Quantification of viral DNA and liver enzymes in plasma improves early diagnosis and management of herpes simplex virus hepatitis

Abstract

Herpes simplex virus (HSV) hepatitis is a rare and potential life-threatening disease. The diagnosis of HSV hepatitis is hampered by its indifferent clinical presentation, which necessitates confirmatory laboratory data to identify HSV in the affected liver. However, liver biopsies are often contraindicated in the context of coagulopathy, are prone to sampling errors and have low sensitivity in mild HSV hepatitis cases. There is an unmet need for less invasive diagnostic tools. The diagnostic and therapeutic value of HSV DNA load and liver enzyme level kinetics was determined in five patients with HSV hepatitis and twenty disease controls with HSV-DNAemia without hepatitis. At time of hospitalization, patients with HSV hepatitis had a higher median (± interquartile range) HSV DNA load (6.0 × 10(6) ± 1.2 × 10(9)) compared to disease controls (171 ± 2845). Viral DNA load correlated with liver transaminase levels and disease severity. Antiviral treatment led to rapid decline of HSV DNA load and improvement of liver function of patients with HSV hepatitis. The data advocate the prompt and consecutive quantification of the HSV DNA load and liver enzyme levels in plasma of patients suspected of HSV hepatitis as well as those under antiviral treatment.

Figure 1

Kinetics of liver enzyme levels and HSV DNA load in blood of five patients with HSV hepatitis starting on the day of hospitalization. Liver enzymes (right y-axis) determined were aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (APT), and lactate dehydrogenase (LDH). HSV load (left y-axis) represents HSV genome equivalent copies (geq) per ml. Start and end point of antiviral therapy are indicated with a horizontal bar. ACV iv, intravenous acyclovir; FOS, foscarnet; valACV, oral valacyclovir.

Figure 2

Liver enzyme levels correlate with HSV DNA load in plasma. Data shown are the HSV DNA load and corresponding liver enzyme levels recorded at the earliest time point of hospitalization of HSV hepatitis patients (n= 12; black symbols) and the peak levels of disease controls (n=20; white dots). The data represent the combination of HSV hepatitis patients recruited in Rotterdam (Netherlands; n=4, dots) and Seattle (n=4, triangles; partially described in references and 17), and HSV hepatitis patients described in reference (n=4, diamonds). The gray symbols represent data of the same HSV hepatitis patients during follow-up. The Spearman’s rank correlation test was used to determine the correlation between HSV DNA load and liver enzymes. Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transpeptidase; LDH, lactate dehydrogenase levels (LDH), APT, alkaline phosphatase; and Bil, bilirubin.