Lactic Acidosis During Entecavir(ETV)Treatment
Condition: Lactic Acidosis
MeSH terms: Acidosis; Acidosis, Lactic
Intervention: entecavir, lamivudine
Intervention description: entecavir: 0.5mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.
lamivudine: 100mg/day p.o until development of lactic acidosis, OLT, death, or improvement of hepatic or renal function to MELD score less than 18 and and participants will be followed for the duration of hospital stay, an expected average of 8 weeks.
Intervention MeSH terms: Lamivudine; Entecavir
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: lactic acidosis; entecavir; lamivudine

Summary:

      The purpose of this study is to investigate whether entecavir treatment increases the
      incidence of lactic acidosis compared to another nucleoside/nucleotide reverse transcriptase
      inhibitors (NRTI), lamivudine, and/or no NRTI treatment, in patients with cirrhosis or
      hepatic failure whose Model for End stage Liver Disease (MELD) scores are over 18.
    

Eligibility criteria:

        1. for ETV or LAM group

             Inclusion criteria:

               -  18 and more than 18 years, and less than 65 years

               -  HBV-related liver cirrhosis or acute-on-chronic liver failure

               -  Prior documentation of chronic HBV infection at least 6 months before
                  randomization

               -  MELD score 18 and more than 18

               -  Venous blood lactate level 2 and less than 2 mmol/L

             Exclusion criteria:

               -  Age of 65 or older, or younger than 18

               -  Patients with acute hepatitis B including acute liver failure

               -  Acute-on-chronic liver failure precipitated by acute hepatitis A or acetaminophen
                  intoxication

               -  MELD score less than 18

               -  entecavir, lamivudine, telbivudine, clevudine, adefovir or tenofovir treatment
                  continued longer than 3 months before entry.

               -  Evidence of genotypic or virological resistance to lamivudine, clevudine,
                  telbivudine, or adefovir

               -  Patients with elevated venous blood lactate levels more than 2 mmol/L

               -  Recent episodes of active infection, hypotension (systolic blood pressure less
                  than 90 mmHg), gastrointestinal or other active bleeding within 2 weeks before
                  entry

               -  Any alcohol intake within 2 weeks before entry

               -  Recent use of acetaminophen, epinephrine, metformin, iron, isoniazid, propofol,
                  salicylate, sulfasalazine, or valproic acid within 2 weeks before entry. Use of
                  lactulose is permitted.

               -  Presence of hepatocellular carcinoma. Patients with hepatocellular carcinoma
                  meeting the Milan criteria can be permitted.

               -  Any cancer other than hepatocellular carcinoma except cervical carcinoma in situ,
                  treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any
                  cancer curatively treated at least 3 years prior to entry is permitted.

               -  Patients with HIV infection

               -  Female patients in pregnancy

          2. for no NRTI group

        Inclusion criteria:

          -  Age of 65 or older, or younger than 18

          -  Liver cirrhosis or acute-on-chronic liver failure not related with HBV

          -  MELD score 18 and more than 18

          -  Venous blood lactate level 2 and less than 2 mmol/L

        Exclusion criteria:

          -  Age of 65 or older, or younger than 18

          -  Patients with positive HBsAg or IgM anti-HBc

          -  Acute-on-chronic liver failure precipitated by acute hepatitis A or acetaminophen
             intoxication

          -  MELD score less than 18

          -  Patients with elevated venous blood lactate levels more than 2 mmol/L

          -  Recent episodes of active infection, hypotension (systolic blood pressure less than 90
             mmHg), gastrointestinal or other active bleeding within 2 weeks before entry

          -  Any alcohol intake within 2 weeks before entry

          -  Recent use of acetaminophen, epinephrine, metformin, iron, isoniazid, propofol,
             salicylate, sulfasalazine, or valproic acid within 2 weeks before entry. Use of
             lactulose is permitted.

          -  Presence of hepatocellular carcinoma. Patients with hepatocellular carcinoma within
             Milan criteria can be permitted.

          -  Any cancer other than hepatocellular carcinoma except cervical carcinoma in situ,
             treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any
             cancer curatively treated at least 3 years prior to entry is permitted.

          -  Patients with HIV infection

          -  Female patients in pregnancy