Limits...
Long-term clinical outcomes in cirrhotic chronic hepatitis B patients treated with tenofovir disoproxil fumarate for up to 5 years.

Buti M, Fung S, Gane E, Afdhal NH, Flisiak R, Gurel S, Flaherty JF, Martins EB, Yee LJ, Dinh P, Bornstein JD, Mani Subramanian G, Janssen HL, George J, Marcellin P - Hepatol Int (2015)

Bottom Line: One HBeAg-negative patient had HBsAg loss.This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status.Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients.

View Article: PubMed Central - PubMed

Affiliation: Servei de Medicina Interna-Hepatologia, Hospital General Universitari Vall d'Hebron, Pg. Vall d'Hebron, 119-129, 08035, Barcelona, Spain, mbuti@vhebron.net.

ABSTRACT

Background: Phase 3 clinical studies have shown that long-term treatment with tenofovir disoproxil fumarate (TDF) can suppress hepatitis B viral load and promote significant fibrosis regression and cirrhosis reversal in a majority of treated chronic hepatitis B (CHB) patients. This retrospective analysis investigated the impact of baseline cirrhosis status on virologic, serologic, and histologic outcomes in patients treated with TDF.

Methods: Patients enrolled in studies GS-US-174-0102 and GS-US-174-0103 who had baseline liver biopsy-diagnosed cirrhosis and entered the open-label phase of the studies were included in the virologic and serologic analyses. Patients (both HBeAg positive and negative) with paired liver biopsies at baseline and 5 years (N = 348) were included in a histologic analysis.

Results: After 5 years on study, comparing patients with and without baseline cirrhosis, respectively: 99.2 and 98.0% achieved virologic response (hepatitis B viral load < 69 IU/ml) (p = 0.686); 79.7 and 81.9% had normal serum levels of alanine aminotransferase (p = 0.586); 4.0 and 1.2% developed hepatocellular carcinoma (p = 0.044). In HBeAg-positive patients with and without baseline cirrhosis, HBsAg loss occurred in 14.4 and 8.3% of patients, respectively (p = 0.188). One HBeAg-negative patient had HBsAg loss.

Conclusions: This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status. Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients.

No MeSH data available.


Related in: MedlinePlus

Histologic changes at year 5 among patients with and without baseline cirrhosis. Among 348 patients with paired biopsies at year 5 of treatment, 96 had baseline cirrhosis and 252 had no baseline cirrhosis. ap value calculated using Fisher’s exact test. Necroinflammatory response (Knodell scores) at year 5. Ninety-four percent of patients in the cohort with baseline cirrhosis and 91 % in the cohort with no baseline cirrhosis experienced improvement in the Knodell necroinflammatory score. Improvement was defined as a decrease in score of ≥1 unit; worsening was defined as an increase in score of ≥1 unit
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4387268&req=5

Fig2: Histologic changes at year 5 among patients with and without baseline cirrhosis. Among 348 patients with paired biopsies at year 5 of treatment, 96 had baseline cirrhosis and 252 had no baseline cirrhosis. ap value calculated using Fisher’s exact test. Necroinflammatory response (Knodell scores) at year 5. Ninety-four percent of patients in the cohort with baseline cirrhosis and 91 % in the cohort with no baseline cirrhosis experienced improvement in the Knodell necroinflammatory score. Improvement was defined as a decrease in score of ≥1 unit; worsening was defined as an increase in score of ≥1 unit

Mentions: The 5-year liver biopsy was obtained in 96 (63.2 %) of 152 patients with baseline cirrhosis and 252 (52.3 %) of 482 patients without cirrhosis. Among these, 93.8 % of patients with cirrhosis achieved an improvement in the Knodell necroinflammatory score of ≥1 unit compared with 90.5 % of patients without cirrhosis (p = 0.746) (Fig. 2). Only two (0.8 %) patients, both initially without cirrhosis, experienced a worsening of the Knodell necroinflammatory score. All other patients had no change in the necroinflammatory score.Fig. 2


Long-term clinical outcomes in cirrhotic chronic hepatitis B patients treated with tenofovir disoproxil fumarate for up to 5 years.

Buti M, Fung S, Gane E, Afdhal NH, Flisiak R, Gurel S, Flaherty JF, Martins EB, Yee LJ, Dinh P, Bornstein JD, Mani Subramanian G, Janssen HL, George J, Marcellin P - Hepatol Int (2015)

Histologic changes at year 5 among patients with and without baseline cirrhosis. Among 348 patients with paired biopsies at year 5 of treatment, 96 had baseline cirrhosis and 252 had no baseline cirrhosis. ap value calculated using Fisher’s exact test. Necroinflammatory response (Knodell scores) at year 5. Ninety-four percent of patients in the cohort with baseline cirrhosis and 91 % in the cohort with no baseline cirrhosis experienced improvement in the Knodell necroinflammatory score. Improvement was defined as a decrease in score of ≥1 unit; worsening was defined as an increase in score of ≥1 unit
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4387268&req=5

Fig2: Histologic changes at year 5 among patients with and without baseline cirrhosis. Among 348 patients with paired biopsies at year 5 of treatment, 96 had baseline cirrhosis and 252 had no baseline cirrhosis. ap value calculated using Fisher’s exact test. Necroinflammatory response (Knodell scores) at year 5. Ninety-four percent of patients in the cohort with baseline cirrhosis and 91 % in the cohort with no baseline cirrhosis experienced improvement in the Knodell necroinflammatory score. Improvement was defined as a decrease in score of ≥1 unit; worsening was defined as an increase in score of ≥1 unit
Mentions: The 5-year liver biopsy was obtained in 96 (63.2 %) of 152 patients with baseline cirrhosis and 252 (52.3 %) of 482 patients without cirrhosis. Among these, 93.8 % of patients with cirrhosis achieved an improvement in the Knodell necroinflammatory score of ≥1 unit compared with 90.5 % of patients without cirrhosis (p = 0.746) (Fig. 2). Only two (0.8 %) patients, both initially without cirrhosis, experienced a worsening of the Knodell necroinflammatory score. All other patients had no change in the necroinflammatory score.Fig. 2

Bottom Line: One HBeAg-negative patient had HBsAg loss.This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status.Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients.

View Article: PubMed Central - PubMed

Affiliation: Servei de Medicina Interna-Hepatologia, Hospital General Universitari Vall d'Hebron, Pg. Vall d'Hebron, 119-129, 08035, Barcelona, Spain, mbuti@vhebron.net.

ABSTRACT

Background: Phase 3 clinical studies have shown that long-term treatment with tenofovir disoproxil fumarate (TDF) can suppress hepatitis B viral load and promote significant fibrosis regression and cirrhosis reversal in a majority of treated chronic hepatitis B (CHB) patients. This retrospective analysis investigated the impact of baseline cirrhosis status on virologic, serologic, and histologic outcomes in patients treated with TDF.

Methods: Patients enrolled in studies GS-US-174-0102 and GS-US-174-0103 who had baseline liver biopsy-diagnosed cirrhosis and entered the open-label phase of the studies were included in the virologic and serologic analyses. Patients (both HBeAg positive and negative) with paired liver biopsies at baseline and 5 years (N = 348) were included in a histologic analysis.

Results: After 5 years on study, comparing patients with and without baseline cirrhosis, respectively: 99.2 and 98.0% achieved virologic response (hepatitis B viral load < 69 IU/ml) (p = 0.686); 79.7 and 81.9% had normal serum levels of alanine aminotransferase (p = 0.586); 4.0 and 1.2% developed hepatocellular carcinoma (p = 0.044). In HBeAg-positive patients with and without baseline cirrhosis, HBsAg loss occurred in 14.4 and 8.3% of patients, respectively (p = 0.188). One HBeAg-negative patient had HBsAg loss.

Conclusions: This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status. Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients.

No MeSH data available.


Related in: MedlinePlus