Hepatitis B virus genotypes from European origin explains the high endemicity found in some areas from southern Brazil

Southern Brazil is considered an area of low Hepatitis B endemicity, but some areas of higher endemicity have been described in the Southwest of Parana and Santa Catarina states. The aim of this study was to evaluate viral genotypes circulating throughout Parana state. PCR amplification and partial sequencing of the S gene was carried out in 228 samples from HBsAg positive candidate blood donors. Samples have been collected in seven different counties (Cascavel, Curitiba, Foz do Iguacu, Francisco Beltrao, Matinga Londrina and Paranagua). The most common HBV genotype in Parana state was D (82.9%; 189/228), followed by A (14.1%; 32/228). Genotypes F (1.3%; 3/228), C (1.3%; 3/228) and H (0.4%; 1/228) were also found. Distribution of genotypes was different in the studied counties, but genotype D was the most frequent in all of them. In Francisco Beltrao, all studied samples belonged to genotype D. The high prevalence of HBV genotype Din South of Brazil is explained by the intense migration of settlers from Europeans countries. Subgenotypes A1 and A2 were identified circulating in all cities where HBV/A was found. As observed in other areas of Brazil, HBV/A1 is more frequent than the HBV/A2 in Parana state and its presence was significantly larger in black and mulatto individuals. Genotype C was found only in individuals with Asian ancestry from Londrina and Maringa. Most HBV/F sequences identified in this study were classified as subgenotype F2a that was previously described in Brazil. The sole case of subgenotype F4 was from Foz do Iguacu city, near to Northern Argentina, where F4 is highly prevalent. The single genotype H sample was from Curitiba. This is the first case of this genotype described in Brazil. Further studies should be carried out to determine if more genotype H samples can be found in other populations from Brazil. (C) 2012 Elsevier B.V. All rights reserved.

Transforming growth factor alpha immunoreactivity. A study in hepatocellular carcinoma and in non-neoplastic liver tissue

Background. Transforming growth factor alpha (TGF alpha) is an important mitogen that binds to epidermal growth factor receptor and is associated with the development of several tumors. Aims. Assessment of the immunoexpression of TGF alpha in hepatocellular carcinoma (HCC) and in non-neoplastic liver tissue and its relationship to morphological patterns of HCC. Material and methods. The immunohistochemical expression of TGF alpha was studied in 47 cases of HCC (27 multinodular, 20 nodular lesions). Five lesions measured up to 5 cm and 15 lesions above 5 cm. Thirty-two cases were graded as I or II and 15 as III or IV. The non-neoplastic tissue was examined in 40 cases, of which 22 had cirrhosis. HBsAg and anti-HCV were positive in 5/38 and 15/37 patients, respectively. The statistical analysis for possible association of immunostaining of TGF alpha and pathological features was performed through chi-square test. Results. TGF alpha was detected in 31.9% of the HCC and in 42.5% of the non-neoplastic. There was a statistically significant association between the expression of TGF alpha and cirrhosis (OR = 8.75, 95% CI = [1.93, 39.75]). The TGF alpha was detected more frequently in patients anti-HCV(+) than in those HBsAg(+). The immunoexpression of TGF alpha was not found related to tumor size or differentiation. In conclusion the TGF alpha is present in hepatocarcinogenesis in HBV negative patients. Further analysis is needed to examine the involvement of TGF alpha in the carcinogenesis associated with HCV and other possible agents. In addition, TGF alpha has an higher expression in hepatocyte regeneration and proliferation in cirrhotic livers than in HCC.

Phylogenetic analysis of complete genome sequences of hepatitis B virus from an Afro-Colombian community: presence of HBV F3/A1 recombinant strain

Background: Hepatitis B virus (HBV) infection is one of the most prevalent viral infections in humans and represents a serious public health problem. In Colombia, our group reported recently the presence of subgenotypes F3, A2 and genotype G in Bogota. The aim of this study was to characterize the HBV genotypes circulating in Quibdo, the largest Afro-descendant community in Colombia. Sixty HBsAg-positive samples were studied. A fragment of 1306 bp (S/POL) was amplified by nested PCR. Positive samples to S/POL fragment were submitted to PCR amplification of the HBV complete genome. Findings: The distribution of HBV genotypes was: A1 (52.17%), E (39.13%), D3 (4.3%) and F3/A1 (4.3%). An HBV recombinant strain subgenotype F3/A1 was found for the first time. Conclusions: This study is the first analysis of complete HBV genome sequences from Afro-Colombian population. It was found an important presence of HBV/A1 and HBV/E genotypes. A new recombinant strain of HBV genotype F3/A1 was reported in this population. This fact may be correlated with the introduction of these genotypes in the times of slavery.

Searching for chronic hepatitis B patients in a low prevalence area – role of racial origin

Abstract Background Clinical studies for testing new drugs against hepatitis B ought to be carried out in low prevalence areas despite difficulties on patient recruitment. In such areas, relatives of chronic hepatitis B patients are considered to be at risk of acquiring the hepatitis B virus (HBV). The aim of this study was to evaluate the prevalence of HBV markers (anti-HBc, HBsAg and anti-HBs) in familial members of chronic hepatitis B (CHB) patients according to their origin (Asian or Western) in a low prevalence area, the city of São Paulo, Brazil. Methods Twenty three Asian CHB probands and their 313 relatives plus 31 CHB probands of Western origin and their 211 relatives were screened for HBV serological markers; the study was carried out in the outpatient clinic of the University of São Paulo School of Medicine. Results Mother to child transmission was greater in the Asian group whereas sexual transmission was more frequent in the Western group (p < 0.0001). Anti-HBc was positive in 90% and 57% of the Asian and Western parents (p = 0.0432) and in 97% and 33% of the Asian and Western brothers (p = 0.0001), respectively. HBsAg was more frequent among the Asian (66%) than the Western (15%) mothers (p = 0.0260) as well as among the Asian (81%) than the Western (19%) brothers (p = 0.0001). We could detect 110 new HBsAg-positive subjects related to the 54 index patients, being the majority (81%) of Asian origin. Conclusion In low prevalence area of hepatitis B, family members and household contacts of chronic HBV carriers are at high risk for acquiring hepatitis B.

Characterization of Hepatitis B virus (HBV) genotypes in patients from Rondônia, Brazil

Abstract Background Hepatitis B virus (HBV) can be classified into nine genotypes (A-I) defined by sequence divergence of more than 8% based on the complete genome. This study aims to identify the genotypic distribution of HBV in 40 HBsAg-positive patients from Rondônia, Brazil. A fragment of 1306 bp partially comprising surface and polymerase overlapping genes was amplified by PCR. Amplified DNA was purified and sequenced. Amplified DNA was purified and sequenced on an ABI PRISM® 377 Automatic Sequencer (Applied Biosystems, Foster City, CA, USA). The obtained sequences were aligned with reference sequences obtained from the GenBank using Clustal X software and then edited with Se-Al software. Phylogenetic analyses were conducted by the Markov Chain Monte Carlo (MCMC) approach using BEAST v.1.5.3. Results The subgenotypes distribution was A1 (37.1%), D3 (22.8%), F2a (20.0%), D4 (17.1%) and D2 (2.8%). Conclusions These results for the first HBV genotypic characterization in Rondônia state are consistent with other studies in Brazil, showing the presence of several HBV genotypes that reflects the mixed origin of the population, involving descendants from Native Americans, Europeans, and Africans.

Detection of Hepatitis B virus subgenotype A1 in a Quilombo community from Maranhão, Brazil

Abstract Background The Brazilian population is mainly descendant from European colonizers, Africans and Native Americans. Some Afro-descendants lived in small isolated communities since the slavery period. The epidemiological status of HBV infection in Quilombos communities from northeast of Brazil remains unknown. The aim of this study was to characterize the HBV genotypes circulating inside a Quilombo isolated community from Maranhão State, Brazil. Methods Seventy-two samples from Frechal Quilombo community at Maranhão were collected. All serum samples were screened by enzyme-linked immunosorbent assays for the presence of hepatitis B surface antigen (HBsAg). HBsAg positive samples were submitted to DNA extraction and a fragment of 1306 bp partially comprising HBsAg and polymerase coding regions (S/POL) was amplified by nested PCR and its nucleotide sequence was determined. Viral isolates were genotyped by phylogenetic analysis using reference sequences from each genotype obtained from GenBank (n = 320). Sequences were aligned using Muscle software and edited in the SE-AL software. Bayesian phylogenetic analyses were conducted using Markov Chain Monte Carlo (MCMC) method to obtain the MCC tree using BEAST v.1.5.3. Results Of the 72 individuals, 9 (12.5%) were HBsAg-positive and 4 of them were successfully sequenced for the 1306 bp fragment. All these samples were genotype A1 and grouped together with other sequences reported from Brazil. Conclusions The present study represents the first report on the HBV genotypes characterization of this community in the Maranhão state in Brazil where a high HBsAg frequency was found. In this study, we reported a high frequency of HBV infection and the exclusive presence of subgenotype A1 in an Afro-descendent community in the Maranhão State, Brazil.

Distribution of hepatitis B virus subgenotype F2a in São Paulo, Brazil

Abstract Background HBV genotype F is primarily found in indigenous populations from South America and is classified in four subgenotypes (F1 to F4). Subgenotype F2a is the most common in Brazil among genotype F cases. The aim of this study was to characterize HBV genotype F2a circulating in 16 patients from São Paulo, Brazil. Samples were collected between 2006 and 2012 and sent to Hospital Israelita Albert Einstein. A fragment of 1306 bp partially comprising HBsAg and DNA polymerase coding regions was amplified and sequenced. Viral sequences were genotyped by phylogenetic analysis using reference sequences from GenBank (n=198), including 80 classified as subgenotype F2a. Bayesian Markov chain Monte Carlo simulation implemented in BEAST v.1.5.4 was applied to obtain the best possible estimates using the model of nucleotide substitutions GTR+G+I. Findings It were identified three groups of sequences of subgenotype F2a: 1) 10 sequences from São Paulo state; 2) 3 sequences from Rio de Janeiro and one from São Paulo states; 3) 8 sequences from the West Amazon Basin. Conclusions These results showing for the first time the distribution of F2a subgenotype in Brazil. The spreading and the dynamic of subgenotype F2a in Brazil requires the study of a higher number of samples from different regions as it is unfold in almost all Brazilian populations studied so far. We cannot infer with certainty the origin of these different groups due to the lack of available sequences. Nevertheless, our data suggest that the common origin of these groups probably occurred a long time ago.

Imunogenicidade da vacina brasileira contra hepatite B em adultos.

OBJETIVO: Avaliar a imunogenicidade e segurança da vacina contra hepatite B, após o aumento na concentração do antígeno HBsAg para 25 μg, em comparação à vacina de referência. MÉTODOS: Ensaio com alocação aleatória e mascaramento simples, comparando a VrHB-IB (Instituto Butantan) com a vacina de referência (Engerix B®, Glaxo Smith Kline). Os voluntários, entre 31 e 40 anos de idade (n=419), foram alocados aleatoriamente ao grupo experimental (n=216) ou ao grupo controle (n=203), e receberam três doses de vacina. A primeira dose foi administrada no momento do recrutamento, a segunda e terceira 30 e 180 dias depois respectivamente, entre 2004 e 2005. Amostras de sangue foram colhidas para análise sorológica antes da randomização, e após a segunda e terceira doses. Foi realizada a vigilância ativa de eventos adversos durante os cinco primeiros dias após a vacinação. As diferenças foram avaliadas pelos testes do qui-quadrado e exato de Fisher, com nível de significância de 5%. RESULTADOS: Não se observaram eventos adversos graves. A soroporteção foi confirmada em 98,6% (213/216) dos voluntários do grupo experimental, em comparação a 95,6% (194/203) do grupo controle. Os títulos geométricos médios foram de 12.557 e 11.673, respectivamente. CONCLUSÕES: A vacina brasileira foi considerada equivalente à vacina de referência e seu uso recomendado para adultos.

Hepatitis C virus and non-Hodgkin's lymphoma: Findings from the Swiss HIV Cohort Study

Infections with hepatitis C virus (HCV) and, possibly, hepatitis B virus (HBV) are associated with an increased risk of non-Hodgkin's lymphoma (NHL) in the general population, but little information is available on the relationship between hepatitis viruses and NHL among people with HIV (PHIV). We conducted a matched case-control study nested in the Swiss HIV Cohort Study (SHCS). Two hundred and ninety-eight NHL cases and 889 control subjects were matched by SHCS centre, gender, age group, CD4+ count at enrollment, and length of follow-up. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using logistic regression to evaluate the association between NHL and seropositivity for antibodies against HCV (anti-HCV) and hepatitis B core antigen (anti-HBc), and for hepatitis B surface antigen (HBsAg). Anti-HCV was not associated with increased NHL risk overall (OR = 1.05; 95% CI: 0.63-1.75), or in different strata of CD4+ count, age or gender. Only among men having sex with men was an association with anti-HCV found (OR = 2.37; 95% CI: 1.03-5.43). No relationships between NHL risk and anti-HBc or HBsAg emerged. Coinfection with HIV and HCV or HBV did not increase NHL risk compared to HIV alone in the SHCS.

Selective immunisation strategy to protect newborns at risk for transmission of hepatitis B: retrospective audit of vaccine uptake

BACKGROUND: 90% of newborns infected perinatally will develop chronic hepatitis B infection with the risk of liver cirrhosis or hepatocellular carcinoma. In Switzerland, screening of all pregnant women for hepatitis B virus (HBV) has been recommended since 1983. Neonates at risk for perinatally acquired HBV are passively and actively immunised immediately after birth as well as at 1 and 6 months of age. The objective of this study was to evaluate the proportion of newborns immunised in accordance with the proposed vaccination schedule. METHODS: Patient records of 3997 mothers who gave birth to a liveborn infant during a two-year period at Zürich University Hospital were screened by computer. 128 women were identified as HBsAg positive or anti-HBc alone positive. Of 133 infants born to these mothers, complete data were available for 94 (71%). RESULTS: Immunisation was started in 88 infants (94%), but only in 78 (83%) within the first 24 hours of life. 85 (90%) received the 2nd immunisation but only 72 (77%) within the given time limit. 80 (85%) of the infants received the 3rd immunisation but only 69 (73%) within the correct time limit. In summary, only 51 (54%) of the infants at risk for HBV infection were immunised correctly (immunoglobulin within 24 hours and active prophylaxis at 0, 1 and 6 months). CONCLUSIONS: The success of the immunisation strategy following maternal screening and selective immunisation of newborns at risk for HBV infection is limited for various reasons (lack of screening results at birth, problems with correct documentation and communication). To overcome these drawbacks, selective vaccination strategy should be improved and general vaccination strategy, including infants, should be reconsidered.

Blood donor screening: how to decrease the risk of transfusion-transmitted hepatitis B virus?

QUESTIONS UNDER STUDY: The risk of transfusion-transmitted HBV remains significant in Switzerland, where routine screening for hepatitis B virus (HBV) in blood donations relies solely on serological hepatitis B surface antigen (HBsAg) testing. This study was designed to determine the prevalence of anti-hepatitis B core (anti-HBc) and HBV nucleic acid testing (NAT) positive donations in two different Swiss donor populations, to help in deciding whether supplemental testing may bring additional safety to blood products. METHODS: In a first population of donors, 18143 consecutive donations were screened initially for HBsAg, anti-HBc (with one EIA assay) and with HBV NAT in minipools of 24 donations. The screening repeatedly reactive anti-HBc donations were then "confirmed" with two supplemental anti-HBc assays, an anti-hepatitis B surface assay (anti-HBs) and with single donation HBV NAT. In a second population of donors, 4186 consecutive donations were screened initially with two different anti-HBc assays in addition to the mandatory HBsAg screening test. The screening repeatedly reactive donations with at least one anti-HBc assay were tested for anti-HBs. RESULTS: In the first subset of 18143 donations, 17593 (97.0%) were negative for HBsAg, anti-HBc and HBV NAT in minipools. 549 (3.0%) were HBsAg and HBV NAT negative, but repeatedly reactive for anti-HBc. Of these 549 donations, 287 could not be "confirmed" with two additional anti-HBc assays and were negative with an anti-HBs assay, as well as with single donation HBV NAT. Only 211 (1.2% of the total screened donations) were "confirmed" positive with at least one of two supplemental anti-HBc assays. One repeatedly reactive HBsAg donation, from a first-time donor, was confirmed positive for HBsAg and anti-HBc, as well as with single donation HBV NAT. In the second subset of 4186 donations, 4014 (95.9%) were screened negative for HBsAg and for anti-HBc, tested with two independent anti-HBc assays. 172 donations (4.1%) were HBsAg negative but repeatedly reactive with at least one of the two anti-HBc assays. Of these 172 samples, 86 were reactive with the first anti-HBc assay only, 13 were reactive with the second anti-HBc assay only and 73 (1.7% of the total screened donations) were "confirmed" positive with both anti-HBc assays. CONCLUSION: The prevalence of anti-HBc "confirmed" positive donations in the two Swiss blood donor populations studied was low (<2%) and we found only one HBV NAT positive (HBsAg positive) donation among more than 18000. Concerning blood product safety, an increase in the deferral rate of less than 2% of anti-HBc positive, potentially infectious donors, would in our opinion make routine anti-HBc testing of blood donations cost-effective. There is however still a need for more specific assays to avoid an unacceptably high deferral rate of "false" positive donors. In contrast, the introduction of HBV NAT in minipools gives minimal benefit due to the inadequate sensitivity of the assay. It remains to evaluate more extensively the value of individual donation NAT, alone or in addition to anti-HBc, as supplemental testing in the context of several Swiss blood donor populations.

Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

Background Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications.

A case-control study of hepatitis C virus and its interaction with hepatitis B virus on the development of hepatocellular carcinoma in the USA

Objective. The aim of this study was to assess the independent risk of hepatitis C virus (HCV) infection in the development of hepatocellular carcinoma (HCC). The independent risk of hepatitis B virus (HBV), its interaction with hepatitis C virus and the association with other risk factors were examined.^ Methods. A hospital-based case-control study was conducted between January 1994 and December 1995. We enrolled 115 pathologically confirmed HCC patients and 230 nonliver cancer controls, who were matched by age ($\pm$5 years), gender, and year of diagnosis. Both cases and controls were recruited from The University of Texas M. D. Anderson Cancer Center at Houston. The risk factors were collected through personal interviews and blood samples were tested for HCV and HBV markers. Univariate and multivariate analyses were performed through conditional logistic regression.^ The prevalence of anti-HCV positive is 25.2% in HCC cases compared to 3.0% in controls. The univariate analysis showed that anti-HCV, HBsAg, alcohol drinking and cigarette smoking were significantly associated with HCC, however, family history of cancer, occupational chemical exposure, and use of oral contraceptive were not. Multivariate analysis revealed a matched odds ratio (OR) of 10.1 (95% CI 3.7-27.4) for anti-HCV, and an OR of 11.9 (95% CI 2.5-57.5) for HBsAg. However, dual infection of HCV and HBV had only a thirteen times increase in the risk of HCC, OR = 13.9 (95% CI 1.3-150.6). The estimated population attributable risk percent was 23.4% for HCV, 12.6% for HBV, and 5.3% for both viruses. Ever alcohol drinkers was positively associated with HCC, especially among daily drinkers, matched OR was 5.7 (95% CI 2.1-15.6). However, there was no significant increase in the risk of HCC among smokers as compared to nonsmokers. The mean age of HCC patients was significantly younger among the HBV(+) group and among the HCV(+)/HBV(+) group, when compared to the group of HCC patients with no viral markers. The association between past histories of blood transfusion, acupuncture, tattoo and IVDU was highly significant among the HCV(+) group and the HBV(+)/HCV(+) group, as compared to HCC patients with no viral markers. Forty percent of the HCC patients were pathologically or clinically diagnosed with liver cirrhosis. Anti-HCV(+) (OR = 3.6 95% CI 1.5-8.9) and alcohol drinking (OR = 2.7 95% CI 1.1-6.7), but not HBsAg, are the major risk factors for liver cirrhosis in HCC patients.^ Conclusion. Both hepatitis B virus and hepatitis C virus were independent risk factors for HCC. There was not enough evidence to determine the interaction between both viruses. Only daily alcoholic drinkers showed increasing risk for HCC development, as compared to nondrinkers. ^

Exploring the role of viral infection in type 2 diabetes

Viral infection is known to play a role in type I diabetes, but there is a paucity of information on the role of viruses in type 2 diabetes. This research examined the seroprevalence of selected viruses in a group of predominantly Mexican-American patients with End Stage Renal Disease (ESRD). Using a case control design, patients with type 2 diabetes were compared with a group of non-diabetic controls. ^ One hundred and thirteen patients, 83 with type 2 diabetes and 30 controls without diabetes, underwent hemodialysis at the same chronic dialysis facility in San Antonio, Texas. AD subjects were tested for IgG, IgM, and neutralizing antibodies against Coxsackie B viruses (CBV), and IgG and IgM antibodies against cytomegalovirus (CMV) and parvovirus B19 (PVB19). Hepatitis B virus antigen (HBVAg), Hepatitis B virus antibody (HBVAb), Hepatitis C virus antibody (HCVAb), and Rubella (IgG) were also measured. A subset of 91 patients, 66 with diabetes and 25 controls, were tested bimonthly for six months. There was a significant difference (P = 0.04) in the seroprevalence of IgG antibodies to CMV between patients with type 2 diabetes (98%) and non-diabetic controls (87%) in the initial sample (OR = 6.2, 95% CI:1.1–36.0). A greater seroprevalence of CMV IgG antibodies was observed over the six month period among patients with type 2 diabetes (M) compared to controls (84%). This difference was also statistically (P < 0.03), with a greater odds ratio (OR = 12.4, 95% CI: 1.3–116.9), but with larger confidence interval related to the small number of subjects. However, when adjusted for age by logistic regression analysis there was no difference between the groups (OR = 1). ^ After one sample, there was a greater seroprevalence of HCVAb in the group without diabetes (28%), compared to those with type 2 diabetes (10%) (P = 0.04). This difference was no longer significant when adjusted for patient age. The prevalence of antibodies to PVB19, HBSAg, HBV, and Rubella was not significantly different in patients with type 2 diabetes and controls. There were significantly more vascular complications (P < 0.02) among patients with diabetes. ^ These results indicate that the significant associations observed in this population between viral infection with CMV, HCV, and type 2 diabetes are confounded by age. Accelerated atherosclerosis has been associated with age, diabetes, as well as CMV. Latent infection may be a factor that links these processes. ^

Elevated AST-to-platelet ratio index is associated with increased all-cause mortality among HIV-infected adults in Zambia.

BACKGROUND AND AIMS We investigated the association between significant liver fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in Zambia METHODS: Among HIV-infected adults who initiated ART, we categorized baseline APRI scores according to established thresholds for significant hepatic fibrosis (APRI ≥1.5) and cirrhosis (APRI ≥2.0). Using multivariable logistic regression we identified risk factors for elevated APRI including demographic characteristics, body mass index (BMI), HIV clinical and immunologic status, and tuberculosis. In the subset tested for hepatitis B surface antigen (HBsAg), we investigated the association of hepatitis B virus co-infection with APRI score. Using Kaplan-Meier analysis and Cox proportional hazards regression we determined the association of elevated APRI with death during ART. RESULTS Among 20,308 adults in the analysis cohort, 1,027 (5.1%) had significant liver fibrosis at ART initiation including 616 (3.0%) with cirrhosis. Risk factors for significant fibrosis or cirrhosis included male sex, BMI <18, WHO clinical stage 3 or 4, CD4+ count <200 cells/mm(3) , and tuberculosis. Among the 237 (1.2%) who were tested, HBsAg-positive patients had four times the odds (adjusted odds ratio, 4.15; 95% CI, 1.71-10.04) of significant fibrosis compared HBsAg-negatives. Both significant fibrosis (adjusted hazard ratio 1.41, 95% CI, 1.21-1.64) and cirrhosis (adjusted hazard ratio 1.57, 95% CI, 1.31-1.89) were associated with increased all-cause mortality. CONCLUSION Liver fibrosis may be a risk factor for mortality during ART among HIV-infected individuals in Africa. APRI is an inexpensive and potentially useful test for liver fibrosis in resource-constrained settings. This article is protected by copyright. All rights reserved.