Background In sub-Saharan Africa, less than 1% of treatment-eligible chronic hepatitis B (CHB) pa... more Background In sub-Saharan Africa, less than 1% of treatment-eligible chronic hepatitis B (CHB) patients receive antiviral therapy. Experiences from local CHB programs are needed to inform treatment guidelines and policies on the continent. Here, we present 5-year results from one of the first large-scale CHB treatment programs in sub-Saharan Africa. Methods Adults with CHB were enrolled in a pilot treatment program in Addis Ababa, Ethiopia, in 2015. Liver enzymes, viral markers, and transient elastography were assessed at baseline and thereafter at 6-month intervals. Tenofovir disoproxil fumarate was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. Survival analysis was performed using the Kaplan–Meier method. Results In total, 1303 patients were included in the program, of whom 291 (22.3%) started antiviral therapy within the initial 5 years of follow-up. Among patients on treatment, estimated 5-year hepatocellular car...
Background Data on renal safety of tenofovir disoproxil fumarate (TDF) treatment among individual... more Background Data on renal safety of tenofovir disoproxil fumarate (TDF) treatment among individuals with chronic hepatitis B (CHB) are inconsistent. The current study aimed to assess the effect of long-term TDF treatment on renal outcomes in adult patients with CHB. Methods From a CHB cohort in Ethiopia, we included 233 patients treated with TDF and 126 untreated controls. Levels of creatinine and creatinine clearance over time were described in patients with and without TDF treatment. Linear mixed effects models with a treatment × time interaction were used to investigate the effect of TDF on creatinine and creatinine clearance. In treated patients only, change in creatinine and creatinine clearance was estimated separately in the first year as compared with subsequent years via linear mixed effects models. Results Median follow-up in the treated group was 51 months (IQR, 27–72), and 75% of patients were male (median age, 33 years; IQR, 26–40). Median follow-up in the untreated grou...
<p>Regression analysis of HBV DNA levels in 23 paired plasma and Dried Blood Spot (DBS) spe... more <p>Regression analysis of HBV DNA levels in 23 paired plasma and Dried Blood Spot (DBS) specimens from Ethiopian hepatitis B patients</p
<p>HBV DNA levels in Dried Blood Spots (DBS) after 2, 6 and 12 weeks of storage at room tem... more <p>HBV DNA levels in Dried Blood Spots (DBS) after 2, 6 and 12 weeks of storage at room temperature.</p
The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from C... more The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from Cepheid could help to scale up treatment for chronic hepatitis B (CHB) in resource-limited settings. This study aimed to assess the performance of the Xpert kit under field conditions in Ethiopia. One-hundred-and-thirty CHB patients with viral loads ranging from <1 log10 to >7 log10 IU/ml were randomly sampled. The viral load was assessed with both the Xpert and the gold standard Abbott RealTime HBV Viral Load assay in each patient. There was a high correlation between the viral loads assessed by Xpert and Abbott (r = 0.948, p < 0.001). The Bland-Altman plot showed a small bias between the two assays, with an on average 0.23 log10 IU/mL higher viral load result of the Xpert kit; 4 samples differed by >1 log10 IU/mL. Using the treatment threshold of 2000 IU/mL in both tests, Xpert had a sensitivity of 94%, specificity of 71%, positive predictive value of 70%, and negative predictive value of 95%. In conclusion, the Xpert kit demonstrated good validity for the measurement of HBV viral load in a real-life setting.
Lay summary Antiviral therapy prevents disease progression and death in patients with chronic hep... more Lay summary Antiviral therapy prevents disease progression and death in patients with chronic hepatitis B (CHB), but the identification of patients in need of treatment is a challenge in lowand middle-income countries. The World Health Organization (WHO) has suggested treatment eligibility criteria for use in such settings, but in our study the WHO criteria detected less than half of those in need of therapy in a large Ethiopian cohort of 1,190 patients with CHB. Our findings suggest that the WHO criteria might be unsuitable in subSaharan Africa. Viral Hepatitis MARCH 28, 201
HCV-RNA in PSC vs plasma in chronic hepatitis B (CHB) and/or C (CHC) patients and its usefulness ... more HCV-RNA in PSC vs plasma in chronic hepatitis B (CHB) and/or C (CHC) patients and its usefulness in reflex molecular testing. Method: Observational study of consecutive samples of CHB and/or CHC patients. HBV and HCV serology and viral loads were tested on plasma samples obtained by venepuncture and on the PSC (Roche Diagnostics) prepared from finger puncture. HBsAg, anti-HBc and anti-HCV were determined in the cobas ® 8000 System (Roche Diagnostics). In HBsAg positive or anti-HCV positive cases, HBV-DNA or HCV-RNA were respectively quantified as reflex test using a second spot in the same PSC in the cobas ® 6800 System-(Roche Diagnostics). Results: 98 patients were included: 56 HBsAg positive, 40 anti-HCV positive, 2 HBsAg+, anti-HCV positives. A 100% correlation was observed in serological markers between PSC card and the conventional method. HCV RNA in PSC and in conventional plasma samples was detectable in 16 (38%) of 42 anti-HCV positive with a R 2 of 0.91 (HCV-RNA 5.6 ± 1.7 logUI/mL vs 3.9 ± 1.4 PSC). HBV DNA in PSC was detected in 29 (50%) of 58 HBsAg positive samples with an R 2 of 0.95 to plasma (3.5 ± 1.9 logUI/mL vs. 1.5 ± 2 PSC). In plasma samples with HBV-DNA>3 logUI/mL 93% was detectable by PSC while in those with HBV DNA ≤3 logUI/mL PSC was only detectable in 20% of samples. Conclusion: The performance of dried plasma samples in PSC for detection of serological markers of hepatitis B and C virus infection is excellent and comparable with conventional techniques. Viremia studies on PSC cards correlates very well with conventional systems allowing viral load reflex testing, but detecting 2 log less of HBV-DNA. However, this does not impact on the selection of patients candidates to therapy since this is recommended when HBV-DNA levels are >3 logUI/mL.
Shimakawa and colleagues, suggesting a new score to determine treatment eligibility in chronic he... more Shimakawa and colleagues, suggesting a new score to determine treatment eligibility in chronic hepatitis B (CHB). 1 This simple score (TREAT-B) is based solely on alanine aminotransferase (ALT) and hepatitis B e-antigen (HBeAg) and could simplify patient assessment in resource-limited settings where sophisticated tools such as viral load and elastography are rarely available. Herein, we present the performance of TREAT-B in a large and well-characterized cohort of patients with CHB in Ethiopia, 2 and compare this with other simplified treatment algorithms. Out of 1,303 patients with CHB enrolled at a public hospital in Addis Ababa, 912 treatment-naïve patients aged 18 years and older were included in this analysis. Patients with hepatitis C/D and HIV co-infections, hepatocellular carcinoma, pregnancy, decompensated cirrhosis, or missing data were excluded. The most recent treatment guidelines from the European Association for the Study of the Liver (EASL) was considered the 'gold standard', 3 which recommend treatment in patients with: a) cirrhosis and detectable viral load, b) significant fibrosis and viral load >2,000 IU/ml, c) ALT >80 U/L and viral load >20,000 IU/ml, d) Metavir ≥A2 and viral load >2,000 IU/ml, e) HBeAg positive and age ≥30 years, or f) family history of hepatocellular carcinoma or cirrhosis. A transient elastography (Fibroscan Ò 402, Echosens, France) threshold of >7.9 kPa was used to define significant fibrosis and >9.9 kPa to define cirrhosis, based on recent data from Africa. 4 The TREAT-B score was obtained by adding HBeAg status
Background: Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Sahar... more Background: Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Saharan Africa; hence, little is known about the prognosis after initiating treatment in African CHB patients. In this study we aimed to assess predictors of mortality in one of the largest CHB cohorts in sub-Saharan Africa. Methods: Two-hundred-and-seventy-six CHB patients who started treatment with tenofovir disoproxil fumarate at a public hospital in Ethiopia between March 18, 2015, and August 1, 2017, were included in this analysis. Patients were followed up until October 1, 2017, and deaths were ascertained through hospital records and telephone interview with relatives. Decompensated cirrhosis was defined as current or past evidence of ascites, either by clinical examination or by ultrasonography. Cox proportional hazard models were used to identify independent predictors of mortality. Results: Thirty-five patients (12.7%) died during follow-up, 33 of whom had decompensated cirrhosis at recruitment. The median duration from start of treatment to death was 110 days (interquartile range 26-276). The estimated survival was 90.3, 88.2 and 86.3% at 6, 12 and 24 months of follow-up, respectively. Independent predictors of mortality were decompensated cirrhosis (adjusted hazard ratio [AHR] 23.68; 95% CI 3.23-173.48; p = 0. 002), body mass index < 18.5 kg/m2 (AHR 3.65; 95% CI 1.73-7.72; p = 0.001) and older age (per 1-year increment; AHR 1.06; 95% CI 1.02-1.10; p = 0.007). Conclusions: Decompensated cirrhosis, low body mass index and older age were independent predictors of mortality. Improved access to antiviral treatment and earlier initiation of therapy could improve the survival of African CHB patients.
To predict ERV, the area under the receiver operator characteristic curve was 0.921 and 0.858 wit... more To predict ERV, the area under the receiver operator characteristic curve was 0.921 and 0.858 with and without the new attachment, respectively (p = 0.043). The positive likelihood ratios were 5.4% and 3.4% with and without the new attachment, respectively. Cutoff values of spleen stiffness measurement were 53.3 and 45.0 kPa with and without new attachment, respectively. Conclusion: In conclusion, the spleen stiffness could be measured easily by virtual B-mode imaging using the new attachment. Moreover, the potential for ERV detection improved. SAT-419 Endotrophin, a fragment of collagen type VI formation (PRO-C6) is associated with progression free survival and mortality in patients with hepatocellular carcinoma
1190 Ethiopian chronic hepatitis B patients 300 eligible for treatment according to 'gold standar... more 1190 Ethiopian chronic hepatitis B patients 300 eligible for treatment according to 'gold standard' criteria 890 ineligible for treatment according to 'gold standard' criteria • 147 correctly classified by WHO criteria • 153 false negative by WHO criteria • 855 correctly classified by WHO criteria • 35 false positive by WHO criteria Performance indicators of the WHO criteria: Sensitivity/specificity (%) 49.0/96.1 Positive/negative predictive value (%) 80.8/84.8 Highlights In 2015, the WHO launched treatment guidelines for chronic hepatitis B. Little is known about the performance of the WHO guidelines in sub-Saharan Africa. In a large Ethiopian cohort, the WHO criteria failed to detect half of those in need of treatment. Most patients identified by the WHO criteria had decompensated cirrhosis. A revision of the WHO guidelines should take into account local data from Africa.
Background: The World Health Organization has set an ambitious goal of eliminating viral hepatiti... more Background: The World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia. Methods: At a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data. Results: Out of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa (p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load (> 1,000,000 IU/mL; adjusted OR 2.41; 95% CI 1.04-5.55) and suboptimal adherence (< 95%; adjusted OR 3.43, 95% CI 1.33-8.88). Conclusions: This pilot program demonstrated that antiviral therapy of CHB can be realized in Ethiopia with good clinical and virologic response. Early mortality was high in patients with decompensated cirrhosis, underscoring the need for earlier detection of hepatitis B virus infection and timely initiation of treatment, prior to the development of irreversible complications, in sub-Saharan Africa. Trial registration: NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
Liver international : official journal of the International Association for the Study of the Liver, Jan 4, 2017
Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chron... more Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results. Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detecte...
Background: In the absence of liver biopsy, the World Health Organization recommends non-invasive... more Background: In the absence of liver biopsy, the World Health Organization recommends non-invasive tests, such as aspartate aminotransferase to platelet ratio index and FIB-4, to assess liver fibrosis in patients with chronic hepatitis B. However, these tests are not well validated in sub-Saharan Africa. Recently, a new marker, gammaglutamyl transpeptidase to platelet ratio, was found to be more accurate in an African setting, but this needs confirmation in other cohorts. Methods: A treatment program for chronic hepatitis B was initiated in Addis Ababa, Ethiopia, in 2015. Non-invasive tests were compared with transient elastography (Fibroscan 402, Echosense, France) using the following thresholds: no fibrosis (≤7.9 kPa), significant fibrosis (>7.9 kPa) and cirrhosis (>11.7 kPa). The diagnostic accuracy was estimated by calculating the area under the receiver operating characteristics curve. Results: Of 582 treatment-naïve patients, 141 (24.2%) had significant fibrosis and 90 (15.5%) had cirrhosis. The area under the receiver operating characteristics curve of aspartate aminotransferase to platelet ratio index, FIB-4 and gamma-glutamyl transpeptidase to platelet ratio was high both to diagnose significant fibrosis (0.79 [95% CI 0.75-0.84], 0.79 [95% CI 0.75-0.84], 0.80 [95% CI 0.75-0.85]) and cirrhosis (0.86 [95%
Treatment for chronic hepatitis B (CHB) is virtually absent in sub-Saharan Africa. Here we presen... more Treatment for chronic hepatitis B (CHB) is virtually absent in sub-Saharan Africa. Here we present early experiences from a pilot program for treatment of CHB in Ethiopia. Adults (≥18 years) with CHB were included in a cohort study at St. Paul's Hospital Millennium Medical College, Addis Ababa, from February 2015. The baseline assessment included liver function tests, viral markers and transient elastography (Fibroscan 402, Echosense, France). Logistic regression models were used to identify predictors of fibrosis. Tenofovir disoproxil fumarate (TDF) was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. The initial 300 patients underwent a more comprehensive evaluation and are presented here. One-hundred-and-thirty-eight patients (46.0%) were women and median age was 30 years (interquartile range 26-40). Co-infections were rare: four patients (1.3%) were anti-HCV positive, 11 (3.7%) were anti-HDV positive, whereas 5 ...
Background & Aims Hepatitis B virus (HBV) quantification is essential in the management of chroni... more Background & Aims Hepatitis B virus (HBV) quantification is essential in the management of chronic hepatitis B, both to determine treatment eligibility and in the monitoring of treatment effect. This test, however, is rarely available in resource-limited settings due to high costs and stringent requirements for shipment and storage of plasma. Dried Blood Spots (DBS) can be a convenient alternative to plasma, but its use for HBV monitoring has not been investigated under real-life conditions in Africa. Methods The performance of DBS in HBV quantification was investigated using a modified commercial test (Abbott RealTime HBV assay). Paired DBS and plasma samples were collected from an HBV positive cohort in Addis Ababa, Ethiopia. DBS were stored at ambient temperature for 4-39 days before shipment to the laboratory. Results Twenty-six paired samples were selected covering the total range of quantification, from 2.14 log IU/ml to >7 log IU/ml. HBV was detected in 21 of 21 (100%) DBS from patients with a corresponding plasma viral load above 2.70 log IU/ml. The mean difference between plasma and DBS was 0.59 log IU/ml, and the correlation was strong (R2 = 0.92). In stability studies there was no significant change in DBS viral load after storage at room temperature for up to 12 weeks. Conclusions This study suggests that DBS can be a feasible and reliable alternative to plasma for quantification of HBV in resource-limited settings. DBS can expand access to antiviral treatment for patients in low-and middle-income countries.
Background In sub-Saharan Africa, less than 1% of treatment-eligible chronic hepatitis B (CHB) pa... more Background In sub-Saharan Africa, less than 1% of treatment-eligible chronic hepatitis B (CHB) patients receive antiviral therapy. Experiences from local CHB programs are needed to inform treatment guidelines and policies on the continent. Here, we present 5-year results from one of the first large-scale CHB treatment programs in sub-Saharan Africa. Methods Adults with CHB were enrolled in a pilot treatment program in Addis Ababa, Ethiopia, in 2015. Liver enzymes, viral markers, and transient elastography were assessed at baseline and thereafter at 6-month intervals. Tenofovir disoproxil fumarate was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. Survival analysis was performed using the Kaplan–Meier method. Results In total, 1303 patients were included in the program, of whom 291 (22.3%) started antiviral therapy within the initial 5 years of follow-up. Among patients on treatment, estimated 5-year hepatocellular car...
Background Data on renal safety of tenofovir disoproxil fumarate (TDF) treatment among individual... more Background Data on renal safety of tenofovir disoproxil fumarate (TDF) treatment among individuals with chronic hepatitis B (CHB) are inconsistent. The current study aimed to assess the effect of long-term TDF treatment on renal outcomes in adult patients with CHB. Methods From a CHB cohort in Ethiopia, we included 233 patients treated with TDF and 126 untreated controls. Levels of creatinine and creatinine clearance over time were described in patients with and without TDF treatment. Linear mixed effects models with a treatment × time interaction were used to investigate the effect of TDF on creatinine and creatinine clearance. In treated patients only, change in creatinine and creatinine clearance was estimated separately in the first year as compared with subsequent years via linear mixed effects models. Results Median follow-up in the treated group was 51 months (IQR, 27–72), and 75% of patients were male (median age, 33 years; IQR, 26–40). Median follow-up in the untreated grou...
<p>Regression analysis of HBV DNA levels in 23 paired plasma and Dried Blood Spot (DBS) spe... more <p>Regression analysis of HBV DNA levels in 23 paired plasma and Dried Blood Spot (DBS) specimens from Ethiopian hepatitis B patients</p
<p>HBV DNA levels in Dried Blood Spots (DBS) after 2, 6 and 12 weeks of storage at room tem... more <p>HBV DNA levels in Dried Blood Spots (DBS) after 2, 6 and 12 weeks of storage at room temperature.</p
The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from C... more The recent launch of the first point-of-care Xpert® hepatitis B virus (HBV) viral load kit from Cepheid could help to scale up treatment for chronic hepatitis B (CHB) in resource-limited settings. This study aimed to assess the performance of the Xpert kit under field conditions in Ethiopia. One-hundred-and-thirty CHB patients with viral loads ranging from <1 log10 to >7 log10 IU/ml were randomly sampled. The viral load was assessed with both the Xpert and the gold standard Abbott RealTime HBV Viral Load assay in each patient. There was a high correlation between the viral loads assessed by Xpert and Abbott (r = 0.948, p < 0.001). The Bland-Altman plot showed a small bias between the two assays, with an on average 0.23 log10 IU/mL higher viral load result of the Xpert kit; 4 samples differed by >1 log10 IU/mL. Using the treatment threshold of 2000 IU/mL in both tests, Xpert had a sensitivity of 94%, specificity of 71%, positive predictive value of 70%, and negative predictive value of 95%. In conclusion, the Xpert kit demonstrated good validity for the measurement of HBV viral load in a real-life setting.
Lay summary Antiviral therapy prevents disease progression and death in patients with chronic hep... more Lay summary Antiviral therapy prevents disease progression and death in patients with chronic hepatitis B (CHB), but the identification of patients in need of treatment is a challenge in lowand middle-income countries. The World Health Organization (WHO) has suggested treatment eligibility criteria for use in such settings, but in our study the WHO criteria detected less than half of those in need of therapy in a large Ethiopian cohort of 1,190 patients with CHB. Our findings suggest that the WHO criteria might be unsuitable in subSaharan Africa. Viral Hepatitis MARCH 28, 201
HCV-RNA in PSC vs plasma in chronic hepatitis B (CHB) and/or C (CHC) patients and its usefulness ... more HCV-RNA in PSC vs plasma in chronic hepatitis B (CHB) and/or C (CHC) patients and its usefulness in reflex molecular testing. Method: Observational study of consecutive samples of CHB and/or CHC patients. HBV and HCV serology and viral loads were tested on plasma samples obtained by venepuncture and on the PSC (Roche Diagnostics) prepared from finger puncture. HBsAg, anti-HBc and anti-HCV were determined in the cobas ® 8000 System (Roche Diagnostics). In HBsAg positive or anti-HCV positive cases, HBV-DNA or HCV-RNA were respectively quantified as reflex test using a second spot in the same PSC in the cobas ® 6800 System-(Roche Diagnostics). Results: 98 patients were included: 56 HBsAg positive, 40 anti-HCV positive, 2 HBsAg+, anti-HCV positives. A 100% correlation was observed in serological markers between PSC card and the conventional method. HCV RNA in PSC and in conventional plasma samples was detectable in 16 (38%) of 42 anti-HCV positive with a R 2 of 0.91 (HCV-RNA 5.6 ± 1.7 logUI/mL vs 3.9 ± 1.4 PSC). HBV DNA in PSC was detected in 29 (50%) of 58 HBsAg positive samples with an R 2 of 0.95 to plasma (3.5 ± 1.9 logUI/mL vs. 1.5 ± 2 PSC). In plasma samples with HBV-DNA>3 logUI/mL 93% was detectable by PSC while in those with HBV DNA ≤3 logUI/mL PSC was only detectable in 20% of samples. Conclusion: The performance of dried plasma samples in PSC for detection of serological markers of hepatitis B and C virus infection is excellent and comparable with conventional techniques. Viremia studies on PSC cards correlates very well with conventional systems allowing viral load reflex testing, but detecting 2 log less of HBV-DNA. However, this does not impact on the selection of patients candidates to therapy since this is recommended when HBV-DNA levels are >3 logUI/mL.
Shimakawa and colleagues, suggesting a new score to determine treatment eligibility in chronic he... more Shimakawa and colleagues, suggesting a new score to determine treatment eligibility in chronic hepatitis B (CHB). 1 This simple score (TREAT-B) is based solely on alanine aminotransferase (ALT) and hepatitis B e-antigen (HBeAg) and could simplify patient assessment in resource-limited settings where sophisticated tools such as viral load and elastography are rarely available. Herein, we present the performance of TREAT-B in a large and well-characterized cohort of patients with CHB in Ethiopia, 2 and compare this with other simplified treatment algorithms. Out of 1,303 patients with CHB enrolled at a public hospital in Addis Ababa, 912 treatment-naïve patients aged 18 years and older were included in this analysis. Patients with hepatitis C/D and HIV co-infections, hepatocellular carcinoma, pregnancy, decompensated cirrhosis, or missing data were excluded. The most recent treatment guidelines from the European Association for the Study of the Liver (EASL) was considered the 'gold standard', 3 which recommend treatment in patients with: a) cirrhosis and detectable viral load, b) significant fibrosis and viral load >2,000 IU/ml, c) ALT >80 U/L and viral load >20,000 IU/ml, d) Metavir ≥A2 and viral load >2,000 IU/ml, e) HBeAg positive and age ≥30 years, or f) family history of hepatocellular carcinoma or cirrhosis. A transient elastography (Fibroscan Ò 402, Echosens, France) threshold of >7.9 kPa was used to define significant fibrosis and >9.9 kPa to define cirrhosis, based on recent data from Africa. 4 The TREAT-B score was obtained by adding HBeAg status
Background: Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Sahar... more Background: Antiviral treatment for chronic hepatitis B (CHB) is largely unavailable in sub-Saharan Africa; hence, little is known about the prognosis after initiating treatment in African CHB patients. In this study we aimed to assess predictors of mortality in one of the largest CHB cohorts in sub-Saharan Africa. Methods: Two-hundred-and-seventy-six CHB patients who started treatment with tenofovir disoproxil fumarate at a public hospital in Ethiopia between March 18, 2015, and August 1, 2017, were included in this analysis. Patients were followed up until October 1, 2017, and deaths were ascertained through hospital records and telephone interview with relatives. Decompensated cirrhosis was defined as current or past evidence of ascites, either by clinical examination or by ultrasonography. Cox proportional hazard models were used to identify independent predictors of mortality. Results: Thirty-five patients (12.7%) died during follow-up, 33 of whom had decompensated cirrhosis at recruitment. The median duration from start of treatment to death was 110 days (interquartile range 26-276). The estimated survival was 90.3, 88.2 and 86.3% at 6, 12 and 24 months of follow-up, respectively. Independent predictors of mortality were decompensated cirrhosis (adjusted hazard ratio [AHR] 23.68; 95% CI 3.23-173.48; p = 0. 002), body mass index < 18.5 kg/m2 (AHR 3.65; 95% CI 1.73-7.72; p = 0.001) and older age (per 1-year increment; AHR 1.06; 95% CI 1.02-1.10; p = 0.007). Conclusions: Decompensated cirrhosis, low body mass index and older age were independent predictors of mortality. Improved access to antiviral treatment and earlier initiation of therapy could improve the survival of African CHB patients.
To predict ERV, the area under the receiver operator characteristic curve was 0.921 and 0.858 wit... more To predict ERV, the area under the receiver operator characteristic curve was 0.921 and 0.858 with and without the new attachment, respectively (p = 0.043). The positive likelihood ratios were 5.4% and 3.4% with and without the new attachment, respectively. Cutoff values of spleen stiffness measurement were 53.3 and 45.0 kPa with and without new attachment, respectively. Conclusion: In conclusion, the spleen stiffness could be measured easily by virtual B-mode imaging using the new attachment. Moreover, the potential for ERV detection improved. SAT-419 Endotrophin, a fragment of collagen type VI formation (PRO-C6) is associated with progression free survival and mortality in patients with hepatocellular carcinoma
1190 Ethiopian chronic hepatitis B patients 300 eligible for treatment according to 'gold standar... more 1190 Ethiopian chronic hepatitis B patients 300 eligible for treatment according to 'gold standard' criteria 890 ineligible for treatment according to 'gold standard' criteria • 147 correctly classified by WHO criteria • 153 false negative by WHO criteria • 855 correctly classified by WHO criteria • 35 false positive by WHO criteria Performance indicators of the WHO criteria: Sensitivity/specificity (%) 49.0/96.1 Positive/negative predictive value (%) 80.8/84.8 Highlights In 2015, the WHO launched treatment guidelines for chronic hepatitis B. Little is known about the performance of the WHO guidelines in sub-Saharan Africa. In a large Ethiopian cohort, the WHO criteria failed to detect half of those in need of treatment. Most patients identified by the WHO criteria had decompensated cirrhosis. A revision of the WHO guidelines should take into account local data from Africa.
Background: The World Health Organization has set an ambitious goal of eliminating viral hepatiti... more Background: The World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia. Methods: At a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data. Results: Out of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa (p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load (> 1,000,000 IU/mL; adjusted OR 2.41; 95% CI 1.04-5.55) and suboptimal adherence (< 95%; adjusted OR 3.43, 95% CI 1.33-8.88). Conclusions: This pilot program demonstrated that antiviral therapy of CHB can be realized in Ethiopia with good clinical and virologic response. Early mortality was high in patients with decompensated cirrhosis, underscoring the need for earlier detection of hepatitis B virus infection and timely initiation of treatment, prior to the development of irreversible complications, in sub-Saharan Africa. Trial registration: NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
Liver international : official journal of the International Association for the Study of the Liver, Jan 4, 2017
Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chron... more Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results. Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detecte...
Background: In the absence of liver biopsy, the World Health Organization recommends non-invasive... more Background: In the absence of liver biopsy, the World Health Organization recommends non-invasive tests, such as aspartate aminotransferase to platelet ratio index and FIB-4, to assess liver fibrosis in patients with chronic hepatitis B. However, these tests are not well validated in sub-Saharan Africa. Recently, a new marker, gammaglutamyl transpeptidase to platelet ratio, was found to be more accurate in an African setting, but this needs confirmation in other cohorts. Methods: A treatment program for chronic hepatitis B was initiated in Addis Ababa, Ethiopia, in 2015. Non-invasive tests were compared with transient elastography (Fibroscan 402, Echosense, France) using the following thresholds: no fibrosis (≤7.9 kPa), significant fibrosis (>7.9 kPa) and cirrhosis (>11.7 kPa). The diagnostic accuracy was estimated by calculating the area under the receiver operating characteristics curve. Results: Of 582 treatment-naïve patients, 141 (24.2%) had significant fibrosis and 90 (15.5%) had cirrhosis. The area under the receiver operating characteristics curve of aspartate aminotransferase to platelet ratio index, FIB-4 and gamma-glutamyl transpeptidase to platelet ratio was high both to diagnose significant fibrosis (0.79 [95% CI 0.75-0.84], 0.79 [95% CI 0.75-0.84], 0.80 [95% CI 0.75-0.85]) and cirrhosis (0.86 [95%
Treatment for chronic hepatitis B (CHB) is virtually absent in sub-Saharan Africa. Here we presen... more Treatment for chronic hepatitis B (CHB) is virtually absent in sub-Saharan Africa. Here we present early experiences from a pilot program for treatment of CHB in Ethiopia. Adults (≥18 years) with CHB were included in a cohort study at St. Paul's Hospital Millennium Medical College, Addis Ababa, from February 2015. The baseline assessment included liver function tests, viral markers and transient elastography (Fibroscan 402, Echosense, France). Logistic regression models were used to identify predictors of fibrosis. Tenofovir disoproxil fumarate (TDF) was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. The initial 300 patients underwent a more comprehensive evaluation and are presented here. One-hundred-and-thirty-eight patients (46.0%) were women and median age was 30 years (interquartile range 26-40). Co-infections were rare: four patients (1.3%) were anti-HCV positive, 11 (3.7%) were anti-HDV positive, whereas 5 ...
Background & Aims Hepatitis B virus (HBV) quantification is essential in the management of chroni... more Background & Aims Hepatitis B virus (HBV) quantification is essential in the management of chronic hepatitis B, both to determine treatment eligibility and in the monitoring of treatment effect. This test, however, is rarely available in resource-limited settings due to high costs and stringent requirements for shipment and storage of plasma. Dried Blood Spots (DBS) can be a convenient alternative to plasma, but its use for HBV monitoring has not been investigated under real-life conditions in Africa. Methods The performance of DBS in HBV quantification was investigated using a modified commercial test (Abbott RealTime HBV assay). Paired DBS and plasma samples were collected from an HBV positive cohort in Addis Ababa, Ethiopia. DBS were stored at ambient temperature for 4-39 days before shipment to the laboratory. Results Twenty-six paired samples were selected covering the total range of quantification, from 2.14 log IU/ml to >7 log IU/ml. HBV was detected in 21 of 21 (100%) DBS from patients with a corresponding plasma viral load above 2.70 log IU/ml. The mean difference between plasma and DBS was 0.59 log IU/ml, and the correlation was strong (R2 = 0.92). In stability studies there was no significant change in DBS viral load after storage at room temperature for up to 12 weeks. Conclusions This study suggests that DBS can be a feasible and reliable alternative to plasma for quantification of HBV in resource-limited settings. DBS can expand access to antiviral treatment for patients in low-and middle-income countries.
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Papers by Hanna Aberra