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 Table of Contents    
REVIEW ARTICLE  
Year : 2009  |  Volume : 6  |  Issue : 1  |  Page : 116-130
Management of HBV-related cirrhosis: Role of nucleoside analogs


Department of Gastroenterology, Stanley Medical College Hospital, Chennai, India

Click here for correspondence address and email

Date of Web Publication19-Feb-2011
 

   Abstract 

In the management of HBV related cirrhosis of the liver, viral suppression with safe and effective antiviral agents is essential. Besides, antiviral therapy for long term use in cirrhotics should be safe and affordable with low risk of drug resistance. Treatment of compensated HBV cirrhosis can diminish the risk of hepatic decompensation and progression to hepatocellular carcinoma [HCC]. Regression of fibrosis and reversal of cirrhosis have also been reported with antiviral therapy. Further, in decompensated cirrhosis, although liver transplantation is considered as the definitive therapy, inhibition of viral replication before transplantation can delay the need for liver transplant and also prevent HBV recurrence in the post-transplantation period. These patients while on antiviral therapy need close monitoring for viral resistance and adverse events, besides continued surveillance for HCC. This article reviews the literature on the role of nucleoside analogues in the management of HBV related chronic liver disease.

Keywords: Cirrhosis, HBV, Hepatitis B virus, hepatocellular carcinoma, nucleoside and nucleotide analogues

How to cite this article:
Mohan P, Jayanthi V. Management of HBV-related cirrhosis: Role of nucleoside analogs. Hep B Annual 2009;6:116-30

How to cite this URL:
Mohan P, Jayanthi V. Management of HBV-related cirrhosis: Role of nucleoside analogs. Hep B Annual [serial online] 2009 [cited 2020 Jun 2];6:116-30. Available from: http://www.hepatitisbannual.org/text.asp?2009/6/1/116/76909



   Introduction Top


Individuals infected with hepatitis B virus (HBV) infection are at an increased risk of developing chronic hepatitis, liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). [1] World over, approximately, 350 million people are infected with HBV and the number of deaths due to HBV infection is approximately 1 million per year. [2]

The introduction of oral nucleoside/tide antiviral agents has revolutionized the management of HBV-related cirrhosis. Today, it is the recommended treatment for HBV-related chronic liver disease. These drugs through an effective inhibition of viral replication, can suppress spontaneous clinical and subclinical flares of activity. The drugs are capable of stabilizing the liver function and can also improve survival by preventing hepatic decompensation and progression to HCC. [3],[4] Although interferon is recommended for compensated cirrhosis, it is relatively contraindicated in decompensated cirrhosis; severe sepsis may set in with worsening of liver failure. [5],[6]


   Natural History Top


A majority of patients with acute hepatitis B infection clear the virus spontaneously, whereas 10% can progress to chronic hepatitis. Chronic infection also occurs with perinatal transmission. [7],[8],9[],[10],[11] Low baseline HBV replication is associated with slow progression of chronic hepatitis to advanced fibrosis, clinically significant chronic liver disease, or HCC and manifests in the fourth or fifth decade of life. [12],[13] The annual incidence of progression of chronic HBV infection to cirrhosis is 2.1% and cirrhosis to HCC is 3%-6%. [14],[15],[16] HBV carriers have a 100-fold relative risk of developing HCC. [1]

Diagnosis is often missed in the slow progressive groups of patients as the majority is asymptomatic. Rapid progression to decompensation and HCC occurs in 20% of patients over a period of 5 years, especially when the patient is older, with persistent elevations of alanine aminotransferase (ALT) levels, [17] the individual is HBeAg positive and has elevated HBV DNA levels. [7],[8],[9],[10],[18],[19],[20]

Host, viral, and environmental factors associated with progression of HBV-related liver disease

Host factors predisposing to progression of HBV-related liver disease includes the following: age of acquisition of HBV infection, older age, concomitant alcohol consumption, smoking, [21] and advanced fibrosis on biopsy. Viral factors include active viral replication, genotype, co-infection with HCV, HDV, or HIV virus and the mutant variants. 13,[22],[23],[24],[25] HBV genotype C individuals in Asian countries often have more active liver disease, with a delayed HBeAg seroconversion, and a rapid progression to cirrhosis. [26],[27] These patients also have higher prevalence of basal core promoter mutants, which is associated with higher HBV viral load and increased rates of HCC. [28],[29],[30]

Aflatoxin has been reported as an environmental factor to be associated with an increased risk of cirrhosis or HCC. [31],[32]


   Perinatal Transmission, Chronic Hepatitis, and HCC Top


In 30%-50% of HCC associated with HBV, HCC occurs in a background of a normal liver or chronic hepatitis. [33] This often follows perinatal acquired infection.

Rationale for antiviral therapy in hepatitis B virus compensated and decompensated cirrhosis

In compensated cirrhosis, the goal of treatment is to prevent decompensation, reverse cirrhosis, and progression to HCC. With the use of nucleoside/tide analogs, one may succeed in achieving a sustained reduction in circulating HBV DNA and clearance of HBeAg with reduction in necro-inflammatory activity on liver biopsy. This can result in significant improvement in the clinical outcome and survival of the patient. [34],[35],[36]

In decompensated cirrhosis, patients would ultimately be listed for a liver transplant. The aim of treatment in these patients will be to maintain/improve the liver function, prevent progression to HCC, and finally to lower the HBV recurrence rates in posttransplant period. Low or undetectable levels of HBV DNA in pretransplant period are associated with a higher survival rate than those with high levels of viral replication.


   Treatment Recommendations Top


Interferon in compensated cirrhosis

Treatment is recommended for compensated cirrhosis irrespective of HBV DNA and ALT levels. A normal ALT level or low HBV DNA levels below 2000 IU/mL does not preclude the institution of drug therapy in these patients.

Interferon in HBeAg-positive compensated chronic liver disease

Interferon-α is considered safe in HBV-related liver disease, including those who are HBeAg positive with compensated cirrhosis. The response to treatment in cirrhosis is similar to those without cirrhosis. Less than 1% develop hepatic decompensaton. [35],[37],[38] Approximately, a third of the patients with HBeAg seroconversion with sustained loss of HBV DNA show reduction of necro-inflammatory activity and fibrosis. [37],[38],[39] Long-term follow-up of IFN-treated cirrhotic patients has shown a significantly reduced incidence of HCC. [18],[40]

Interferon in HBeAg-negative compensated chronic liver disease

The virologic and histologic response to IFN-α is suboptimal. [41],[42],[43] High rates of relapse after discontinuation of treatment has been reported. The reported overall sustained response is 20%-25%.

There are fewer studies on the role of PEG-IFN in the treatment of HBV-related cirrhosis. Buster et al[44] have shown PEG-IFN-α 2b to be safe and effective in patients with advanced fibrosis or cirrhosis.

Compared with interferon, which at times requires a 12- or 24-month therapy, orally administered antiviral drugs, such as lamivudine and adefovir dipivoxil are easier to administer with fewer adverse effects in HBeAg-negative patients.


   Role of Nucleoside Analogs Irrespective of HBeAg Status Top


Compensated cirrhosis

Long-term treatment with lamivudine can prevent disease progression and complications of compensated HBV infection but the benefit on survival is unclear. [45] A major drawback with lamuvidine is the development of resistance at the end of 1 year. This has been overcome by introducing a combination of lamuvidine and adefovir dipivoxil. Adding adefovir to lamuvidine [46],[47],[48] is a better option than switching over to adefovir, which has been associated with a higher risk of adefovir resistance. Long-term use of adefovir toward viral suppression may be effective in reversing fibrosis and even cirrhosis. [49],[50],[51] Nephrotoxicity is a major concern with adefovir when used for a long term.

Decompensated cirrhosis

Patients with decompensated cirrhosis are difficult to treat and carry a poor prognosis. Antiviral therapy is mandatory. [19],[52] Most patients with decompensation are candidates for liver transplantation and the primary aim is to prevent reactivation following transplantation. Treatment is indicated even in patients with low HBV DNA levels. Ideally, the treatment should be initiated early when a significant clinical response can be predicted with control of viral replication. Reversal of early cirrhosis is also possible at this stage. The drugs are not as effective in advanced cirrhosis.

In mild decompensation, low doses of interferon with careful titration can result in the loss of HBV DNA and normalization of serum aminotransferase levels. Clinical improvement and recovery in liver function is noticeable in these cases. [5],[6],[53],[54] Acute flares of hepatitis in 50%-86% in Childs B or C cirrhosis prohibits the use of interferon in decompensated state. Spontaneous bacterial peritonitis, septicemia, and worsening of liver cell failure, are other drawbacks with interferon. [5],[6],[53],[55],[56]

As in compensated state, lamivudine, is well tolerated and is safe in HBeAg-positive and -negative patients with decompensated cirrhosis. [16],[57],[58] The drug suppresses HBV replication, normalizes ALT levels and reduces hepatic necro-inflammation and fibrosis. Reversal of cirrhosis has also been noted when the drug is introduced early in the course of illness. [59],[60] The results of clinical improvement or stabilization with lamuvidine is seen at the end of 6 months treatment. [61],[62] Overall, there is reduction in the rate of hepatic decompensation and progression to HCC. [3],[4],[62],[63],[64],[65],[66],[67] Posttransplant recurrence of HBV is also low. A major concern with lamuvidine apart from lamuvidine resistance is the hepatitis flares in cirrhosis, associated with breakthrough infection. The latter can worsen liver failure and even result in death. [58] The risk of HBV recurrence in posttransplant is likely to increase if pretransplant HBV DNA levels are high. [68],[69]

Adefovir is recommended in lamuvidine-resistant individuals as an add-on therapy to reduce the risk of flares and development of resistance to adefovir. [70],[71],[72] The combination has been associated with a 3-4 log reduction in serum HBV DNA levels during the course of treatment. [70] Schiff and colleagues reported a marked inhibition of viral replication, HBeAg loss in 48%, and HBeAg seroconversion in 23% of lamuvidine-resistant patients. [73] Blood urea and serum creatinine levels need to be closely monitored when on adefovir.

Results of the studies on the safety and efficacy of Entecavir in patients with decompensated cirrhosis are awaited. Tenofovir has been tried in decompensated cirrhosis is a few case reports. Significant clinical improvement has been reported in lamivudine- and adefovir-resistant cases. [74],[75] The role of telbivudine in decompensated cirrhosis is not clear.

The 3 drugs, Entecavir, telbivudine, and tenofovir have similar mechanisms of action with near identical safety profile. They are likely to be more effective and potent or at least as effective as lamivudine with lower or nearly no drug resistance and nephrotoxicity.


   Conclusion Top


Viral suppression with safe and effective antiviral agents is the cornerstone in the management of HBV cirrhosis. The ideal antiviral therapy for long-term use in HBV cirrhosis should be safe and affordable for long-term use and with a low risk of drug resistance. The treatment of compensated HBV cirrhosis can reduce the risk of hepatic decompensation and development of HCC. Regression of fibrosis and reversal of cirrhosis has been reported.

In patients with compensated cirrhosis and normal liver synthetic function, the outcome of antiviral therapy is similar in patients with and without cirrhosis. In decompensated cirrhosis, liver transplantation is considered as the definitive therapy. Inhibition of viral replication before transplantation can delay the need for liver transplant and also prevent HBV recurrence in the posttransplantation period.

Importantly, despite the use of an ideal antiviral agent in cirrhosis liver with close monitoring for viral resistance and adverse events, medical management of cirrhosis with continued surveillance for HCC is the most important aspect of management of patients with liver cirrhosis.

 
   References Top

1.Beasley RP. Hepatitis B virus: The major etiology of hepatocellular carcinoma. Cancer 1988;61:1942-56.  Back to cited text no. 1
[PUBMED]    
2.Merican I. Treatment of chronic hepatitis B virus infection in special groups of patients: Decompensated cirrhosis, immunosuppressed and paediatric patients. J Gastroenterol Hepatol 2000;15:E71-8.  Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Andreone P, Biselli M, Gramenzi A, Cursaro C, Morelli MC, Sama C, et al. Efficacy of lamivudine therapy for advanced liver disease in patients with precore mutant hepatitis B virus infection awaiting liver transplantation. Transplantation 2002;74:1119-24.   Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Villeneuve JP, Condreay L, Willems B, Pomier-Layrargues G, Fenyves D, Bilodeau M, et al. Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B. Hepatology 2000;31:207-10.  Back to cited text no. 4
    
5.Hoofnagle JH, Di Bisceglie AM, Waggoner JG, Park Y. Interferon alfa for patients with clinically apparent cirrhosis due to chronic hepatitis B. Gastroenterology 1993;104:1116-21.   Back to cited text no. 5
[PUBMED]    
6.Perrillo R, Tamburro C, Regenstein F, Balart L, Bodenhemier H, Silva M, et al. Low-dose, titratable interferon alfa in decompensated liver disease caused by chronic infection with hepatitis B virus. Gastroenterology 1995;109:908-16.  Back to cited text no. 6
    
7.Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002;347:168-74.   Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.Yu MW, Yeh SH, Chen PJ, Liaw YF, Lin CL, Liu CJ, et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: A prospective study in men. J Natl Cancer Inst 2005;97:265-72.   Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130:678-86.   Back to cited text no. 9
[PUBMED]  [FULLTEXT]  
10.Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65-73.   Back to cited text no. 10
[PUBMED]  [FULLTEXT]  
11.Harris RA, Chen G, Lin WY, Shen FM, London WT, Evans AA. Spontaneous clearance of high-titer serum HBV DNA and risk of hepatocellular carcinoma in a Chinese population. Cancer Causes Control 2003;14:995-1000.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.Manno M, Camma C, Schepis F, Bassi F, Gelmini R, Giannini F, et al. Natural history of chronic HBV carriers in northern Italy: Morbidity and mortality after 30 years. Gastroenterology 2004;127:756-63.   Back to cited text no. 12
    
13.Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23:47-58.   Back to cited text no. 13
    
14.Hsu YS, Chien RN, Yeh CT, Sheen IS, Chiou HY, Chu CM, et al. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology 2002;35:1522-7.  Back to cited text no. 14
[PUBMED]  [FULLTEXT]  
15.Chen YC, Chu CM, Yeh CT, Liaw YF. Natural course following the onset of cirrhosis in patients with chronic hepatitis B: A long-term follow-up study. Hepatol Int 2007;1:267-73.  Back to cited text no. 15
[PUBMED]  [FULLTEXT]  
16.Chu CM, Liaw YF. Hepatitis B virus-related cirrhosis: Natural history and treatment. Semin Liver Dis 2006;26:142-52.   Back to cited text no. 16
[PUBMED]  [FULLTEXT]  
17.Park BK, Park YN, Ahn SH, Lee KS, Chon CY, Moon YM, et al. Long-term outcome of chronic hepatitis B based on histological grade and stage. J Gastroenterol Hepatol 2007;22:383-8.  Back to cited text no. 17
[PUBMED]  [FULLTEXT]  
18.Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, et al. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol 2007;46:45-52.  Back to cited text no. 18
[PUBMED]  [FULLTEXT]  
19.de Jongh FE, Janssen HL, de Man RA, Hop WC, Schalm SW, Van Blankenstein M. Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. Gastroenterology 1992;103:1630-5.  Back to cited text no. 19
[PUBMED]    
20.Chou YC, Yu MW, Wu CF, Yang SY, Lin CL, Liu CJ, et al. Temporal relationship between hepatitis B virus enhancer II/basal core promoter sequence variation and risk of hepatocellular carcinoma. Gut 2008;57:91-7.  Back to cited text no. 20
[PUBMED]  [FULLTEXT]  
21.Chen ZM, Liu BQ, Boreham J, Wu YP, Chen JS, Peto R. Smoking and liver cancer in China: Case-control comparison of 36,000 liver cancer deaths vs 17,000 cirrhosis deaths. Int J Cancer 2003;107:106-12.  Back to cited text no. 21
[PUBMED]  [FULLTEXT]  
22.Colin JF, Cazals-Hatem D, Loriot MA, Martinot-Peignoux M, Pham BN, Auperin A, et al. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology 1999;29:1306-10.   Back to cited text no. 22
[PUBMED]  [FULLTEXT]  
23.Ikeda K, Saitoh S, Suzuki Y, Kobayashi M, Tsubota A, Koida I, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: A prospective observation in 2215 patients. J Hepatol 1998;28:930-8.   Back to cited text no. 23
[PUBMED]  [FULLTEXT]  
24.Sagnelli E, Coppola N, Scolastico C, Fillipini P, Sanantonio T, Stroffolini T, et al. Virologic and clinical expressions of reciprocal inhibitory effect of hepatitis B, C and delta viruses in patients with chronic hepatitis. Hepatology 2000;32:1106-10.  Back to cited text no. 24
    
25.Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: What we knew in 1981 and what we know in 2005. Hepatology 2006;43:S173-81.  Back to cited text no. 25
[PUBMED]  [FULLTEXT]  
26.Chu CJ, Hussain M, Lok AS. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology 2003;122:1756-62.  Back to cited text no. 26
    
27.Sumi H, Yokosuka O, Seki N, Arai M, Imazeki F, Kurihara T, et al. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 2003;37:19-26.  Back to cited text no. 27
[PUBMED]  [FULLTEXT]  
28.Kao JH, Chen PJ, Lai MY, Chen DS. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology 2003;124:327-34.   Back to cited text no. 28
[PUBMED]  [FULLTEXT]  
29.Lin CL, Liao LY, Wang CS, Chen PJ, Lai MY, Chen DS, et al. Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B. Liver Int 2005;25:564-70.   Back to cited text no. 29
[PUBMED]  [FULLTEXT]  
30.Tong MJ, Blatt LM, Kao JH, Cheng JT, Corey WG. Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma. World J Gastroenterol 2006;12:6620-6.  Back to cited text no. 30
[PUBMED]  [FULLTEXT]  
31.Murugavel KG, Mathews S, Jayanthi V, Shankar EM, Hari R, Surendran R, et al. Alpha-fetoprotein as a tumor marker in hepatocellular carcinoma: Investigations in south Indian subjects with hepatotropic virus and aflatoxin etiologies. Int J Infect Dis 2008;12:e71-6.   Back to cited text no. 31
[PUBMED]  [FULLTEXT]  
32.Murugavel KG, Naranatt PP, Shankar EM, Mathews S, Raghuram K, Rajasambandam P, et al. Prevalence of aflatoxin B1 in liver biopsies of proven hepatocellular carcinoma in India determined by an in-house immunoperoxidase test. J Med Microbiol 2007;56:1455-9.  Back to cited text no. 32
[PUBMED]  [FULLTEXT]  
33.Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis 2005;9:191-211.  Back to cited text no. 33
    
34.Liaw YF, Tai DI, Chu CM, Chen TJ. The development of cirrhosis in patients with chronic type B hepatitis: A prospective study. Hepatology 1988;8:493-6.  Back to cited text no. 34
[PUBMED]    
35.Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med 1996;334:1422-7.  Back to cited text no. 35
[PUBMED]  [FULLTEXT]  
36.Lau DT, Everhart J, Kleiner DE, Park Y, Vergalla J, Schmid P, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology 1997;113:1660-7.  Back to cited text no. 36
[PUBMED]  [FULLTEXT]  
37.Perrillo RP, Schiff ER, Davis GL, Bodenheimer HC Jr, Lindsay K, Payne J, et al. A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B: The Hepatitis Interventional Therapy Group. N Engl J Med 1990;323:295-301.  Back to cited text no. 37
[PUBMED]  [FULLTEXT]  
38.Lok AS, Wu PC, Lai CL, Lau JY, Leung EK, Wong LS, et al. A controlled trial of interferon with or without prednisone priming for chronic hepatitis B. Gastroenterology 1992;102:2091-7.   Back to cited text no. 38
[PUBMED]    
39.Perrillo RP, Brunt EM. Hepatic histologic and immunohistochemical changes in chronic hepatitis B after prolonged clearance of hepatitis B e antigen and hepatitis B surface antigen. Ann Intern Med 1991;115:113-5.   Back to cited text no. 39
[PUBMED]    
40.Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology 1999;29:971-5.  Back to cited text no. 40
[PUBMED]  [FULLTEXT]  
41.Merle P, Trepo C. Therapeutic management of hepatitis B-related cirrhosis. J Viral Hepat 2001;8:391-9.   Back to cited text no. 41
[PUBMED]  [FULLTEXT]  
42.Brunetto MR, Giarin M, Saracco G, Oliveri F, Calvo P, Capra G, et al. Hepatitis B virus unable to secrete e antigen and response to interferon in chronic hepatitis B. Gastroenterology 1993;105:845-50.   Back to cited text no. 42
[PUBMED]    
43.Adachi H, Kaneko S, Matsushita E, Inagaki Y, Unoura M, Kobayashi K. Clearance of HBsAg in seven patients with chronic hepatitis B. Hepatology 1992;16:1334-7.  Back to cited text no. 43
[PUBMED]    
44.Buster EH, Hansen BE, Buti M, Delwaide J, Niederau C, Michielsen PP, et al. Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis. Hepatology 2007;46:388-94.   Back to cited text no. 44
[PUBMED]  [FULLTEXT]  
45.Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004;351:1521-31.  Back to cited text no. 45
[PUBMED]  [FULLTEXT]  
46.Fung SK, Chae HB, Fontana RJ, Conjeevaram H, Marrero J, Oberhelman K, et al. Virologic response and resistance to adefovir in patients with chronic hepatitis B. J Hepatol 2006;44:283-90.   Back to cited text no. 46
[PUBMED]  [FULLTEXT]  
47.Lampertico P, Vigano M, Manenti E, Iavarone M, Sablon E, Colombo M. Low resistance to adefovir combined with lamivudine: A 3-year study of 145 lamivudine-resistant hepatitis B patients. Gastroenterology 2007;133:1445-51.   Back to cited text no. 47
    
48.Rapti I, Dimou E, Mitsoula P, Hadziyannis SJ. Adding-on versus switching- to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. Hepatology 2007;45:307-13.  Back to cited text no. 48
[PUBMED]  [FULLTEXT]  
49.Hadziyannis S, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, et al. Adefovir dipivoxil for the treatment of hepatitis B e-antigen-negative chronic hepatitis B. N Engl J Med 2003;348:800-7.   Back to cited text no. 49
    
50.Marcellin P, Chang TT, Lim SG, Tong M, Sievert W, Schiffman M, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen positive chronic hepatitis B. N Engl J Med 2003;348:808-16.   Back to cited text no. 50
    
51.Goodman Z, Marcellin P, Chang TT, Lim SG, Tong M, Sievert W, et al. 48 weeks of adefovir dipivoxil (ADV) results in improvement in fibrosis and decreased progression of fibrosis in a double-blind, randomized, placebo-controlled study for the treatment of patients with HBeAg + chronic hepatitis B. Hepatology 2003;36:373A.  Back to cited text no. 51
    
52.Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B: The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatology 1995;21:77-82.  Back to cited text no. 52
[PUBMED]    
53.Nevens F, Goubau P, Van Eyken P, Desmyter J, Desmet V, Fevery J. Treatment of decompensated viral hepatitis B-induced cirrhosis with low doses of interferon alfa. Liver 1993;13:15-9.   Back to cited text no. 53
[PUBMED]    
54.Dimopoulou M, Fafoutis K, Basiliou K, Ketikoglou J, Karvountzis G. Interferon alfa-2b for decompensated liver disease caused by either chronic hepatitis B or C: Preliminary results of a pilot study. Gut 1993;34:S104-5.  Back to cited text no. 54
[PUBMED]  [FULLTEXT]  
55.Marcellin P, Giuily N, Loriot MA, Durand F, Samuel D, Bettan L, et al. Prolonged interferon-alpha therapy of hepatitis B virus-related decompensated cirrhosis. J Viral Hepat 1997;4:21-6.  Back to cited text no. 55
[PUBMED]    
56.Nevens F, Main J, Honkoop P, Tyrrell DL, Barber J, Sullivan MT, et al. Lamivudine therapy for chronic hepatitis B: A six-month randomized dose-ranging study. Gastroenterology 1997;113:1258-63.  Back to cited text no. 56
[PUBMED]  [FULLTEXT]  
57.Leung N. Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues. Hepatol Int 2008;2:163-78.  Back to cited text no. 57
[PUBMED]  [FULLTEXT]  
58.Manolakopoulos S, Karatapanis S, Elefsiniotis J, Mathou N, Vlachogiannakos J, Iliadou E, et al. Clinical course of lamivudine monotherapy in patients decompensated cirrhosis due to HbeAg negative chronic HBV infection. Am J Gastroenterol 2004;99:57-63.  Back to cited text no. 58
[PUBMED]    
59.Tassopoulos N, Volpes R, Pastore G, Heathcote J, Buti M, Goldin R, et al. Efficacy of lamivudine in patients with hepatitis B e antigen negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B: Lamivudine Precore Mutant Study Group. Hepatology 1999;29:889-96.   Back to cited text no. 59
    
60.Dienstag JL, Goldin RD, Heathcote EJ, Hann HW, Woessner M, Stephenson SL, et al. Histological outcome during long-term lamivudine therapy. Gastroenterology 2003;124:105-17.  Back to cited text no. 60
[PUBMED]  [FULLTEXT]  
61.Chien RN, Lin CH, Liaw YF. The effect of lamivudine therapy in hepatic decompensation during acute exacerbation of chronic hepatitis B. J Hepatol 2003;38:322-7.   Back to cited text no. 61
[PUBMED]  [FULLTEXT]  
62.Fontana RJ, Hann HW, Perrillo RP, Vierling JM, Wright T, Rakela J, et al. Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy. Gastroenterology 2002;123:719-27.  Back to cited text no. 62
[PUBMED]  [FULLTEXT]  
63.Perrillo RP, Wright T, Rakela J, Levy G, Schiff E, Gish R, et al. A multicenter United States-Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B. Hepatology 2001;33:424-32.  Back to cited text no. 63
[PUBMED]  [FULLTEXT]  
64.Yao FY, Bass NM. Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection. J Hepatol 2000;33:301-7.  Back to cited text no. 64
[PUBMED]  [FULLTEXT]  
65.Yao FY, Terrault NA, Freise C, Maslow L, Bass NM. Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: A comparative study using a matched, untreated cohort. Hepatology 2001;34:411-6.  Back to cited text no. 65
[PUBMED]  [FULLTEXT]  
66.Fontana RJ, Keeffe EB, Carey W, Fried M, Reddy R, Kowdley K, et al. Effect of lamivudine treatment on survival of 309 North American patients awaiting liver transplantation for chronic hepatitis B. Liver Transpl 2002;8:433-9.  Back to cited text no. 66
    
67.Kapoor D, Guptan RC, Wakil SM, Kazim SN, Kaul R, Agarwal SR, et al. Beneficial effects of lamivudine in hepatitis B virus related decompensated cirrhosis. J Hepatol 2000;33:308-12.  Back to cited text no. 67
[PUBMED]  [FULLTEXT]  
68.Rosenau J, Bahr MJ, Tillmann HL, Trautwein C, Klempnauer J, Manns MP, et al. Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B reinfection after liver transplantation possible role of mutations in the YMDD motif prior to transplantation as a risk factor for reinfection. J Hepatol 2001;43:895-902.   Back to cited text no. 68
    
69.Seehofer D, Rayes N, Steinmuller T, Muller AR, Settmacher U, Neuhaus R, et al. Occurrence and clinical outcome of lamivudine-resistant hepatitis B infection after liver transplantation. Liver Transpl 2001;7:976-82.  Back to cited text no. 69
    
70.Schiff ER, Lai CL, Hadziyannis S, Neuhaus P, Terrault N, Colombo M, et al. Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients. Hepatology 2003;38:1419-27.  Back to cited text no. 70
[PUBMED]  [FULLTEXT]  
71.Westland CE, Yang H, Delaney WE 4th, Gibbs CS, Miller MD, Wulfsohn M, et al. Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B. Hepatology 2003;38:96-103.  Back to cited text no. 71
[PUBMED]  [FULLTEXT]  
72.Angus P, Vaughan R, Xiong S, Yang H, Delaney WE, Gibbs C, et al. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology 2003;125:292-7.   Back to cited text no. 72
    
73.Schiff E, Lai CL, Hadziyannis S, Neuhaus P, Terrault N, Colombo M, et al. Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine resistant hepatitis B: Final long-term results. Liver Transpl 2007;13:349-60.  Back to cited text no. 73
[PUBMED]  [FULLTEXT]  
74.Taltuvull TC, Chahri N, Verdura B, Gornals J, Lopez C, Casanova A, et al. Successful treatment with tenofovir in a child C cirrhotic patient with lamivudine-resistant hepatitis B virus awaiting liver transplantation: Post-transplant results. Transpl Int 2005;18:879-83.   Back to cited text no. 74
    
75.Ratziu V, Thibault V, Benhamou Y, Poynard T. Successful rescue therapy with tenofovir in a patient with hepatic decompensation and adefovir resistant HBV mutant. Comp Hepatol 2006;5:1.  Back to cited text no. 75
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Correspondence Address:
V Jayanthi
Department of Gastroenterology, Stanley Medical College Hospital, Chennai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-9747.76909

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    Abstract
    Introduction
    Natural History
    Perinatal Transm...
    Treatment Recomm...
    Role of Nucleosi...
    Conclusion
    References

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