Current Tools to Diagnose and Predict Hepatocellular Carcinoma: Relevance to HIV and Hepatitis B Virus Coinfection.

Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiologic studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the United States.

Hepatitis B (HBV) and C virus (HCV) coinfection are the major causes of liver-related morbidity and mortality among people living with Human Immunodeficiency Virus (HIV). The burden of hepatitis among HIV-positive individuals has not been studied in the Afar region. Therefore, this study aimed to determine the prevalence of HBV and HCV coinfection and associated factors among HIV-positive patients in Afar Regional State, northeast Ethiopia. A cross-sectional study was conducted on 477 HIV-positive patients between February 2019 and May 2019. A structured and pretested questionnaire was used to collect socio-demographic data and associated factors. Five milliliters of blood was collected, and Hepatitis B surface antigen (HBsAg) and HCV antibodies were detected using rapid test kits. Positive samples were confirmed using enzyme-linked immunosorbent assay (ELISA). Binary and multivariable logistic regression analyses were performed to identify associated factors. Statistical significance was set at P <0.05. Among the 477 study participants, 320/477(67.1%) of them were females and 157(32.9%) males. The overall prevalence of HIV-HBV and HIV-HCV coinfection was 25(5.2%) and 7(1.5%), respectively. Multi-sexual practice was significantly associated with HIV-HBV coinfection (AOR = 5.3; 95% CI: 1.2-24.4, P = 0.032). The prevalence of both HIV-HBV and HIV-HCV coinfection was intermediate. Multi-sexual practice was significantly associated with HIV-HBV coinfection. Screening of all HIV-positive patients for HBV and HCV and health education regarding the transmission modes should be considered.

There is limited data on the effect of antiviral therapies on clinical outcomes in HIV and hepatitis B virus (HBV)-infected individuals in sub-Saharan Africa. Single center, prospective longitudinal cohort study at Management and Development for Health supported HIV Care and Treatment clinics in Dar es Salaam, Tanzania. Between April 2014 and December 2015, HIV-infected, HBV-infected and HIV/HBV-coinfected, treatment naïve, Tanzanian adults more than 18 years of age were eligible for enrollment and followed for 10-18 months after initiating antivirals. All HIV-infected and HIV/HBV-coinfected participants received tenofovir, lamivudine and efavirenz; HBV-infected participants received lamivudine. Multivariate regression models were constructed to identify factors associated with mortality in HIV-infected and HIV/HBV-coinfected participants. A total of 265 HIV-infected, 165 HBV-infected and 64 HIV/HBV-coinfected participants were analyzed. At baseline, HBV-infected participants were younger and had a higher BMI than HIV-infected and HIV/HBV-coinfected participants. After a median of 371 (interquartile range 50) days on treatment, there were 40 deaths. Mortality was significantly higher among HIV/HBV-coinfected participants compared with HIV and HBV-infected participants [HIV/HBV-coinfected 12 of 64 (19%) vs. HIV-infected 26 of 265 (10%) and HBV-infected two of 265 (1%), P < 0.01]. High baseline HIV RNA and low hemoglobin levels, but not HBV coinfection were independently associated with early mortality in multivariate analyses of HIV-infected participants. High rates of early mortality were observed after treatment initiation in HIV/HBV-coinfected individuals compared with participants with HIV or HBV alone, despite robust aspartate aminotransferase to platelet ratio index declines and high rates of virologic suppression. HIV rather than HBV-related factors are more important contributors to mortality in these individuals.

BackgroundHepatitis B virus (HBV) affects people worldwide but the local burden especially in pregnant women and their new born babies is unknown. In Rwanda HIV-infected individuals who are also infected with HBV are supposed to be initiated on ART immediately. HBV is easily transmitted from mother to child during delivery. We sought to estimate the prevalence of chronic HBV infection among pregnant women attending ante-natal clinic (ANC) in Rwanda and to determine factors associated with HBV and HIV co-infection.MethodsThis study used a cross-sectional survey, targeting pregnant women in sentinel sites. Pregnant women were tested for hepatitis B surface antigen (HBsAg) and HIV infection. A series of tests were done to ensure high sensitivity. Multivariable logistic regression was used to identify independent predictors of HBV-HIV co-infection among those collected during ANC sentinel surveillance, these included: age, marital status, education level, occupation, residence, pregnancy and syphilis infection.ResultsThe prevalence of HBsAg among 13,121 pregnant women was 3.7% (95% CI: 3.4–4.0%) and was similar among different socio-demographic characteristics that were assessed. The proportion of HIV-infection among HBsAg-positive pregnant women was 4.1% [95% CI: 2.5–6.3%]. The prevalence of HBV-HIV co-infection was higher among women aged 15-24 years compared to those women aged 25–49 years [aOR = 6.9 (95% CI: 1.8–27.0)]. Women residing in urban areas seemed having HBV-HIV co-infection compared with women residing in rural areas [aOR = 4.3 (95% CI: 1.2–16.4)]. Women with more than two pregnancies were potentially having the co-infection compared to those with two or less (aOR = 6.9 (95% CI: 1.7–27.8). Women with RPR-positive test were seemed associated with HBV-HIV co-infection (aOR = 24.9 (95% CI: 5.0–122.9).ConclusionChronic HBV infection is a public health problem among pregnant women in Rwanda. Understanding that HBV-HIV co-infection may be more prominent in younger women from urban residences will help inform and strengthen HBV prevention and treatment programmes among HIV-infected pregnant women, which is crucial to this population.

6.0 <scp>HIV</scp> and hepatitis virus coinfections

Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?

Liver cancer is the second leading cause of cancer death worldwide, responsible for an estimated 746,000 deaths and 782,000 new cases in 2012 [1]. The countries in the Western Pacific region accounts for 64% and China alone accounts for 51% of the new liver cancer cases and deaths each year. Approximately 80% of hepatocellular carcinoma (HCC), the most common type of liver cancer, is associated with viral hepatitis [1]. In countries with high prevalence of hepatitis B virus (HBV) infection, such as China, up to 80% of HCC is associated with hepatitis B [2]. Liver cancer carries a poor prognosis with a global mortality to incidence ratio of 0.95 [1]. In the USA, the 1-year survival rate remains less than 50% [3]. Asians and Pacific Islanders have the highest incidence of HCC among the different racial/ethnic groups. While every individual with chronic hepatitis B infection (CHB) or HBV carrier is at risk for developing HCC, disease progression leading to cirrhosis is associated with the greatest risk [2]. In an effort to improve survival through early detection of HCC, the American Association for the Study of Liver Diseases recommended HCC screening with abdominal ultrasound (US) at 6–12 month intervals of HBV carriers considered at increased risk for HCC, including those with cirrhosis, family history of liver cancer and Asian male HBV carriers above the age of 40 [4,5]. However, it remains controversial whether population-wide HCC screening of CHB patients results in a reduction in HCC mortality particularly in resource-constraint regions of the world that have the highest burden of HCC. The only two randomized trials available to date are both from China [6,7]. A population-based study in the city of Shanghai, conducted by the Liver Cancer Institute of Fudan University, reported 1-year HCC survival rates improved from 31.2% in the control group to 65.9% in the screened group among 18,816 CHB patients aged 35–59 years with or without cirrhosis, who were randomized into either a group using US and AFP screening every 6 months or a control group [6]. The second study from a rural setting in Qidong, using AFP screening every 6 months without US, did not show any improvement in survival [7]. According to the National Cancer Institute [8], screening for HCC

Quality of care metrics in chronic hepatitis B.

BackgroundThe study assessed the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection paradigm among the human immunodeficiency virus (HIV) infected patients attending a tertiary hospital in Ghana. Also, the immunological and virological characterisation of these viruses, prior to antiretroviral therapy (ART) initiation was investigated.MethodA total of 400 HIV infected (HIV type-1) treatment naïve subjects ≥18 years were enrolled and tested for HBsAg and anti-HCV. Hepatitis B virus serological profile was performed on samples that were HBV positive. CD4+ T-cell count and HIV-1 RNA viral loads were determined using BD FacsCalibur analyzer (USA) and COBAS AmpliPrep/COBAS TaqMan Analyzer (USA) respectively.ResultsThe overall prevalence of HBV/HCV co-infection among the HIV-1 patients was 18.0%. The prevalence of HIV-HBV and HIV-HCV co-infections were 12.5% and 5.5% respectively. The prevalence of active viral hepatitis (HBeAg-positive) among HIV-HBV co-infected patients was 40%. None of the patients had anti-HBc IgM. HIV-HBV co-infection was associated with lower CD4+ T-cell count as well as higher HIV-1 viral load compared to both HIV mono- infection and HIV-HCV co- infection (p<0.05) respectively. HBeAg positivity was associated with severe immunosuppression and higher HIV viral load. Patients aged 18–33 years [aOR = 9.66(1.17–79.61); p = 0.035], male gender [aOR = 2.74(1.15–6.51); p = 0.023], primary education [aOR = 9.60(1.21–76.08); p = 0.032], secondary education [aOR = 14.67(1.82–118.08); p = 0.012] and being single [aOR = 2.88(1.12–7.39); p = 0.028] were independent risk factors of HIV-HBV co-infections but not HIV-HCV co-infections.ConclusionThe present study highlights the predominance of HBV exposure among the HIV infected patients in Ghana. HBV coinfection was associated with severe immunosuppression and higher HIV-1 viral load.

Reducing the incidence of hepatocellular carcinoma (HCC) in HIV-infected patients has become a serious problem when managing these patients. There are many explanations for this disease evolution, which notably include their longer survival under effective antiviral therapy and also the more rapid evolution of chronic liver disease. Despite recent advances in the management of hepatitis B (HBV) and hepatitis C (HCV) viral diseases, which will probably increase the number of patients achieving a virological response, HIV-infected patients with cirrhosis are still at risk of the onset of HCC. This evolution to HCC is also correlated to other comorbidities such as excessive alcohol consumption and nonalcoholic steatohepatitis (NASH). HCC thus remains a public health issue in this population. The poor prognosis and aggressiveness of HCC have been fully demonstrated, but the mechanisms underlying this aggressiveness are not yet well defined. As well as underlying mechanisms that contribute to accelerating hepatocarcinogenesis in HIV-infected patients, there are other reasons why HIV-infected patients should be considered a higher risk population. This review discusses the principal epidemiological determinants; the mechanisms of pathogenesis; and the treatment of HCC in HIV/HBV and HIV/HCV coinfected patients. It also discusses the probable need to develop a specific screening policy for HCC in this population in order to prevent the rapid development and to make them more amenable to a curative treatment.

Presentation, treatment and long-term outcomes of hepatocellular carcinoma in patients with and without HIV: a comparative observational cohort study.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.

The impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection on CD4 cells in patients with human immunodeficiency virus (HIV) is unclear. We aimed to examine the impact of HBV and HCV coinfection on CD4 cell count and CD4/CD8 ratio in adults with HIV. We conducted a longitudinal retrospective study in Brazil between January 1, 2002, and June 30, 2016, including 205 patients with HIV monoinfection, 37 with HIV-HBV coinfection, 35 with HIV-HCV coinfection, and 62 with HIV-HCV (48 HCV genotype 1 and 14 HCV genotype 3). Median duration of follow-up was 2,327 (interquartile range: 1,159-3,319) days. An increased CD4 cell count and CD4/CD8 ratio over time was observed in all groups receiving combined antiretroviral therapy (cART). Patients with HIV-HBV or HIV-HCV coinfection and those with HIV monoinfection, showed comparable CD4 cell counts and CD4/CD8 ratios during pre-ART. There was also no statistically significant difference in CD4/CD8 ratio between HIV-HBV or HIV-HCV coinfection groups and the HIV monoinfection group during follow-up on cART. However, CD4 cell counts were significantly lower in HIV-HCV patients than in HIV monoinfection patients during follow-up on cART. HIV patients with HCV genotype 3 coinfection showed significantly lower CD4/CD8 ratio during follow-up on cART than those coinfected with HCV genotype 1 coinfection. No statistically significant effect of coinfection was observed on the efficacy of cART. HIV-infected patients are more likely to show better immunological responses to cART when they are not coinfected with HCV.

Therapy for chronic hepatitis B with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) or emtricitabine (FTC) is currently recommended for HIV-HBV coinfection. However, there is limited randomized data on the efficacy of combined therapy with TDF and FTC, especially in antiretroviral (ARV)-naive patients. This was a prospective randomized clinical trial comparing the efficacy of HBV monotherapy with FTC versus TDF/FTC combination therapy in ARV-naive HIV-HBV coinfection. HIV-HBV-coinfected patients initiating ARV were randomized to either FTC/zidovudine/efavirenz (EFV; n=6) or TDF/FTC/EFV (n=10). The primary end point was the time-weighted area under the curve (TWAUC) of HBV DNA at 48 weeks. The median baseline CD4(+) T-cell count was 64 cells/μl (interquartile range [IQR] 36-172), plasma HIV type-1 RNA was 4.90 log(10) copies/ml (IQR 4.58-5.44) and plasma HBV DNA was 8.76 log(10) copies/ml (IQR -8.45-8.82). A total of 11/16 (69%) patients were hepatitis B e antigen (HBeAg)-positive. The median TWAUC decrease in HBV DNA was -5.32 log(10) copies/ml in the TDF/FTC group compared with -3.25 log(10) copies/ml in the FTC group (P=0.03). At week 48, 90% of the TDF/FTC group and 33% of the FTC group had plasma HBV DNA<170 copies/ml (P=0.036, intention-to-treat analysis). HBeAg loss was observed in 4/11 (36%) HBeAg-positive patients. Hepatic flares were observed in 3/16 (19%) of patients. TDF/FTC combination therapy resulted in a significantly greater decrease in HBV DNA than FTC monotherapy, with a greater proportion of patients with undetectable HBV DNA at week 48. Our study supports the current recommendation of ARV containing TDF/FTC as the treatment of choice for patients with HIV-HBV coinfection.

To assess the prevalence and risk factors for HBV and HCV coinfection in the Australia HIV Observational Database (AHOD), and examine outcomes of HIV disease following initiation of highly active antiretroviral therapy (HAART). Analyses were based on 2086 participants recruited to AHOD by September 2002. Of these, 1605 (77%) had been tested for HBV surface antigen, 1704 (82%) for anti-HCV antibody and 1453 (70%) for both. Demographic and clinical predictors of HBV and HCV coinfection were examined. The impact of HBV and HCV coinfection on HIV disease progression was assessed by Kaplan-Meier survival curves and Cox proportional hazard model of time to AIDS events and death. Among those tested, prevalence of HBV surface antigen and HCV antibody were 6.3% and 13.1%, respectively (4.8% and 10.7%, respectively, among the entire cohort). In multivariate analyses, the only independent risk factor for HIV/HBV coinfection was coinfection with HCV. Independent risk factors for HIV/HCV coinfection were HIV exposure category (with people who reported injecting drug use [MSM & IDU, IDU only] or receipt of blood or blood products at markedly increased risk) and HBV coinfection. HIV disease outcomes following first initiation of a HAART regimen were similar for HIV/HBV and HIV/HCV coinfected patients compared with HIV-only patients in terms of AIDS-free survival and detectable HIV virus during the first 12 months. However, patients coinfected with HIV/HCV appeared to have a poorer response to HAART in terms of CD4 count changes, with a CD4 count increase of 32 cells/microL (95% CI 1-67) less than HIV-only patients. Coinfection with HBV or HCV is relatively common among HIV-infected participants in AHOD. HIV disease outcomes following HAART do not appear to be adversely affected by HBV/HCV coinfection, except for slightly poorer CD4 count responses in HIV/HCV coinfected patients.