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"The Long-Term Outcome of HBeAg-negative Patients with Cirrhosis Treated with Lamivudine Monotherapy: a 5 year prospective cohort"
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Reported by Jules Levin
P Lampertico (Div of Hepatology and Hygiene, IRCC8 Maggiore Hospital, Milan, Italy) reported results from this study in an oral presentation at EASL (April 14-18, 2004, Berlin, Germany). Here is his report.
BACKGROUND
HBeAg negative cirrhosis is a severe progressive disease associated with a high risk of clinical decompensation and hepatocellular carcinoma. Suppression of HBV replication is the only practical approach for increasing survival rates, as has already been demonstrated in patients responding to interferon alpha.
The aim of this study was to assess the safety and eficacy of long-term treatment of patients with HBeAg-negative cirrhosis with lamivudine monotherapy.
This was an open-label, prospective cohort study of 84 patients with HBeAg-, HBV DNA+ cirrhosis (1997-2000). Patients received lamivudine 100 mg/day continuously. Followup was 48 months. Assays used: HBV DNA (LLD: 7 x 105 eq/ml, bDNA; <200cp/ml, Cobas Amplicor. Genotype (direct sequencing). Lamivudine resistance (YMDD -INNO-LIPA Innogenetics). Monitoring was conducted t baselin& every two months with abdominal ultrasound and AFP every 6 months.
PRE-TREATMENT DEMOGRAPHIC AND VIROLOGICAL CHARACTERISTICS
Age: 55
Men: 73
ALT, IU/L: 127
HBV DNA, Meq/ml: 112
IgM anti-HBc, index: 0.61
Genotype D: 77 (91%)
Childs Pugh A/B: 77 (92%)
AFP >7 ng/ml: 35 (41%)
UNDETECTABLE SERUM HBV DNA AFTER 6 MONTHS OF TREATMENT
--95% of patients had <7 x 105eq/ml
--68% of patients <2 x 102 cp/ml (PCR)
CUMULATIVE PROBABILITY of DEVELOPING GENOTYPIC RESISTANCE after 5 yrs: 82%
CLINICAL RESISTANCE: 55%
PRE-TREATMENT CHARACTERISTICS ASSOCIATED WITH THE DEVELOPMENT OF CLINICAL RESISTANCE
| Responders | Resistant | | n=50 | n=34 | | Age | 54 | 56 | | Men | 44 (88%) | 29 (85%) | | ALT - IU/L | 100 | 125 | | HBV-DNA log cp/ml | 6.4 | 6.0 | | IgM anti-HBc; Index | 0.62 | 0.57 | | Genotype D: | 47 (94%) | 30 (88%) | | Previous IFN therapy: | 17 (34%) | 14 (41%) | | BMI: | 25 | 25 |
Clinical decompensation in 77 patients with compensated liver disease at baseline according to clinical resistance occurred in none of responders but in 7 lamivudine-resistant cirrhotics (0% vs 32%, p<0.01) whereas hepatocellular carcinoma occurred in both groups at similar rates (responders:30%, n=15; resistant: 27%, n=9).
OUTCOME ACCORDING TO CLINICAL RESISTANCE
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Outcome
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All
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Responders
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Resistant
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p-value
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n=54
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n=50
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n=34
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Dead
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4(5%)
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0
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4(12%)
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Rescue ADV
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6(7%)
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0
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6(18%)
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OLT or listed
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15(18%)
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10(20%)
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5(15%)
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OVERALL
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25(30%)
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10(20%)
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15(44%)
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0.01
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SUMMARY by authors
The 5-yr cumulative probability of developing genotypic and clinical resistance to lamivudine was 82% and 55%, respectively.
While clinical decompensation was strictly dependent upon lamivudine resistance, HCC occurred with similar frequency in both virological responders and resistant patients.
Liver related deaths or rescue therapy, i.e. OLT and ADV for decompensated patients, occurred less frequently in responders than in resistant patients.
CONCLUSION by authors: In HBeAg-negative cirrhotics, persistent suppression of HBV replication by lamivudine was associated with prevention of clinical decompensation but not hepatocellular carcinoma.
Five-year administration of lamivudine monotherapy led to prolonged control of viral replication in approximately one third of HBeAg-negative cirrhotics, but complete suppression in only 10%. Lamivudine resistance was associated to increased risk of liver-related complications, particularly HCC
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