A new hepatitis C virus-like flavivirus in patients with cryptogenic liver disease associated with elevated GGT and alkaline phosphatase serum levels.

The intriguing co-infection of two flaviviruses (GBV-A and GBV-B) in tamarins and the recent discovery of another flavivirus (GBV-C/HGV) in humans raises the question of the relations between hepatitis C virus (HCV) and GBV-C/HGV. To address this issue the sera of 285 patients with liver disease (102 patients with cryptogenic and 183 with known forms of chronic liver disease) and 19 patients without liver disease were tested for HGV-RNA. GBV-C/HGV-RNA was detected by RT-PCR using primers encompassing 5'NC and NS5 regions and hybridization with specific biotinilated and radiolabelled probes. GBV-C/HGV RNA was found in 11 of 20 (55%) acute hepatitis C patients, in 13 of 117 (11.1%) patients with chronic hepatitis C, in 11 of 27 patients with a liver transplant (40.7%), one of 19 (5.3%) patients with chronic HBV infection, 15 out of 102 (14.7%) patients with cryptogenic liver disease and two out of 19 patients with inflammatory bowel disease. In cryptogenic patients, elevated serum gammaglutamyl transpeptidase (GGT, higher than twice the normal values) and alkaline phosphatase (ALP, above normal values) levels were significantly associated with GBV-C/HGV-RNA infection (P < 0.001). In conclusion GBV-C/HGV appears to be transmitted in humans by blood exposure and to be associated with liver disease in HCV co-infected patients and in a minority of patients with cryptogenic disease. The virus is only occasionally pathogenic for the liver and when liver damage is present; the association with the combined elevation of GGT and APH serum levels might represent a specific feature of the liver tropism of the agent.

Hepatitis G virus RNA in the serum of patients with elevated gamma glutamyl transpeptidase and alkaline phosphatase: a specific liver disease? [corrected].

We tested the sera of 67 consecutive patients for hepatitis G virus (HGV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). These patients (42 males and 25 females, median age 35 years, range 13-64 years) had liver disease of unknown aetiology and were without markers of hepatitis (A-E) viruses or signs of genetically determined, autoimmune, alcoholic or drug-induced liver disease. The controls in this study were 110 patients (50 females and 60 males, median age 45 years, range 9-65 years) with chronic hepatitis B virus (HBV) infection (19 patients) or hepatitis C virus (HCV) infection (91 patients). Ten of 67 (14.9%) patients with cryptogenic disease were positive for HGV RNA by at least three separate tests; HGV RNA was also detected in one of 19 (5.3%) hepatitis B surface antigen (HBsAg) carriers and in nine of 91 (16.6%) patients with antibody to HCV. These data suggest that HGV occurs as frequently in HCV-infected patients as in those with cryptogenic disease. Elevated serum gamma glutamyl transpeptidase (gamma-GT) (higher than twice the normal value) and alkaline phosphatase levels were found in eight of 10 (80%) HGV RNA positive patients and in six of 57 (10.5%) HGV RNA negative patients (P < 0.0001). Five (50%) HGV RNA positive patients had non-specific inflammatory bile duct lesions. A statistically significant difference was observed between HGV RNA positive and negative patients with chronic HBV or HCV infections (P < 0.029). Therefore, the spectrum of liver disease associated with HGV is wide, but a characteristic lesion of the bile duct leading to elevation of cholestatic enzymes might be specific for this virus.