Are physicians following guidelines? A survey of Hepatitis B management strategies

Purpose

Practice guidelines for chronic hepatitis B (CHB) assist physicians in management; however, there are also areas where they provide no guidance. This paper aimed to examine treatment preferences for CHB among physicians based upon the Asia Pacific Association for the Study of the Liver (APASL) consensus guidelines 2008.

Methods

A questionnaire was prepared consisting of 18 questions grouped into 8 sections: basic information of participants, the proportion and number of CHB patients on treatment, case scenarios of treatment initiation, preferences for antiviral therapy, scenarios for stopping and continuing antiviral therapy, monitoring patients during therapy, and viral resistance management. The questionnaire was introduced to the APASL 2009 conference delegates.

Results

A total of 508 participants from 34 countries participated in the survey. Lamivudine or peg-interferon monotherapy was the preferred first-line therapy, while lamivudine/adefovir combination was the drug of choice for rescue therapy. Drug efficacy and cost were the most important factors to consider before initiating treatment, while viral resistance had a low priority. In general, the APASL guideline was strictly followed in about 50–60 % of the scenarios (initiating, stopping, or continuing antiviral therapy).

Conclusions

The survey concluded that clinical management preferences differed from APASL guidelines in many instances.     

Therapeutic potential of a combined hepatitis B virus surface and core antigen vaccine in patients with chronic hepatitis B

Purpose

The safety and clinical efficacy of a vaccine containing both hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (HBsAg/HBcAg) were evaluated in patients with chronic hepatitis B (CHB).

Methods

Eighteen patients with CHB were administered a vaccine containing 100 μg of HBsAg and 100 μg of HBcAg. The vaccine was administered ten times at 2-weekly intervals, the first five times via the nasal route only and the subsequent five times via both nasal and subcutaneous routes. The safety and efficacy of this therapeutic approach were assessed by periodic assessment of the patients’ general condition, viral kinetics, and biochemical parameters during treatment and 24 and 48 weeks after therapy. The production of cytokines by peripheral blood mononuclear cells (PBMC) and antigen-pulsed dendritic cells (DC) was evaluated to assess the immunomodulatory effects of the HBsAg/HBcAg vaccine in CHB patients.

Results

The HBsAg/HBcAg vaccine was safe in all patients. No flare of HBV DNA or alanine aminotransferase (ALT) was recorded in any patient. Sustained HBV DNA negativity and persistently normalized ALT were detected in 9 (50 %) and 18 (100 %) patients with CHB, respectively. PBMC and HBsAg/HBcAg-pulsed DCs from HBsAg/HBcAg-vaccinated CHB patients produced significantly higher levels of various cytokines [interleukin 1β (IL-1β), IL-6, IL-8, IL-12, and tumor necrosis factor α (TNF-α)] than those from control unvaccinated CHB patients (p < 0.05) after stimulation with HBsAg/HBcAg in vitro.

Conclusion

HBsAg/HBcAg vaccine seems a safe and efficient therapeutic approach for patients with CHB.     

Use of Tenofovir Disoproxil Fumarate in Highly Viremic,Hepatitis B Mono-Infected Pregnant Women

Background

Antiviral therapy in addition to immunoprophylaxis at birth has been shown to further reduce perinatal transmission of hepatitis B virus (HBV) in highly viremic women.

Aims

The aim of this study was to describe the use of tenofovir disoproxil fumarate (TDF) prophylaxis to reduce maternal HBV DNA levels and potentially vertical transmission in highly viremic women.

Methods

After receiving IRB approval, we performed a retrospective chart review of mothers positive for hepatitis B surface antigen (HBsAg) who delivered between 2009 and 2012. We identified women with HBV DNA levels ≥6 log copies/mL who were treated with TDF in pregnancy.

Results

There were 22 women identified. The majority were of Micronesian ethnicity. All were negative for hepatitis C antibody and HIV infection. The median gestational age of TDF initiation was 31 weeks with a median duration of treatment of 45 days. There was a reduction in median HBV DNA levels from baseline 9.0 ± 2.0 to 5.4 ± 1.1 log copies/mL after treatment. There were five (22.7 %) preterm deliveries and five (22.7 %) cesarean deliveries. All infants received immunoprophylaxis at birth. Postnatal HBsAg testing at 9–12 months was available for 13 infants, 12 of which were negative. There was one case of perinatal transmission.

Conclusions

This is the second published case series to date on the use of TDF prophylaxis in HBV mono-infected, highly viremic mothers. This series suggests the use of TDF in pregnancy reduces maternal HBV DNA levels and is well tolerated.     

Increased spontaneous apoptosis, but not survivin expression, is associated with histomorphologic response to neoadjuvant chemoradiation in rectal cancer

Purpose

Survivin has been shown to be an important mediator of cellular radioresistance in vitro. This study aims to compare survivin expression and apoptosis to histomorphologic responses to neoadjuvant radiochemotherapy (RCT) in rectal cancer.

Materials and methods

Thirty-six pre-treatment biopsies were studied. Survivin mRNA and protein expression plus TUNEL staining for apoptosis was performed. Response to treatment was assessed using a 5-point tumour regression grade.

Results

Survivin expression was not found to be predictive of response to RCT (p?=?NS). In contrast, spontaneous apoptosis was significantly (p?=?0.0051) associated with subsequent response to RCT. However, no association between survivin expression and levels of apoptosis could be identified.

Conclusions

This in vivo study failed to support in vitro studies showing an association between survivin and response to chemotherapy and radiation therapy. These results caution against the translation of the in vitro properties of survivin into a clinical setting.     

The co-inhibitory pathway and cellular immune imbalance in the progress of HBV infection

Objective

Chronic hepatitis B (CHB) affects 400 million people and is the most common cause of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) worldwide. Cellular immune regulation plays an important role in determining the infection outcome. Co-signal molecules and Th17/Treg were studied to explore their association with the progression of HBV infection.

Methods

Ninety-four HBV-infected patients were categorized into three groups: 31 patients with LC caused by CHB, 30 with HCC caused by CHB and 33 with HCC caused by CHB. Co-signal molecules, Th17/Treg, and Stat3 and Stat5 were analyzed by flow cytometry.

Results

CHB patients who progressed to LC or HCC showed a significantly higher level of co-inhibitory molecules such as BTLA and PD-1, while there was no significant difference in co-stimulatory molecules among LC, HCC and CHB. Stat3 and Stat5 were significantly increased in LC and HCC compared to CHB patients.

Conclusion

Co-inhibitory molecules play more important roles than co-stimulatory molecules. Increased PD-1 and BTLA/HVEM inhibited immune cells and the immune process. At the same time activated Stat3 and Stat5 stimulate the key factors in differentiation of Th17 and Treg, thus leading to imbalanced expansion of Th17 and Treg; immune tolerance was induced and HBV persistent. This resulted in hepatic inflammation that progressed to cirrhosis and carcinoma.     

Cholecystectomy in Sweden 2000 – 2003: a nationwide study on procedures, patient characteristics, and mortality

Background

The role of leptin in the course of liver disease due to chronic viral hepatitis (CVH) remains controversial. Our aims were to investigate the relationship between serum leptin concentrations and the severity of liver disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB) and C (CHC) and to analyze the effect of body composition, the leptin system and insulin resistance together with viral factors on virologic response to antiviral treatment.

Methods

We studied 50 (36 men) consecutive patients suffering from biopsy-proven CVH due to HBV (n = 25) or HCV (n = 25) infection. Thirty-two (17 men) healthy volunteers served as controls. Levels of serum leptin and insulin were determined by immunoassays at baseline and at the end of the treatment.

Results

A significant association between serum leptin levels and the stage of hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs 6028.5 pg/ml, p = 0.03), CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An inverse correlation between lower leptin levels and response to lamivudine monotherapy was noted in patients with CHB; those with a virologic response presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003) than non-responders. In genotype 1 CHC patients, insulin resistance played a significant role in the response to antiviral therapy.

Conclusion

Our data clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin levels. Increased serum leptin levels represent a negative prognostic factor for response to lamivudine monotherapy in patients with CHB. In CHC patients insulin resistance strongly influences the response to antiviral treatment in patients infected with genotype 1.     

Clinical significance and evolution of hepatic HBsAg expression in HBeAg-positive patients receiving interferon therapy

Background

Serum hepatitis B surface antigen (HBsAg) level is important in the management of chronic hepatitis B (CHB). However, it is unclear whether serum HBsAg reflects its expression in liver and the hepatic HBsAg evolution following interferon therapy.

Methods

Forty-five HBeAg-positive CHB patients receiving interferon-based therapy within a randomized, controlled, multicenter study during 1998–1999 were included. The hepatic HBsAg expressions were categorized into cytoplasmic, inclusion, marginal and negative patterns by immunohistochemical staining. The HBsAg-positive hepatocytes were quantified by image-based cytometry and correlated to HBV serological and virological profiles for clinical implications. The evolution of hepatic HBsAg levels was analyzed among 22 patients with paired liver biopsies before and after interferon therapy, sequentially.

Results

There was a positive correlation between pretreatment serum HBsAg and hepatic HBsAg levels (r = 0.67, P < 0.0001). The hepatic HBsAg expression pattern significantly evolved from cytoplasmic/inclusion pattern to marginal/negative pattern after interferon treatment. The serum HBV-DNA, HBsAg and hepatic HBsAg levels all decreased significantly after interferon therapy. Among 36 % patients with HBeAg loss after therapy, pretreatment hepatic HBsAg levels were significantly lower compared with those without HBeAg loss. After multivariate analysis, low pretreatment hepatic HBsAg levels rather than serum HBsAg titers were associated with a higher rate of HBeAg loss (OR: 4.97, 95 % CI: 1.12–22.00, P = 0.035).

Conclusions

The serum HBsAg level positively reflects the HBsAg level in liver which evolves significantly after interferon therapy. A lower hepatic HBsAg level is associated with HBeAg loss after interferon treatment. Hepatic HBsAg may have clinical significance in CHB patients receiving interferon treatment.     

Entecavir plus tenofovir combination therapy for chronic hepatitis B in patients with previous nucleos(t)ide treatment failure

Background and aims

In patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen.

Methods

In this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1 mg) plus TDF (300 mg) and treated for 96 weeks.

Results

At baseline, 62 % of patients were HBeAg(+) and mean HBV DNA was 4.4 log₁₀IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53 %), lamivudine (LVD 22 %), TDF (12 %), adefovir (ADV 4 %), or telbivudine (2 %), or combinations of these agents (7 %); 58 % had evidence of single- or multidrug resistance mutations (LVD 52 %, ETV 26 %; ADV 7 %). Response rates for HBV DNA <50 IU/mL were 76 % (70/92) at week 48 (primary endpoint), and 85 % (78/92) at week 96, including 80 % (16/20) in prior LVD failures, 100 % (4/4) in ADV failures, 82 % (9/11) in TDF failures, and 88 % (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed.

Conclusions

In NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96 weeks in the majority (85 %), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.

     

Current management and recommendations on hepatitis B therapy in HIV-coinfected patients

Background

The match between the real-life therapeutic management of chronic hepatitis B (CHB) in HIV-infected patients and the recommendations that existed at the time has never been assessed on a case-by-case basis.

Methods

A total of 73 HBV–HIV coinfected patients, 34 of whom were first followed in 2003–2005 and 39 in 2006–2008 (before and after the 2005 European Consensus Conference on the treatment of chronic viral hepatitis in HIV coinfected patients), were included. All the data were retrospectively collected from their first visit to October 2008 through a standardised questionnaire.

Results

Baseline HBV DNA quantification and/or liver histology were missing in 44.1 and 28.2% of cases before and after 2005, respectively (p = 0.16). The observed management significantly differed from the recommendations for the whole population (p = 0.009), for the 2003–2005 group (p = 0.02), and tended to differ for the 2006–2008 group (p = 0.07). Therapeutic management of CHB was in accordance with the recommendations in 27 (57.4%) cases, with a higher rate of untreated patients in the 2003–2005 group, and a high rate of patients on dual therapy in both groups despite the fact that HBV therapy was not recommended.

Conclusion

Even though global management of HBV–HIV coinfected patients is improving, baseline evaluation of CHB though necessary is still often insufficient. The strong rationale for early dual anti-HIV and anti-HBV therapy, and the reality of everyday clinical practice, bring support to the recent simplification of the recommendations widening the use of tenofovir and emtricitabine in HBV–HIV coinfected patients, irrespective of immunological, virological, or histological considerations.     

Serum HBsAg quantification in treatment-naïve Indian patients with chronic hepatitis B

Background and Aims

There is paucity of Indian data regarding serum HBsAg levels (qHBsAg) in treatment-naïve chronic hepatitis B (CHB). This study was done to determine correlation of qHBsAg with hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels and its ability to independently categorize subgroups of CHB.

Methods

We studied 131 treatment-naive CHB patients and initially classified them based on HBeAg status. The HBeAg-positive group was further classified into immune tolerance (IT) and immune clearance (IC) phases based on serum alanine aminotransferase. HBeAg-negative patients were classified into low replicators (LR) and HBeAg-negative chronic hepatitis (ENH) based on DNA levels. HBsAg quantification was performed using the Architect chemiluminescence system.

Results

HBeAg-positive patients had higher DNA (7.89 vs. 2.69 log₁₀?IU/mL) and higher qHBsAg (4.60 vs. 3.85 log₁₀?IU/mL) compared to the HBeAg-negative group. Good correlation between qHBsAg and DNA was seen in HBeAg-positive (ρ?=?0.6, p?<?0.001) but not in HBeAg-negative CHB (ρ?=?0.2). A qHBsAg level greater than 4.39 log₁₀?IU/mL predicted HBeAg-positive state with 81 % sensitivity and 85 % specificity. However, among HBeAg-negative CHB, qHBsAg failed to discriminate between LR and ENH.

Conclusions

A single point estimation of qHBsAg in treatment-naïve patients could predict replicative HBeAg-positive CHB, but was not helpful in defining replicative status in the HBeAg-negative CHB.     

Efficacy and Safety of Tenofovir-Based Rescue Therapy for Chronic Hepatitis B Patients with Previous Nucleo(s/t)ide Treatment Failure

Background/Aims

We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies.

Methods

Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored.

Results

Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log₁₀ IU/mL to 2.0 log₁₀ IU/mL and to 1.6 log₁₀ IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (≤20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed.

Conclusions

TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients'' adherence to medication is related to viral rebound.     

Efficacy of Tenofovir Disoproxil Fumarate Therapy in Nucleoside-Analogue Naive Iranian Patients Treated for Chronic Hepatitis B

Background:

Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB).

Objectives:

To evaluate TDF efficacy in nucleos(t)ide analogues (NAs)-naive Iranian patients with CHB.

Patients and Methods:

The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability.

Results:

In all, 93 patients (64.5% hepatitis B e antigen [HBeAg]-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia.

Conclusions:

The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF.     

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.     

Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification

BACKGROUND

Clinicians caring for patients seeking alcohol detoxification face many challenges, including lack of evidence-based guidelines for treatment and high recidivism rates.

OBJECTIVES

To develop a standardized protocol for determining which alcohol dependent patients seeking detoxification need inpatient versus outpatient treatment, and to study the protocol’s implementation.

DESIGN

Review of best evidence by ad hoc task force and subsequent creation of standardized protocol. Prospective observational evaluation of initial protocol implementation.

PARTICIPANTS

Patients presenting for alcohol detoxification.

INTERVENTION

Development and implementation of a protocol for evaluation and treatment of patients requesting alcohol detoxification.

MAIN MEASURES

Number of admissions per month with primary alcohol related diagnosis (DRG), 30-day readmission rate, and length of stay, all measured before and after protocol implementation.

RESULTS

We identified one randomized clinical trial and three cohort studies to inform the choice of inpatient versus outpatient detoxification, along with one prior protocol in this population, and combined that data with clinical experience to create an institutional protocol. After implementation, the average number of alcohol related admissions was 15.9 per month, compared with 18.9 per month before implementation (p?=?0.037). There was no difference in readmission rate or length of stay.

CONCLUSIONS

Creation and utilization of a protocol led to standardization of care for patients requesting detoxification from alcohol. Initial evaluation of protocol implementation showed a decrease in number of admissions.     

Long-term efficacy of interferon therapy in patients with chronic hepatitis B virus infection in Japan

Background

Few studies have investigated the long-term effects of interferon (IFN) therapy for chronic hepatitis B (CHB). In this retrospective study, we investigated the efficacy of and predictors of response to IFN therapy in CHB patients.

Methods

We analyzed data for 615 Japanese CHB patients (hepatitis B e antigen [HBeAg]-positive 414, HBeAg-negative 201) treated with IFN, and conducted follow up for a median duration of 8.1 years (range 0.5–23.2). Responders were defined as patients who showed continuously normalized alanine transaminase (ALT) levels, HBeAg clearance, and low hepatitis B virus (HBV) DNA levels at 6?months post-treatment or for a span of more than 6?months until each test point at 1, 3, 5, and 10?years.

Results

The IFN response rates of all patients were 21, 18, 21, 23, and 25% at 6?months and 1, 3, 5, and 10?years, respectively. On multivariate analysis, significant determinants of the outcome of IFN therapy were as follows: at 6?months and 1?year, young age, low HBV DNA levels, and long duration of treatment; at 3?years, long duration of treatment, young age, and high level of albumin; at 5?years, high level of albumin, female, and pretreated with IFN; and at 10?years, HBeAg-negative. Sixty-nine of the 615 patients (11%) achieved seroclearance of hepatitis B surface antigen (HBsAg). On multivariate analysis, age ≥30?years, HBV genotype A, and male were all independent factors predicting the achievement of HBsAg seroclearance.

Conclusion

HBeAg, HBV DNA level, age, sex, albumin, duration of treatment, pretreatment with IFN, and HBV genotype were important factors in determining long-term response to IFN therapy.     

Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China

Background

Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF.

Methods

Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF.

Results

In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively.

Conclusions

For Chinese chronic hepatitis B patients, ETV is still the most cost-effective strategy over TDF and other nucleos(t)ide analogs, with a threshold of $20,466 USD/QALY gained.

     

Systematic review: extracorporeal bio-artificial liver-support system for liver failure

Background

Orthotopic liver transplantation (OLT) is the only effective long-term treatment for liver failure by now. However, it is not yet a perfect choice due to donor-organ shortage and the need of a lifelong immunosuppressive therapy. Therefore, it is necessary to find a new approach to fighting the disease. Several published clinical trials have reported the therapeutic effect of bio-artificial liver (BAL) for liver failure.

Objective

To overview and evaluate the current clinical application and outcomes of extracorporeal BAL support system during the past 15?years.

Methods

Relevant studies were retrieved from PubMed and Cochrane Library databases. Independent assessments and the final consensus decision were performed by three independent reviewers. Acceptable study designs included randomized controlled trials, controlled clinical trials, and case reports. A total of 31 studies were tabulated and critically appraised in terms of characteristics, methods, and outcomes.

Results

There was a trend of falling into the normal ranges with the clinical and biochemical parameters after the BAL treatment. The neurological status of most patients was improved or stabilized during BAL treatment as well. No significant effect on survival could be seen after the BAL treatment.

Conclusions

Although BAL system proved to be a success in some clinical cases reported, it still needs to be improved greatly.     

Epidemiologie von Non-CF-Bronchiektasen

Background

Recent and representative data on the epidemiology of non-CF bronchiectasis is limited.

Objectives

The objective of the present article is to provide a literature overview regarding the few studies on the epidemiology of non-CF bronchiectasis in Germany and worldwide and to point out arising consequences for future research priorities.

Materials and methods

Narrative and selective literature review.

Results

Due to the fact that (high resolution) computed tomography of the chest is increasingly used in routine care, bronchiectasis is diagnosed easier and earlier, resulting in an apparently increasing prevalence. High quality studies on the epidemiology of bronchiectasis are still exceedingly limited. Data from the US have demonstrated an increase of the outpatient as well as the inpatient treatment burden of bronchiectasis over the last years. Recently, comparable data on a significantly increasing rate of bronchiectasis-associated hospitalizations as a surrogate for the burden of disease in heath care became available for Germany. In this context, chronic obstructive pulmonary disease as an associated condition appears to be of particular clinical relevance.

Conclusions

Given the heterogeneous etiology, the set-up of national and international epidemiological patient registries is necessary in order to define the optimal clinical management as well as prognostic factors in non-CF bronchiectasis.