Long-term Outcome Of Chronic Hepatitis Research Articles

Higher hepatitis B core-specific T cell response is associated with a lower risk of clinical relapse after discontinuation of oral antiviral treatment

BackgroundHepatitis B virus (HBV)-specific T cell response is a major host immune response to control the virus. However, it is still unclear how it affects long-term outcomes of chronic hepatitis B patients, especially those who stop nucleos(t)ide analogue (NA) therapy. We aimed to explore whether the HBV-specific T cell response at the end of treatment (EOT) was associated with clinical outcomes. MethodsIn a prospective cohort study, 51 HBeAg-negative patients who discontinued NA therapy were enrolled. ResultsIn a mean follow-up of 25.3 months, 25 patients developed clinical relapse. We found that a stronger hepatitis B core (HBc)-specific T cell response at EOT was associated with a lower risk of clinical relapse. Compared to the low-response group, the high-response group had a lower risk of clinical relapse with hazard ratio of 0.21 (95% CI: 0.05–0.88). The high HBc-specific T cell response was associated with reduced surge of HBV DNA and HBcrAg during the first year of follow-up. The T cell response at EOT was comparable between different NA treatments. Notably, the overall HBV-specific T cell response could be partially restored along with clinical relapse; however, such reinvigorated T cell response was not associated with HBsAg seroclearance. ConclusionsA higher HBc-specific T cell response at EOT was associated with lower risk of clinical relapse and reduced surge of HBV DNA and HBcrAg levels off NA therapy.

LncRNA-HEIM Facilitated Liver Fibrosis by Up-Regulating TGF-β Expression in Long-Term Outcome of Chronic Hepatitis B.

BackgroundChronic liver fibrosis is an inevitable stage for the development of patients with chronic hepatitis B (CHB). However, anti-fibrotic therapies have been unsuccessful so far. The biological functions and molecular mechanisms of long non-coding RNAs (lncRNAs) in the host immune system during chronic hepatitis B virus (HBV) infection, especially in fibrosis, are still largely unknown.MethodThe total RNA of peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers (ASCs) or CHB receiving at least 8 years of anti-viral treatments was analyzed using Arraystar microarray and validated via quantitative real-time PCR (qRT-PCR). Correlation analysis was conducted based on correlation coefficients, Clusterprofile, and RNA Interactome Database (RAID). The functions of lncRNA in monocytes were determined via loss-of-function RNAi or gain-of-function lentivirus assays. The expression levels of mRNAs or proteins were evaluated using qRT-PCR, western blotting assay, or enzyme linked immunosorbent assays (ELISA).ResultsA total of 1,042 mRNA transcripts (630 up-regulated and 412 down-regulated) were identified being differentially expressed between ASC and CHB patients. Through enrichment analysis we focused on the transforming growth factor beta (TGF-β) signaling pathway and validated their expression in a larger cohort. Moreover, we found that lncRNA ENST00000519726 (lncRNA-HEIM) was highly expressed in monocytes and further up-regulated upon HBV infection. LncRNA-HEIM played an important role in CHB patients with long-term antiviral treatments, and its elevated expression was remarkably correlated with the TGF-β signaling pathway, especially with the two members namely TGF-β and SMAD4. Furthermore, altering the endogenous lncRNA-HEIM level in monocytes significantly affected the production of TGF-β, as well as the fibrosis of hepatic stellate cells by affecting the expression of collagen I and α-smooth muscle actin (α-SMA).ConclusionThese findings not only added knowledge to the understanding of the roles of which lncRNA-HEIM played in the activation of HSCs in CHB patients with long-term medication, but also provided a promising therapeutic target in the future treatment for liver fibrosis.

Current status of the treatment of chronic hepatitis B

Chronic hepatitis B caused by hepatitis B virus (HBV) infection is a global public health issue. Antiviral therapy for chronic HBV infection plays a critical role, and the goal of antiviral therapy is mainly defined by virological, serological, and biochemical parameters. As the two types of antiviral drugs approved for marketing, both interferon and nucleos(t)ide analogues can alleviate liver inflammation and liver fibrosis and reduce the incidence rates of liver cirrhosis and hepatocellular carcinoma. However, the ideal goal of antiviral therapy is functional cure, which significantly improves the long-term outcome of chronic hepatitis B. The limitation of current treatment is that it can inhibit HBV replication, but cannot clear the virus, with low serological clearance rates of HBeAg and HBsAg. Development of new drugs with the goal of functional cure and evaluation of the synergistic and combined effects of existing drugs are important directions for HBV treatment and development.

Okuda lecture: Challenges of hepatitis B in the era of antiviral therapy.

Nucleos(t)ide analogs (NAs) are effective, safe, and convenient antiviral therapy to suppress replication of hepatitis B virus, which can be translated into improved long-term outcome of chronic hepatitis B patients. The current recommended first-line NAs, namely, entecavir and tenofovir, are largely free from problems of drug resistance. Nonetheless, there are still a few challenges in the era of NA. First, the risk of hepatocellular carcinoma can only be reduced but not eliminated, particularly among cirrhotic patients. For cirrhotic patients who have persistent low-level viremia on NA, that is, partial responders, the risk of hepatocellular carcinoma is higher than those with complete viral suppression. The best strategy to manage partial responders to entecavir or tenofovir is uncertain. Second, immune-tolerant patients are very difficult to treat with NA. A significant proportion of immune-tolerant patients will have detectable viremia despite a few years of continuous NA treatment, and the rate of hepatitis B e-antigen seroconversion is very low. Third, most patients need long-term treatment as NA cannot eliminate covalently closed circular DNA in the hepatocytes. Some patients can consider stop NA according to treatment guidelines, but viral and clinical relapses often occur after treatment cessation. There is no concrete consensus on when one should stop NA in a hepatitis B e-antigen-negative patient among different treatment guidelines. New biomarkers such as hepatitis B surface antigen level can be used to select patients to stop NA, but the data are still preliminary.

Inactive hepatitis B carriers: outcomes of patients followed at Hôpital Principal de Dakar, Senegal.

The evolutive profile of inactive HBV carriers is variable. Patients can remain inactive, or may evolve into chronic active hepatitis or hepatocellular carcinoma. Aim: to describe the long-term outcome of chronic hepatitis B inactive carriers followed at Hôpital Principal de Dakar. This is a retrospective study including all inactive HBV carriers, followed since 2001, and with regular monitoring of at least 5 years. Transaminases, viral load and screening for hepatocellular carcinoma were performed every 6 to 12 months. We included 52 patients. The mean follow-up was 76.2 months (60-162), the mean age 36 years (13-62 years) and the sex ratio 0.93 (25 men, 27 women). Four patients (7.7%) had an ALT above the normal. Eleven patients (21.1%) had persistently elevated viral load greater than 2000 IU/ml, while in three cases (5.8%), this increase was transient. Twenty-six patients (50%) had a detectable viral load, but still below 2000 IU/ml. Twelve patients (23.1%) had an undetectable viral load for the duration of monitoring. Eleven patients (21.2%) underwent liver biopsy. The activity or fibrosis were minimal in all cases (A or F = 1) or absent (A or F = 0). Only four patients (7.7%), had HBs seroconversion after a follow-up of six, seven and ten years. There was no focal lesion or cirrhosis detected during the follow-up. After a follow-up of at least 5 years, inactive HBV carriers remain inactive in 92.3% of cases. Their evolutive profile is characterized by an absence of elevated liver enzymes but with fluctuations of the viral load. HBs seroconversion rate is low and the risk of progression to hepatocellular carcinoma almost nil.

Long-term outcome of chronic hepatitis C virus infection in a real-world setting: The German LOTOS study.

There are few large-scale, prospective studies comparing liver-associated events in treated and untreated patients with CHC managed in routine clinical practice. Patients with CHC were prospectively enrolled in a non-interventional study. Data from patients with available documentation who had either achieved a sustained virological response, or were non-responders, relapsers, or had virological breakthrough following treatment with peginterferon alfa-2a±ribavirin, or who had been diagnosed but never treated at least 3years previously, and who remained under medical observation were analyzed. Primary endpoint was liver-associated events (composite of decompensation/liver failure, ascites, hepatocellular carcinoma, or liver transplant/placement on a transplant list). In all, 1444 eligible patients were identified. Mean follow-up was 4.7 (standard deviation; SD 1.1) years. Patients with sustained virological response had a lower incidence of liver-associated events vs non-responders, relapsers, or virological breakthrough and never treated patients (1.7% vs 4.7% and 4.7% respectively). The proportion of patients with cirrhosis increased from baseline in the non-responders, relapsers, or virological breakthrough (6.8%-10.5%) and never treated group (3.7%-8.4%), with an associated increase in severity, but was unchanged in the sustained virological response group (2.1%). Event-free survival was significantly higher in sustained virological response patients (P=.0082). In this "real-world" cohort, the achievement of sustained virological response almost eliminated liver-related morbidity and mortality compared with patients who failed to achieve sustained virological response and those who were untreated. Overall, the LOTOS cohort highlights the importance of timely and effective treatment for patients with CHC.

Successful anti-viral treatment improves survival of patients with advanced liver disease due to chronic hepatitis C.

Long-term outcome of chronic hepatitis C patients with successful viral eradication seems to be promising. To evaluate mortality, incidence of hepatocellular carcinoma (HCC), liver failure and liver transplantation in sustained virological responders (SVR) and non-SVR patients with different stages of fibrosis. Seven hundred and fourteen patients with a follow-up of 7.2 (1-21.1) years (age: 51.4 ± 12.0 years, 276 female, IFN-monotherapy: n = 19, IFN/RBV: n = 122, peg-IFN/RBV: n = 573, SVR: 551, non-SVR: 163) were studied. Two hundred and ten of 540 patients with a liver biopsy prior to treatment had advanced stages of fibrosis (Metavir F3/F4). Forty-eight patients died during follow-up, 15 with SVR and 33 without (P < 0.001). Five- and 10-year mortality rates were 1.8% (10/551) and 2.7% (15/551) in the SVR group and 8.6% (14/163) and 19.1% (31/163) in the non-SVR patients (P < 0.001). In 29 patients, decompensation of liver disease [SVR: 9 (1.6%) vs. non-SVR: 20 (12.3%); P < 0.001] occurred and in 29 patients, HCC developed during follow-up [SVR: 10 (1.8%) vs. non-SVR: 19 (11.7%); P < 0.001]. Non-SVR was an independent predictor for developing (i) HCC [HR: 2.36 (95% CI: 1.07-5.23; P = 0.034], (ii) liver-related complications [HR: 2.62; (95% CI: 1.18-5.81; P = 0.018] and (iii) mortality (HR: 3.46; 95% CI: 1.91-6.29; P < 0.001). For patients with early stages of fibrosis (F0-F2), a survival benefit of SVR patients could not be demonstrated. Successful anti-viral therapy decreases mortality, incidence of hepatocellular carcinoma and liver failure in patients with advanced fibrosis. However, hepatocellular carcinoma development or liver failure are not prevented completely, and further follow-up of patients is advisable.

PIN6 - Long-Term Outcomes of Chronic Hepatitis C in the Population of Newly Diagnosed Russian Patients

To predict the future incidence of chronic hepatitis C in Russia and assess potential impact of the available antiviral therapies (pegylated interferon a-2a/a-2b or standard interferon a-2b combined with ribavirin) on long-term morbidity and mortality rates in the population of newly diagnosed Russian patients with chronic hepatitis C. Based on the national epidemiologic data and published natural history studies, the prognostic Markov model was developed. Depending on the results of antiviral therapy, patients’ flows over 25-year time frame were simulated. End points of interests included: the incidence of compensated and decompensated cirrhosis, hepatocellular carcinoma and cumulative time that patients will spend in each state, the number of patients, who will require liver transplantation, and HCV-related mortality rates. During years 2013-2017 about 276,000 new cases of chronic hepatitis C will be diagnosed in Russia. After 25 years since being diagnosed 130, 189 and 227 of 1,000 patients received pegylated interferon a-2a, pegylated interferon a-2b and standard interferon a-2b, respectively, will develop compensated cirrhosis. The cumulative time that patients will spend in compensated cirrhosis state will be 848, 1,218 and 1,482 patient-years, respectively. During the established time frame, there will be expected 25, 36 and 43 cases of hepatocellular carcinoma and 35, 51 and 62 HCV-related deaths. 28, 40 and 49 patients, respectively, will require liver transplantation. The findings from the present study provide the opportunity to plan volumes of medical care that will be required to Russian patients with chronic hepatitis C during 25 years since disease was first diagnosed. The treatment with pegylated interferon alfa-2a is considered the most preferable strategy due to considerably lower long-term morbidity and mortality rates as compared to pegylated interferon a-2b and standard interferon a-2b treatment.

Long‐term outcome of chronic hepatitis C after sustained virological response to interferon‐based therapy

Although the short-term benefits of a sustained virological response (SVR) to interferon-based therapies of chronic hepatitis C (CHC) are well known, the long-term consequences of SVR are less clear. To assess changes in markers of disease activity and fibrosis in patients followed up to 23 years post-SVR. The first 103 SVR patients (from 1984 to 2003) at the National Institutes of Health Clinical Center were evaluated. Serum markers before treatment and at the last visit were compared. Evaluations after 2007 included transient elastography (TE). Of 103 patients, three subsequently relapsed 0.7, 6.3 and 6.5 years post therapy. The remaining 100 patients (56 men, mean age 56 years) maintained SVR at final follow-up. No patients developed hepatic decompensation, but one with pre-treatment cirrhosis died 12 years post SVR of hepatocellular carcinoma. In comparison to pre-treatment values, markers improved at follow-up, including mean ALT (152-27 U/L), AST (87-24 U/L), alkaline phosphatase (78-69 U/L), IgG (1463-1113 mg/dL), platelet count (209 000-239 000/μL) and AST to platelet count ratio index (APRI: 1.31-0.33). TE was performed in 69 patients and was normal (<7.0 kPA) in 60%, moderately elevated (7.1-13.8) in 31% and cirrhotic range (>13.8) in 9%. TE and platelet counts at follow-up correlated with fibrosis on pre-treatment liver biopsy (P < 0.001). In 97% of patients with CHC, SVR is durable without evidence of disease progression, although some degree of hepatic fibrosis may persist and patients with pre-treatment cirrhosis are at continuing low risk for hepatocellular carcinoma.

Moderate, excessive or heavy alcohol consumption: each is significantly associated with increased mortality in patients with chronic hepatitis C

The impact of moderate alcohol consumption on long-term outcomes of chronic hepatitis C (CH-C) infected patients remains controversial. To assess the impact of moderate alcohol consumption on long-term outcomes of CH-C patients using population-based data. Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES III)-mortality linked files. Alcohol consumption was estimated as grams/day. Multivariate Cox proportional hazards model was utilized to assess the effects of CH-C and alcohol consumption on mortality (all causes, cardiovascular disease, and liver disease). A total of 8985 participants were included as the study cohort. Of these, 218 had CH-C. The follow-up time was 162.95months for CH-C and 178.27months for controls. CH-C patients had increased risk for both overall mortality and liver-related mortality. CH-C patients with excessive alcohol consumption had even higher risks for overall mortality and liver-related mortality. The risk of overall mortality associated with CH-C increased with moderate alcohol consumption of 1-19g/day and heavy alcohol consumption ≥30g/day. Although chronic hepatitis C is associated with increased risks for overall and liver-related mortality, these risks are even higher for patients consuming moderate and excessive amounts of alcohol.

Clinical course of chronic hepatitis B patients who were off-treated after lamivudine treatment: analysis of 138 consecutive patients

Background/aimsLittle is known about the long-term outcome of chronic hepatitis B (CHB) patients who discontinued antiviral therapy. We intended to analyze the long-term outcome of CHB patients who discontinued lamivudine therapy and to evaluate predictors for post-treatment outcome.Material/methodsFrom 2007 to 2008, 138 lamivudine off-treated CHB patients with alanine aminotransferase normalization were consecutively enrolled. Post-treatment virologic relapse, biochemical breakthrough, hepatitis flare, and retreatment results were retrospectively analyzed.ResultsAmong 138 patients, 102 were initially HBeAg-positive at the start of lamivudine treatment. Virologic relapse, biochemical breakthrough, and hepatitis flare were observed in 45.2, 52.9, and 12.7% of HBeAg-positive and 29.4, 30.6, and 8.3% of HBeAg-negative patients during the median follow-up of 28 and 30 months, respectively. The cumulative virologic relapse and biochemical breakthrough rates were significantly lower in patients with HBV DNA <50 copies/mL than 50-104 copies/mL at lamivudine cessation. Hepatitis flare was observed in 4.8 and 11.8% of HBeAg-positive and HBeAg-negative patients with HBV DNA <50copies/mL, respectively. Thirty-eight among 138 patients received retreatment and most of them achieved biochemical (37/38) and virologic response (35/38) within 1 year of retreatment. Undetectable serum HBV DNA (<50 copies/mL) and young age at lamivudine cessation were inversely associated with virologic relapse. Undetectable HBV DNA at cessation, female, and initial HBeAg-negative were inversely associated with biochemical breakthrough.ConclusionsPost-treatment virologic relapse and biochemical breakthrough incidence were low in patients who achieved undetectable viral titer at lamivudine cessation. Retreatment after biochemical breakthrough or virologic relapse was safe and effective. Intermittent antiviral therapy might be cautiously considered in appropriately selected CHB patients.

Long-term outcomes of chronic hepatitis C patients treated with pegylated interferon 2a plus ribavirin in Iran

Accepted 14 December, 2011 Combination of interferon alfa and ribavirin is the first therapeutic choice in chronic hepatitis C. The aim of this study is to assess long-term outcome of chronic hepatitis C patients treated with pegasys plus ribavirin. We evaluated a cohort of 49 chronic hepatitis C patients who were treated for 48 weeks with pegylated interferon alpha 2a and ribavirin and followed up till week 72 in order to evaluate sustained virological response (SVR) and more than 70% of the patients were followed up over 5 years. In week 72 (the time of achieving SVR), 28 patients were found with SVR (57.14%), 10 were relapse and 11 no response. Long-term viral response (LTR) was defined as remained HCV RNA negativity during long time after SVR. LTR was found in 96.3% of those who had SVR. Late viral relapse occurred within first year after SVR in one patient. Three of 10 patients (30%) who were retreated, obtained SVR. Among the whole patients, 4 had cirrhosis in pre-treatment liver biopsy in which 2 of them got progress to clinical cirrhosis during follow up. No hepatocellular carcinoma occurred during the follow up. The patients who achieved SVR; remained in it chronically and had predictable outcome throughout longterm.

The effect of NAFLD (non-alcoholic fatty liver disease) on long-term outcome of chronic hepatitis B in Iranian patients

Background: The influence of Non-Alcoholic Fatty Liver Disease on the outcome of chronic hepatitis B disease, including viral, biochemical and histologic characteristics, in Iranian patients is not yet fully un- derstood. Aim: To evaluate the effect of Non-Alcoholic Fatty Liver Disease (NAFLD) on long-term histology- cal, biochemical and viral outcome of chronic he- pa-tictis B in Iranian patients. Methods: We retro- spec-tively evaluated 94 “e Ag” negative chronic hepatitis B patients (with NAFLD: 44, without NAFLD: 50). Non-Alcoholic Fatty Liver Disease was diagnosed based on liver biopsy according to Kleiner classifica-tion. Liver biopsy was done for all patients. Serologi-cal and biochemical variables were evaluated with repeated measure analysis. Results: Non-Alcoholic Fat- ty Liver Disease (NAFLD) was present in 47% of the patients (44 out of 94 patients). In the NAFLD group, increase in AST, ALT, stage (P = 0.002), grade, and total score of liver biopsy were independently related to non-alcoholic fatty liver disease, while HBV-DNA viral load did not correlate with the presence of a fatty liver. Conclusion: Abnormalities of liver enzymes and liver histopathology are more prevalent in concurrent chronic hepatitis B and Non-Alcoholic Fatty Liver Disease (NAFLD).

13C-Aminopyrine breath test accurately predicts long-term outcome of chronic hepatitis C

Although numerous non-invasive tests are currently available to explore liver function and disease activity in patients with HCV-related chronic diseases, none of these indicate the likelihood of disease progression in the individual patient. We aimed at assessing the prognostic ability of (13)C(2)-aminopyrine breath test ((13)C-ABT) in the prediction of liver fibrosis progression in patients with HCV chronic hepatitis who prospectively entered a long-term follow-up. Fifty patients with HCV-related chronic disease who underwent paired liver biopsy (at baseline and after a mean period of 86 months) were included in the study. (13)C-ABT was carried out at baseline and every 3 years. Histological progression was defined as increase of at least 2 fibrosis units according to Ishak score. Fourteen patients progressed of at least 2 fibrosis units during the follow-up. These patients were more frequently infected with a HCV-1b genotype and had, at baseline, a significantly older age, higher BMI, AST levels, and AST to platelet ratio index (APRI). (13)C-ABT was altered in 57% of cases at baseline and in 100% of the cases at 3-year follow-up. In the univariate analysis, age (p=0.005), BMI (p=0.006), platelet count (p=0.03), AST (p=0.012) and ALT (p=0.04) levels, APRI (p=0.03), and baseline (13)C-ABT results (p<0.0001) were all independently associated with progression of liver fibrosis. By Cox's multiple regression analysis, the (13)C-ABT was the only covariate that significantly predicted liver fibrosis progression (HR 6.7; 95% CI 2.3-20.1; p<0.001). (13)C-ABT accurately predicts the risk of disease progression in patients with HCV-related chronic hepatitis.

Longterm outcome of chronic hepatitis C virus infection in a real-world setting: the German LOTOS study

Longterm outcome of chronic hepatitis C virus infection in a real-world setting: the German LOTOS study

Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin

To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

An updated follow‐up of chronic hepatitis C after three decades of observation in pediatric patients cured of malignancy

The aim of the study was to evaluate the clinical characteristics and the long-term outcome of chronic hepatitis C in a cohort of Caucasian children cured of pediatric malignancy. The study population included 83 consecutive patients, referred to our Center with a diagnosis of leukemia/lymphoma (50) or solid tumors (33) between 1977 and 1989 and infected with hepatitis C virus (HCV) during chemotherapy. At enrollment 77 subjects were HCV-RNA positive. After a median follow-up of 21 years (range 13-36), a sustained virological response (SVR) was obtained in 3 of 29 patients (10%) treated with interferon (IFN), in 1 of 3 patients (33%) treated with IFN and ribavirin, and in 5 of 11 patients (42%) treated with pegylated-IFN and ribavirin (P = 0.03). Forty-two patients remained untreated and only one (2.5%) cleared viremia. Four of 77 patients (5%) developed cirrhosis while other 4 patients died of causes not related to liver. At last follow-up, 72% of HCV-RNA positive patients had abnormal ALT. In patients cured of pediatric malignancy chronic hepatitis C tends to run an indolent course during childhood and adolescence but more than 70% of treated and more than 80% of untreated cases children maintained HCV viremia. Moreover, after 2-3 decades of observation, 60% of HCV-RNA positive patients had abnormal ALT and 5% had developed cirrhosis. Among treated patients, IFN or pegylated-IFN and ribavirin obtained the higher rate of HCV-RNA clearance.

W1807 Long-Term Outcome of Chronic Hepatitis B Patients Initially Treated with Entecavir in a Real-Life Clinical Setting

W1807 Long-Term Outcome of Chronic Hepatitis B Patients Initially Treated with Entecavir in a Real-Life Clinical Setting

Hepatitis B therapy in children

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease throughout the world, leading to cirrhosis and hepatocellular carcinoma in many individuals. Children are more likely to develop chronic HBV infection as they demonstrate greater immunotolerance to the virus, and response to therapy in children remains disappointing. Three therapeutic agents for chronic HBV infection in children have been approved in the USA, including standard IFN-α, lamivudine and adefovir. IFN-α has been the most effective (∼30% hepatitis B e antigen [HBeAg] seroconversion; 10% hepatitis B surface antigen [HBsAg] seroconversion), although benefits are primarily observed in children with alanine aminotransferase levels over two-times the upper limit of normal and must be weighed against significant side effects. Studies comparing the long-term outcome of chronic hepatitis B in children treated with IFN-α and in untreated controls show that the rate of anti-HBeAb seroconversion tends to overlap in treated and untreated patients within a few years of follow-up, suggesting that IFN-α simply accelerates a spontaneous event. Lamivudine’s virologic response rates mirror those of IFN-α (23–31% HBeAg seroconversion) with easier administration and a better safety profile but lower HBsAg seroconversion (2–3%) and high rates of drug resistance. Adefovir data show low rates of resistance and a good safety profile, but virologic response was limited to adolescent patients and was lower than that of lamivudine (16% HBeAg seroconversion; <1% HBsAg seroconversion). Entecavir and tenofovir, both approved therapies for adults with chronic HBV infection, are in trials for use in children. Future therapies will probably include these agents as well as combined therapies. Finally, watchful waiting of children is an option since current therapies are only 30% effective at best, although the long-term impact of therapy in childhood on rates of cirrhosis and hepatocellular carcinoma remains unknown.

Long-Term Outcome of Chronic Hepatitis B Patients Initially Treated with Adefovir Dipivoxil in a Community Practice

Long-Term Outcome of Chronic Hepatitis B Patients Initially Treated with Adefovir Dipivoxil in a Community Practice