Table 1. Baseline characteristics of patients receiving NAs for AE of CHB.
| Year Ref. | Area | No. of subjects | No. and type of controls | Key inclusion criteria | Key exclusion criteria | No. and definition of hepatic decompensation | ALT at entry | No. of liver cirrhosis | No. of HBeAg+ | Genotype A−B−C−B+C | Duration treatment (months) |
| Studies using LAM | |||||||||||
| 2001[8] † | Japan | 10 | NA | jaundice, PT<60% | HAV, HCV, HDV, HIV co-infections, AIH | 3 HE and severe coagulopathy | 300 U/L | 4 | 8 | NA | 15 |
| 2002[15] | Taiwan | 31 | NA | HBeAg+, naïve | LC | NA | 5×ULN | 0 | NA | NA | 9.5 |
| 2002[17] †† | Hong Kong | 28 | 18 historical controls | jaundice | HAV, HCV, HDV, HEV co-infections, HE | 0 HE | 5×ULN | NA | 16 | NA | 1–34 |
| 2003[6] * | Taiwan | 60 | 31 historical controls | naïve, IgM anti - HBc - | HAV, HCV, HDV co-infections, alcohol abuse | 0 prolongation of PT>3 s, jaundice, ascites and/or features of HE | 300 U/L | 19 | 23 | NA | 1.5 (1–12) |
| 2003[16]♂ | Japan | 21 | 63 non AE | TB≥3.0 mg/dL, PT<75% | HAV, HCV, HDV co-infections, ALD, metabolic disease | NA | 300 U/L | 3 | 21 | *-*-19-* | 23 |
| 2005[7] | Japan | 25 | 25 historical controls | TB≥3.0 mg/dL, PT<70%,naïve | AIH, ALD, DM, liver tumor, hepatotoxins exposure | NA | 10×ULN | 4 | 21 | 2-23-0-0 | 25 |
| 2006[19] ** | Taiwan | 75 | NA | HBV DNA+, YMDD- | HCV, HDV, HIV co-infections | 0 ascites, jaundice, prolonged PT | 5×ULN | 19 | 75 | 0-39-35-1 | 18 |
| 2006[18] | Hong Kong | 32 | NA | TB≥30 ummol/L, naïve | HAV, HCV, HDV, HEV co-infections, HCC, AIH, ALD | NA | 10×ULN | 7 | 0 | 0-23-9-0 | 33 |
| 2008[13] ‡ | Hong Kong | 45 | 31 non AE | TB≥3 ULN, naïve | HAV, HCV, HEV co-infections, HCC | NA | 10×ULN | 15 | 45 | 1-30-8-2 | 34 |
| 2008[20]♂♂ | Taiwan | 253 | NA | ALT≥5 ULN | HCV, HDV, HIV co-infections, autoimmune liver disease | 0 TB>2 mg/dl or prolongation of PT>3 s | 5×ULN | 9 | 253 | *-73-31-* | 12–18 |
| 2009[14] | Taiwan | 102 | 52 untreated controls | HBV DNA + | HCV, HDV, HIV co-infections, pregnancy | 0 prolongation of PT over 3 s, TB≥2.0 mg/dl | 5×ULN | NA | 102 | 0-45-46-11 | 18 |
| 2011[11] | Taiwan | 146 | NA | HBeAg +, naïve, Age>18 years | HAV, HCV, HDV co-infections, HCC | 62 prolongation of PT>3 s, TB≥2 mg/dL | 5×ULN | 7 | 146 | 0-104-35-0 | 19.1 |
| Year Ref. | Area | No. of subjects | No. and type of controls | Key inclusion criteria | Key exclusion criteria | No. and definition of hepatic decompensation | ALT at entry | No. of liver cirrhosis | No. of HBeAg+ | Genotype A-B-C-B+C | Duration treatment (months) |
| Studies using LAM | |||||||||||
| 2011[10]○ | Hong Kong | 117 | 36 ETV | TB>45 µmol/L, naïve | HAV, HCV, HEV co-infections, HCC, HE, biliary obstruction | NA | 10×ULN | 25 | 55 | NA | 12 |
| 2012[21] | Japan | 24 | 10 ETV | HBV DNA≥4.5 log IU/mL, naïve | HAV, HCV, HDV, HEV, HIV co-infections, HCC | NA | 10×ULN | 2 | 18 | NA | 12 |
| Studies using ETV | |||||||||||
| 2011[10] | Hong Kong | 36 | 117 LAM historical controls | TB>45 µmol/L, naïve | HAV, HCV, HEV co-infections, HCC, HE, biliary obstruction | NA | 10×ULN | 5 | 13 | NA | 12 |
| 2012[21] | Japan | 10 | 24 LAM historical controls | HBV DNA≥4.5 log IU/mL, naïve | HAV, HCV, HDV, HEV, HIV co-infections, HCC | NA | 10×ULN | 0 | 4 | NA | 12 |
| Studies using LDT | |||||||||||
| 2010[9] | China | 40 | 40 non AE | HBV DNA>5 log copies/mL, naïve | HCV, HDV, HIV co-infections, HCC, LC, ALD | NA | 10–20×ULN | 0 | 40 | NA | 12 |
AIH, autoimmune hepatitis; ALD, alcoholic liver disease; ALT, alanine aminotransferase; DM, diabetes mellitus; ETV, entecavir; HAV, hepatitis A virus; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDV, hepatitis D virus; HE, hepatic encephalopathy; HEV, hepatitis E virus; HIV, Human immunoddficiency virus; LAM, lamivudine; LDT, telbivudine; NA, not available; NAs, nucleos(t)ide analogues; PT, prothrombin time; TB, serum total biliruin; ULN, upper limit of normal.
Of 10 enrolled, 6 patients with dose of LAM 300 mg/day, 4 had undergone interferon or corticosteroid treatment for liver disease.
Patients had comorbid illnesses in both groups.
Dose of LAM 150 mg/day; otherwise the doses of drugs were as follows: LAM 100 mg/day, ETV 0.5 mg/day, LDT 600 mg/day.
IgM anti-HBc seronegative patients were recruited as control group.
Patients without AE were recruited as control group, and subset data on 45 patients with AE were abstracted.
♂15 patients with SAE were treated with LAM 300 mg/day for only a short term at the start of therapy.
♂♂ 38.3% and 4.8% of patients had exposed to LAM and had definitely LAM resistance before enrolment, 104 were examined for HBV genotypes.
○ Detection limit for HBV DNA was 100 copies/ml for calculation.