What’s eating your liver?

A report from the interactive case-based workshop “What’s eating your liver?” with presentations from Susanna Nagie and Darcy Wooton and from the Symposium on PMTCT of Hepatitis B by Yusuke Shimakawa

While there were major frustrations with CROI this year (including the very late notice that it would be held virtually), overall they did a great job of changing the format of the conference at  such short notice.  This “interactive” case based workshop was a fascinating review of the changing epidemiology and mortality from some of the major infectious diseases globally (HIV, Tuberculosis, Malaria and viral hepatitis). It highlighted the growing importance of addressing viral hepatitis as the leading cause. While working as a GP and Sexual Health Physician in a high HIV-caseload practice in Sydney I am more involved in the day to day care of patients, I find it refreshing attending international conferences where I am reminded of how our daily work fits into the global context.

Susanna Naggy framed these talks by presenting the WHO data below showing that global hepatitis mortality has now overtaken mortality from HIV, Malaria or Tuberculosis. The alarming projections made by David Thomas also shown in this graph show the rapid escalation of deaths from chronic HBV and HCV and are largely attributed to the ageing population living with viral hepatitis.

Mortality due to Viral Hepatitis

Hepatocellular carcinoma is the major cause of mortality and results from chronic infection with Hepatitis B or C.  Approximately 30% of chronic untreated HBV infection will develop cirrhosis and of those 10-15% will develop a HCC within 5 years. The advent of Neucleotide/Nucleoside analogue therapy decreases this risk by inducing regression of cirrhosis by >50% over a 5-year period, however HBV is carcinogenic in itself and 5-10% of patients will develop HCC without cirrhosis. Susanna highlighted the importance of HCC screening in higher risk HBV patients with and without cirrhosis.

Hepatitis B and HCC

Chronic Hepatitis C patients with cirrhosis develop HCC at the rate of 1-4% per year. The number of patients living with chronic HCV has reduced with increasing access to Direct Acting Antiviral therapy, and Australia has been in a privileged position in providing universal access to DAAs over the past few years.  The audience was reminded however that HCC remains a risk after sustained virological response for patients with cirrhosis and ongoing screening is needed.
Dr Shimakawa from the Istitute Pasteur in Paris presented on “Mother to child transmission of Hepatitis B – can it be eliminated?”  This was a fascinating talk on the changing epidemiology of Hepatitis B, and how mother to child transmission of Hepatitis B now makes up an increasing proportion of new chronic Hepatitis B infections. The age of acquisition of Hepatitis B infection is inversely related to the development of chronicity, and acquisition at birth carries 5 times the risk of developing liver fibrosis. This highlights the importance of interventions that focus on PMTCT, and the stand-out point for me during this talk, was the importance of the timing of the “birth” dose of Hep B vaccination - that this is given within 24 hours of birth for optimal efficacy. 

Hepatitis B vaccination is offered to all infants in Australia and has done well with 94.7% of infants vaccinated by 12 months in 2017. I was unable to find data of the proportion who had started vaccination within 24 hours of birth, which is deemed to be a critical component of successful PMTCT.  

Hepatitis A update
Darcy Wooton from San Diego gave a great update. There have been outbreaks of Hepatitis A in the US, EU, Taiwan and Canada over the last few years, and while the majority of cases are self-limiting, about 10% have a relapsing course (after symptoms improve, LFTs elevate again with or without symptoms) and may last up to 12 months. Other complications include cholestatic hepatitis, autoimmune hepatitis and of course the small risk of acute liver failure.
The presenter reminded us of the indications for Post-Exposure Prophylaxis for Hepatitis A (summarised in the slide below).
 
While 95% of healthy adults seroconvert after 1st Hep A immunisation (and 100% after 2nd dose with >90% having protective antibodies 40 years later), rates of seroconversion in PLWHA are much lower at 45-95%. Predictors of non-response are not surprising with those with a low CD4, high viral load and HCV co-infection being less likely to seroconvert. Durability is also lower in PLWHA with only 75% having protective antibodies at 5 years. A Hepatitis A booster every 10 years in PLWHA was recommended, something I will certainly be more mindful of recommending for the longterm HIV patients under my care.

Take home messages

  • Hepatitis is an increasingly important cause of global mortality when compared with deaths from TB, Malaria and HIV
  • Patients who achieve SVR after HCV treatment, still require surveillance for HCC if there is underlying cirrhosis
  • Hepatitis B virus is itself a carcinogen and 5-10% of patients without cirrhosis go on to develop HCC underlying the importance of screening in high risk HBV patients with or without cirrhosis
  • PMTCT of Hepatitis B is vital when addressing global mortality from hepatitis and the timing of the first infant vaccination is crucial (within 24 hours of birth)
  • Not all of Hepatitis A will run a benign course, and up to 10% will suffer a relapsing, remitting course or more severe complications
  • Only 75% of PLWHA have detectable antibodies to Hepatitis A 5 years after vaccination, and boosters should be carried out every 10 years
  • PLWHA who are exposed to Hepatitis A should be considered for Post-Exposure prophylaxis with Hep A vaccination and immunoglobulin