= 0.07). Conclusion The addition of IM to hyper-CVAD is associated with high rates of CR (97%) in newly diagnosed Ph+ ALL. In this relatively small cohort with a short follow-up, peripheral blood PCR did not predict outcomes. Ph+ALL patients are candidates for novel maintenance regimens. Disclosures: Off Label Use: Imatinib combined with the hyper-CVAD chemotherapy. Khoury:Novartis Oncology: Honoraria.

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P589 Longer-term outcomes in patients with Crohn’s disease who are primary non-responders to anti-TNF in a single UK centre

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.717 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S492-S493

Author(s):

P HODGES ◽

J Saunders ◽

F Betteridge

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Electronic Patient Records ◽

Biologic Drugs ◽

Significant Treatment ◽

Inflammatory Bowel ◽

Small Cohort ◽

Trial Drug ◽

Lost To Follow Up

Abstract Background Primary non-response (PNR) is reported to occur in up to 24% patients with inflammatory bowel disease treated with anti-TNF drugs. The longer-term outcomes of these patients are less well documented however it is recognised that this group represents a significant treatment challenge. We report retrospective outcomes for these patients from a single centre. Methods All patients with Crohn’s disease who stopped anti-TNF therapy because of PNR from 2013 to 2017 were identified from our database. Data were retrospectively collected from electronic patient records. Results 124 patients were started on anti-TNF therapy in this 4-year period and PNR occurred in 26 of these (21%). Median follow-up was 43.5 months. Following PNR 9 (34.6%) patients had surgery as next treatment although in the majority of these cases (6/9) this was before alternative class biologic drugs were available. 7 (26.9%) switched to an alternative anti-TNF again with the majority of these (5/7) being prior to the availability of other biologic class drugs. The subsequent outcomes for these patients are; 3 remain in remission, 1 failed to respond to an alternative anti-TNF and went on to have surgery within 1 year, 1 was in remission for 2 years then switched to vedolizumab, 2 were lost to follow-up or died for unrelated reasons. 6 (23.1%) switched to a different biologic class. Of these, 4 remain in remission, 1 required subtotal colectomy within 3 years, and 1 had 3 further biologic agents all of which failed and is now awaiting a trial drug or surgery. 2 (7.7%) switched to other immunomodulators. Two (7.7%) were lost to follow-up. Conclusion Overall 11 of the 26 (42%) patients required surgery within 3 years of primary anti-TNF failure. These data span a period during which vedolizumab and ustekinumab became available; therefore, the proportion of patients requiring surgery as next intervention is likely to be less now that these alternative drugs are available. In this cohort 4/6 patients who received alternative biologic class drugs who would previously have gone on to have surgery as the next intervention remains in remission (median follow-up 37 months). Although this is a small cohort, PNR response is shown to be a marker of poor prognosis with the availability of alternative biologics appearing to reduce the short-and medium-term need for surgery.

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Prevalence of Hepatitis C Virus Genotypes in the Southern Region, Saudi Arabia

10.1101/603902 ◽

2019 ◽

Author(s):

Abdullah M AlKahtani ◽

Meaad N Alsultan ◽

Abdulrahim R Hakami ◽

Mohammad Alamri

Keyword(s):

Saudi Arabia ◽

Viral Load ◽

Blood Transfusion ◽

Blood Donation ◽

Direct Sequencing ◽

Southern Region ◽

Genotype 1 ◽

Genotype 4 ◽

Genotype 2 ◽

History Of

ABSTRACTAimThe aim of this study was to investigate the prevalence of HCV genotypes in the Southern Region, Saudi Arabia.Materials & methodsA total of 76 HCV-positive individuals were selected for this study, including 34 males and 42 females, both acute and chronic patients. All HCV isolates were genotyped by direct sequencing of the 5’UTR region. The Chemistry profile, viral load and history of blood transfusion were collected from the hospital record.ResultsThe most common genotype was gt 4 (48.7%) followed by gt 1 (34.2%) and gt 3 (14.5%). Genotype 2 (2.6%) was only found in elderly male individuals. Patients with history of blood transfusion showed a high percentage of genotype 1 compared to the total number of all patients with genotype 1 (23% and 11% respectively). Biochemical assay showed high level of ALT particularly in genotype 4. No significant relationship was observed between HCV genotype and AST level between genotypes. The viral load was higher in HCV patients received blood transfusion than other genotypes.ConclusionThe prevalence of genotypes in this study confirmed the observation of other investigations, but no link was found between sex and genotype. There might be an association between blood donation in the past and infections with genotype 1.

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Lost to Follow-Up

Skin & Allergy News ◽

10.1016/s0037-6337(09)70596-0 ◽

2009 ◽

Vol 40 (12) ◽

pp. 13

Author(s):

ALAN ROCKOFF

Keyword(s):

Lost To Follow Up

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Predicting the risk of becoming lost to follow-up in a lifestyle weight-loss intervention

PsycEXTRA Dataset ◽

10.1037/e546872013-106 ◽

2013 ◽

Author(s):

Danielle M. Lespinasse ◽

Kristen E. Medina ◽

Stacey N. Maurer ◽

Samantha A. Minski ◽

Renee T. Degener ◽

...

Keyword(s):

Weight Loss ◽

Weight Loss Intervention ◽

Lost To Follow Up

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Pediatrics’ Total Parenteral Nutrition: Initiative and implementation of standardized formulation in Saudi Arabia

Research in Pharmacy and Health Sciences ◽

10.32463/rphs.2018.v04i03.16 ◽

2018 ◽

Vol 4 (3) ◽

pp. 492-496

Author(s):

Yousef Ahmed Alomi ◽

Hussam Saad Almalki ◽

Aisha Omar Fallatah ◽

Awatif Faraj Alshammari ◽

Nesreen Al-Shubbar

Keyword(s):

Saudi Arabia ◽

Clinical Outcome ◽

Parenteral Nutrition ◽

Drug Related Problems ◽

Kingdom Of Saudi Arabia ◽

Parental Nutrition ◽

Management Project ◽

Improve Patient ◽

New System

The national total parental nutrition program with an emphasis on pediatrics started before several ago at Ministry of health hospitals In Kingdom of Saudi Arabia. The program covered several regions and consisted from the foundation of Intravenous Admixture and preparation of pediatric parenteral nutrition to administration and follow up of patients outcomes. In addition to the prior system, the new initiative project with the standardized formulation of pediatric’s parenteral nutrition is the complementary project of the parental nutrition for pediatrics. The project initiated to prevent drug-related problems of parental nutrition, improve patient clinical outcome and reduce the unnecessary economic burden on the healthcare system. It is the new system in the Middle East and Gulf counties in additional to Saudi Arabia. The initiatives are the systemic implementation of standardized pediatrics formulation using management project tools of starting new idea until finding in the ground.

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