Biomedical subjects

S W Schalm

Publications and source records attributed to S W Schalm.

At least 19 recordsLinked to original sources

PubMed2007

Impact of hepatic steatosis on viral kinetics and treatment outcome during antiviral treatment of chronic HCV infection.

Liver steatosis is highly prevalent in chronic hepatitis C virus (HCV) infection, especially in patients infected with genotype 3 virus, but its significance for the outcome of antiviral treatment is not fully understood. We have monitored steatosis in liver biopsies from 231 patients with chronic HCV infection who received pegylated recombinant interferon-alpha and ribavirin in a phase III study (DITTO trial). The degree of steatosis, along with relevant metabolic parameters, was correlated with the early disappearance of virus and with the final outcome of treatment. Our data suggest that the presence of steatosis impairs the early reduction of viral load during treatment in patients infected with HCV genotype 3 and non-3. Steatosis negatively affected the final outcome of treatment mainly in patients infected with HCV genotype non-3 virus. Based on these findings, we propose that interventions aiming at reducing hepatic steatosis prior to the onset of antiviral therapy may be of benefit to patients infected with HCV of the non-3 genotypes. Patients infected with genotype 3, on the other hand, should be offered early antiviral treatment.

Adult↗

PubMed2006

Determinants of quality of life in chronic liver patients.

BACKGROUND AND AIM: Health-related quality of life of patients with chronic liver disease has been shown to be impaired in numerous studies. However, the factors which influence health-related quality of life in treated chronic liver patients are not quite known. This is the first study to assess the impact of physical and psychosocial determinants on a weighted score of health-related quality of life in patients with chronic liver disease. METHODS: The data of 1175 chronic liver patients were used to assess the relationship between items of the disease-specific Liver Disease Symptom Index 2.0 and the Short Form (SF)-6D weighted utility score by means of linear regression analyses. RESULTS: Health-related quality of life was most strongly related to disease severity (B = -0.029) and joint pain (B = -0.023). Depression (B = -0.014), pain in the right upper abdomen (B = -0.014), decreased appetite (B = 0.014) and fatigue (B = -0.013) were also strongly related to health-related quality of life. In hepatitis C virus patients, disease severity (B = -0.037) and depression (B = -0.030) were strong determinants of health-related quality of life. CONCLUSIONS: This study shows that health-related quality of life in chronic liver patients is clearly determined by disease severity, joint pain, depression, decreased appetite and fatigue. These patients may benefit most from interventions aimed at improving adaptation to the symptoms described.

Activities of Daily Living↗

PubMed2006

Different composition of intrahepatic lymphocytes in the immune-tolerance and immune-clearance phase of chronic hepatitis B.

Based on virological and biochemical parameters patients with chronic hepatitis B virus (HBV) are divided into distinct clinical phases: the immune-tolerance phase, the immune-clearance phase, and the inactive carrier state. Unclear is whether these phases have characteristic intrahepatic immune responses. The composition of liver-derived lymphocytes in patients with chronic HBV infection was studied. In 47 patients the composition of liver-derived lymphocytes was analyzed by flow cytometry of fine needle aspiration biopsies of the liver. The proportion natural killer (NK) cells in the liver was significantly higher in immune-tolerant than in immune-clearance patients and inactive carriers. No differences were found in proportion CD4+ T-cells and CD8+ T-cells, in these phases. However, when patients in the immune-clearance phase, with similar alanine transaminase (ALT), were grouped according to viral load, the proportion CD8+ T-cells was higher in those with high viral load. In contrast, the proportion CD4+ T-cells was increased in patients with low HBV-DNA. These differences were absent in the peripheral blood (PB). Intrahepatic HBV-specific CD8+ T-cells were mainly found in immune-clearance patients with low viral load. In conclusion, clear differences in the intrahepatic cellular infiltrate were found between the various clinical phases of chronic HBV infection. These findings are relevant to the design of new, individualized anti-viral strategies.

Adolescent↗

PubMed2006

Hepatitis B virus (HBV) DNA levels and the management of HBV-infected health care workers.

Different guidelines exist for the management of hepatitis B virus (HBV)-infected health care workers (HCWs). Various HBV DNA levels are used as a cutoff level to determine whether an HBV-infected HCW is allowed to perform exposure-prone procedures (EPPs) or not. In this paper we discuss the factors that determine HBV DNA levels and the implications of different HBV DNA cutoff levels for EPP performing HCWs. If the level of HBV DNA in the serum of HCWs is used to determine acceptability for the conduct of EPPs, it is necessary to take into account the variability in time of HBV DNA levels in HBV carriers and the reliability and reproducibility of the molecular diagnostic test involved. The issue of standardization has to be addressed, before a universal, maximum level of viraemia for EPP performing HCWs can be introduced.

DNA, Viral↗

PubMed2006

Quantitative HBV DNA levels as an early predictor of nonresponse in chronic HBe-antigen positive hepatitis B patients treated with interferon-alpha.

To reduce unnecessary exposure to treatment, physicians must decide at an early stage whether continuation of treatment has a reasonable chance of success for the individual patient. The objectives of our study were to evaluate the previously described quantitative hepatitis B e antigen (HBeAg) measurements vs quantitative hepatitis B virus (HBV) DNA measurements for prediction of nonresponse and response in interferon (IFN)-alpha treated HBeAg positive chronic HBV patients. Serum HBV DNA and HBeAg levels were assessed at baseline and weeks 8 and 12. For each test (HBV DNA level at baseline, HBV DNA decrease between baseline and weeks 8 and 12, or the combination of these two, as well as HBeAg level at baseline, HBeAg decrease between baseline and weeks 8 and 12, and the combination of these two), we calculated the positive predictive value, negative predictive value, sensitivity and specificity. Monitoring with quantitative HBV DNA levels (area under ROC 0.87) was superior to monitoring with quantitative HBeAg levels (0.76, P < 0.05). Step-wise logistic regression identified HBV DNA at baseline and decrease in HBV DNA from baseline to week 12, as independent predictors of response. The overall test performance of predicting nonresponse (predictive value 100%) was best for log HBV DNA testing at week 12 compared with testing at week 8 due to a better prediction of sustained response (46%vs 38%) and lower misidentification of nonresponse (39%vs 54%). This study showed that quantitative HBV DNA testing at baseline in combination with a decrease between baseline and week 12 has a high predictive value for identifying patients who have virtually no chance of reaching a sustained response with IFN therapy.

Adolescent↗

PubMed2005

Flares in chronic hepatitis B patients induced by the host or the virus? Relation to treatment response during Peg-interferon {alpha}-2b therapy.

BACKGROUND AND AIMS: Flares are a well known phenomenon during antiviral treatment for chronic hepatitis B. Little is known about the effect of flares on response. We investigated the timing and characteristics of flares, in relation to treatment response (hepatitis B e antigen loss). PATIENTS: A total of 266 patients, participating in a global randomised controlled study, were assigned to 52 weeks of 100 mug pegylated (Peg)-interferon alpha-2b weekly, combined with either daily lamivudine 100 mg or placebo. RESULTS: Sixty seven patients (25%) exhibited 75 flares, with 38 (51%) flares in the combination therapy and 37 (49%) in the monotherapy groups. Overall, 30% of patients with and 38% of patients without a flare responded to therapy (p = 0.25). In 24 patients (36%) the flare was followed by a decrease in hepatitis B virus (HBV) DNA (host induced flare). In 25 (38%) patients the flare was preceded by an increase in HBV DNA (virus induced flare). In 17 (26%) patients the flare did not meet one of these criteria (indeterminate flare). Of patients with host induced flare, 58% responded whereas only 20% of patients with virus induced flares responded (p = 0.008). Hepatitis B surface antigen loss (n = 8) was exclusively seen in patients experiencing a host induced flare. Multivariate logistic analysis showed that host induced flares was an independent predictor of response (p = 0.043). CONCLUSION: Flares are not more common in responders than in non-responders to Peg-interferon alpha-2b therapy. Virus induced flares, which occur after an increase in HBV DNA level, and most probably are indicative for increased expression of viral antigens, did not lead to treatment response. In contrast, host induced flares which were followed by a HBV DNA decrease were highly associated with treatment response.

Adult↗

PubMed2005

The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation.

BACKGROUND: Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events. AIM: To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease. METHODS: Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way. RESULTS: The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation. CONCLUSION: We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.

Adult↗

PubMed2005

Dynamic decision analysis to determine optimal treatment duration in chronic hepatitis C.

BACKGROUND: Current guidelines for stopping treatment of chronic hepatitis C are based on hepatitis C ribonucleic acid measurements at 12 and 24 weeks. AIM: To explore an alternative approach for making individualized recommendations about treatment duration, based on simple alanine aminotransferase tests and on cost-per-cure. METHODS: We analysed individual patient data from 13 randomized, controlled trials with interferon alone or combined with ribavirin. Using multiple logistic regression, we built a model that estimated the probability of sustained virological response for treatment durations of 24 and 48 weeks. Decisions to prolong treatment were based on an increase in probability of sustained virological response. If the increase was 10%, the cost-per-cure became decisive with a limit of 50,000. RESULTS: Noncirrhotics with genotype 2 or 3 did not benefit when treatment was continued beyond 24 weeks. Sustained virological response rates in cirrhotic patients increased by 14-47% if treatment was continued up to 48 weeks. In noncirrhotic genotype 1 or 4 patients who had elevated alanine aminotransferase levels at week 4, the probability of sustained virological response increased by <10% if treatment was continued up to 48 weeks; the cost-per-cure for these patients would exceed 50,000. CONCLUSION: The dynamics of alanine aminotransferase levels and cost-per-cure provides a useful alternative to determine the duration of therapy in chronic hepatitis C.

Adult↗

PubMed2005

The optimal treatment strategy for chronic hepatitis C.

The treatment of chronic hepatitis C forms a considerable burden for society. The present standard treatment with PEG-Interferon and Ribavirin is costly, has side effects and is not always effective. The current trend is to prolong treatment from 24 to 48 or even 72 weeks in patients infected with genotypes 1 and 4 virus, in order to prevent relapses after cessation of therapy. There are, however, suggestions that treatment of relapses gives a response rate similar to that of first-time treatment. We, therefore, compared the sustained response rates and the mean treatment durations of one-time treatment and cyclic treatment in a model that incorporates the rates of non-response to antiviral therapy, of breakthrough during and of relapse after cessation of treatment. Our calculations show that, even under the most unfavourable assumptions, repeated 6-month treatment lowers the mean treatment duration from 9.6 to 7.5 months when compared to a single 12-month treatment, without jeopardising the overall effectiveness. If the results of our model calculations can be confirmed, current guidelines for the treatment of infections with genotype 1 hepatitis C virus ought to be reconsidered.

Antiviral Agents↗

PubMed2005

Viral dynamics during tenofovir therapy in patients infected with lamivudine-resistant hepatitis B virus mutants.

Tenofovir, an antihuman immunodeficiency virus (HIV) drug, has activity against lamivudine-resistant hepatitis B virus (HBV) mutants. To describe the efficacy of tenofovir in patients with lamivudine-resistant hepatitis B we applied two investigative approaches based on mathematical models of viral dynamics: the individual nonlinear fitting and the mixed-effect group fitting approaches. Eleven chronic HBV patients on lamivudine for a median of 176 weeks (range: 72-382) with YMDD mutation-related HBV-DNA breakthrough received 'add-on' tenofovir 300 mg once-daily, while maintaining their existing therapy. Sequential sera were taken at day 1 (t = 0 and t = 8 h), days 2, 4, 7, 10, 14, 21, 28 and every 4 weeks thereafter, and HBV-DNA levels were assessed using a validated quantitative polymerase chain reaction (PCR) assay. Median baseline log HBV-DNA was 8.62 (range: 6.48-9.76 log HBV-DNA). Tenofovir treatment resulted in a mean (+/-SD) log HBV-DNA decline of 1.37 +/- 0.51 in the first phase, 2.54 +/- 0.91 after 4 weeks, and 4.95 +/- 0.90 log HBV-DNA after 24 weeks. The median effectiveness of blocking viral replication in the individual fit model was 93% (range: 73-99) for eta = 0 and 93% (range: 59-99) for eta = 1. There was only a small difference between the efficacy parameter 'epsilon' of the individual nonlinear fitting and mixed-effect group fitting on the biphasic exponential model. These data show that tenofovir has good efficacy in blocking viral replication in HBV patients with lamivudine-induced drug-resistant HBV mutants, but effectiveness varies greatly among individuals. Both models can be used to describe viral decay during tenofovir therapy.

Adenine↗

PubMed2005

Flow cytometry of fine-needle-aspiration biopsies: a new method to monitor the intrahepatic immunological environment in chronic viral hepatitis.

SUMMARY: Information about the character and grade of the intrahepatic immune response in viral hepatitis is important for the evaluation of disease stage and effect of therapy. Complications like haemorrhage limit the frequent performance of tissue-needle biopsies (TB), and the cells of peripheral blood have to be used as surrogate markers instead. Fine-needle-aspiration biopsy (FNAB) of the liver represents a safe and atraumatic method that allows frequent cytological sampling. Our aim was to investigate whether flow cytometry of FNAB specimens allows co-analysis of phenotype, function and specificity of key populations of liver-infiltrating lymphocytes (LIL). In 20 consecutive patients with chronic viral hepatitis [10 hepatitis B virus (HBV), 10 hepatitis C virus (HCV)], flow cytometry was performed on FNAB cytology, and simultaneously on lymphocytes isolated from a TB and peripheral blood mononuclear cells (PBMC). The ratio of CD8+/CD4+ lymphocytes in FNAB correlated well with LIL from TB (r =0.78, P < 0.05) but differed from PBMC (mean ratio: 2.6, 2.1 and 0.7, respectively). Similarly, a correlation was observed for percentage CD56+ natural killer (NK) cells (mean %: 29.9, 32.3 and 14.5, respectively; r = 0.69, P < 0.05). The percentage of interferon (IFN)-gamma-producing CD3+ lymphocytes in both FNAB and TB was higher than in PBMC (mean %: 41, 44 and 22, respectively; P < 0.05). Furthermore, tetrameric complexes allowed analysis of HBV-specific T cells in FNAB specimens. In conclusion, flow cytometry of FNAB allows easy, atraumatic and reliable analysis of lymphocytes obtained from the intrahepatic compartment. Therefore, the FNAB is a valuable tool in the study of the immunopathology of viral hepatitis, and it may contribute to the improved clinical evaluation of chronic viral liver disease.

Biopsy, Fine-Needle↗

PubMed2004

Human hepatic lymph nodes contain normal numbers of mature myeloid dendritic cells but few plasmacytoid dendritic cells.

We investigated whether the hyporesponsiveness of the adaptive arm of the liver immune system is related to the composition of the dendritic cell (DC) population in hepatic lymph nodes. Noninflamed human hepatic lymph nodes (LN) were obtained from multiorgan donors, inflamed hepatic LN from liver transplant recipients with autoimmune cholestatic liver diseases, and inguinal LN from kidney transplant recipients. Quantitative immunohistochemistry showed that all three types of LN contained comparable numbers of mature and immature myeloid DC, but that noninflamed and inflamed hepatic LN contained significantly fewer plasmacytoid DC as compared to inguinal LN. Likewise, DC-enriched cell preparations from hepatic LN contained relatively few plasmacytoid DC. The difference in numbers of plasmacytoid DC was confirmed in comparisons of hepatic LN and ileacal LN from the same organ-donors. Myeloid DC from hepatic LN showed similar expressions of HLA-DR, CD83, and CD86, and higher expression of CD80 compared to myeloid DC from inguinal LN. In conclusion, hepatic LN contain similar numbers of myeloid DC as muscle/skin lymph-draining LN, with no signs of immaturity, but relatively few plasmacytoid DC.

Antigens, CD↗

PubMed2004

Doctor-to-patient transmission of hepatitis B virus: the potential of antiviral therapy for prevention.

Hepatitis B virus (HBV)-infected health-care workers (HCWs) have infected patients during medical procedures. In many countries HBV-infected HCWs are restricted in performing exposure prone procedures based on either HBeAg status or serum HBV DNA level. To prevent loss of skilled HCWs and to minimize transmission risk, highly viraemic HCWs can be offered antiviral therapy. Nucleoside analogues have proven to be effective in reducing transmission of HIV and HBV in the setting of vertical mother-to-infant transmission. Following the same rationale, suppression of viral load in HBV-infected HCWs could minimize the risk of doctor-to-patient transmission to such an extent that job modifications are no longer indicated. To limit the risk of drug resistance, the use of combination therapy is advocated. We describe two chronic HBV-infected HCWs treated with antiviral therapy, eventually leading to well-tolerated and highly effective combination therapy with lamivudine and tenofovir, with continuation of medical practice.

Antiviral Agents↗

PubMed2004

Monitoring intrahepatic CD8+ T cells by fine-needle aspiration cytology in chronic hepatitis C infection.

Infection of the liver with hepatitis C virus (HCV) causes compartmentalization of CD8+ cytotoxic T cells to the site of disease. These cells are thought to be involved in viral clearance during interferon therapy. The repetitive analysis of the intrahepatic immune response is hampered by the difficulty to obtain the intrahepatic T cells. The fine-needle aspiration biopsy (FNAB) technique was evaluated for its use to obtain liver-derived CD8+ T cells in a minimally invasive way. In 26 chronic HCV patients who were evaluated for Peg-interferon and ribavirin combination therapy, pre-treatment FNABs and peripheral blood specimens were obtained simultaneously with liver tissue biopsies, and CD3+ and CD8+ T cells were quantified by immunocytochemistry. The CD8+/CD3+ ratio was significantly higher in the FNABs than in peripheral blood (P < 0.01), and similar to those in portal areas in the tissue biopsies. A significant correlation was observed between numbers of CD3+CD8+ T lymphocytes in the FNABs and the numbers of CD8+ cells in the lobular fields or in the portal tracts of the liver tissue biopsies, but not with CD3+CD8+ T lymphocytes in peripheral blood. Finally, the ratio of CD8+/CD3+ T lymphocytes in FNABs was significantly higher in those patients who responded rapidly to therapy when compared with slow responders at 4 weeks of treatment (P = 0.02). These findings demonstrate that the intrahepatic T-cell composition is reflected in FNABs, and that the FNAB technique can be used for predicting early virological response to therapy of patients chronically infected with HCV.

Biopsy, Fine-Needle↗

PubMed2004

Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy.

BACKGROUND: The key end point for treatment efficacy in chronic hepatitis C is absence of detectable virus at six months after treatment. However, the incidence of clinical events during long term follow up of patients with sustained virological response is still poorly documented and may differ between the Eastern and Western world. AIMS: To assess clinical end points during long term follow up of European patients with a sustained virological response to interferon monotherapy. METHODS: Meta-analysis of individual patient data from eight European protocolled follow up studies of interferon treatment for chronic hepatitis C. RESULTS: A total of 286 sustained virological responders and 50 biochemical responders (detectable virus but normal alanine aminotransferase levels) were followed up for 59 months. Fifteen sustained virological responders (5.2%) had cirrhosis before treatment and 112 (39%) had genotype 1. The late virological relapse rate after five years of follow up was 4.7% (95% confidence interval (CI) 2.0-7.4) among sustained virological responders; all late relapses occurred within four years after treatment. Among sustained virological responders, the rate of decompensation after five years of follow up was 1.0% (95% CI 0.0-2.3) and none developed hepatocellular carcinoma (HCC). Survival was comparable with the general population, matched for age and sex, the standard mortality ratio being 1.4 (95% CI 0.3-2.5). Clinical outcome of patients with cirrhosis was similar to other sustained virological responders. For biochemical responders, the rates of development of decompensation and HCC during long term follow up were 9.1% (95% CI 0.5-17.7) and 7.1% (95% CI 0-15.0), respectively. CONCLUSIONS: Five year survival of European sustained virological responders was similar to the overall population, matched for age and sex. No HCCs were detected during long term follow up.

Adolescent↗

PubMed2004

The treatment of hepatitis C: history, presence and future.

The treatment of chronic hepatitis C has made remarkable progress over the past two decades. For interferon-alpha monotherapy, sustained virological response rates were between 2 and 9% in genotype 1 and between 16 and 23% in genotypes 2 and 3. By adjusting treatment duration up to 48 weeks for genotype 1 and combining regular interferon-alpha with ribavirin, sustained response rates could be improved to 28 to 31% in genotype 1 and around 65% in genotypes 2 and 3. Attempts to further increase efficacy included the addition of amantadine without conclusive evidence up till now. With the recent introduction of long-acting pegylated interferon-alpha in combination with ribavirin, sustained virological response rates of 8o% can be obtained in genotypes 2 and 3. However, sustained virological response rates for patients with either genotype 1, nonresponse to prior treatment, cirrhosis or a combination of these characteristics are still less than 50%. In view of results with daily high-dose interferon-alpha induction in combination with prolongation of treatment duration up to 18 months, such patients might benefit from induction and prolonged PEG-IFN-alpha treatment and should be treated in an experimental setting.

Amantadine↗

PubMed2003

[The treatment of hepatitis C].

The recent advances in the antiviral therapy of hepatitis C have significantly lowered the threshold for offering such therapy to patients. Sustained virological response rates of 42-46% are achieved after 48 weeks of combination therapy with peginterferon alpha and ribavirin in patients with genotype 1 infection. In patients with a genotype 2 or 3 infection, 24 weeks of combination therapy leads to a sustained response rate of almost 80%. The U.S. National Institutes of Health consensus states that every patient with hepatitis C should be considered for antiviral therapy. Identification of the patients, selection for therapy, the provision of good information, guidance of the patient during therapy and a successful management of side effects lead to better treatment compliance and are of paramount importance in obtaining maximal therapeutic efficacy. Supportive guidance during substance abuse withdrawal programmes and the adequate use of selective serotonin reuptake inhibitors should be part of these measures.

Antiviral Agents↗

PubMed2003

Doctor to patient transmission of hepatitis B virus: implications of HBV DNA levels and potential new solutions.

Hepatitis B virus (HBV)-infected health care workers (HCWs) can infect patients undergoing exposure prone procedures. Until now reviews have focused on the problem of the HBeAg-positive HCWs. After transmission of HBV by HBeAg-negative surgeons, the focus of Public Health Policy in the UK and the Netherlands has changed from HBeAg status to serum HBV DNA level. Viral load and the volume of blood transmitted determine the transmission risk of HBV. We have estimated the number of infectious particles transmitted by needlesticks, in comparison with those attributed in maternal-fetal transfusion. The blood volume transmitted by needlestick is roughly 1-30% of that of delivery. As vertical transmission with maternal HBV DNA levels below 10(7) g Eq./ml is rarely documented, HBV transmission by needlesticks is, according to our assumptions, unlikely to occur with HBV DNA levels below 10(7) g Eq./ml. Sera of transmitting HCWs contained HBV DNA levels between 5.0 x 10(9) and 6.35 x 10(4) g Eq./ml. Interpretation of these levels is hampered as the sera were taken at least 3 months after transmission. To prevent both loss of expertise and nosocomial infection, highly viremic HCWs can be offered antiviral therapy. Lamivudine and alpha-interferon can now be complemented with adefovir, tenofovir and entecavir to provide effective new therapies for chronic HBV-infected HCWs.

Adenine↗