An Update on National Consensus Practice Guidelines for the Treatment of Hepatitis C & Literature Review in Epidemiology of Hepatitis C in Pakistan - 2022

Hepatitis C is a global health problem affecting around 58 million people worldwide and killing almost 0.29 million in on one year [1]. The world has united to fight against this lethal disease in 2016 with a moto to eliminate hepatitis by 2030. To achieve this goal WHO’s World Health Assembly has set some targets and individual countries have developed their own strategies to achieve those targets [2].  Pakistan has the 2nd highest prevalence of hepatitis C in the world with 5.8% viremia positive patients [3]. Pakistan is amongst the few countries that have been assisted by the Center for Disease Control and Prevention(CDC) to prevent and control Hepatitis[4].    With the availability of Direct Acting Antivirals(DAAs), the whole paradigm of treatment of hepatitis C has changed not only globally but also in Pakistan. However, the patients in Pakistan are unable to gain access to the latest DAAs at the pace, as they are available globally. International guidelines are being updated on regular basis as per global evidence, recommending such combinations which are not readily available to many parts of the world. Hence there is a dire need to develop national guidelines, keeping in consideration the efficacy of the drugs as well as their availability, in the broader canvas of achieving the targets of eliminating Hepatitis set by WHO.   In this context, our consensus guidelines are an effort to fill the gap created because of upgraded scientific evidence and possible combinations available in our part of the world. Furthermore, quite some good research and evidence has also been shared in the literature from Pakistan during last five years (2016-2021). Hence a literature review has also been carried out to update our own epidemiologic data, risk factors and treatment responses to Hepatitis C in Pakistan

Communication Problems in Second Language Learning at Federal Government Secondary Schools

ABSTRAC

Floods and flood management and its socio-economic impact on Pakistan: A review of the empirical literature

Flood is one of the most damaging natural disasters as the recent floods have shown their serious impact on Pakistan. Flood control and regulation policies are essential to reduce the risks of economic downturn, a threat to human existence, and to sustain the ecology. The severity of flood catastrophe activities represents a constant and severe issue in the world. Floods are rising year by year in severity and duration, causing negative impacts on the social and economic conditions of the nation concerned. While the frequency of floods cannot be avoided, their adverse impacts can be considerably reduced by adopting careful planning and efficient training. This paper reviews the socioeconomic impact of floods, and the existing condition of flood control policies outlines the flood protection problems and discusses opportunities for successful and efficient flood control in Pakistan. The paper also intends to propose several suggestions for efficient and sustainable flood control in Pakistan

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance

Efficacy and safety of generic daclatasvir + sofosbuvir ± ribavirin in treatment of genotype 3 infected hepatitis C patients - a real life experience from Pakistan

Aim: Genotype 3 is the most prevalent genotype in Pakistan. Despite a revolution in the treatment of Hepatitis C, genotype 3 is still thought to be difficult to treat genotype. The price of patent direct acting antivirals was thought to a great limiting factor especially for low income countries. In Pakistan low cost generics of daclatasvir and sofosbuvir are easily available for treatment. The aim of our study is to provide real life local data to determine their efficacy and safety.Methods: This open-label, non-randomized, uncontrolled study was carried out at Center for Liver and Digestive Diseases, Holyfamily Hospital, Rawalpindi. We enrolled patients from March 2016 through March 2018 who were 18 years or older having chronic hepatitis C infection with detectable polymerase chain reaction (PCR), regardless of whether they were treatment naïve or have experienced Interferon in the past. The patients were offered generic sofosbuvir 400 mg and daclatasvir 60 mg once daily with or without ribavirin for a period of 12 to 24 weeks. Follow-up PCRs were performed at 4th week of treatment, end of treatment and 12 weeks post treatment. All those patients were included in the study that had at least one follow-up PCR during or after the course of treatment.Results: A total of 102 patients were enrolled in the study with a mean age of 48.11 ± 12.70 including 63% males and 37% females. All patients were genotype 3. On 4th week follow up, 31/36 (86.11%) patients had quantitative PCR negative. Out of 102 patients, 78 patients had follow up PCR at the completion of therapy with an end of treatment response of about 96.1%. Thirty patients had a follow up at 12 weeks post treatment with a SVR12 of 83.33% (25/30) amongst which treatment Naïve had a response rate of 84% (21/25), treatment experience 80% (4/5), non-cirrhotics 85.71% (12/14), cirrhotics 81.25% (13/16) and decompensated chronic liver disease patients have a SVR12 of about 83.33% (10/12) respectively. The combination was well tolerated with few side effects, 18.6% patients had itching, 10.8% had insomnia, 8.8% had oral ulcers and 6.9% had fatigue.Conclusion: Generic sofosbuvir and daclatasvir are cheap, safe and efficacious with a SVR12 of about 83.33% amongst genotype 3 patients. These generics will act as a pivot in the eradication of hepatitis C infection from developing world

Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance

Groundwater budgeting of Nari and Gaj formations and groundwater mapping of Karachi, Pakistan

Groundwater depletion is an emerging problem worldwide due to changes in climate and an increase in urbanization. Two significant water-bearing formations, the Oligocene-aged Nari and the Miocene-aged Gaj, were utilized as a case study exposed near Karachi, Pakistan. Groundwater budgeting was performed through a classical equation. The inflow of groundwater in the formations was calculated by thermo-pluviometric data and water loss of Hub Dam. The potential of evapotranspiration (PET) was calculated by the Thornthwaite method. The groundwater inflow from Hub Dam was estimated by using 20 years of annual water loss data by removing PET. The total mean annual inflow of groundwater in the formations was 2414.12 US Gallons per Second (gps). The annual mean outflow was estimated by calculation of groundwater usage for industries and domestic purposes and the mean annual groundwater outflow was 5562.61 US gps and an annual deficit of groundwater was 3148.5 US gps. The research is composed of validating the groundwater budget. Direct Current Electrical Resistivity (DCER) and static water level data from existing industrial wells were used for groundwater maps. The DCER data indicates A-Type and K-Type sub-surface with high resistivity in the three-layer model. The average water table of residential areas in 2019 was 60 m and in industrial areas was 130 m. The oscillation of the groundwater table over the last 20 years and the deficit of the groundwater budget shows an alarming condition for the future. If the same scenario persists, then by 2025, the water table will decline up to 140 m.Validerad;2022;Nivå 2;2022-11-03 (sofila)</p

Effect of IL-28 B Polymorphisms on Early Virological Response (EVR) in Chronic Hepatitis C Patients Treated with Interferon and Ribavirin

Background: To determine the frequency of EVRin chronic hepatitis C (CHC) patients treated withInterferon and Ribavirin and to compare the effect ofIL-28B SNP rs12979860 (CC and non CC genotypes)on frequency of EVR.Methods: In this cross-sectional study 100 patientswith Chronic Hepatitis C (CHC) with genotype 3who received Interferon and Ribavirin in thestandard doses were categorized in two groupsdepending upon the IL-28B SNP rs12979860 CC andnon CC genotypes. Results of Qualitative PCR forHCV RNA after 12 weeks of treatment and EVRwere entered. Frequency of EVR in the two groups(CC and non CC) was compared.Results: Among the 100 patients with ChronicHepatitis C treated with Interferon and Ribavirin, 72patients achieved EVR (72%). Out of the 100patients, 52 had CC genotype and 48 had non-CCgenotype (40 with CT and 8 with TT genotype). Inthe CC group 47 out of 52 patients achieved EVR(90%) while in the non-CC group 25 out of 48patients achieved EVR (52%). The p value in ourstudy was 0.00Conclusion: The frequency of EVR is 72% inChronic Hepatitis C patients infected with genotype3 treated with Interferon and Ribavirin which iscomparable with Pegylated Interferon and Ribavirin.Patients with IL-28B SNP rs12979860 CC genotypehave a better chance to achieve EVR (90%) ascompared to the non-CC genotype (52%)