From HIV and the Liver: Co- infection and Complications
Nikoloz Chkhartishvilli presented an overview of the co-infection care cascade from Georgia, a country which has a high disease burden of HIV/HCV co-infection. Despite the differences in our countries political and presumably health care systems, the roll out of their HCV elimination program recalled similar population priorities to the Australian model.
During 2011- 2015, the Global Fund supported Georgia to reduce the disease burden of HCV by offering PEG/RBV to people living with HCV. From 2015, in partnership with Gilead Sciences and U.S. CDC to launch their National HCV Elimination Program and DAAs became available. Similar to the Australian model, there was no cost to the patients and current injection drug use was not a barrier to accessing treatment.
The care cascade is described as follows: 1) HIV/HCV co-infected; 2) Diagnosed for both HIV & HCV, 3) Treated for HCV, 4) Achieve SVR . Data were obtained from the national AIDS health information system
Results: Among 3300 co-infected individuals, 2201 (67%) were not aware of their HIV status, 1099 (33%) were diagnosed with both HIV/HCV, and of those 1099 (33%) persons, 697 (63%) were treated with either PEG/RBV or DAAs. 480 (69%) of those treated attained SVR with 44% for PEG/RBV and 89% with DAAs. So of the 697 (21% of the original cohort) individuals treated, approx. 480 achieved SVR, this being 69% of the treated cohort and 15% of the original co-infected cohort.
A gap in care was identified from time of diagnosis to time of treatment as the major contributor to the low uptake and completion of treatment, calling for tighter systems to support the elimination plan. Highlighted that it’s not just free or subsidised treatment availability, but also the systems and infrastructure required to support programs such as this.
Nadine Kronfli presented on trends in cause- specific mortality in HIV/HCV co- infected patients in Canada 2003- 2016 and the impact of early HCV treatment.
Liver related deaths (ESLD & viral hepatitis) account for 20-25% of deaths in Canadian co-infected population. Mortality rates have decreased since introduction of DAAs achieving SVR>85% and opportunity to reverse fibrosis, decrease sequelae.
Looking at which modifiable risk factors may contribute to excess mortality in co-infected population to help prevent potentially preventable deaths in an already high risk population (lifestyle, exposures related to IDU in co-infected pop).
They used the Canadian Co-infection Cohort which is a prospective multicentre cohort of 1695 co-infected patients from 19 sites in Canada (resulting in 6675 person- years follow up from 1477 eligible patients). Deaths were classified using a ‘coding of cause of death in HIV’ protocol. Event rates per 1000 person- years before (2003- 2009) and after (2010- 2016) the availability of widespread effective treatment stratified by age 20-50, 50-80 yrs were calculated.
75% of the cohort were current smokers at baseline, 84% taking ART, 64% HV VL <50 copies/ml, 81% HCV treatment naïve, 21% APRI > 1.5, 9% prior ESLD dx.
Overall and cause specific mortality, with cause of death divided into 5 categories: ESLD (20%), smoking related (17%), drug OD (16%), other- including AIDS/infections/ cancer/ trauma/ suicide (22%), unknown (25%).
20- 50 yrs: 2003- 2009: 26.04 (13.91, 48.75); 2010- 2016: 19.29 (11.59, 32.11)
50- 80 yrs: 2003- 2009: 56.61 (28.09, 114.1); 41.97 (28.2, 62.46)
Key point from deaths- most had poorly treated HIV and did not achieve SVR as higher deaths on ‘non- ideal’ patient population (CD4 <350, APRI > 1.5, HIVRNA>50).
Concluded that all cause mortality decreased in both age groups over time, explained by a reduction in mortality from a variety of competing causes, no significant decrease in ESLD deaths overall however ESLD appears to be declining in 50-80 year olds, or those who have been successfully treated; immediate impact of HCV therapy most profound among those with fibrosis, and targeting modifiable risk factors such as smoking may confer the highest benefit.
Maud Lemoine presented ‘metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV monoinfected patients: results of the METAFIB study’
Metabolic syndrome and its hepatic manifestation, NAFLD, have emerged as new concerns for PLHIV (prevalence 25% and 35% respectively).
METAFIB study proposed to assess the impact of metabolic syndrome on the proportion and severity of liver fibrosis and analyse association between met syndrome, liver fibrosis, markers of adipose tissue and macrophage activation.
METAFIB is a single centre exposed- non exposed cohort of HIV monoinfected individuals without excessive alcohol consumption, viral hepatitis, or other causes of CLD.
Fibroscan used to measure liver stiffness.
Results from 405 participants (203 with metabolic syndrome, 202 without). Patients with met syndrome were older and 49% had insulin resistance, risk factors for fibrosis: Obesity with BMI >30, T2DM, elevated GGT and leptin.
Liver transaminase levels, ART exposure or HIV parameter levels were not associated with liver fibrosis.
Take home message was that HIV monoinfected patients with metabolic syndrome are at risk of liver fibrosis irrespective of transaminase levels and should be systematically screened. Mass fat measured by BMI and circulating leptin is strongly associated with fibrosis independent of HIV parameters or ART exposure. Adipose tissue, insulin resistance and macrophage activation are likely key players in the development of fibrosis.
There was an audience question regarding impact of some ART in regards tocausing/ association with insulin resistance. Answered that the cohort was older, and treatment experienced, however patients with good virological control were selected so didn’t feel the results could answer that question.
Recommendation to screen all PLHIV with metabolic syndrome regardless of LFTs for fibrosis using fibroscan cheap, easy, non-invasive.
Hugo Perazzo Pedroso Barbosa presented data from the PROSPEC- HIV study looking at predictor factors associated with liver fibrosis and steatosis in a monoinfected population.
Cross sectional study from a cohort of 4000 patients who have been followed from 1990. Exclusion was viral hepatitis co-infection and ART naïve.
Heavily pre- treated population inc. AZT and other early ART.
Clinical evaluation including alcohol assessment, fasting bloods and fibroscan was used.
A total of 348 HIV mono-infected patients [61% female, median (IQR) age=44 (34-52) years, BMI=25.4 (23.0-29.3) kg/m²] were included. Median (IQR) time under c-ART and under the current c-ART regimen were 7.3 (4.1-12.8) and 4.3 (1.9-7.5) years, respectively. LSM and CAP were unreliable in 6% and 12%. Liver fibrosis and steatosis prevalence were 9% (n=30/326) and 33% (n=102/305). In age and gender adjusted multivariate analysis, factors associated [OR (95%CI)] with liver fibrosis were: age > 45 years [2.91 (1.19-7.15); p=0.020]; CD4 count < 200 cells [5.00 (1.38-18.21); p=0.014] and type-2 diabetes [3.04 (0.97-9.55); p=0.056]. Male gender [5.69 (2.68-12.04); p< 0.001]; dyslipidemia [2.86 (1.46-5.60); p=0.002]; type 2 diabetes [6.00 (2.08-17.28); p=0.001] and central obesity [10.24 (4.11-25.50); p< 0.001] were independently associated with liver steatosis.
Concluded that low CD4 count was independently associated with presence of liver fibrosis, metabolic syndrome features were independently associated with steatosis by CAP, higher duration of ART especially AZT as a backbone was associated with steatosis independently of metabolic factors.
Take home message from session: Importance of reducing modifiable risk factors to improve patient’s health outcome, especially smoking and factors contributing to development of metabolic syndrome.