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Abstract Background Hepatitis C virus (HCV) antibody self-testing (HCVST) may help expand screening access and support HCV elimination efforts. Despite potential benefits, HCVST is not currently implemented in Pakistan. This study aimed to assess the usability and acceptability of HCVST in a high HCV prevalence informal settlement in Karachi, Pakistan. Methods We performed a cross-sectional study in a hepatitis C clinic from April through June 2023. Participants were invited to perform a saliva-based HCVST (OraSure Technologies, USA) while following pictorial instructions. A study member evaluated test performance using a standardized checklist and provided verbal support if a step could not be completed. Perceived usability and acceptability were assessed using a semi-structured questionnaire. The HCVST was considered successful if the participant was able to complete all steps and correctly interpret test results. Overall concordance and positive and negative agreement were estimated in comparison with the HCVST result read by the study member (inter-reader concordance and agreement) and result of a second rapid HCV test (Abbott Diagnostics Korea Inc, South Korea) performed by a trained user (inter-operator concordance and agreement). Results The study included 295 participants of which 97 (32%) were illiterate. In total, 280 (95%, 95% CI 92–97%) HCVSTs were successful. Overall, 38 (13%) people performed the HCVST without verbal assistance, 67 (23%) needed verbal assistance in one step, 190 (64%) in two or more. Assistance was most often needed in managing the test buffer and test reading times. The inter-reader concordance was 96% and inter-operator concordance 93%. Inter-reader and inter-operator positive percent agreement were 84 and 70%, respectively. All participants reported they would use HCVST again and would recommend it to friends and family. Conclusion Saliva-based HCVST was very well accepted in this clinic-based setting. However, many people requested verbal support in several steps, highlighting the need for clear instructions for use and test devices that are simple to use, particularly in low literacy settings. Moderately low positive percent agreement with the results of a rapid test performed by a trained user highlights potential uncertainty in the accuracy of HCVST in the hands of lay users.

[This corrects the article DOI: 10.1371/journal.pmed.1003818.].

Abstract Background Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization’s goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. Methods This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. Conclusion The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. Study registration This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Abstract Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Summary: Chronic infection with hepatitis delta virus (HDV) affects between 12-20 million people worldwide and represents the most severe form of viral hepatitis, leading to accelerated liver disease progression, cirrhosis and its complications, such as end-stage-liver disease and hepatocellular carcinoma. From the discovery of HDV in 1977 by Prof. Mario Rizzetto, knowledge on the HDV life cycle and mechanisms of viral spread has expanded. However, little is still known about the natural history of the disease, host-viral interactions, and the role of the immune system in HDV persistence. Diagnosis of HDV is still challenging due to a lack of standardised assays, while accurate viral load quantification is needed to assess response and endpoints of antiviral treatment. Until recently, interferon has represented the only treatment option in patients with chronic hepatitis delta; however, it is associated with low efficacy and a high burden of side effects. The discovery of the entry inhibitor bulevirtide has represented a breakthrough in HDV treatment, by demonstrating high rates of viral suppression in phase II and III trials, results which have been confirmed in real-world settings and in patients with compensated advanced liver disease. In the meantime, other compounds (i.e. lonafarnib, new anti-hepatitis B virus drugs) are under development to provide alternative or combined strategies for HDV cure. The first international Delta Cure meeting was organised in Milan in October 2022 with the aim of sharing and disseminating the latest data; this review summarises key takeaway messages from state-of-the-art lectures and research data on HDV.

Summary: Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits.

Cement kiln dust (CKD) is released as an accidental product in large quantities and is classified as solid waste and has negative effects on the environment to benefit from these wastes and achieve an environmental and economic return, this research was carried out to study the effect of cement dust produced from Kufa Cement Factory on the properties of concrete by preparing four concrete mixtures by adding cement dust as a partial substitute for cement in proportions: 5%, 10%, 15%, and 20% and comparing it with the reference mixture and conduct the ripening process for ages 7, 28, and 90 days, a set of tests were carried out: (compressive strength, slump, hardening time, density, absorption, porosity, The results of the tests showed, in general, a decrease in the compressive strength, slump and density of concrete, an increase in the water percentage, the initial hardening time, porosity and absorption with an increasing the percentage of addition of cement dust, but by a small amount to 10%, and the percentage of increase or decrease becomes more clear when the percentage of adding cement dust is increased by more than 10%. , on the level of laboratory application, a hollow block was produced by pressing method with an added percentage of cement dust (5%, 10%, 15%, and 20%) of the weight of the cement, a compression and absorption resistance test was conducted, and the results were in accordance with the approved specification and for all percentages of addition.

Abstract Patients with preexisting chronic liver disease (CLD) may experience a substantial burden from both coronavirus 2019 (COVID‐19) infection and pandemic‐related life disruption. We assessed the impact of the COVID‐19 pandemic on patients with CLD. Patients enrolled in our Global Liver Registry were invited to complete a COVID‐19 survey. As of June 2021, 2500 patients (mean age ± SD, 49 ± 13 years; 53% men) from seven countries completed the survey. Of all survey completers, 9.3% had COVID‐19. Of these patients, 19% were hospitalized, 13% needed oxygen support, but none required mechanical ventilation. Of all patients including those not infected with COVID‐19, 11.3% reported that the pandemic had an impact on their liver disease, with 73% of those reporting delays in follow‐up care. The Life Disruption Event Perception questionnaire confirmed worsening in at least one area (food/nutrition, exercise, social life, vocation/education, financial situation, housing, or health care) in 81% and 69% of patients with and without a history of COVID‐19, respectively (p = 0.0001). On a self‐assessed Likert health score scale (range, 1–10; 10 indicates perfect health), patients with a COVID‐19 history scored lower (mean ± SD, 6.7 ± 2.2 vs. 7.4 ± 2.2, respectively; p

A Sorghum flour (SF) is a leading and prominent food source for humans in African countries. Recently extensive studies have been conducted on Sorghum bread (SB) or sorghum composite bread (SCB), covering various aspects. However, there are many technical challenges in the formation of SF and sorghum composite flour (SCF) that impact the quality of the bread and fail to meet the consumer’s desires and expectations. This review primarily focuses on the characteristics of SF, SCF, SB, and SCB, with discussions encompassing the rheological and morphological properties of the dough, improvement strategies, and bread quality. Moreover, a comprehensive analysis has been conducted to investigate the behavior of SF and SCF along with a discussion of the challenges affecting bread quality and the strategies applied for improvement. The significant demand for nutrients-rich and gluten-free bread indicates that sorghum will become one of the most vital crops worldwide. However, further comprehensive research is highly demanded and necessary for an in-depth understanding of the key features of SF and the resulting bread quality. Such understanding is vital to optimize the utilization of sorghum grain in large-scale bread production.

Abstract Background Globally, just 21% of the estimated 58 million people living with hepatitis C virus (HCV) know their status. Thus, there is considerable need to scale-up HCV testing if the World Health Organization (WHO) 2030 hepatitis elimination goals are to be achieved. HCV self-testing may assist with this; however, there are currently no data on the real-world impact of HCV self-testing. With an estimated 5% of the general population living with HCV, Pakistan has the second highest HCV burden in the world. This study aims to evaluate the acceptability and impact of home delivery of HCV self-testing for secondary distribution in the context of a house-to-house HCV micro-elimination programme in Pakistan. Methods This is a parallel group, non-blinded, cluster randomised trial comparing secondary distribution of HCV self-testing with secondary distribution of information pamphlets encouraging individuals to visit a testing facility for HCV screening. The cluster allocation ratio is 1:1. Clusters will be randomised either to HCV self-testing distributed via study staff or control clusters where information on HCV will be given and the participant will be requested to attend their local hospital for HCV screening. In both clusters, only households with a member who has not yet been screened as part of the larger micro-elimination project will be included. The primary outcome is the number and proportion of participants who report completion of testing. Secondary outcomes include the number and proportion of participants who a) receive a positive result and are made aware of their status, b) are referred to and complete HCV RNA confirmatory testing, and c) start treatment. Acceptability, feasibility, attitudes towards HCV testing, and cost will also be evaluated. The target sample size is 2,000 participants. Discussion This study will provide the first ever evidence regarding secondary distribution of HCV self-testing. By comparing HCV self-testing with facility-based testing, we will assess whether HCV self-testing increases the uptake of HCV testing. The findings will inform micro-elimination programmes and determine whether HCV self-testing can enable individuals to be reached who may otherwise be missed. Trial Registration This study and was registered on clinicaltrials.gov ( NCT04971538 ) 21 July 2021.

BackgroundModelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included.Methods and findingsWe adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY). Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV.ConclusionsInvestment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan.

Despite growing prevalence of ovarian cancer (OC) in Pakistan, no literature evidence exists regarding its clinic-pathological characteristics, survival and compliance of patients with recurrent ovarian cancer on various chemo-protocols. An observational study was conducted by enrolling 251 recurrent OC patients on 7 different chemo-protocols, from a specialized cancer care hospital, Lahore, Pakistan, using convenient judgmental sampling. The study was conducted for a period of 6 months. Most of the patients were between 18 and 70 years of age, with IIIC FIGO stage and papillary serous histological grade. As per RECIST, improved partial response (PR) (63.3 %) and complete response (CR) (52.1 %) was observed in the CP (carboplatin + paclitaxel) arm, substantiated by improved median progression free survival (PFS) and overall survival (OS) in CP and CD (carboplatin + docetaxel) arms, respectively, yet with no significant differences in survival curves, PFS (p = 0.12) and OS (p = 0.22). Interestingly, the highest and the lowest patient non-compliance were observed in CG (carboplatin + gemcitabine) (81.6 %) and paclitaxel (4.5 %) arms, resp. As per the hazard model for survival, topotecan showed significant association with the therapy related events/deaths compared to other protocols. These data suggest that CP regimen exhibited improved clinical efficacy and decreased toxicity related non-compliance in recurrent ovarian cancer patients of Lahore.

Lactic acid bacteria have been considered to be a very important species during sourdough fermentation. In order to explore the effects of bifidobacteria fermentation on thermal, physico-chemical and structural properties of wheat starch during dough fermentation, starch granules were separated from the fermented dough at different fermentation times, including 0 h, 2 h, 6 h, 9 h and 12 h. The results showed that the morphology of starch granules was destroyed gradually as the fermentation time increased, which appeared as erosion and rupture. With the increase in fermentation time, the solubility showed a significant increase, which changed from 8.51% (0 h) to 9.80% (12 h), and the swelling power was also increased from 9.31% (0 h) to 10.54% (12 h). As for the gelatinization property, the enthalpy was increased from 6.77 J/g (0 h) to 7.56 J/g (12 h), indicating a more stable thermal property of fermented starch, especially for the longer fermentation. The setback value was decreased with short fermentation time, indicating that the starch with a longer fermentation time was difficult to retrograde. The hardness of the gel texture was decreased significantly from 50.11 g to 38.66 g after fermentation for 12 h. The results show that bifidobacteria fermentation is an effective biological modification method of wheat starch for further applications.

Abstract Objective: To measure the success rate of endoscopic retrograde cholangiopancreaticography biliary cannulation of a recently credentialed endoscopist at a tertiary hospital. Methods: The clinical audit was conducted at the Aga Khan University Hospital. Karachi, and comprised data of all patients who underwent endoscopic retrograde cholangiopancreaticography under the care of a single operator during 2016. Data was retrospectively extracted from patient charts by an assistant blinded to the study. Data extracted included demographics, admission type, details and indication for the procedure, diagnosis, cannulation outcome, duct clearance, complications, follow-up surgical intervention, radiological imaging and mortality post-endoscopy. Data was analysed using SPSS 19. Results: Of 143 procedures performed, 102(71.3%) were included. The mean age was 52±17 years and 54(52.9%) of them were females. Most common indication was choledocholithiasis in 70(68.6%). The average procedure time was 41.5±5.5 minutes. Cannulation success rate was 96(94.1%). Complications included post-procedure pancreatitis in 5(4.9%), minimal bleeding in 8(7.8%) and oesophageal perforation in 1(0.98%). There was no procedure-related mortality. Conclusion: The success rate was high and complications were low Continuous...

Summary: Background: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. Methods: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018–30. We calibrated the model to country-level demographic data for 1960–2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007–08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. Findings: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4–14·1) individuals being screened and 350 000 (315 000–385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5–30·7) over 2018–30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1–55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. Interpretation: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. Funding: UNITAID.

The diagnosis of Hepatitis C virus (HCV) infection can be challenging due to its cost and a lack of access to centralized testing. There is an urgent need to develop simplified HCV testing algorithms. The aim of this study was to evaluate the performance characteristics of a Hepatitis C core antigen (HCVcAg) assay in a decentralized, resource-limited setting. This is a descriptive cross-sectional study from a highly endemic area of Karachi, Pakistan. Between October 2019 and July 2020, subjects aged 12 years and above who screened positive for HCV antibodies were simultaneously tested for HCV RNA (Xpert HCV Viral Load, GeneXpert® IV, Cepheid, France) and HCVcAg (ARCHITECT HCV Ag assay, Abbott® Diagnostics) to confirm active HCV infection. An Abbott ARCHITECT® i1000SR Immunoassay Analyser was installed at a local district hospital as a point-of-care (POC) facility for HCVcAg testing, while samples for HCV RNA were tested in a central lab. Two hundred individuals (mean age 46.4 ± 14.5 years, 71.5% females), who screened positive for HCV antibody, were included in the study. HCV RNA was detected in 128 (64.0%) while HCVcAg was reactive in 119 (59.5%) cases. Performance of the Immunoassay Analyser was excellent with a higher throughput and quicker readout value compared to the GeneXpert System. The sensitivity and specificity of HCVcAg (≥10 fmol/L) at HCV RNA thresholds of ≥12 was 99.1% (95% CI: 95–100%) and 87.6% (95%CI: 78.4–94%). A strong agreement was observed between the HCVcAg assay and HCV RNA. The ARCHITECT HCV Ag assay showed high sensitivity and specificity compared to HCV RNA in a decentralized, resource-limited setting. It can therefore be used as a confirmatory test in HCV elimination programs, particularly for low-income countries such as Pakistan.

Background/Aim: We aimed to assess the influence of Helicobacter pylori and its virulent factors, cytotoxin associated gene (cag) A and E, on portal hypertensive gastropathy (PHG) and the levels of interleukin (IL)-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Patients and Methods: The patients with cirrhosis underwent screening endoscopy and the lesions related to PHG were graded. Biopsies were obtained for histology, and polymerase chain reaction (PCR) of H. pylori 16S rRNA, cagA, cagE, and tissue cytokine levels was carried out. Absent or mild PHG was compared with moderate to severe PHG. Results: One hundred and forty patients with cirrhosis were studied; males numbered 92 and the mean age of the patients was 50.3 ± 12.0 years, H. pylori positivity in 87 (62.1%) patients was associated with male gender (P = 0.032), younger age (P = 0.029), hepatitis D etiology (P = 0.005), higher serum albumin (0.000), lower Child Pugh score (P = 0.001), and lower portal vein diameter (P = 0.001). There was no significant difference in the levels of TNF-α and IL-8. However, a decrease in the anti-inflammatory cytokine IL-10 was noted with moderate to severe gastropathy. Four H. pylori strains were positive for both cagA and cagE, while four were positive for cagA only. All the four patients with both virulent factors had mild gastropathy only. Conclusion: The presence of H. pylori infection neither affected the severity of PHG nor augmented the IL-8 and TNF-α levels. There was a decline of virulent H. pylori strains and IL-10 levels in patients with advanced PHG.

[This corrects the article DOI: 10.1371/journal.pone.0175562.].

BACKGROUND:The burden of hepatitis C (HCV) infection in Pakistan is among the highest in the world, with a reported national HCV prevalence of 6.7% in 2014. In specific populations, such as in urban communities in Karachi, the prevalence is suspected to be higher. Interferon-free treatment for chronic HCV infection (CHC) could allow scale up, simplification and decentralization of treatment to such communities. We present an interim analysis over the course of February-December 2015 of an interferon-free, decentralised CHC programme in the community clinic in Machar Colony, Karachi, Pakistan. DESIGN:A retrospective analysis of a treatment cohort. RESULTS:There were 1,089 patients included in this analysis. Aspartate to platelet ratio index score was used to prioritize patients in terms of treatment initiation, with 242 patients placed in high priority for treatment and 202 starting treatment as scheduled. 169 patients started HCV treatment with Sofosbuvir-Ribavirin regimen according to HCV genotype over the course of 2015: of these, 35% had Hemoglobin reductions below 11.0 g/dl during the treatment course. Among the 153 patients (85%) with genotype 3 HCV infection, 84% of patients achieved sustained virologic response at 12 weeks following treatment completion (SVR 12). CONCLUSION:Outcomes of HCV treatment with all oral combination in an integrated, decentralized model of care for CHC in a primary care setting, using simplified diagnostic and treatment algorithms, are comparable to the outcomes achieved in clinical trial settings for Sofosbuvir-based regimens. Our results suggest the feasibility and the pertinence if including interferon-free treatment regimens in the national programme, at both provincial and national levels.

Background/Aim: Hepatitis D virus (HDV) superinfection in patients with chronic hepatitis B leads to accelerated liver injury, early cirrhosis, and decompensation. It may be speculated that hepatocellular carcinoma (HCC) may differ in these patients from hepatitis B virus (HBV) monoinfection. The aim of this study was to compare clinical aspects of hepatocellular carcinoma in patients of hepatitis D with HBV monoinfection. Patients and Methods: A total of 92 consecutive HCC cases seropositive for antibody against HDV antigen (HDV group) were compared with 92 HBsAg-positive and anti-HDV-negative cases (HBV group). Results: The features including sex, body mass index, presence of ascites, serum biochemistry, gross tumor appearance, child class, barcelona cancer liver clinic and okuda stages were not significantly different between the 2 groups. Decreased liver size was noticed more in cases of HDV compared with HBV group where the liver size was normal or increased (P=0.000). HDV patients had lower platelets (P=0.053) and larger varices on endoscopy (P=0.004). Multifocal tumors and elevated alpha-fetoprotein level >1000 IU/mL were more common in HBV group (P=0.040 and P= 0.061). TNM classification showed more stage III-IV disease in HBV group (P=0.000). Conclusion: Decreased liver size and indirect evidence of more severe portal hypertension and earlier TNM stage compared with HBV monoinfection indicate that HDV infection causes HCC in a different way, possibly indirectly by inducing inflammation and cirrhosis.

Background /Aim: The symptoms of irritable bowel syndrome resemble those of small intestinal bacterial overgrowth (SIBO). The aim of this study was to determine the frequency of SIBO and lactose intolerance (LI) occurrence in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) according to Rome III criteria. Patients and Methods: In this retrospective case-control study, patients over 18 years of age with altered bowel habit, bloating, and patients who had lactose Hydrogen breath test (H 2 BT) done were included. The "cases" were defined as patients who fulfill Rome III criteria for IBS-D, while "controls" were those having chronic nonspecific diarrhea (CNSD) who did not fulfill Rome III criteria for IBS-D. Demographic data, predominant bowel habit pattern, concurrent use of medications, etc., were noted. Results: Patients with IBS-D were 119 (51%) with a mean age of 35 ± 13 years, while those with CNSD were 115 (49%) with mean age 36 ± 15 years. Patients in both IBS-D and CNSD were comparable in gender, with male 87 (74%) and female 77 (64%). SIBO was documented by lactose H 2 BT in 32/234 (14%) cases. It was positive in 22/119 (19%) cases with IBS-D, while 10/115 (9%) cases had CNSD (P = 0.03). LI was positive in 43/234 (18%) cases. Of these, 25/119 (21%) cases had IBS-D and 18/115 (16%) cases had CNSD (P = 0.29). Conclusion: SIBO was seen in a significant number of our patients with IBS-D. There was no significant age or gender difference in patients with or without SIBO.

Background. The psychiatric disorders like anxiety and depression could have a profound influence on onset, expression, and course of Irritable bowel syndrome (IBS). Aim. To estimate the frequency and strength of association of common mental disorders (CMDs) in patients with IBS and patients with other chronic diseases, that is, migraine and hypertension. Method. This was a case control study. Individuals aged 18–70 years diagnosed as IBS were enrolled as cases. The control groups consisted of patients without IBS but diagnosed to have a chronic disease, that is, migraine or HTN. Self-Reporting Questonnaire-20(SRQ-20) was used as a screening tool for the detection of CMD. Results. 82 patients were enrolled in each group. Mean SRQ score was significantly higher in IBS group than controls (9.9±4.5 versus 4.9±3.6, 𝑃

Background/Objectives: Fexofenadine hydrochloride is a widely prescribed drug for treating histamine-mediated allergic reactions. This review systematically collates existing research on the clinical pharmacokinetics (PK) of fexofenadine, with a copious emphasis on examining the impact of stereoisomerism, disease states, and drug interactions. Methods: The search engines PubMed, Science Direct, Google Scholar, and Cochrane were scanned systematically for articles concerning the clinical PK of fexofenadine in humans. The extensive literature search yielded 85 articles meeting the inclusion standards. Results: The PK parameters of fexofenadine showed a linear correlation between increasing doses and proportional elevations in PK parameters such as area under the curve from time 0 to infinity (AUC0–∞) and maximum plasma concentration (Cmax). Under fed conditions, its bioavailability was reduced by approximately 50%. Findings from patients with end-stage renal disease (ESRD) displayed a 63% decline in oral clearance (CL/F) of fexofenadine. A drug–food interaction study has displayed that grapefruit juice decreased Cmax (201 ng/mL vs. 128 ng/mL), accompanied by a 30% reduction in the bioavailability of fexofenadine. Furthermore, a drug–herb interaction study with St John's Wort (SJW) has reported a reduction in CL/F by 10% after a single dose, but long-term administration reversed this effect, resulting in elevated CL/F by 17% of fexofenadine. Conclusions: Since no prior systematic review on the PK of this drug exists, this review amalgamates all pertinent PK parameters in humans by pooling up-to-date data from published studies. This detailed literature review can be advantageous for researchers who want to develop and assess PK models. [ABSTRACT FROM AUTHOR]