SOFIA-LTT Study: A Study of Intermittent Long Term Treatment With PEGASYS (Peginterferon Alfa-2a (40KD)) in Patients With HBeAg Negative Chronic Hepatitis B (CHB).

Stable virological response is serum Hepatitis B virus deoxyribonucleic acid (HBV DNA) \<20 000 copies/ml during the treatment (after each 12 weeks) and after the follow-up period (24 weeks after the last treatment period).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

Fibrosis-4 (FIB-4) and Aspartate Aminotransferase to Platelet Ratio Index (APRI) are non-invasive scoring systems, which are calculated on the basis of laboratory tests that indicates the level of liver fibrosis. The APRI scores are calculated based on Aspartate Aminotransferase (AST) levels and platelet counts whereas FIB-4 scores are calculated based on platelets, ALT, AST and age. For APRI, the scores are interpreted as ≤ 0.5 is 81% sensitive and 50% specific for a diagnosis of significant fibrosis in chronic hepatitis C (CHC), where as a cut-off \> 1.5 is 35% sensitive and 91% specific for the diagnosis of significant fibrosis. The majority of biomarker panels will produce inconclusive results for a proportion of participants falling within the indeterminate range (between 0.5 and 1.5) for a specific fibrosis end-point. For FIB-4, the scores are interpreted as FIB-4 score of \< 1.45: absence of cirrhosis, FIB-4 score of 1.45 to 3.25: inconclusive, FIB-4 score \> 3.25: cirrhosis.

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The laboratory parameters included bilirubin indirect and bilirubin direct. All laboratory parameters were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The blood glucose was measured for change from baseline. All blood glucose values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The blood urea was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The clinical chemistry parameters included alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP). All laboratory parameters were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The creatinine and uric acid values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

An early decrease in HBsAg from baseline to Weeks 12 or 24 has been identified as further on-treatment predictor for sustained HBsAg clearance and virological response in HBeAg negative participants.

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation. Data of participants available at the time of the assessment were included in the analysis.

The hematology parameters included erythrocytes, leucocytes, basophils, eosinophils, lymphocytes, monocytes, thrombocytes. All laboratory parameters were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The hemoglobin values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The clinical chemistry parameters included indirect protein and albumin. All laboratory parameters were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and no intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The TSH was planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The Triiodothyronine (T3) and thyroxine (T4) values were planned to be calculated as arithmetic mean by treatment groups (PEGASYS and No Intervention).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

The development of antibodies against HBsAg is known as HBsAg seroconversion. It signifies clearance of HBsAg and resolution of the chronic infection. НBsAg seroconversion is the final goal of anti-hepatitis B virus treatment and it is closest to the definition of cure but in practice it is very rare in HBeAg-negative chronic hepatitis B (CHB).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation. Data of participants available at the time of the assessment were included in the analysis. Only participants with HBsAg clearance were analyzed.

HBV DNA level, or viral load, is an indicator of viral replication. Higher HBV DNA levels are usually associated with an increased risk of liver disease and hepatocellular carcinoma. HBV DNA level typically falls in response to effective antiviral treatment.

Time frame: Up to Week 108

Population: Safety population included all randomized participants who passed during at least one treatment period and had at least one efficacy and safety evaluation. HBV DNA levels below lower limit for significant quantity were not studied for no intervention arm participants.

Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.

All participants who achieved virological response (serum HBV DNA \< 20 000 copies/ml) and biochemical response (stable normalization of their alanine transaminase \[ALT\]) during the treatment cycle (after each 12 weeks) and after the follow-up period (24 weeks after the last treatment period).

Time frame: Up to Week 108

Population: Safety population included all the randomized participants who passed during at least one treatment period, and had at least one efficacy and safety evaluation.