High TT virus load as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus‐related chronic liver disease

Abstract

The TT virus (TTV) load was estimated in sera obtained from 237 patients with hepatitis C virus (HCV)-related chronic liver disease including 42 patients with hepatocellular carcinoma (HCC), by real-time detection PCR using primers and a probe derived from the well-conserved untranslated region of the TTV genome, which can detect all known TTV genotypes. Of the 237 patients studied, 18 (8%) were negative for TTV DNA, 87 (37%) had low TTV viremia (1.3 x 10(2)-9.9 x 10(3) copies/ml), and 132 (56%) had high TTV viremia (1.0 x 10(4)-2.1 x 10(6) copies/ml). Various features were compared between the patients with high TTV load (n = 132) and those with no TTV viremia or low viral load (n = 105). High TTV viremia (> or =10(4) copies/ml) was significantly associated with higher age (P < 0.05), past history of blood transfusion (P < 0.001), complication of cirrhosis (P < 0.05) or HCC (P < 0.0005), lower HCV RNA titer (P < 0.05), and lower platelet count (P < 0.01). On multivariate logistic regression analysis, high TTV viral load was a significant risk factor for HCC (P < 0.05), independent from known risk factors such as complication of liver cirrhosis (P < 0.0001) and high age (> or =65 years, P < 0.05), among all 237 patients. Furthermore, high TTV viral load was an independent risk factor for HCC among the 90 cirrhotic patients (P < 0.05). These results suggest that a high TTV viral load is associated independently with the complication of HCC and may have prognostic significance in patients with HCV-related chronic liver disease, although whether high TTV viremia mediates the progression of HCV-related chronic liver disease remains to be defined.

Development of PCR Assays with Nested Primers Specific for Differential Detection of Three Human Anelloviruses and Early Acquisition of Dual or Triple Infection during Infancy

“…For comparison, previously reported PCR methods for detection of TTV DNA (52) and TTMV DNA (6,56) were also used.…”

Current and Future Prospects of Torque Teno Virus

“…The NS5A plays an important role in suppressing the Interferon-induced anti-viral response [147]. TTV co infection with HCV has been studied across the world but it is yet to be known that whether TTV is an "accidental visitor", "helper" or "responsible cause" for HCV associated liver damage [148].…”

Role of Hematopoietic Cells in the Maintenance of Chronic Human Torquetenovirus Plasma Viremia

“…Plasma loads of TTVs vary extensively in both healthy and diseased individuals, usually ranging between 10 3 and 10 7 DNA copies per ml of plasma. However, some patients, including those with selected inflammatory or neoplastic disorders, transplant recipients, and human immunodeficiency virus-infected individuals, have a tendency to carry especially high burdens of TTVs (1,6,13,(22)(23)(24).By studying the dynamics of TTV viremia in individuals treated with alpha interferon for hepatitis C, the kinetics of virus replication was found to be quite high, with numbers of virions released into plasma and cleared from it daily on the same order of magnitude as other chronic plasma viremiainducing viruses, such as the hepatitis B, hepatitis C, and human immunodeficiency viruses (16). Yet, due to considerable difficulties encountered in propagating TTVs in culture and in distinguishing the virions passively adsorbed onto the cells from the ones replicating inside cells, the tissue or tissues where these large numbers of TTV virions originate have yet to be established.…”

“…Plasma loads of TTVs vary extensively in both healthy and diseased individuals, usually ranging between 10 3 and 10 7 DNA copies per ml of plasma. However, some patients, including those with selected inflammatory or neoplastic disorders, transplant recipients, and human immunodeficiency virus-infected individuals, have a tendency to carry especially high burdens of TTVs (1,6,13,(22)(23)(24).…”