Longitudinal Changes in Serum HBV DNA Levels
Longitudinal Changes in Serum HBV DNA Levels
We evaluated the longitudinal changes of viraemia and predictors of progression in a prospectively followed cohort of 150 untreated patients with HBeAg-negative chronic hepatitis B virus (HBV) infection. According to the first year of follow-up, 85 patients were classified into inactive carrier state and 65 into chronic hepatitis B (CHB). Serum HBV DNA levels were determined at baseline in all patients, at year-1 in carriers or last pretherapy visit in CHB patients and during alanine aminotransferase (ALT) elevations in carriers progressing to CHB. HBV DNA levels at any occasion were ≥80, ≥2000 or ≥20 000 IU/mL in 81%, 23% or 0% of carriers and 100%, 95% or 83% of CHB patients. The cumulative progression rate from carrier to CHB was 11%, 16%, 24% at 2-, 3-, 4 years and was independently associated with higher baseline ALT (always within traditional normal range) and baseline HBV DNA ≥2000 or ≥5000 IU/mL. In 12 carriers progressed to CHB, HBV DNA increased by >1 log10 IU/mL. During 7.5 months of median follow-up, HBV DNA change ≥1 log10 IU/mL was observed in 49% of CHB patients. In conclusion, serum HBV DNA levels are detectable in the majority of inactive HBV carriers exceeding 2000 IU/mL in only 23% and 20 000 IU/mL in none of them. Carriers have approximately 15% 3-year risk of progression to CHB, which is associated with higher baseline ALT and viraemia ≥2000-5000 IU/mL, and thus should be closely followed. Approximately 20% of HBeAg-negative CHB patients have HBV DNA <20 000 IU/mL with fluctuations >1 log10 occurring in many of them.
The clinical spectrum of HBeAg-negative chronic hepatitis B virus (HBV) infection may range from the biochemically and histologically inactive chronic HBsAg carrier state to active chronic hepatitis with or without cirrhosis and often with hepatocellular carcinoma (HCC). The differential diagnosis between inactive chronic HBsAg carriers and patients with HBeAg-negative chronic hepatitis B (CHB) is mandatory, as the former need just to be followed up regularly, while the latter usually require therapeutic intervention. As both groups share the same serological profile (HBsAg positive, HBeAg negative and usually anti-HBe positive), their definitions are based on alanine (ALT) with or without aspartate (AST) aminotransferase, serum HBV DNA levels and perhaps liver histological changes. In particular, HBeAg-negative patients who maintain persistently normal ALT/AST and low viraemia levels are considered to be inactive chronic HBsAg carriers and to have no indication for liver biopsy. On the other hand, the diagnosis of HBeAg-negative CHB is straightforward even without a liver biopsy in cases with increased ALT/AST activity, high serum HBV DNA levels and no other cause of liver disease. However, the differential diagnosis may not be simple in HBeAg-negative patients with normal ALT/AST activity and/or low serum HBV DNA levels, as the optimal frequency of ALT/AST determinations and the cut-off level between high and low viraemia have not been clearly defined. Moreover, strong relevant longitudinal data are lacking, whereas the probability of progression from the inactive carrier state to HBeAg-negative CHB and its association with changes of viraemia levels have not been adequately studied.
In this study, we evaluated the longitudinal changes of serum HBV DNA levels as well as potential predictors of progression in a well defined, prospectively followed cohort of untreated patients with HBeAg-negative chronic HBV infection.
We evaluated the longitudinal changes of viraemia and predictors of progression in a prospectively followed cohort of 150 untreated patients with HBeAg-negative chronic hepatitis B virus (HBV) infection. According to the first year of follow-up, 85 patients were classified into inactive carrier state and 65 into chronic hepatitis B (CHB). Serum HBV DNA levels were determined at baseline in all patients, at year-1 in carriers or last pretherapy visit in CHB patients and during alanine aminotransferase (ALT) elevations in carriers progressing to CHB. HBV DNA levels at any occasion were ≥80, ≥2000 or ≥20 000 IU/mL in 81%, 23% or 0% of carriers and 100%, 95% or 83% of CHB patients. The cumulative progression rate from carrier to CHB was 11%, 16%, 24% at 2-, 3-, 4 years and was independently associated with higher baseline ALT (always within traditional normal range) and baseline HBV DNA ≥2000 or ≥5000 IU/mL. In 12 carriers progressed to CHB, HBV DNA increased by >1 log10 IU/mL. During 7.5 months of median follow-up, HBV DNA change ≥1 log10 IU/mL was observed in 49% of CHB patients. In conclusion, serum HBV DNA levels are detectable in the majority of inactive HBV carriers exceeding 2000 IU/mL in only 23% and 20 000 IU/mL in none of them. Carriers have approximately 15% 3-year risk of progression to CHB, which is associated with higher baseline ALT and viraemia ≥2000-5000 IU/mL, and thus should be closely followed. Approximately 20% of HBeAg-negative CHB patients have HBV DNA <20 000 IU/mL with fluctuations >1 log10 occurring in many of them.
The clinical spectrum of HBeAg-negative chronic hepatitis B virus (HBV) infection may range from the biochemically and histologically inactive chronic HBsAg carrier state to active chronic hepatitis with or without cirrhosis and often with hepatocellular carcinoma (HCC). The differential diagnosis between inactive chronic HBsAg carriers and patients with HBeAg-negative chronic hepatitis B (CHB) is mandatory, as the former need just to be followed up regularly, while the latter usually require therapeutic intervention. As both groups share the same serological profile (HBsAg positive, HBeAg negative and usually anti-HBe positive), their definitions are based on alanine (ALT) with or without aspartate (AST) aminotransferase, serum HBV DNA levels and perhaps liver histological changes. In particular, HBeAg-negative patients who maintain persistently normal ALT/AST and low viraemia levels are considered to be inactive chronic HBsAg carriers and to have no indication for liver biopsy. On the other hand, the diagnosis of HBeAg-negative CHB is straightforward even without a liver biopsy in cases with increased ALT/AST activity, high serum HBV DNA levels and no other cause of liver disease. However, the differential diagnosis may not be simple in HBeAg-negative patients with normal ALT/AST activity and/or low serum HBV DNA levels, as the optimal frequency of ALT/AST determinations and the cut-off level between high and low viraemia have not been clearly defined. Moreover, strong relevant longitudinal data are lacking, whereas the probability of progression from the inactive carrier state to HBeAg-negative CHB and its association with changes of viraemia levels have not been adequately studied.
In this study, we evaluated the longitudinal changes of serum HBV DNA levels as well as potential predictors of progression in a well defined, prospectively followed cohort of untreated patients with HBeAg-negative chronic HBV infection.
Source...