Background Pakistan has a hepatitis C virus (HCV) infection prevalence of 6-9% and aims to achiev... more Background Pakistan has a hepatitis C virus (HCV) infection prevalence of 6-9% and aims to achieve World Health Organization (WHO) targets for elimination of HCV by the year 2030 through scaling HCV diagnosis and accelerating access to care. The clinical and economic benefits of various HCV testing strategies have not yet been evaluated in Pakistan. Objective To evaluate the potential cost-effectiveness of a reference laboratory-based (CEN) confirmatory testing approach vs a molecular near-patient point-of-care (POC) confirmatory approach to screen the general population for HCV in Pakistan. Methods We developed a decision-analytic model comparing HCV testing under two scenarios: screening with an anti-HCV antibody test (Anti-HCV) followed by either POC nucleic acid testing (NAT) (Anti-HCV-POC), or reference laboratory NAT (Anti-HCV-CEN), using data from published literature, the Pakistan Ministry of Health, and expert judgment. Outcome measures included: number of HCV infections id...
Wilson\u27s disease (WD) is a rare autosomal recessive disorder of copper metabolism. Data regard... more Wilson\u27s disease (WD) is a rare autosomal recessive disorder of copper metabolism. Data regarding WD is not available from Pakistan. A cross-sectional study was conducted at The Aga Khan University Hospital, Karachi, and all patients admitted with primary and secondary diagnosis of Wilson\u27s disease were added. A total of 47 patients were seen; 68% (n = 32) were male. The mean age was 26.6 ± 9.97 years. Most of the patients presented with hepatic, (n = 22, 46.8%), neurological, (n = 17, 36.2%) and psychiatric (n = 8, 17%) symptoms. Mean ceruloplasmin level was 0.17 ± 0.13 g/dl; it was \u3c 0.25 g/dl in 39 (86.6%) patients. Serum copper (Cu) was reduced in 32 (68.1%) patients and 24-hr-urinary Cu was raised in 22 (47.6%) patients. Slit lamp examination for Kayser-Fleischer (KF) rings was done on 15 (31.9%) patients and 9 (60%) of them had KF rings. Mean serum aspartate transaminase (AST) / alanine transaminases (ALT) ratio was 1.92 and median alkaline phosphatase / total bilirub...
Objective: To compare Model for End-stage Liver Disease Score (MELD Score, MS) and King’s College... more Objective: To compare Model for End-stage Liver Disease Score (MELD Score, MS) and King’s College Hospital (KCH) criteria for finding correlation of mortality in non-acetaminophen induced acute liver failure (NAI-ALF). Study Design: An analytical cross-sectional study. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from 2005 to 2007. Methodology: The study included patients with NAI-ALF. KCH criteria were labelled as good and bad prognosis groups. MELD score were calculated by using the MELD calculator. ROC was plotted and sensitivity analysis was done. ETA was used to see correlation between MELD and KCH. Results: Ninety-one patients with mean age of 32.5 + 16.3 years were studied; 49 were males (54%). Out of these, 57 patients died (63%); two leading causes of non-acetaminophen induced acute liver failure (NAI-ALF) were hepatitis hepatitis B virus (HBV) (n = 30, 33%) followed by hepatitis E virus in (n = 23, 25.3%). According to King\u27s College Hospital ...
BACKGROUND Since the release of the first global hepatitis elimination targets in 2016, and until... more BACKGROUND Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. METHODS This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age ≥0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. FINDINGS Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0·7% (95% UI 0·7-0·9), corresponding to 56·8 million (95% UI 55·2-67·8) infections, on Jan 1, 2020. This number represents a decrease of 6·8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63·6 million (61·8-75·8) infections (0·9% [0·8-1·0] prevalence). By the end of 2020, an estimated 12·9 million (12·5-15·4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. INTERPRETATION At the beginning of 2020, there were an estimated 56·8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. FUNDING John C Martin Foundation, Gilead Sciences, AbbVie, ZeShan Foundation, and The Hepatitis Fund.
Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) can lead to chronic liver dis... more Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) can lead to chronic liver disease and hepato-cellular carcinoma (HCC). This cross-sectional study estimated the prevalence and identified risk factors associated with Hepatitis B surface antigen (HBsAg) and HCV antibody (anti-HCV) sero-positivity among children 1 to 15 years of age. The study targeted the low to middle socioeconomic population that comprises 80% to 85% of the population. Consent was obtained from parents of the eligible children before administering questionnaire and collected a blood sample for anti-HCV and HBsAg serology. 3533 children were screened for HBsAg and anti-HCV. 1826 (52 %) were males. 65 (1.8 %) were positive for HBsAg, male to female ratio 38:27; mean age 10 +/- 4 years. 55 (1.6 %) were positive for anti-HCV with a mean age 9 +/- 4 years. 3 (0.11%) boys were positive for both HBsAg and anti-HCV. The overall infection rate was 3.3 % in the studied population. Hepatitis BsAg was more pr...
A single substitution within the hepatitis C virus core antigen sequence, A48T, which is observed... more A single substitution within the hepatitis C virus core antigen sequence, A48T, which is observed in ∼30% of individuals infected with genotype 2a virus, reduces the sensitivity of a commonly used chemiluminescence enzyme immunoassay. Quantitation of the antigen is improved by using a distinct anticore antibody with a different epitope.
JPMA. The Journal of the Pakistan Medical Association, 2004
Interferon alpha (IFN-alpha) with or without ribavirin is an approved therapy for patients with c... more Interferon alpha (IFN-alpha) with or without ribavirin is an approved therapy for patients with chronic hepatitis C. However, a sustained response is achieved in less than 40% of all treated cases. Retreatment of relapsers or non-responders usually fails. Thymosin alpha 1 (Ta-1) is a polypeptide with immunomodulatory properties that has been suggested to increase response rates in patients with chronic hepatitis C. The aim of present study was to evaluate the efficacy of a novel triple regimen which includes Ta-1 for relapsers and non-responders to the combination of TA-1 and ribavirin. In the present study, 11 patients who relapsed (n=5) or did not respond (n=6) to previous INF-alpha-based therapy were retreated with combination Ta-1, INF-alpha and ribavirin for 12 months, and followed up for a further six months. Four out of five relapsers had a sustained response. One of the non-responders cleared the HCV RNA during the post-treatment follow-up. Minor adverse effects were observe...
Research article Hepatitis B and C: prevalence and risk factors associated with seropositivity am... more Research article Hepatitis B and C: prevalence and risk factors associated with seropositivity among children in Karachi, Pakistan
Background Pakistan has a hepatitis C virus (HCV) infection prevalence of 6-9% and aims to achiev... more Background Pakistan has a hepatitis C virus (HCV) infection prevalence of 6-9% and aims to achieve World Health Organization (WHO) targets for elimination of HCV by the year 2030 through scaling HCV diagnosis and accelerating access to care. The clinical and economic benefits of various HCV testing strategies have not yet been evaluated in Pakistan. Objective To evaluate the potential cost-effectiveness of a reference laboratory-based (CEN) confirmatory testing approach vs a molecular near-patient point-of-care (POC) confirmatory approach to screen the general population for HCV in Pakistan. Methods We developed a decision-analytic model comparing HCV testing under two scenarios: screening with an anti-HCV antibody test (Anti-HCV) followed by either POC nucleic acid testing (NAT) (Anti-HCV-POC), or reference laboratory NAT (Anti-HCV-CEN), using data from published literature, the Pakistan Ministry of Health, and expert judgment. Outcome measures included: number of HCV infections id...
Wilson\u27s disease (WD) is a rare autosomal recessive disorder of copper metabolism. Data regard... more Wilson\u27s disease (WD) is a rare autosomal recessive disorder of copper metabolism. Data regarding WD is not available from Pakistan. A cross-sectional study was conducted at The Aga Khan University Hospital, Karachi, and all patients admitted with primary and secondary diagnosis of Wilson\u27s disease were added. A total of 47 patients were seen; 68% (n = 32) were male. The mean age was 26.6 ± 9.97 years. Most of the patients presented with hepatic, (n = 22, 46.8%), neurological, (n = 17, 36.2%) and psychiatric (n = 8, 17%) symptoms. Mean ceruloplasmin level was 0.17 ± 0.13 g/dl; it was \u3c 0.25 g/dl in 39 (86.6%) patients. Serum copper (Cu) was reduced in 32 (68.1%) patients and 24-hr-urinary Cu was raised in 22 (47.6%) patients. Slit lamp examination for Kayser-Fleischer (KF) rings was done on 15 (31.9%) patients and 9 (60%) of them had KF rings. Mean serum aspartate transaminase (AST) / alanine transaminases (ALT) ratio was 1.92 and median alkaline phosphatase / total bilirub...
Objective: To compare Model for End-stage Liver Disease Score (MELD Score, MS) and King’s College... more Objective: To compare Model for End-stage Liver Disease Score (MELD Score, MS) and King’s College Hospital (KCH) criteria for finding correlation of mortality in non-acetaminophen induced acute liver failure (NAI-ALF). Study Design: An analytical cross-sectional study. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from 2005 to 2007. Methodology: The study included patients with NAI-ALF. KCH criteria were labelled as good and bad prognosis groups. MELD score were calculated by using the MELD calculator. ROC was plotted and sensitivity analysis was done. ETA was used to see correlation between MELD and KCH. Results: Ninety-one patients with mean age of 32.5 + 16.3 years were studied; 49 were males (54%). Out of these, 57 patients died (63%); two leading causes of non-acetaminophen induced acute liver failure (NAI-ALF) were hepatitis hepatitis B virus (HBV) (n = 30, 33%) followed by hepatitis E virus in (n = 23, 25.3%). According to King\u27s College Hospital ...
BACKGROUND Since the release of the first global hepatitis elimination targets in 2016, and until... more BACKGROUND Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. METHODS This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age ≥0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. FINDINGS Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0·7% (95% UI 0·7-0·9), corresponding to 56·8 million (95% UI 55·2-67·8) infections, on Jan 1, 2020. This number represents a decrease of 6·8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63·6 million (61·8-75·8) infections (0·9% [0·8-1·0] prevalence). By the end of 2020, an estimated 12·9 million (12·5-15·4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. INTERPRETATION At the beginning of 2020, there were an estimated 56·8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. FUNDING John C Martin Foundation, Gilead Sciences, AbbVie, ZeShan Foundation, and The Hepatitis Fund.
Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) can lead to chronic liver dis... more Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) can lead to chronic liver disease and hepato-cellular carcinoma (HCC). This cross-sectional study estimated the prevalence and identified risk factors associated with Hepatitis B surface antigen (HBsAg) and HCV antibody (anti-HCV) sero-positivity among children 1 to 15 years of age. The study targeted the low to middle socioeconomic population that comprises 80% to 85% of the population. Consent was obtained from parents of the eligible children before administering questionnaire and collected a blood sample for anti-HCV and HBsAg serology. 3533 children were screened for HBsAg and anti-HCV. 1826 (52 %) were males. 65 (1.8 %) were positive for HBsAg, male to female ratio 38:27; mean age 10 +/- 4 years. 55 (1.6 %) were positive for anti-HCV with a mean age 9 +/- 4 years. 3 (0.11%) boys were positive for both HBsAg and anti-HCV. The overall infection rate was 3.3 % in the studied population. Hepatitis BsAg was more pr...
A single substitution within the hepatitis C virus core antigen sequence, A48T, which is observed... more A single substitution within the hepatitis C virus core antigen sequence, A48T, which is observed in ∼30% of individuals infected with genotype 2a virus, reduces the sensitivity of a commonly used chemiluminescence enzyme immunoassay. Quantitation of the antigen is improved by using a distinct anticore antibody with a different epitope.
JPMA. The Journal of the Pakistan Medical Association, 2004
Interferon alpha (IFN-alpha) with or without ribavirin is an approved therapy for patients with c... more Interferon alpha (IFN-alpha) with or without ribavirin is an approved therapy for patients with chronic hepatitis C. However, a sustained response is achieved in less than 40% of all treated cases. Retreatment of relapsers or non-responders usually fails. Thymosin alpha 1 (Ta-1) is a polypeptide with immunomodulatory properties that has been suggested to increase response rates in patients with chronic hepatitis C. The aim of present study was to evaluate the efficacy of a novel triple regimen which includes Ta-1 for relapsers and non-responders to the combination of TA-1 and ribavirin. In the present study, 11 patients who relapsed (n=5) or did not respond (n=6) to previous INF-alpha-based therapy were retreated with combination Ta-1, INF-alpha and ribavirin for 12 months, and followed up for a further six months. Four out of five relapsers had a sustained response. One of the non-responders cleared the HCV RNA during the post-treatment follow-up. Minor adverse effects were observe...
Research article Hepatitis B and C: prevalence and risk factors associated with seropositivity am... more Research article Hepatitis B and C: prevalence and risk factors associated with seropositivity among children in Karachi, Pakistan
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