Longitudinal Changes in Serum HBV DNA Levels and Predictors of Progression During the Natural Course of HBeAg-negative Chronic Hepatitis B Virus Infection

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FULL TEXT: http://www.medscape.com/viewarticle/579284?src=mp & spon=20 & uac=31238BR

From Journal of Viral Hepatitis

Longitudinal Changes in Serum HBV DNA Levels and Predictors of Progression

During the Natural Course of HBeAg-negative Chronic Hepatitis B Virus Infection

Posted 09/10/2008

G. V. Papatheodoridis; N. Chrysanthos; E. Hadziyannis; E. Cholongitas; E. K.

Manesis

Summary and Introduction

Summary

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. rs 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 1 log10 occurring in many of them.

Introduction

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).[1,2] 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.[2] 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.[3-5] 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.[3-5]

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.[3-6] 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.[5-7] 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.

[Guest guest]

FULL TEXT: http://www.medscape.com/viewarticle/579284?src=mp & spon=20 & uac=31238BR

From Journal of Viral Hepatitis

Longitudinal Changes in Serum HBV DNA Levels and Predictors of Progression

During the Natural Course of HBeAg-negative Chronic Hepatitis B Virus Infection

Posted 09/10/2008

G. V. Papatheodoridis; N. Chrysanthos; E. Hadziyannis; E. Cholongitas; E. K.

Manesis

Summary and Introduction

Summary

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. rs 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 1 log10 occurring in many of them.

Introduction

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).[1,2] 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.[2] 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.[3-5] 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.[3-5]

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.[3-6] 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.[5-7] 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.