How Can We Make Decision for Patients With Chronic Hepatitis B According to Hepatitis B Virus (HBV) DNA Level?

Background:

HBeAg negative hepatitis B infection exerts both inactive carrier state and chronic active hepatitis, which are sometimes difficult to differentiate. Serial hepatitis B virus (HBV) DNA quantification, alanine transaminase (ALT) measurement, and liver histology assessment can help to differentiate these forms of hepatitis B infection.

Objectives:

We aimed to clarify the clinical and laboratory characteristics of HBeAg negative hepatitis B patients.

Patients and Methods:

Patients with hepatitis B, referred to Tehran Blood Transfusion Hepatitis Clinic from 2011 to 2013, were included and followed for one year. Laboratory assessments including liver function tests, HBV DNA quantification, and liver biopsy (for some cases) were performed.

Results:

Two hundred forty-three HBeAg negative hepatitis B patients were stratified into three groups based on to their HBV DNA level including group 1 (G1) with HBV DNA level < 2000 IU/mL, group 2 (G2) with HBV DNA level 2000-20000 IU/mL, and group 3 (G3) with HBV DNA level > 20000 IU/mL. The G2 had more similarity to G1 than G3 regarding their clinical characteristics.

Conclusions:

It is concluded that most HBeAg negative hepatitis B patients with serum HBV DNA level of 2000-20000 IU/mL, persistent normal ALT concentration, and no or mild liver damage on biopsy can be clinically managed as HBV inactive carriers.     

Virologic Response and Safety of Tenofovir Versus Entecavir in Treatment-Na?ve Chronic Hepatitis B patients

Background/Aims:

This study aimed to evaluate the antiviral response and safety of tenofovir (TDF) versus entecavir (ETV) in treatment-naïve CHB patients.

Patients and Methods:

We performed a retrospective cohort study of treatment-naive CHB patients who were treated with TDF or ETV. We analyzed virologic, biochemical, and serologic responses at 3, 6, and 12 months.

Results:

A total of 107 patients (TDF group = 49, ETV group = 58) were included. Baseline characteristics were similar between the two groups. The estimated proportion of complete virologic response (CVR) in the TDF or ETV group was 44.9% versus 39.7% at 6 months and 89.6% versus 83.2% at 12 months, respectively (P = 0.991). Viral breakthrough was not observed in both groups. One patient in the TDF group and two patients in the ETV group experienced HBeAg loss, respectively (P = 0.657). High HBV DNA level at baseline was a significant negative predictor of virologic response by Cox regression analysis (P = 0.007). The safety profile was similar between the two groups. There was no case with serious adverse event.

Conclusions:

Both TDF and ETV were effective in achieving CVR and had a favorable safety profile in treatment-naïve CHB patients. High viral load at baseline was a negative predictive factor of CVR.     

Continuous Long-Term Entecavir Therapy in Na?ve Chronic Hepatitis B Patients Showing Partial Virologic Response

Background/Aims

We investigated the efficacy of continuous long-term entecavir 0.5 mg treatment in naïve chronic hepatitis B patients showing a partial virologic response (PVR).

Methods

A total of 227 patients were included. PVR was defined as a more than 1 log₁₀ IU/mL decline in detectable serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR; ≥20 IU/mL) at week 48. A complete virologic response (CVR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL) at week 48.

Results

At week 48, the rate of the PVR was 64/227 (28.2%). Among patients with PVR, the cumulative rates of virologic response (serum HBV DNA <20 IU/mL) at weeks 96 and 144 were 45.2% and 73.8%, respectively. The cumulative rates of genotypic resistance were not significantly different between patients with a PVR and patients with a CVR (p=0.057). However, the cumulative rates of virologic breakthrough were higher in patients with PVR than in patients with CVR (4% vs 0% and 11.2% vs 0% at weeks 96 and 144, respectively; p<0.001).

Conclusions

Long-term continuous entecavir 0.5 mg treatment in patients with a PVR resulted in an additional virologic response without a significant increase in genotypic resistance. However, the rate of virologic breakthrough was higher in the partial responders.     

Similar Response to Entecavir 0.5 and 1.0 Mg in Treatment-Naïve Chronic Hepatitis B Patients: A Case-Control Study

Background and Aims

The dose recommendation for entecavir (ETV) is 0.5 mg daily for treatment-naïve chronic hepatitis B (CHB) patients and 1.0 mg daily for lamivudine-refractory patients; however, few data are available for the efficacy of a 1.0-mg daily dose in treatment-naïve CHB patients. Our goal is to examine the treatment outcome of treatment-naïve patients placed on ETV 0.5 mg or ETV 1.0 mg daily through week 48.

Methods

Cases were 40 consecutive hepatitis B e antigen (HBeAg)-positive CHB patients treated with ETV 1.0 mg daily between January 2005 and September 2010, and controls were 40 consecutive CHB patients treated with ETV 0.5 mg daily between January 2005 and September 2010 at three US gastroenterology/liver clinics. Controls were matched for age (±5 years), sex, HBeAg, and baseline hepatitis B virus (HBV) DNA (±0.5 log₁₀ IU/ml). Complete viral suppression was defined as undetectable HBV DNA by polymerase chain reaction (<100 IU/ml).

Results

Both groups had similar distributions of age (38 ± 11 years), male patients (55 %), and mean HBV DNA (7.7 ± 1.1 log₁₀ IU/ml). The complete viral suppression rate was similar in both cases and controls through week 24 (15 vs. 15 %, p = 1.00) and week 48 (22 vs. 36 %, p = 0.17). Non-adherence was reported in three patients in the ETV 1.0 mg daily cohort at week 48.

Conclusions

There were no significant differences in the proportion of patients with complete viral suppression in patients treated with ETV 0.5 mg daily or the higher daily dose of 1.0 mg.     

Long-Term Treatment Efficacy and Safety of Clevudine Therapy in Na?ve Patients with Chronic Hepatitis B

Background/Aims

Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naïve patients with CHB were investigated.

Methods

In this retrospective study, 152 naïve Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated.

Results

The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level ≥6 log₁₀ IU/mL (p=0.032) and detectable serum HBV DNA (≥12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients.

Conclusions

The results of long-term CLV therapy for the treatment of naïve patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naïve patients given the availability of other more potent, safer antiviral agents.     

Is Hepatitis C Virus Positivity a Contributing Factor to Occult Hepatitis B Virus Infection in Hemodialysis Patients?

Hepatitis B (HBV) infections continue to occur in adult hemodialysis units. Occult HBV infection (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive) may be a contributing factor in these patients. This study was designed to (1) investigate the prevalence of occult HBV infection in hemodialysis patients and (2) compare the prevalence of occult HBV infection among hepatitis C (HCV)-positive and HCV-negative hemodialysis patients. The study included 138 patients on chronic hemodialysis. Eighty-four patients were HCV positive and 54 were HCV negative. HBV DNA testing was performed by polymerase chain reaction. We also recorded general characteristics of the patients, duration of hemodialysis, and serum alanine aminotransferase and aspartate aminotransferase levels. Twenty-one (15.2%) of the 138 hemodialysis patients were HBV DNA positive. Nine (16.6%) of the 54 anti-HCV antibody negative hemodialysis patients were HBV DNA positive. Twelve (14.2%) of the 84 anti-HCV antibody positive patients were HBV DNA positive. The prevalence in anti-HCV Ab positive and negative hemodialysis patients were same (P > .05). Hemodialysis duration, demographic features, and biochemical parameters were not significantly different in patients with and without occult HBV infection in both HCV-positive and -negative hemodialysis patients (P > .05). HCV positivity is not a contributing factor to occult HBV infection in hemodialysis patients. None of the parameters tested help to distinguish patients with occult HBV infection from those who are HBV DNA negative.     

HBeAg-negative Patients with Chronic Hepatitis B Virus Infection and Normal Alanine Aminotransferase: Wait or Treat?

Alanine aminotransferase (ALT) is a common clinical indicator of liver inflammation. The current Chinese guidelines for the management of chronic hepatitis B (CHB) recommend antiviral treatment for patients with detectable hepatitis B virus (HBV) DNA and persistent ALT levels (ALTs) exceeding the upper limit of normal. However, it has been recently reported that patients with chronic HBV infection, especially HBeAg-negative patients with persistently normal ALTs, may have liver biopsy findings of significant inflammation and fibrosis. For HBeAg-negative patients with chronic HBV infection and normal ALTs, many controversial questions have been asked. To treat or not? When to initiate the treatment? Which drug is appropriate? In this review, we summarize the available data on the management of HBeAg-negative patients with chronic HBV infection and normal ALTs with the aim of improving the current clinical management.     

Partial Response to Entecavir and Tenofovir in Na?ve Patients with Chronic Hepatitis B: Clinical Relevance and Management

Entecavir and tenofovir are the currently recommended first line analogues for treatment of na?ve patients with chronic hepatitis B. Despite their overall efficacy and high genetic barrier granting for a low risk of resistance, both regimens will fail to completely suppress HBV DNA at week 48 in 10% of HBeAg-negative and 30% of HBeAg-positive patients. A pre-treatment level >8 log₁₀ IU/mL HBV DNA and poor medication adherence were the most significant predictors of a partial virological response (PVR). While the clinical relevance of PVR is still poorly understood, nucleos(t)ide (NUC)-naive PVR patients who maintained detectable levels of viremia in follow up, were at risk of developing resistance to ETV. Patients with a suboptimal decline of viremia during the first 48?weeks of therapy with ETV and/or a residual viremia >1,000?IU/mL, can be protected by a rescue switch to TDF. Resistance to TDF has not been described so far, yet the long-term risk of PVR in TDF-treated patients remains unclear.     

Clinical Analysis of Polyethylene Glycol Interferon-α Treatment in 155 Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) Patients

PurposeThis study aims to investigate the antiviral effect of polyethylene glycol (PEG)-interferon α-2a and PEG-interferon α-2b treatment on hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) at the 48th week of treatment and the 24th and 48th week after withdrawal, in order to provide guidance on the antiviral treatment of HBeAg-positive CHB patients.Material and methodsAntiviral treatment was performed on 155 HBeAg-positive CHB patients. Among these patients, 66 patients received PEG-interferon α-2a treatment and 89 patients received PEG-interferon α-2b treatment; and these treatments were administered by subcutaneous injection, once per week, which lasted for 48 weeks. Other antiviral and hepatoprotective drugs were not used during the treatment.ResultsAt the 48th week of treatment, ALT recovery rate, HBsAg seroconversion rate, HBeAg seroconversion rate and HBV DNA titers dropped below 200 IU/mL rate were 69.7%, 6.1%, 27.3% and 50.0%, respectively, in the PEG-interferon α-2a group; and were 70.8%, 6.7%, 33.7% and 62.9%, respectively, in the PEG-interferon α-2b group. At the 24th and 48th week of follow-up after withdrawal, HBsAg seroconversion rate in these two groups did not change; and HBeAg seroconversion rate further increased. Furthermore, HBV DNA revealed a low recurrence rate. The difference between these two groups was not significantly significant.ConclusionsPEG-interferon α-2a and PEG-interferon α-2b are effective antiviral drugs for the treatment of HBeAg-positive CHB, which has a HBsAg seroconversion rate of more than 5%. Furthermore, this sustained response effect was maintained at the 24th and 48th week of follow-up after withdrawal.     

Clinical Course of Partial Virologic Response with Prolonged Tenofovir Therapy in Nuclos(t)ides-Naïve Patients with Chronic Hepatitis B

Digestive Diseases and Sciences - The clinical course of chronic hepatitis B (CHB) patients with partial virologic response (PVR) during tenofovir disoproxil fumarate (TDF) therapy remains unclear....     

Effect of Acute Self-Limited Hepatitis C Virus (HCV) Superinfection on Hepatitis B Virus (HBV)-Related Cirrhosis. Virological Features of HBV–HCV Dual Infection

We investigated the virological impact of acute hepatitis C virus (HCV) superinfection on two patients with hepatitis B virus (HBV)-related cirrhosis. In both patients, chronic HBV-infection persisted while acute HCV infection resolved spontaneously. HBV DNA was transiently suppressed in both patients but increased with HCV resolution. In Case 1 (HBeAg-positive; wild type of basic core promoter [BCP] and precore [PreC]), fluctuations of HBV DNA and HBeAg state were accompanied by mutations of the BCP and PreC. In Case 2 (HBeAg-negative; mutant type of the BCP and PreC), changes in HBV DNA levels were associated with mutations of PreC. In both cases, mutant PreC changed to the wild type upon HCV resolution, and no nucleotide A insertion at position 193 of the HCV 5'-untranslated region, which influences HCV spontaneous clearance, was detected. The putative DNA-binding motif in the HCV core was SPRG (amino acids 99-102). HCV infection was associated with changes in the nucleotide sequences of the binding site for the nuclear receptor family in HBV enhancer 2 (Enh2) including the BCP rather than Enh1. Our results suggest that the impact of acute HCV infection on chronic HBV infection varies according to HBV virological state.     

Digital Quantification Is More Precise than Traditional Semiquantitation of Hepatic Steatosis: Correlation with Fibrosis in 220 Treatment-Naïve Patients with Chronic Hepatitis C

Background  

Steatosis, as associated with chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD), has been considered a risk factor for development of fibrosis.     

Prophylaxis against Recurrence in Liver Transplantation Patients with Hepatitis B Virus: What is New?

Hepatitis B virus (HBV) causes an endemic infection that affects nearly 2 billion patients worldwide. It is one of the leading causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). Recurrence of HBV infection after LT is due to specific HBV-host genome interactions. Although hepatitis B immunoglobulin treatment constituted the backbone of HBV recurrence, use of the nucleoside and nucleotide analogs (especially the ones with a higher genetic barrier to resistance), either alone or in combination, offer us new and powerful options in overcoming this serious issue.     

Pentraxin-3: A Novel Marker for Indicating Liver Fibrosis in Chronic Hepatitis B Patients?

Background: Pentraxin-3 (PTX-3) is an important marker that plays a role in suppressing inflammation and tissue repair. The aim of this study is to investigate the diagnostic and prognostic characteristics of PTX-3 in chronic hepatitis B (CHB) patients and the relationship between PTX-3 levels and fibrosis.Methods: A total of 52 CHB patients and 40 healthy subjects were included in the study. All of the CHB patients underwent liver biopsy and were then scored using an Ishak histologic scoring system. Blood samples were collected to evaluate the PTX-3 levels.Results: Of the subjects who participated in the study, 53% were female. The PTX-3 levels were determined as 5.63 ng/mL in the control group, and as 0.88 ng/mL in the CHB patient group. PTX-3 levels were found to be 1.19 ng/mL in stage 1, 0.89 ng/mL in stage 2, 0.68 ng/mL in stage 3, and 0.55 ng/mL in stage 4. Of the CHB patients, 44.2% had significant fibrosis, while 55.7% were identified as not having significant fibrosis. The PTX-3 values were 0.64 and 1.0 ng/mL in patients with and without significant fibrosis, respectively. The cut-off value for PTX-3 in predicting the absence of significant fibrosis was estimated as 0.9 ng/mL.Conclusion: The CHB patients were found to have lower serum PTX-3 levels compared to the control group, and these levels decreased even further as the stage of fibrosis progressed. In addition, the significant decrease in PTX-3 levels in patients with stage 1 fibrosis compared to the control group shows that PTX-3 can be used as a non-invasive marker for the early detection of fibrosis (P < .001).     

Very Low Viral Load (VLVL) Relapse Following Treatment of Naïve Patients with Chronic Hepatitis C

Background

Sustained virologic response (SVR) to treatment of naïve patients with chronic hepatitis C (HCV) with pegylated interferon and ribavirin is 50–60%. Patients who relapse have a poor response to re-treatment. We report a group of relapse patients with SVR to low-dose re-treatment after 6 months.

Aim

Characterization of HCV relapse patients with very low viral load (VLVL) (HCV RNA <5,000 IU/ml) 6 months after stopping full-dose initial treatment.

Methods

We identified 120 consecutive naïve patients over 4 years treated with pegylated interferon alpha-2a and ribavirin with full-dose therapy for 24 weeks (non-genotype 1) or 48 weeks (genotype 1) with baseline liver biopsy and at least 6 months of follow-up after treatment. HCV RNA by PCR and hepatic blood tests were obtained monthly during treatment and at least 1, 3, and 6 months post treatment.

Results

Of the initially treated patients, 54.2% had SVR, 25% non-response and 20.8% relapsed. Four of 25 who relapsed (16%) and one similar patient referred to our program had HCV RNA <5,000 IU/ml 6 months after stopping treatment (VLVL relapse). Significant differences (P < 0.05) compared with the 21 other relapse patients included all five patients who were genotype 1; 4/5 had cirrhosis, baseline HCV RNA was lower, and all had SVR to less intensive re-treatment for 6 months.

Conclusion

VLVL relapse patients should be sought, because SVR to re-treatment is common despite genotype 1 cirrhosis.

     

Clinical Outcomes of Hepatitis B Virus–Related Hepatocellular Carcinoma Patients with Undetectable Serum HBV DNA Levels

Digestive Diseases and Sciences - Some hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients show undetectable serum HBV DNA levels at HCC diagnosis. The risk of HBV reactivation...     

Can Nucleos(t)ide Analogue (NA) Therapy Ever be Stopped in HBeAg-Negative Chronic Hepatitis B?

In this review, evidence is presented that the majority of HBeAg-negative CHB patients previously treated with lamivudine and subsequently with adefovir and entecavir, experience virological and clinical relapse if these therapies were discontinued. Thus current treatment guidelines both of AASLD and EASL recommend indefinite duration of NA treatment in such patients. However, the recommendations of APASL are different, advising a stop of NA treatment if HBV-DNA is negative in three consecutive assays at least 6 months apart. It is clear that the duration of post-treatment sustained remission is variable and its final outcome unpredictable. However, fluctuations of post-treatment HBV-DNA levels are not uncommon and HBeAg-negative CHB patients may experience long periods of transient HBV-DNA undetectability. Data on the frequency of post-treatment HBsAg loss are promising but still limited. The need for prospective, multinational, multicenter studies is stressed.     

Tenofovir in the Treatment of Na?ve and Refractory Chronic Hepatitis B: A Single Center Experience in Saudi Arabia

Background/Aims:

Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used in the treatment of chronic hepatitis B (CHB) infection. This study evaluated the efficacy of TDF in achieving undetectable HBV DNA after 48 weeks of treatment in a Saudi cohort of CHB patients.

Patients and Methods:

This retrospective study included patients treated at a tertiary care center in Saudi Arabia from January 2009 to December 2012. Of the 68 eligible patients, 51 were treatment naïve and 17 were treatment-refractory. Twenty-three patients tested positive for HBeAg. The remaining 45 patients were HBeAg-negative.

Results:

The mean HBV DNA viral load decreased from 95 million IU/mL at baseline to 263 IU/mL after 48 weeks of treatment (P < 0.001). Overall, 62% of patients achieved a complete virological response (CVR) and 37% a partial virological response (PVR). Respective CVR and PVR rates according to subgroup were: HBeAg-positive (21.7% and 78.3%) and HBeAg-negative (84.4% and 15.6%). At 48 weeks, HBV DNA was undetectable in 66.7% of treatment-naïve and 53% of treatment-refractory patients (P = 0.3). Seroconversion occurred in 13 (57%) of HBeAg-positive patients. Two (3%) of the HBeAg-negative patients lost HBsAg at follow up. Mean alanine aminotransferase decreased significantly from 134 U/L before treatment to 37 U/L at 48 weeks (P < 0.001). Significant adverse events were not encountered during the study period.

Conclusion:

Forty-eight weeks of treatment with TDF reduced HBV DNA to undetectable levels in more than half of our patients regardless of whether they were treatment-naïve or refractory. HBeAg-negative (vs positive) patients experienced a better response rate.