Clinical Course of Lamivudine Monotherapy in Patients with Decompensated Cirrhosis due to HBeAg negative chronic HBV infection

Manolakopoulos, Spilios; Karatapanis, Stylianos; Elefsiniotis, J.S.; Mathou, Nicoletta; Vlachogiannakos, Jiannis; Iliadou, Elissabet; Kougioumtzan, Anastasios; Economou, Michael; Triantos, Christos; Tzourmakliotis, Dimitrios; Avgerinos, Alec

doi:10.1046/j.1572-0241.2003.04021.x

Cited by 69 publications

(78 citation statements)

References 23 publications

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“…This was associated with a slow improvement in liver function in most patients, as measured by a decrease in the Child-Pugh score. Similar findings have been reported in several other studies (6)(7)(8). Yao et al showed that the rate of transplantation, time to transplantation, and survival were all improved in treated patients compared with a matched control cohort (6).…”

Section: S27supporting

confidence: 84%

Optimizing Management Strategies in Special Patient Populations

Sherman¹

2006

Am J Gastroenterology

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Section: S27supporting

confidence: 84%

Optimizing Management Strategies in Special Patient Populations

Sherman¹

2006

Am J Gastroenterology

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“…11,14,15 Lamivudine, which was the first agent used as longterm maintenance therapy in HBeAg-negative CHB since the late 1990s, is associated with high initial on-therapy remission rates, but with progressively increasing rates of viral resistance usually followed by biochemical breakthrough phenomena. [16][17][18] The recent introduction of ADV, an agent active against both wild and mutant lamivudine-resistant HBV strains, offered an effective therapeutic option for the increasing numbers of patients with resistance to lamivudine. However, data on the clinical efficacy and particularly on the incidence of major clinical events in patients under long-term antiviral therapy are rather limited.…”

mentioning

confidence: 99%

“…However, data on the clinical efficacy and particularly on the incidence of major clinical events in patients under long-term antiviral therapy are rather limited. Besides the initial partially conflicting results on the impact of emergence of YMDD HBV mutants under lamivudine, [17][18][19][20][21][22][23] cases of liver failure have only occasionally been described, mostly in patients with preexisting cirrhosis, 21 and hepatic decompensation was recently reported to develop in fewer than 1% of 998 patients with HBeAg-positive CHB treated with lamivudine for a median of 4 years. 24 The aim of this study was to determine the incidence of major events, such as death, HCC, and liver decompensation, among patients with HBeAg-negative CHB treated with long-term nucleos(t)ide analog therapy starting with lamivudine and to compare it with the same incidence in 2 historical cohorts of HBeAg-negative CHB patients, one treated with IFN␣ and the other remaining untreated.…”

mentioning

confidence: 99%

Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine

et al. 2005

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We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 ؎ 1.4 years and 2 historical similar cohorts: 1 treated with interferon-alfa (n ‫؍‬ 209) and 1 untreated (n ‫؍‬ 195). Virological or biochemical remission rate at 48 months under lamivudine was 34% or 36%, respectively, whereas adefovir was administered in 79 patients with virological-biochemical breakthroughs or no response. Of the lamivudinetreated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event-free survival was 93%. The major event-free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow-up, both survival and major event-free survival were independently associated with type of and response to treatment, being significantly better in patients under long-term antiviral therapy or interferon sustained responders than in interferon non-sustained responders or untreated cases (5-year survival: 96% or 98% vs. 88% or 90%, respectively). In conclusion, in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non-sustained responders or untreated patients. In such patients with advanced fibrosis, close follow-up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered. (HEPATOLOGY 2005;42:121-129.) H epatitis e antigen (HBeAg)-negative chronic hepatitis B (CHB) represents a rather late phase in the course of chronic hepatitis B virus (HBV) infection 1,2 usually associated with replication of HBV variants that are unable to produce HBeAg because of mutations either at the precore or basic core promoter region of the viral genome. 2,3 HBeAg-negative CHB is a potentially severe and progressive form of chronic liver disease with rare spontaneous remissions, frequent progression to cirrhosis, and increased risk of hepatocellular carcinoma (HCC). [4][5][6][7] The management of CHB has improved over the last years with the addition of lamivudine and more recently adefovir dipivoxil (ADV), but it is still suboptimal in achieving sustained off-therapy responses. [8][9][10][11] In particular in HBeAg-negative CHB, interferon-alfa (IFN␣), the first available effective therapeutic option in CHB, is the agent offering the higher chances for sustained-off therapy response ranging between 18% and 30%. 10-13 Conversely, both lamivudine and ADV, 2 oral, safe, and well-

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“…Furthermore, treatment with lamivudine is associated with histologic improvement not only in terms of necroinflammatory score but also in terms of fibrosis score after long-term treatment [24] . One advantage of lamivudine is that it can be used safely in patients with decompensated cirrhosis [3][4][5][6][7][8][9][10] . In contrast to IFN-α, lamivudine is well tolerated without any significant side effects even in patients with decompensated cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

“…Lamivudine is effective for controlling chronic hepatitis B and currently recommended as the first line of treatment for chronic active hepatitis B [1,2] . Even for patients with decompensated liver cirrhosis, lamivudine improves liver function and extends transplantation free intervals [3][4][5][6][7][8][9][10] . Since more than 10% of patients with chronic HBV infection are estimated to develop liver cirrhosis and may eventually suffer from decompensated liver cirrhosis or hepatocellular carcinoma, the role of lamivudine in the treatment of advanced liver disease caused by chronic HBV infection is large [11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: A case report

Suzuki

Yotsuyanagi²,

Okuse³

et al. 2007

WJG

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We present a case of fetal liver failure caused by the activation of lamivudine-resistant hepatitis B virus (HBV) nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decompensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase (ALT) decreased transiently. However, after the start of α-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtL80I/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtL80I/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

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Clinical Course of Lamivudine Monotherapy in Patients with Decompensated Cirrhosis due to HBeAg negative chronic HBV infection

Abstract: Lamivudine significantly improves liver function in HBeAg-negative decompensated cirrhosis. However, the development of the biochemical breakthrough due to YMDD mutants is associated with fatal outcome.

Cited by 69 publications

References 23 publications

Optimizing Management Strategies in Special Patient Populations

Optimizing Management Strategies in Special Patient Populations

Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term nucleos(t)ide analog therapy starting with lamivudine

Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: A case report

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