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Sirs,

We read with great interest the randomised clinical trial of combination therapy with adefovir plus lamivudine for chronic hepatitis B (CHB) patients,[1] which demonstrated a clear benefit of combination therapy. A recent article has reviewed the different antiviral therapeutic options for patients with CHB.[2] Thus, abundant information about CHB therapy exists. Hence, we would like to draw attention to the absence of publications on the treatment of acute hepatitis B (AHB).

In our opinion, AHB continues to be of great importance, since it is a major cause of acute liver failure. There are very few studies dealing with AHB therapy, some of them with doubtful methodological quality, and all have used monotherapy with lamivudine. As expected, the number of patients included is small and only two of these studies were designed as randomised clinical trials (Table 1).

Table 1. Characteristics of the main studies on acute hepatitis B
 Study typeTreatmentPatients (ALF)INRBilirubin (mg/dL)Treatment duration (m)Mortality
  1. ALF, acute liver failure.

Schmilowitz- Weiss et al.3Time seriesLamivudine 100 mg/24h15 (5)4.5 ± 6.418 ± 6.83—620
Tillman  et al.8Historical cohortLamivudine 100—150 mg/24h17 (7)4.15 ± 2.1914.44 ± 7.77HBsAg  negative18
  No treatment203.91 ± 1.5919.18 ± 12.04 80
Kumar  et al.4Randomised clinical trialLamivudine 100 mg/24h31 (2)2 ± 0.8610.9 ± 5.73 0
  Placebo40 (1)1.89 ± 0.4112.3 ± 6.7  0
Miyake  et al.9Retrospective cohortLamivudine 100—150 mg/24h10 (10)8.730
  No treatment23 (23)10.7 74
Yu et al.5Randomised clinical trialLamivudine 100 mg/24h401.5 ± 0.1014.56 ± 3.42HBsAg  negative 8
  Placebo401.48 ± 0.1213.5 ± 3.65 25

The first prospective study dates from 2004, where Scmilowitz-Weiss et al.[3] treated 15 patients with severe AHB (INR >1.6, serum bilirubin levels >10 mg/dL or hepatic encephalopathy) with 100 mg of lamivudine, achieving a response rate of 86%. The first randomised clinical trial was carried out 3 years later and included a total of 71 patients with AHB (31 randomised to lamivudine for 3 months and 40 to placebo) and showed no biochemical or clinical benefit to lamivudine; the lack of response to therapy was observed in the subset of 47 patients of the study with the diagnosis of severe AHB.[4] By contrast, Yu et al.,[5] conducted a more recent clinical trial that included 80 AHB patients, and showed statistically significant differences in mortality (7.5% lamivudine vs. 25% placebo) and incidence of acute liver failure (20% vs. 42.5%). The study also showed that the sooner the treatment is initiated, the better the results obtained. In two additional studies,[6, 7] patients with severe acute or fulminant hepatitis B were treated with lamivudine, demonstrating the safety and efficacy of this antiviral drug, with a capacity for improving the prognosis of these patients.

On the basis of these studies, it appears reasonable to recommend antiviral treatment for patients with severe AHB, as it improves survival rates and reduces the incidence of acute liver failure. Despite the absence of studies with tenofovir or entecavir, these are the drugs that could be recommended by major clinical practice guidelines.[8, 9]

Acknowledgement

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  2. Acknowledgement
  3. References

Declaration of personal and funding interests: None.

References

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  3. References