Would early treatment with antiviral therapy prevent the need for a liver transplant?
Despite a thorough evaluation, a specific etiology cannot be identified in 14% of children with acute liver failure. Over half of these fortunately rare cases are severe enough to require liver transplantation.
A team from Vanderbilt University Medical Center compared the results of pathological examination in five previously-healthy children with acute liver failure associated with HHV-6, three of whom required liver transplantation, to the findings in two comparison groups:
- A consecutive series of nine previously healthy children with acute liver failure collected in the past;
- Eleven previously healthy children with unexplained severe acute hepatitis and concurrent human adenovirus (HAdV) infection.
The HHV-6 cases were included only if confirmed by PCR or immunohistochemistry (IHC) with HHV-6 late antigens. Pathological examination of the liver tissue the five cases detected HHV-6 structural protein in biliary epithelium (but not in hepatocytes) in all cases, and a predominance of CD8+ T cells in the perivenular inflammatory infiltrate. In contrast, there was no evidence of HHV-6 in the two comparison groups.
Several pathological findings were found in the five cases associated with HHV-6, but not in the two comparison groups:
- A centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis;
- Confluent centrilobular to panlobular necrosis accompanied by marked hepatocellular swelling and milder portal inflammation.
- Central perivenulitis.
Among the four patients with acute liver failure, the one who received early HHV-6 specific antiviral treatment survived without a transplant, while the other three received either general prophylactic antiviral treatment only (n= 2) or late anti-HHV-6 therapy (n=1): all three required liver transplantation.
A previously-reported French study reported a similar association of HHV-6 with periportal confluent necrosis in transplant patients with acute graft hepatitis (Buyse 2013). A study in Brazil found HHV-6 in 22% of 27 patients with acute liver failure (Raposo 2019). HHV-6B reactivates in liver transplantation (Phan 2018) and a team at Stanford found high levels of HHV-6 in the biopsies of children with liver failure (Yang 2018).
The authors speculate that the natural course of acute liver injury associated with HHV-6 may initially occur as acute hepatitis with mild central perivenulitis and focal perivenular hepatocyte dropout, but then progress to acute liver failure.
The small size of this series (5 cases) makes firm conclusions impossible. However, this study may have identified some standard pathological findings that increase the likelihood that acute liver failure in previously-healthy young children is due to HHV-6. The fact that the one child given early HHV-6-specific antiviral treatment was the only one of the five to avoid the need for liver transplantation suggests that a randomized controlled trial would be valuable in assessing the possible value of such therapy.
Read the full article: Wang 2024