| 1. |
- Kamal, Habiba, et al.
(författare)
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Age-specific and sex-specific risks for HCC in African-born persons with chronic hepatitis B without cirrhosis
- 2023
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Ingår i: Hepatology Communications. - : Wolters Kluwer. - 2471-254X. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The international recommendations of HCC surveillance for African-born persons with chronic hepatitis B (CHB) without cirrhosis are divergent, probably due to scarce data on incidence rate (IR) for HCC.Methods: We assembled a cohort with prospectively collected data of Swedish residents of African origin with diagnosed CHB without cirrhosis at baseline from 1990 to 2015. Data from nationwide registers were used to calculate the sex-specific IR and IR ratio (incidence rate ratios) in relation to age, comorbidities, and birth region, using a generalized linear model with a log-link function and Poisson distribution.Results: Among 3865 African-born persons with CHB without cirrhosis at baseline, 31 (0.8%; 77.4% men) developed HCC during a median of 11.1 years of follow-up, with poor survival after HCC diagnosis. The mean age at HCC diagnosis was 46.8 (SD±14.7; range 23–79) in men. HCC IR exceeded the recommended surveillance threshold of 0.2%/year at ages 54 and 59 years in men and women, respectively, and at ages 20–40 years if HCV or HDV co-infection was present. African-born men with CHB had an incidence rate ratios of 10.6 (95% CI 4.4–31.5) for HCC compared to matched African-born peers without CHB, and an incidence rate ratios of 35.3 (95% CI 16.0–88.7) compared to a matched general population.Conclusions: African-born men with CHB without cirrhosis reached an IR of 0.2%/year between 50 and 60 years, and at younger ages if HCV or HDV co-infection was present. Our findings need further confirmation, and new cost-effectiveness analyses specific for young populations are needed, to provide personalized and cost-effective HCC surveillance.
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| 2. |
- Kamal, Habiba, et al.
(författare)
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Age-specific and sex-specific risks for HCC in African-born persons with chronic hepatitis B without cirrhosis
- 2023
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Ingår i: Hepatology communications. - : Wiley Periodicals Inc. on behalf of the American Association for the Study of Liver Diseases. - 2471-254X. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The international recommendations of HCC surveillance for African-born persons with chronic hepatitis B (CHB) without cirrhosis are divergent, probably due to scarce data on incidence rate (IR) for HCC.METHODS: We assembled a cohort with prospectively collected data of Swedish residents of African origin with diagnosed CHB without cirrhosis at baseline from 1990 to 2015. Data from nationwide registers were used to calculate the sex-specific IR and IR ratio (incidence rate ratios) in relation to age, comorbidities, and birth region, using a generalized linear model with a log-link function and Poisson distribution.RESULTS: Among 3865 African-born persons with CHB without cirrhosis at baseline, 31 (0.8%; 77.4% men) developed HCC during a median of 11.1 years of follow-up, with poor survival after HCC diagnosis. The mean age at HCC diagnosis was 46.8 (SD±14.7; range 23-79) in men. HCC IR exceeded the recommended surveillance threshold of 0.2%/year at ages 54 and 59 years in men and women, respectively, and at ages 20-40 years if HCV or HDV co-infection was present. African-born men with CHB had an incidence rate ratios of 10.6 (95% CI 4.4-31.5) for HCC compared to matched African-born peers without CHB, and an incidence rate ratios of 35.3 (95% CI 16.0-88.7) compared to a matched general population.CONCLUSIONS: African-born men with CHB without cirrhosis reached an IR of 0.2%/year between 50 and 60 years, and at younger ages if HCV or HDV co-infection was present. Our findings need further confirmation, and new cost-effectiveness analyses specific for young populations are needed, to provide personalized and cost-effective HCC surveillance.
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| 3. |
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| 4. |
- Kamal, Habiba, et al.
(författare)
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Risk of hepatocellular carcinoma in hepatitis B and D virus co-infected patients : A systematic review and meta-analysis of longitudinal studies
- 2021
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Ingår i: Journal of Viral Hepatitis. - : John Wiley & Sons. - 1352-0504 .- 1365-2893. ; 28:10, s. 1431-1442
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Forskningsöversikt (refereegranskat)abstract
- Hepatitis D virus (HDV) infection causes a severe chronic viral hepatitis with accelerated development of liver cirrhosis and decompensation, but whether it further increases the risk of hepatocellular carcinoma (HCC) is unclear. We performed a comprehensive systematic review of the published literature and meta-analysis to assess the risk of HCC in HDV and hepatitis B virus (HBV) co-infected, compared to HBV mono-infected patients. The study was conducted per a priori defined protocol, including only longitudinal studies, thus excluding cross-sectional studies. Random-effects models were used to determine aggregate effect sizes (ES) with 95% confidence intervals (CI). Meta-regression was used to examine the associations among study level characteristics. Twelve cohort studies comprising a total of 6099 HBV/HDV co-infected and 57,620 chronic HBV mono-infected patients were analysed. The overall pooled ES showed that HBV/HDV co-infected patients were at 2-fold increased risk of HCC compared to HBV mono-infected patients (ES = 2.12, 95% CI 1.14-3.95, I2 = 72%, N = 12). A six-fold significant increased risk of HCC was noted among HIV/HBV/HDV triple-infected, compared to HIV/HBV co-infected patients. The magnitude of ES did not differ significantly after adjustment for study design and quality, publication year and follow-up duration in univariable meta-regression analysis. This systematic review and meta-analysis shows that infection with HDV is associated with a 2-fold higher risk of HCC development compared to HBV mono-infection. HCC surveillance strategies taking this increased risk into account, and new treatment options against HDV, are warranted.
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| 5. |
- Kamal, Habiba
(författare)
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Risk of hepatocellular carcinoma, liver-related complications, and death in persons living with chronic hepatitis B and D
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic hepatitis B virus (HBV) infection affects 257 million individuals and is a leading cause of liver-related morbidity and mortality. Hepatitis D virus (HDV) is a satellite virus, that needs HBV for packing and propagation, hence infecting only individuals with HBV infection. It is estimated that around 9-19 million individuals are living with chronic hepatitis Delta (CHD), hence it is the least common among viral hepatides. CHD demonstrates a severe course of liver disease than CHB. The treatment options are still limited, and approved therapies are at a high price. This thesis aims to characterize the natural course of HBV and HDV infection in a low-endemic setting, predictors of disease progression, and the effect of therapy on the disease course. In Study I, we identified 337 patients with positive anti-HDV antibody from 11 infectious disease clinics in Sweden assembling a nationwide cohort. During a mean follow-up of 6.5 years, HDV RNA replication was significantly associated with a composite outcome of any liver-related decompensation, HCC, and liver transplantation. The response to IFN therapy was suboptimal; 18.8% had a virological response defined as negative or more than 2 log decline of HDV RNA level and a more benign disease course was seen in virological responders compared to non-responders. HDV RNA replication was independently associated with liver decompensation events, undergoing liver transplantation, and a trend toward higher HCC risk. In Study II, we conducted a systematic review and meta-analysis of published peerreviewed cohort studies examining the risk of HCC in patients with HBV/HDV infection compared to peers with HBV mono-infection. The pooled relative risk was 2.12 (95% confidence interval CI 1.14-3.95), with a particularly higher risk in patients with HIV/HBV/HDV co-infection and substantial heterogeneity between studies. In Study III, we present the HDV cascade of care during three decades at Karolinska University Hospital (KUH) as a secondary care referral facility in the Southern Stockholm region. In 4095 patients with positive HBsAg, (90.4%, n=3703) have undergone an anti- HDV test. Anti-HDV positive was prevalent in (83.7%, n=310) and (65.2%, n=202) patients who had HDV RNA replication. Older age, cirrhosis, and getting a late anti-HDV diagnosis were independently associated with any prevalent liver outcome. Despite the high screening rate reaching 95%, 8% of persons meeting the criteria of the American Association for the Study of the Liver (AASLD) as “high-risk” of infection did not receive any screening test and 28% of persons with cirrhosis received a remote screening test (after two years). Persons with concurrent HIV and HBV infection were less likely to receive a screening test. In Study IV, we analyze a nationwide cohort of African-born Swedish residents with CHB without cirrhosis (n=3865), followed for a mean of 12 years from the date of HBV diagnosis in Sweden to the incidence of HCC. The cohort was compared to individuals without HBV in 1 to ≤3 on age, sex, and county of residence to persons from the same area of birth (n=8,488) and in 1 to ≤ 10 on age, sex, and county of residence with a cohort from the general population (n=39,278). African-born men with CHB were significantly younger at HCC development compared to women and peers from comparator cohorts. The costeffectiveness surveillance threshold at 0.2% was exceeded at age 54 years (IR=0.20/100PYs, 95%CI 0.10-0.40) in men and at age 59 years (IR=0.21/100 PYs, 95%CI 0.10-0.45) in women, while at 20-40 years in the presence of concomitant HDV and HCV co-infection in men. The probability of HCC was more pronounced at younger ages in men compared to women. African-born men with CHB had 10.6 times higher risk to develop HCC compared to African-born peers without HBV and a 35.3 times higher risk than the general population. The study provides absolute and relative estimates of HCC development in a nationwide large cohort of African-born first-generation persons with CHB, without cirrhosis at baseline living in a different environmental setting. To conclude, HDV RNA replication, older age, and cirrhosis in patients with anti-HDV positive are independent predictors of progressive liver disease and need for liver transplantation. Lack of response to IFN therapy might be associated with a worse disease outcome. Based on our pooled analyses, HDV infection is associated with two-times higher risk to develop HCC, compared to HBV mono-infection with a higher risk in persons with triple HIV/HBV/HDV infection. Nine out of 10 patients with CHB received an anti-HDV test at KUH. Delayed HDV diagnosis was independently associated together with older age and cirrhosis with a liver-related outcome. Liver cirrhosis is a fertile ground for cancer development, but some people with CHB can develop cancer without cirrhosis. Costeffectiveness analysis to surveil persons with CHB without cirrhosis identified a threshold of 2 per 1000 persons per year to conduct a semi-annual ultrasound examination. Nevertheless, the age to start liver cancer surveillance, in persons of African origin is different across guidelines due to few studies examining this risk in this population for a long time. It is unclear if the current 0.2% cost-effectiveness threshold for HCC surveillance in persons without cirrhosis might miss a population of younger patients with co-morbidities who are at increased risk to develop HCC. Our research highlights the need for cost-effectiveness studies in contemporary cohorts of persons living with CHB particularly in African-born men given the substantial number of HCCs occurring at younger ages in this population.
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| 6. |
- Kamal, Habiba, et al.
(författare)
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The cascade of care for patients with chronic hepatitis delta in Southern Stockholm, Sweden for the past 30 years
- 2024
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Ingår i: Liver international. - : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 44:1, s. 228-240
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Previous studies have shown suboptimal screening for hepatitis D virus (HDV) among patients with chronic hepatitis B (CHB). This study presents the cascade of care for HDV infection in a major secondary referral centre in Southern Stockholm, Sweden.METHODS: HBsAg+ve patients attending Karolinska University Hospital (KUH) from 1992 to 2022 were identified. The prevalence of anti-HDV and/or HDV RNA positivity, interferon (IFN) therapy and maintained virological responses (MVR) after HDV treatment were assessed. Also, time to anti-HDV testing was analysed in relation to liver-related outcomes with logistic regression.RESULTS: Among 4095 HBsAg+ve persons, 3703 (90.4%) underwent an anti-HDV screening; within a median of 1.8 months (range 0.0-57.1) after CHB diagnosis. This screening rate increased over time, to 97.9% in the last decade. Overall, 310 (8.4%) were anti-HDV+ve, of which 202 (65.2%) were HDV RNA+ve. Eighty-five (42%) received IFN, and 9 (10.6%) achieved MVR at the last follow-up. The predictive factors for anti-HDV screening were Asian origin, diagnosis after the year 2012, HIV co-infection (negative factor) and HBV DNA level < 2000 IU/mL in univariable analysis, while HIV co-infection was the only remaining factor in multivariable analysis. Delayed anti-HDV test >5 years was independently associated with worsened liver-related outcomes (adjusted odds ratio = 7.6, 95% CI 1.8-31.6).CONCLUSION: Higher frequency of HDV screening than previously published data could be seen among CHB patients at KUH in a low-endemic setting. Receiving a delayed screening test seems to be associated with worse outcomes, stressing the need of a strategy for timely HDV diagnosis.
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| 7. |
- Razavi, Homie A., et al.
(författare)
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Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
- 2023
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Ingår i: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
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