Severe Form Of Viral Hepatitis Research Articles

Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options.

Chronic hepatitis D is the most severe form of viral hepatitis, affecting ∼20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs. Thus, the only clinical regimen for HDV is IFNα, which shows some efficacy but long-term virological responses are rare. Insights into the receptor-mediated entry of HDV, and the observation that HDV assembly requires farnesyltransferase, have enabled novel therapeutic strategies to be developed. Interference with entry, for example through blockade of the HBV-HDV-specific receptor sodium/taurocholate cotransporting polypeptide NTCP by Myrcludex B, and inhibition of assembly by blockade of farnesyltransferase using lonafarnib or nucleic acid polymers such as REP 2139-Ca, have shown promising results in phase II studies. In this Review, we summarize our knowledge of HDV epidemiology, pathogenesis and molecular biology, with a particular emphasis on possible future developments.

Evidence of an Exponential Decay Pattern of the Hepatitis Delta Virus Evolution Rate and Fluctuations in Quasispecies Complexity in Long-Term Studies of Chronic Delta Infection.

Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand hepatitis B e antigen seroconversion, and has helped to predict whether hepatitis C infection will resolve or become chronic. It is likely that characterization of the hepatitis delta virus (HDV) quasispecies will ultimately have similar value for the management of this infection. This study sought to determine the RNA evolution rates in serum of chronic hepatitis delta (CHD) treatment-naïve patients, using next-generation sequencing methods. The region selected for study encompassed nucleotide positions 910 to 1270 of the genome and included the amber/W codon. Amber/W is a substrate of the editing process by the ADAR1 host enzyme and is essential for encoding the 2 delta antigens (HDAg). The amber codon encodes the small (unedited) HDAg form and the W codon the large (edited) HDAg form. The evolution rate was analyzed taking into account the time elapsed between samples, the percentage of unedited and edited genomes, and the complexity of the viral population. The longitudinal studies included 29 sequential samples from CHD patients followed up for a mean of 11.5 years. In total, 121,116 sequences were analyzed. The HDV evolution rate ranged from 9.5x10-3 to 1.2x10-3 substitutions/site/year and showed a negative correlation with the time elapsed between samples (p<0.05). An accumulation of transition-type changes was found to be responsible for higher evolution rates. The percentages of unedited and edited genomes and the quasispecies complexity showed no relationships with the evolution rate, but the fluctuations in the percentages of genomes and in complexity suggest continuous adaptation of HDV to the host conditions.

Limited Genetic Diversity of Hepatitis B Virus in the General Population of the Offin River Valley in Ghana.

Hepatitis B virus (HBV) infections account for approximately 780,000 deaths per year, most of which occur in the developing world. Co-infection with HBV and hepatitis delta virus (HDV) may lead to the most severe form of viral hepatitis. In Ghana, knowledge on the prevalence of HBV and HDV in the general population is scanty and the few genetic analyses of the prevailing HBV genotypes are dating back more than a decade. In the present study, 1,323 serum samples from individuals living in a rural area (Offin river valley) of Ghana were analyzed for the presence of the hepatitis B surface antigen (HBsAg). Positive sera were subsequently tested for the presence of anti-HDV antibodies. A total of 107 (8%) sera were HBsAg positive with an 8.4% prevalence of anti-HDV antibodies among the HBsAg positives. Phylogenetic analysis based on HBV pre-S/S sequences, attributed all 52 typable samples to genotype E. All belonged to serotype ayw4. While 19 sequences clustered with those from a number of African countries, the other 33 formed a separate cluster distinguished by an intergroup mean distance of 1.5% from the pan-African HBV/E cluster. Successful implementation of HBV vaccination in the region was reflected by the low HBsAg carrier rate of 1.8% among children ≤11 years.

Delta Hepatitis: New Approaches to Therapy

Hepatitis delta virus (HDV) infection is a neglected disease despite causing the most severe form of viral hepatitis. Over 15 million people are infected worldwide. IFN-α is largely inefficient and poorly tolerated. The discovery of sodium taurocholate cotransporting polypeptide as the cell receptor for HBV (and consequently for HDV) has allowed development of viral entry inhibitors (i.e., myrcludex-B). More recently, prenylation inhibitors (i.e., lonafarnib) that disrupt virion assembly are being tested. At this time, sustained suppression of HDV replication is the primary goal of hepatitis delta treatment, being associated with normalization of liver enzymes and histological improvement. The lack of persistent forms of HDV-RNA could provide unique opportunities for hepatitis delta cure using specific antivirals, even in the face of persistent HBV cccDNA.

Current Management of HBV/HDV Coinfection and Future Perspectives

The hepatitis delta virus (HDV) is the smallest virus known to infect humans. It depends on the helper function of the hepatitis B surface antigen (HBsAg), and HDV infection is therefore only possible in patients infected with hepatitis B. Worldwide, an estimated 10–20 million individuals are coinfected with HDV. Migration of patients from highly prevalent areas accounts for the majority of hepatitis delta cases in Europe and North America. Chronic hepatitis delta is the most severe form of viral hepatitis with accelerated fibrosis progression, more frequent development of liver cirrhosis, earlier hepatic decompensation, and reduced survival rates compared to HBV monoinfection. Currently, only pegylated interferon alfa can be used to treat HDV, leading to HDV RNA suppression in 25–47 % of cases. However, interferon alfa rarely induced cure of HDV infection as long-term relapses have been described in many patients. Currently, alternative treatment options like prenylation inhibitors and HBV entry inhibitors are tested in early clinical trials. Moreover, other novel compounds aiming to achieve serological cure of HBV infection would be of particular importance for hepatitis delta as HBsAg elimination would be the ultimate goal also for hepatitis delta. In this review, we summarize the current state of the art on the management of HDV infection and highlight some perspectives for novel therapies.

Herpes Simplex Hepatitis

Introduction: Herpes Simplex Virus Hepatitis (HSVH) is a severe form of viral hepatitis with very high mortality that can be averted if diagnosed and treated early as seen in the patient below. Case: A 59 y/o M with history of diabetes mellitus (DM), hypertension and seizures was admitted with 2-week history of abdominal pain, fever and mild confusion. He denied recent sexual activity, genital/oral rash, new medications, chronic liver disease or alcohol use. Labs: AST/ALT gradually increased from baseline normal to 1670/800, leukopenia and thrombocytopenia (L&T), negative for ALP, bilirubin, INR, toxicology, hepatitis A/B/C, autoimmune hepatitis panel, septic screen, HIV, CT head, liver CT/ultrasound. HSV IgM and IgG were positive. Liver biopsy revealed 30% patchy lobular necrosis containing nuclei with HSV I&II viral cytopathic effects including ground glass changes and margination of the chromatin but was negative for CMV and adenovirus. He was started on Acyclovir and showed dramatic improvement in mentation and improvement of AST/ALT and L&T back to normal. Discussion: HSVH first described in 1969, is a rare, cause of acute liver failure (ALF) that often leads to liver transplantation or death. It accounts for < 1% of all causes of ALF and < 2% of all viral causes of ALF. It is often seen in immunocompromised patients as seen in our patient with poorly controlled DM (A1c 10.6) and pregnant women. It is associated with impaired cellular and macrophage immunity with consequent antigen dissemination. It is a diagnostic challenge due to lack of specificity of symptoms and signs with about 58% of diagnosis made post-mortem. Mucocutaneous lesions are often lacking in > half of cases of HSVH as seen in our patient. When present, skin biopsy in the appropriate clinical setting can provide a definitive diagnosis especially when coagulopathy precludes liver biopsy. Elevated transaminases often > 1000 occur during the acute stages due to hepatic necrosis. L&T are often present but resolve with treatment as seen in our case. HSV serum serologies are insensitive even in advanced disease. Radiological findings are usually non-specific. Liver biopsy is the gold standard for diagnosis. Early treatment with Acyclovir decreases mortality. Conclusion: HSVH is a rare, potentially fatal viral cause of ALF that can be appropriately treated if detected and treated early. A high index of suspicion should be maintained especially in the appropriate clinical setting.

Therapy of Delta Hepatitis.

Delta hepatitis is the less frequently encountered but most severe form of viral hepatitis. Acute delta hepatitis, as a result of coinfection with hepatitis B and hepatitis delta, is rare, but may lead to fulminant hepatitis, and no therapy exists for this form. Chronic delta hepatitis (CDH) mostly develops as a result of superinfection of a hepatitis B surface antigen (HBsAg) carrier with hepatitis delta virus (HDV). In general, HDV is the dominant virus. However, a dynamic shift of the dominant virus may occur with time in rare instances, and hepatitis B virus (HBV) may become the dominant virus, at which time nucleos(t)ide analog therapy may be indicated. Otherwise, the only established management of CDH consists of conventional or pegylated interferon therapy, which has to be administered at doses used for hepatitis B for a duration of at least 1 year. Posttreatment week-24 virologic response is the most widely used surrogate marker of treatment efficacy, but it does not represent a sustained virologic response, and late relapse can occur. As an easy-to-use simple serological test, anti-HDV-immunoglobulin M (IgM) correlates with histological inflammatory activity and clinical long-term outcome; however, it is not as sensitive as HDV RNA in assessing treatment response. No evidence-based rules for treating CDH exist, and treatment duration needs to be individualized based on virologic response at end of treatment or end of follow-up. Effective treatment may decrease liver-related complications, such as decompensation or liver-related mortality. In patients with decompensated cirrhosis, interferons are contraindicated and liver transplantation has to be considered. Alternative treatment options are an urgent need in CDH. New treatment strategies targeting different steps of the HDV life cycle, such as hepatocyte entry inhibitors or prenylation inhibitors, are emerging and provide hope for the future.

Pegylated Interferon α Therapy in Chronic Delta Hepatitis: A One-Center Experience.

Background:The only established therapy for chronic viral delta hepatitis, the most severe form of viral hepatitis is treatment with pegylated-interferon α (Peg IFN α).Objectives:In this study, we aimed to determine the efficacy of pegylated-interferon α 2a (Peg-IFN α 2a) and 2b (Peg IFN α 2b) in the treatment of patients infected with chronic delta hepatitis virus.Patients and Methods:The sample size was based on available patients potentially to be recruited. Data of 63 patients receiving either Peg IFN alpha 2a or Peg IFN alpha 2b were retrospectively assessed in the present cohort study performed in Turkey. Of 56 patients completed the study, 41 received Peg IFN α 2a and 15 received Peg IFN α 2b for 12 months. Patients were evaluated for biochemical and virological responses at the end of given treatment and six months after the treatment.Results:Stage of fibrosis was found high in both groups (85.4% vs. 86.7%), while cirrhosis was higher in the group of Peg IFN α 2b (53.3% vs. 34.1%). At the end of treatment, either hepatitis delta virus RNA (HDV RNA) alone or both HDV RNA and hepatitis b virus DNA (HBV DNA) had negative results in 32% of patients. Although HDV RNA negativity was sustained in 30.3% of patients, negativity of both HDV RNA and HBV DNA was decreased to 19.6% six months after completion of the treatment. HBV DNA became positive in one third of patients with response at six months after completion of the treatment (10.7% of all patients). HDV RNA negativity at month six was found as a predictor of positive response. No significant difference was found between Peg IFN α 2a and Peg IFN α 2b for virological response rate.Conclusions:Treatment with Peg IFN α achieved a sustained negativity of HDV RNA in about one third of patients. Duration of Peg IFN α therapy might be prolonged to at least 24 months or more to prevent the occurrence of Hepatitis B virus (HBV) relapse encountered six months after completion of the treatment.

Biomarkers to predict the clinical outcome of hepatitis delta

Background: Hepatitis delta is the most severe form of viral hepatitis. Pegylated interferon alpha is effective in only 25 – 30% of patients and associated with frequent side effects. Thus, it is crucial to identify patients with benign courses of liver disease who may not require treatment.

Development and evaluation of a baseline‐event‐anticipation score for hepatitis delta

Hepatitis delta is considered the most severe form of viral hepatitis, but variables associated with disease progression are poorly defined. This study aimed to identify risk factors associated with worse clinical outcome in patients with hepatitis delta and to develop a clinical score to determine their risk of experiencing liver-related morbidity or mortality. We followed 75 HBsAg–anti-HDV-positive patients with hepatitis delta for up to 16 years (median 5 years). The baseline-event-anticipation score (BEA score) was developed based on variables associated with the development of liver-related clinical complications. Age, region of origin, presence of cirrhosis, albumin, INR, hyperbilirubinemia and thrombocytopenia were all associated with the development of an event in the training cohort. The BEA score included age, sex, region of origin, bilirubin, platelets and INR. Points were allocated according to hazard ratios, and three risk groups were defined: BEA-A mild risk, BEA-B moderate risk and BEA-C high risk. Hazard ratios of BEA-B and BEA-C patients for liver-related clinical endpoints were 9.01 and 25.27 vs BEA-A with an area under curve of the receiving operating characteristic curve of 0.88. The accuracy of the BEA score was confirmed in two independent validation cohorts followed in Barcelona (n = 77) and Düsseldorf (n = 62). Delta hepatitis is associated with a very severe long-term outcome. The BEA score is easy to apply and predicts with a very high accuracy the development of liver-related complications in patients with hepatitis delta.

Dynamics of natural killer cell responses to hepatitis delta virus infection during the course of interferon alpha treatment (P6070)

Abstract Infection with the hepatitis delta virus (HDV) causes the most severe form of viral hepatitis. 15-20 million people are chronically infected with HDV. Hepatitis delta is believed to be an immune-mediated disease however adaptive immune responses against HDV are hardly detectable. This suggests a possible role of natural killer (NK) cells in the pathogenesis of HDV infection. To study this, we collected blood samples from 34 patients with hepatitis delta, 16 out of which were sampled during antiviral treatment with pegylated interferon alpha (peg-IFNalpha). Expression levels of activation and inhibitory NK cell receptors and multi-functional NK cell responses were assessed using 15-color flow cytometry. HDV infected patients exhibited higher baseline frequencies of NK cells. Peg-IFNalpha treatment was associated with a redistribution of NK cell subsets with increased numbers of CD56bright NK cells whereas total and CD56dim NK cells decreased. During treatment the most mature CD56dim NK cell subsets disappeared from the periphery and the frequency of immature CD56dim NK cells increased. Furthermore, the treatment resulted in decreased multi-functional NK cell responses against K562 cells, with and without additional IFNα stimulation. Taken together, we show that HDV infection increases the amount of NK cells. Furthermore our data suggest a reshaping of the NK pool by IFNα during treatment resulting in a loss of mature cells and decreased functional responses.

Hepatitis Delta Virus: A Peculiar Virus

The hepatitis delta virus (HDV) is distributed worldwide and related to the most severe form of viral hepatitis. HDV is a satellite RNA virus dependent on hepatitis B surface antigens to assemble its envelope and thus form new virions and propagate infection. HDV has a small 1.7 Kb genome making it the smallest known human virus. This deceivingly simple virus has unique biological features and many aspects of its life cycle remain elusive. The present review endeavors to gather the available information on HDV epidemiology and clinical features as well as HDV biology.

Extracorporeal methods of detoxication in the complex treatment hepatitis

Aim. To study the effectiveness of extracorporeal methods of detoxification in the complex treatment of hepatitis’. Methods. Observed were 39 servicemen who received treatment for viral hepatitis’ A, B and C, at the age of 18 to 40 years (in 13 people - a severe form of viral hepatitis A, in 3 - a moderate form of hepatitis A, in 18 - severe form, and in 5 - moderate form of hepatitis B and C). Diagnostic criteria for chronic viral hepatitis’ include data of virological, clinical, laboratory and morphological studies. Percutaneous needle biopsy of the liver made it possible to make a diagnosis during chronic viral hepatitis based on a histological study, to monitor the effectiveness of treatment, to exclude congenital metabolic liver disease. Results. On the background of administration of the traditional scheme of treatment (regimen, diet, interferon therapy, detoxification, metabolic support, glucocorticosteroids, immune stimulants, antihistamines, bile acid absorbents, adsorbents, cholagogues drugs, hepatoprotectors), the average duration of treatment of viral hepatitis was 30-45 days. During the usage of extracorporeal methods of detoxification (plasmapheresis and hemosorption) the duration of treatment was significantly shorter. Conclusion. The usage of extracorporeal detoxification methods can shorten the treatment of viral hepatitis A, B and C.

Update on the Management of HBV-HDV Coinfection

Hepatitis Delta is caused by coinfection with the hepatitis B virus and the hepatitis D virus and has to be considered as the most severe form of viral hepatitis. HDV infection may affect between 15 and 20 Million individuals worldwide with significant regional differences of HDV prevalence rates. The diagnosis of hepatitis delta in HBsAg-positive individuals is based on the detection of HDV antibodies and HDV RNA. Interferon alpha remains the only effective treatment as currently available nucleoside or nucleotide analogous are not effective against HDV. Recent trials showed that about 25 % of HDV-infected patients may clear HDV RNA by therapy with pegylated interferon alpha. Liver transplantation remains the only treatment option for the majority patients with advanced liver disease

Treatment of Chronic Delta Hepatitis: A Nine-Year Retrospective Analysis

: Background: Chronic delta hepatitis is the most severe form of viral hepatitis, for which interferon administration is the only available treatment. However, the efficacy of interferon treatment is affected by the dose and duration of treatment, and relapse rates are high. Objectives: In this study, we sought to evaluate the efficacy of treatment with pegylated interferon and observe the relapse rates of delta hepatitis after treatment.Patients and Methods: Forty-six patients with chronic delta hepatitis were retrospectively studied between January 2002 and December 2010. Patients were evaluated for biochemical, virological, and histological responses. They were then followed-up for at least 1 year after discontinuation of the treatment.Results: All the 46 patients in the study received PEG-IFN therapy. Of the 46 patients, 25 were treated with PEG-IFN for 1 year and 21 were treated for 2 years. Sixteen patients (34.7%) showed a biochemical response, 27 (58.6%) showed a virological response, and 39 (84.7%) showed a histological response. Sustained virological and biochemical responses were achieved in 41% and 47.8% of the patients, respectively. Sixteen (84.2%) patients of the 19 with high levels of hepatitis delta virus RNA (HDV RNA) (HDV RNA level > 1 × 105) and 10 (71.4%) of the 14 patients with high titers of hepatitis B surface antigen (HbsAg) (HbsAg > 102 IU/mL) at the beginning of the treatment showed relapse after treatment.Conclusions: We found no significant differences between 1-year and 2-year treatments. However, the relapse rate was lower in the 2-year treatment group. Higher HDV RNA and HbsAg levels before treatment were associated with higher relapse rates. Younger age was a significant factor in predicting response. Keywords: Chronic delta hepatitis; Pegylated interferon; Treatment Implication for health policy/practice/research/medical education:There are still many unresolved questions regarding delta hepatitis. This study aims to investigate every aspect of delta hepatitis and recommended all clinicians engaged in the treatment of patients with hepatitis delta. Please cite this paper as: Gulsun S, Tekin R, Bozkurt F. Treatment of Chronic Delta Hepatitis: A Nine-Year Retrospective Analysis. Hepat Mon. 2011;11(9):731-5. DOI: 10.5812/kowsar.1735143X.728 ©2011 Kowsar M.P.Co. All rights reserved.

Hepatitis D virus‐specific cytokine responses in patients with chronic hepatitis delta before and during interferon alfa‐treatment

Hepatitis delta is caused by infection with the hepatitis D virus (HDV) and is considered the most severe form of viral hepatitis. Treatment options for hepatitis delta are limited, with only 25% of patients responding to interferon (IFN)-alfa-based therapies. The role of the adaptive immune system in controlling HDV infection during spontaneous or treatment-induced viral clearance is not well understood. We studied HDV-specific cytokine production of peripheral blood mononuclear cells stimulated with HDV peptide pools as well as serum cytokine levels in well-characterized patients with chronic HDV infection before and during pegylated-interferon-alfa±adefovir therapy. Hepatitis D virus-specific interleukin (IL)-2, IFN-γ-, interferon-inducible protein-10 and IL-10-responses were detectable in 53%, 35%, 65% and 6% of hepatitis delta patients. HDV-specific IFN-γ responses tended to be more common in patients with low HDV viral loads. HDV-specific cytokine responses declined during pegylated (PEG)-IFNa therapy and patterns of changes were associated with the treatment response. Serum cytokine levels also showed distinct changes during PEG-IFNa treatment. We suggest that cellular HDV-specific immune responses contribute to the control of HDV infection and that cytokine responses may indicate response to type-I-IFN-based antiviral therapy of hepatitis delta.

Reviving pegylated interferon as a therapeutic agent for hepatitis D: No more room for nucleos(t)ides?

Chronic infection with hepatitis B virus and hepatitis delta virus (HDV) results in the most severe form of viral hepatitis. There is no currently approved treatment. We investigated the safety and efficacy of 48 weeks of treatment with peginterferon alfa-2a plus adefovir dipivoxil, peginterferon alfa-2a alone,and adefovir dipivoxil alone. We conducted a randomized trial in which 31 patients with HDV infection received treatment with 180 lg of peginterferon alfa-2a weekly plus 10 mgof adefovir daily, 29 received 180 lg of peginterferon alfa-2a weekly plus placebo, and 30 received 10 mg of adefovir alone weekly for 48 weeks. Follow-up was conducted for an additional 24 weeks. Efficacy end points included clearance of HDV RNA,normalization of alanine aminotransferase levels, and a decline in levels of hepatitis B surface antigen (HBsAg). The primary endpoint—normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48--was achieved in two patients in the group receiving peginterferon alfa-2a plus adefovir and two patients in the group receiving peginterferon alfa-2a plus placebo but in none of the patients in the group receiving adefovir alone. At week 48, the test for HDV RNA was negative in 23% of patients in the first group, 24% of patients in the second, and none of those in the third (P¼ 0.006 for the comparison of the first and third groups; P¼ 0.004 for the comparison of the second and third). The efficacy of peginterferon alfa-2a was sustained for 24 weeks after treatment, with 28% of the patients receiving peginterferon alfa-2a plus adefovir or peginterferon alfa-2a alone having negative results on HDV-RNA tests; none of the patients receiving adefovir alone had negative results. A decline in HBsAg levels of more than 1 log10 IU per milliliter from baseline to week 48 was observed in 10 patients in the first group, 2 in the second, and none in the third (P<0.001 for the comparison of the first and third groups and P¼0.01 for the comparison of the first and second). Treatment with peginterferon alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection.

Peginterferon plus Adefovir versus Either Drug Alone for Hepatitis Delta

Chronic infection with hepatitis B virus and hepatitis delta virus (HDV) results in the most severe form of viral hepatitis. There is no currently approved treatment. We investigated the safety and efficacy of 48 weeks of treatment with peginterferon alfa-2a plus adefovir dipivoxil, peginterferon alfa-2a alone, and adefovir dipivoxil alone. We conducted a randomized trial in which 31 patients with HDV infection received treatment with 180 μg of peginterferon alfa-2a weekly plus 10 mg of adefovir daily, 29 received 180 μg of peginterferon alfa-2a weekly plus placebo, and 30 received 10 mg of adefovir alone weekly for 48 weeks. Follow-up was conducted for an additional 24 weeks. Efficacy end points included clearance of HDV RNA, normalization of alanine aminotransferase levels, and a decline in levels of hepatitis B surface antigen (HBsAg). The primary end point--normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48--was achieved in two patients in the group receiving peginterferon alfa-2a plus adefovir and two patients in the group receiving peginterferon alfa-2a plus placebo but in none of the patients in the group receiving adefovir alone. At week 48, the test for HDV RNA was negative in 23% of patients in the first group, 24% of patients in the second, and none of those in the third (P = 0.006 for the comparison of the first and third groups; P = 0.004 for the comparison of the second and third). The efficacy of peginterferon alfa-2a was sustained for 24 weeks after treatment, with 28% of the patients receiving peginterferon alfa-2a plus adefovir or peginterferon alfa-2a alone having negative results on HDV-RNA tests; none of the patients receiving adefovir alone had negative results. A decline in HBsAg levels of more than 1 log(10) IU per milliliter from baseline to week 48 was observed in 10 patients in the first group, 2 in the second, and none in the third (P<0.001 for the comparison of the first and third groups and P = 0.01 for the comparison of the first and second). Treatment with peginterferon alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection. (Current Controlled Trials number, ISRCTN83587695.).

Treatment of Chronic Delta Hepatitis: A Nine-Year Retrospective Analysis

Chronic delta hepatitis is the most severe form of viral hepatitis, for which interferon administration is the only available treatment. However, the efficacy of interferon treatment is affected by the dose and duration of treatment, and relapse rates are high. In this study, we sought to evaluate the efficacy of treatment with pegylated interferon and observe the relapse rates of delta hepatitis after treatment. Forty-six patients with chronic delta hepatitis were retrospectively studied between January 2002 and December 2010. Patients were evaluated for biochemical, virological, and histological responses. They were then followed-up for at least 1 year after discontinuation of the treatment. All the 46 patients in the study received PEG-IFN therapy. Of the 46 patients,25 were treated with PEG-IFN for 1 year and 21 were treated for 2 years. Sixteen patients(34.7%) showed a biochemical response, 27 (58.6%) showed a virological response, and 39 (84.7%) showed a histological response. Sustained virological and biochemical responseswere achieved in 41% and 47.8% of the patients, respectively. Sixteen (84.2%) patients of the 19 with high levels of hepatitis delta virus RNA (HDV RNA) (HDV RNAlevel > 1 × 105) and 10 (71.4%) of the 14 patients with high titers of hepatitis B surface antigen(HbsAg) (HbsAg > 102 IU/mL) at the beginning of the treatment showed relapse after treatment. We found no significant differences between 1-year and 2-year treatments.However, the relapse rate was lower in the 2-year treatment group. Higher HDV RNA and HbsAg levels before treatment were associated with higher relapse rates. Younger age was a significant factor in predicting response.

Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead

Hepatitis D is caused by infection with the hepatitis D virus (HDV) and is considered to be the most severe form of viral hepatitis in humans. Hepatitis D occurs only in individuals positive for the HBV surface antigen (HBsAg) as HDV is a defective RNA viroid that requires HBsAg for transmission. At least eight different HDV genotypes have been described and each has a characteristic geographic distribution and a distinct clinical course. HDV and HBV coinfection can be associated with complex and dynamic viral dominance patterns. Chronic HDV infection leads to more severe liver disease than HBV monoinfection and is associated with accelerated fibrosis progression, earlier hepatic decompensation and an increased risk for the development of hepatocellular carcinoma. So far, only IFN-alpha treatment has proven antiviral activity against HDV in humans and has been linked to improved long-term outcomes. Studies conducted in the past 2 years on the use of PEG-IFN-alpha show that a sustained virologic response to therapy, measured in terms of undetectable serum HDV RNA levels, can be achieved in about one quarter of patients with hepatitis D. Novel alternative treatment options including prenylation inhibitors are awaiting clinical development for use in hepatitis D.