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Introduction: Prevalence and severity of pruritus among US patients with chronic hepatitis B and C (HBV, HCV) are not well-documented. Chronic Hepatitis Cohort Study (CHeCS) patients were surveyed to examine pruritus prevalence and impact on quality of life (QoL). Methods: Patients who reported experiencing pruritus ≥3 on a Numeric Rating Scale (NRS) within the past 30 days were invited to participate in a 6-month study using the SF-36 questionnaire. General regression (univariate followed by multivariable modelling) was used to analyse pruritus intensity and eight QoL dimensions. Results: Among 1654 patients (HBV = 358, HCV = 1296, HBV/HCV = 6), pruritus prevalence was significantly higher among patients with HCV than those with HBV (44% vs. 35%; p < .05). One hundred and twenty-three patients (21 HBV and 102 HCV) participated in the QoL study (72% ≥60 years; 50% men; 25% Black; 37% with cirrhosis; 66% had BMI > 25). Mean NRS was 4.9--5.3. QoL responses for social functioning and emotional well-being were higher (70--72 points) than responses for energy/fatigue (50--51). Antiviral treatment rates were higher in HCV (92%, SVR 99%) than HBV (71% ever, 43% ongoing). Multivariable analyses showed no significant effect of hepatitis type or antiviral treatments on itch. Antihistamines were associated with severe itch. Higher NRS was associated with significantly reduced QoL. Each unit increase in NRS was associated with a 2--3 unit decline in emotional well-being, general health, physical function, energy/fatigue, social functioning and emotional health. Conclusion: Pruritus negatively affects many viral hepatitis patients, regardless of antiviral treatment status. Improved treatment options are needed to address its impact on QoL. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) is a defective agent that only infects individuals with hepatitis B virus (HBV). Around 5–10% of chronic hepatitis B patients worldwide are superinfected with HDV, which means 15–25 million people. Hepatitis delta is the most severe of all chronic viral hepatitis, leading to cirrhosis, liver cancer and/or transplantation in most patients. Despite it, many HDV patients remain undiagnosed. The only treatment available until recently was peginterferon alfa, with poor results and significant side effects. The recent approval of bulevirtide, a lipopeptide that blocks HBV/HDV entry, has revolutionized the field. Another drug, lonafarnib, already approved to treat progeria, is expected to be available soon as HDV therapy. Since there is no cell reservoir for the HDV RNA genome, hypothetically viral clearance could be achieved if complete blocking of viral replication occurs for a minimum time frame. This is what happens in hepatitis C using direct‐acting antivirals, with the achievement of cure in nearly all treated patients. We envision the cure of hepatitis delta using combination antiviral therapy. Given that sexual and parenteral transmission routes are the most frequent for the acquisition of HBV and HDV, shared with HIV infection and HBV/HDV and HIV coinfection. The clinical outcome of hepatitis delta is worst in the HIV setting, with more frequent liver complications. Since most persons infected with HIV are on regular health care follow‐up, we propose that HIV‐HDV patients should be prioritized for moving forward new and potentially curative treatments for hepatitis delta. [ABSTRACT FROM AUTHOR]

Background & Aims: Chronic infection with hepatitis B and C viruses (HBV & HCV) is a major contributor to liver disease and liver‐related mortality in Uzbekistan. There is a need to demonstrate the feasibility of large‐scale simplified testing and treatment to implement a national viral hepatitis elimination program. Methods: Thirteen polyclinics were utilized to screen, conduct follow‐up biochemical measures and treat chronic HBV and HCV infection in the general adult population. Task shifting and motivational interviewing training allowed nurses to provide rapid screening and general practitioners (GPs) to treat individuals on‐site. An electronic medical system tracked individuals through the cascade of care. Results: The use of rapid tests allowed for screening of 60 769 people for HCV and HBV over 6 months and permitted outdoor testing during the COVID‐19 pandemic along with COVID testing. 13%–14% of individuals were lost to follow‐up after the rapid test, and another 62%–66% failed to come in for their consultation. One stop testing and treatment did not result in a statistically increase in retention and lack of patient awareness of viral hepatitis was identified as a key factor. Despite training, there were large differences between GPs and patients initiating treatment. Conclusions: The current study demonstrated the feasibility of large‐scale general population screening and task shifting in low‐ and middle‐income countries. However, such programs need to be proceeded by awareness campaign to minimize loss to follow up. In addition, multiple trainings are needed for GPs to bolster their skills to talk to patients about treatment. [ABSTRACT FROM AUTHOR]

Background and Aims: Advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) therapies have improved morbidity and mortality, but global disparities in viral hepatitis outcomes remain. We evaluate global trends in the impact of HBV and HCV on disability‐adjusted life years (DALYs). Methods: Using data from the 2010–2019 Global Burden of Diseases Study (GBD), overall all‐cause DALYs for patients with acute HBV or HCV, HBV‐ or HCV‐related cirrhosis, and HBV‐ or HCV‐related hepatocellular carcinoma (HCC) was calculated as the sum of years of life lost because of premature death and years lived with disability. DALYs were presented as age‐standardized rates per 100 000 population stratified by age and sex. Results: From 2010 to 2019, the overall global impact of HBV on DALYs per 100 000 decreased from 27.6 to 20.9 for acute HBV and 168.6 to 129.8 for HBV‐related cirrhosis but remained stable for HBV‐related HCC. The impact of HCV on DALYs per 100 000 decreased from 5.23 to 3.3 for acute HCV, 159.2 to 146.2 for HCV‐related cirrhosis, and 37.5 to 34.9 for HCV‐related HCC. We observed significant differences in the impact of HBV and HCV on DALYs when stratified by world regions. Conclusion: Decreases in HBV and HCV DALYs from 2010 to 2019 were observed. Disparities in DALY improvements across world regions suggest unequal access to viral hepatitis care and treatment. Achieving goals of viral hepatitis elimination will require enhanced prevention efforts and funding for high‐burden regions and regions that have not had substantial reductions in DALYs because of HBV and HCV. [ABSTRACT FROM AUTHOR]

Novel treatments for hepatitis Delta virus (HDV) infection provide promising opportunities to treat patients with hepatitis B virus (HBV) and HDV co‐infection. However, current clinical trials on HDV treatment rarely explore patients' barriers to treatments. In Europe, HDV infection mostly affects young migrants from HDV‐endemic areas who experience early liver‐related mortality. Migrants are more likely to face multiple situations of statutory and socioeconomic insecurity and structural barriers than non‐migrants. These obstacles may impact their quality of life and can (i) lead them to give secondary importance to certain HDV care options, (ii) delay treatment initiation and (iii) affect their adherence and commitment to care. Preliminary results from the ANRS CO22 HEPATHER cohort show that the majority (61.6%) of HBV‐HDV co‐infected migrants live in poverty. Moreover, half were diagnosed and a quarter of those who initiated HBV treatment had been in France for no more than two years, a period when language skills are often still poor and when knowledge of the health and administrative system may be lacking. We advocate for increased social science research, in particular qualitative studies, to investigate the effects that multiple forms of precarity (weak access to social rights, language barriers, housing insecurity, unexpected expenditures and other difficulties) may have on HDV screening opportunities, follow‐up, and treatment pathways in migrants. This will help adapt communication and care around viral hepatitis, as well as inform and orient medical services and public health actors about the difficulties that migrants encounter. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is a worldwide health problem leading to severe liver dysfunction, including liver cirrhosis and hepatocellular carcinoma. Although current antiviral therapies for chronic HBV infection have been improved and can lead to a strong suppression of viral replication, it is difficult to completely eliminate the virus with these therapies once chronic HBV infection is established in the host. Furthermore, chronic HBV infection alters intracellular metabolism and signalling pathways, resulting in the activation of carcinogenesis in the liver. HBV produces four viral proteins: hepatitis B surface‐, hepatitis B core‐, hepatitis B x protein, and polymerase; each plays an important role in HBV replication and the intracellular signalling pathways associated with hepatocarcinogenesis. In vitro and in vivo experimental models for analyzing HBV infection and replication have been established, and gene expression analyses using microarrays or next‐generation sequencing have also been developed. Thus, it is possible to clarify the molecular mechanisms for intracellular alterations, such as endoplasmic reticulum stress, oxidative stress, and epigenetic modifications. In this review, the impact of HBV viral proteins and intracellular alterations in HBV‐associated hepatocarcinogenesis are discussed. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex®) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real‐life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2 mg/d in subcutaneous injection) and pegylated interferon (PEG‐IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1 log10 and 3/3 of 2 log10 of HDV‐VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV‐VL relapse was notified 24 weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV‐VL during the therapy (<100 IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV‐VL by 1 log10 at 8 weeks and 1/1 by 2 log10 at 28 week on‐treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long‐term clinical benefit (fibrosis reversibility and reduction in hepato‐cellular carcinoma [HCC]). [ABSTRACT FROM AUTHOR]

[[2], [4]] If HBV BD vaccination is provided only to infants born to HBV+ mothers (HBV-negative mothers would have zero viral load by definition), 57 000 infants need to receive HBV BD annually with >23 000 of those in rural areas. We fully agree that prevention of hepatitis B virus (HBV) mother to child transmission is critical to all viral hepatitis elimination programmes. Response to overcoming the challenges in eliminating viral hepatitis in low- and middle-income countries. [Extracted from the article]

Background & Aim: Chronic infections with hepatitis B or C (HBV and HCV) are associated with adverse clinical outcomes and patient‐reported outcomes (PROs). The aim is to compare PRO scores in patients with chronic HBV and HCV without advanced liver disease before and after suppression/clearance of their infection. Methods: Patients with HCV and HBV infection prior to initiation of antiviral treatment and after viral suppression/eradication completed PRO questionnaires. Results: We included 132 patients with HBV and 132 matched patients with HCV. Baseline PRO scores were significantly higher in patients with HBV in the domains of Physical Functioning, Role Physical, Bodily Pain, Social Functioning, and Role Emotional of SF‐36, SF‐6D utility, Emotional and Fatigue domains of CLDQ, Presenteeism and total Work Productivity Impairment of WPAI:SHP in comparison to patients with HCV by 5.8%‐13.2% of a PRO score range (all P < 0.05). After viral suppression (HBV DNA < 20 IU/mL after 48 weeks of treatment for HBV) or eradication (SVR‐12 for HCV), only Physical Functioning and Role Physical scores remained higher in HBV by 6.7%‐9.9%, while other PRO scores became similar between HBV and HCV groups (P > 0.05). The most prominent improvement of PROs in HCV was noted in Vitality, Emotional, Fatigue and Worry domains. In addition, General Health, Worry and Work Productivity scores were the most improved in HBV. Conclusions: Prior to treatment, PRO scores were lower in patients with HCV in comparison to HBV. After successful treatment, both groups of patients experienced improvement in some PRO domains confirming the positive impact of treatment. [ABSTRACT FROM AUTHOR]

Background & Aims: The recently published manuscript by Zhu and colleagues "Hepatitis B virus infection and risk of non‐alcoholic fatty liver disease: A population‐based cohort study" found no correlation between presence of chronic HBV and presence of common risk factors for non‐alcoholic fatty liver disease on primary analysis. A limitation to this study, like most population based research, is the absence of liver histology, which is considered gold standard for assessment of non‐alcoholic fatty liver disease. Methods: Our group studied the association between hepatitis B viral activity and non‐alcoholic fatty liver disease activity as measured by grade of steatohepatitis/fibrosis on liver biopsy by analysing consecutive liver histology samples from patients with chronic hepatitis B at a single quaternary liver transplant centre. Results: Linear regression modelling for active viral hepatitis on histological examination against degree of steatohepatitis showed no correlation (r2 =.018, all P>.1). Linear regression of degree of steatohepatitis vs hepatitis B viral load also showed no correlation. Conclusions: Our work is concordant with the manuscript from Zhu et al; we found no significant correlation between hepatitis B viral activity and degree of steatohepatitis. [ABSTRACT FROM AUTHOR]

One approach is that all countries may systematically implement routine testing for HDV seroprevalence for everyone diagnosed with hepatitis B virus (HBV), so-called reflex testing. This will result in more accurate prevalence data and address the bias created when only those patients with abnormal liver function tests are tested for HDV.[3] For instance, patients with a mild HDV infection can present with normal liver enzymes that may worsen as time progresses or during flare-ups[4]; in this respect, many HDV infections may go undetected. We sincerely thank Dr Waked for the knowledgeable letter related to our scoping review[1] and for sharing the additional information on hepatitis D virus (HDV) infection prevalence in Egypt, a country well known for its success in addressing viral hepatitis.[2] Egypt was not included in the original search criteria; therefore, our article did not analyse or discuss the prevalence rate of HDV in the country. [Extracted from the article]

Background & Aims Differences in intrahepatic gene expression patterns may be associated with therapy response in peginterferon-treated chronic hepatitis B ( CHB) patients. Methods We employed gene expression profiling in baseline liver biopsies of 40 CHB patients (19 HBeAg-positive; 21 HBeAg-negative) treated with peginterferon and adefovir for 48 weeks, and compared expression patterns of combined responders ( HBeAg loss, HBV- DNA <2000 IU/ml, alanine aminotransferase normalization after 1 year of treatment-free follow-up) with non-responders. Genes identified by transcriptome analysis in 15 biopsies were confirmed in 25 additional biopsies by RT- qPCR. Results Transcriptome analysis demonstrated significant differences in expression of 41 genes between responders and non-responders. In responders, pathway analysis showed specific upregulation of genes related to the immune response, including chemotaxis and antigen processing and presentation. Genes upregulated in responders exhibited strongest similarity with a set of genes induced in livers of chimpanzees with acute Hepatitis B infection. Differential expression was confirmed for eight selected genes. A 2-gene subset ( HLA- DPB1, SERPIN-E1) was found to predict response most accurately. Incorporation of these genes in a multivariable model with HBeAg status, HBV genotype and baseline HBsAg level correctly classified 90% of all patients, in which HLA- DPB1 and SERPIN-E1 were independent predictors of response. Conclusion We identified an intrahepatic transcriptional signature associated with enhanced immune activation which predicts therapy response. These novel associations could lead to better understanding of responsiveness to peginterferon in CHB patients, and may assist in selecting possible responders to interferon-based treatment. [ABSTRACT FROM AUTHOR]

Background & Aims We aimed to assess the association between the patatin-like phospholipase domain-containing-3 ( PNPLA3) I148M polymorphism, liver histology and long-term outcome in chronic hepatitis B ( CHB) patients. Methods We enrolled 531 consecutive treatment naïve CHB patients diagnosed from 1985 to 2012 with an available liver biopsy for reassessment, and sample for genetic testing. Data on all-cause mortality and hepatocellular carcinoma ( HCC) at long-term follow-up were obtained from national database registries. Results The prevalence of steatohepatitis increased with PNPLA3 CC (14%), CG (20%) and GG (43%) ( P < 0.001). The association was altered by both gender ( P = 0.010) and overweight ( P = 0.015): the effect of PNPLA3 on steatohepatitis was most pronounced among non-overweight females (adjusted OR 13.4, 95% CI: 3.7-51.6, P < 0.001), and non-overweight males (adjusted OR 2.4, 95% CI: 1.4-4.3, P = 0.002). Furthermore, PNPLA3 GG genotype was associated with iron depositions ( OR 2.8, 95% CI: 1.2-6.4, P = 0.014) and lobular inflammation ( OR 2.2, 95% CI: 1.1-4.5, P = 0.032), but not with advanced fibrosis ( OR 1.1, 95% CI: 0.7-1.8, P = 0.566). The median follow-up was 10.1 years (interquartile range 5.6 - 15.8), during which 13 patients developed HCC and 28 died. Steatohepatitis was associated with all-cause mortality [Hazard ratio ( HR) 3.1, 95% CI: 1.3-7.3, P = 0.006] and HCC ( HR 2.8, 95% CI: 0.9-9.2, P = 0.078), but no significant association was observed for PNPLA3. Conclusions In this cohort of biopsied CHB patients, PNPLA3 was independently associated with steatosis, steatohepatitis, lobular inflammation and iron depositions, but not with advanced fibrosis, HCC development or all-cause mortality. The effect of PNPLA3 on steatohepatitis was particularly pronounced among female patients without severe overweight. [ABSTRACT FROM AUTHOR]

Current agents for the treatment of chronic hepatitis B (CHB) can be classified into interferon-α (standard or pegylated) (IFN) and nucleos(t)ide analogues (NAs). IFN therapy has the advantage of a finite duration (48 weeks) with a chance for durable sustained off-treatment response in HBeAg positive CHB patients. However, these benefits are limited to approximately 30% of HBeAg positive patients, while parenteral administration and potential side effects are common patient concerns. Thus, patients who can benefit from IFN therapy must be carefully selected and monitored. Recently, stopping rules for IFN non-responders were developed based on 12-week HBsAg levels. NAs are currently used in most CHB patients. They are administered in one tablet daily and can be used in all patients with excellent tolerability and a good safety profile. The current first-line options, entecavir (ETV) and tenofovir (TDF), are highly potent with a minimal risk of resistance during long-term monotherapy. Prolongation of entecavir or tenofovir maintains the initially high virological remission rates in adherent HBeAg positive patients and modifies the long-term outcomes. The need for a long-term, perhaps indefinite, treatment duration is the main limitation of ETV or TDF, which may sometimes be safely discontinued in HBeAg positive patients who achieve stable HBeAg seroconversion. Since there will always be safety concerns and family planning issues with long-term therapy, NAs should be used carefully particularly in young HBeAg positive patients with minimal-mild liver disease. [ABSTRACT FROM AUTHOR]

HBeAg negative chronic hepatitis B (CHB) is a frequent, progressive and difficult- to-cure phase of CHB. The end-point of therapy is to persistently suppress viral replication to halt progression of liver disease. Two different treatment strategies are currently available: a short-term course of pegylated interferon alpha (PEG-IFN) or long-term therapy with nucleot(s)ide analogues (NA), i.e. entecavir or tenofovir. Young patients with mild-to-moderate stages of liver disease can benefit from a 48-week course of PEG-IFN, while NA may be preferred in patients with more severe liver disease, in older patients, and in those who do not respond, are unwilling or have contraindications to PEG-IFN. Nucleot(s)ide analogues provide persistent viral suppression and biochemical normalization in almost all patients, together with the regression of fibrosis and the prevention of decompensation, but the effect on hepatocellular carcinoma rates is limited. Thus, NAs have become the most popular treatment strategy worldwide but lifelong administration is associated with high cost, unknown safety and adherence issues and an unknown risk of drug-resistance over time as well as limited rates of HBsAg seroclearance. On the other hand, PEG-IFN treatment may achieve a SVR in nearly a quarter of patients ultimately leading to HBsAg loss in almost 30- 50%. Interestingly, response rates to PEG-IFN may further increase with more careful patient selection based on age, ALT and HBV DNA levels at baseline and by applying early on-treatment stopping rules based on HBV DNA and HBsAg kinetics. The combination of NA and PEG-IFN is not currently recommended but numerous studies are ongoing. [ABSTRACT FROM AUTHOR]

Taiwan is an endemic area of hepatitis B and is the first country to implement the nationwide infant hepatitis B immunization program. Keywords: diagnosis; HCC; prognosis EN diagnosis HCC prognosis 1173 1174 2 04/19/21 20210501 NES 210501 We read with interest the paper "Epidemiological projections of viral-induced hepatocellular carcinoma in the perspective of WHO global hepatitis elimination" published in an upcoming issue of Liver International.1 It is an important article that specifically focused on the goal of viral hepatitis elimination by the WHO before 2030 that can be accelerated by improving the access to hepatocellular carcinoma (HCC) screening programs. Post hepatitis B-eliminated hepatocellular carcinoma: New challenges. [Extracted from the article]

Background & Aims Liver histological assessment is essential for predicting antiviral therapy in HBeAg negative chronic hepatitis B ( CHB) patients with serum alanine aminotransferase ( ALT) ≤2 upper limit of normal ( ULN). The aim was to establish a model to predict antiviral treatment for those patients without liver biopsy. Methods Three hundred and one consecutive treatment naive HBeAg negative CHB patients with HBV DNA ≥2000 IU/ml and ALT ≤2 ULN were retrospectively enrolled, among which 158 patients were for the training set and 143 for validation set. A multivariate logistic regression model was constructed in the training set and validated in the validation set. Results Our model identified four independent factors for the timing of treatment: Age ( OR 1.050, 95% CI 1.004-1.098), Ln(aspartate aminotransferase) ( OR 17.425, 95% CI 5.394-56.292), Log10 [ HBV DNA] ( OR 0.704, 95% CI 0.514-0.963) and platelet ( OR 0.980, 95% CI 0.970-0.990). It showed 94% sensitivity, 88% negative predictive value ( NPV) in the training set and 93% sensitivity, 85% NPV in the validation set using the low cut-off point of 5.16. Meanwhile, it showed 92% specificity, 88% positive predictive value ( PPV) in the training set and 94% specificity, 92% PPV in the validation set using the high cut-off point of 7.26. It could predict treatment for 179 of 301(59%) patients without biopsy. Conclusions We established a model to predict antiviral therapy in HBeAg negative CHB patients with ALT ≤2 ULN. Antiviral treatment should be initiated if the model value >7.26 and not if its value ≤5.16. Liver biopsy is needed only when its value between the two points. [ABSTRACT FROM AUTHOR]

Pegylated interferon-α (PEG-IFN) is still an important treatment option for both HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) patients even with the availability of potent nucleos(t)ide analogues (NUCs) with a low risk of resistance. The major advantages of PEG-IFN-based treatment include the limited duration of treatment and the good probability of achieving a sustained off-treatment response. Responders to PEG-IFN have an increased probability of HBsAg loss and survival. However, the limited number of patients who achieve a response and the high costs and side-effects associated with PEG-IFN limit its clinical use. The potent NUCs entecavir and tenofovir are therefore often used as a first-line treatment option. Unfortunately, the off-treatment durability of response to NUCs is generally low, requiring long-term continuous therapy. Recent progress making it possible to select patients with a high probability of achieving a response to PEG-IFN, and to adapt therapy early on in probable non-responders, should help further optimize the utilization of PEG-IFN in CHB. [ABSTRACT FROM AUTHOR]

Background: Elevated pretreatment alanine aminotransferase (ALT) over two times the upper limit of normal reference range has been accepted as a marker for predicting HBeAg loss and an indicator for initiating antiviral therapy. Recently, several opinions argued that in patients aged over 40 years, the treatment should be started if they have elevated serum hepatitis B virus (HBV) DNA without elevated ALT. However, initiating treatment in these patients might be argued against by the concept that the rate of HBeAg loss depends on the pretreatment ALT. Aim: This study was conducted to investigate the usefulness of pretreatment ALT in predicting HBeAg loss in patients aged over 40 years under lamivudine treatment. Methods: We retrospectively analyzed 820 HBeAg-positive patients treated with lamivudine. The patients with hepatocellular carcinoma at or after initiating the lamivudine treatment and patients with evident liver cirrhosis were excluded. Three hundred fifty-five patients met the criteria and were divided into two groups: ≤40 years of age (Group 1) and >40 years of age (Group 2). Results: Analysis using the Kaplan–Meier method and the log rank test showed that the cumulative rate of HBeAg loss was not different in the two groups. Multivariate modelling indicated that an elevated pretreatment ALT level was a predictor of HBeAg loss in Group 1 ( P<0.05), whereas it failed to act as a predictor in Group 2. Conclusion: Antiviral therapy might not need to be deferred until the ALT level increases in order to enhance the chance of HbeAg loss in HBV DNA-(+) patients aged over 40 years. [ABSTRACT FROM AUTHOR]

Aim: To correlate liver stiffness with demographical factors and routine liver biochemistry and to assess the predictive value of these as potential markers of fibrosis. Methods: Transient elastography was performed in 1268 chronic hepatitis B (CHB) patients. According to a previous validated study for CHB, liver stiffness of >8.1 and >10.3 kPa were used as cut-off values for defining severe fibrosis and cirrhosis respectively. Results: Liver stiffness correlated positively with bilirubin, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), globulin, α-fetoprotein (AFP) and HBV DNA levels and negatively with albumin and platelet levels ( P<0.05 for all correlations). From 13 parameters (age, sex, platelet, AST, ALT, GGT, AFP, albumin, globulin, bilirubin, ALP, HBV DNA and hepatitis B e-antigen), four best parameters (AST, platelet, GGT and AFP) were used to derive a liver stiffness model. Using log (index)=1.44+0.1490(GGT)+0.3308 log (AST)−0.5846 log (platelets)+0.1148 log (AFP+1) to predict both severe fibrosis and cirrhosis had area under the receiver operating characteristics curve of 0.85. Conclusion: Routine liver biochemistry correlated well with liver stiffness in Asian CHB patients. A model using simple serum markers can predict liver stiffness, and further studies are required to validate the usefulness of these simple tests as non-invasive markers of fibrosis in CHB. [ABSTRACT FROM AUTHOR]

Background/Aims: The short- and long-term benefits of interferon (IFN)-α therapy in young patients with chronic hepatitis B (CHB) acquiring infection perinatally or during early childhood have been questioned. Methods: Twenty-one Taiwanese hepatitis B envelope antigen (HBeAg)-positive CHB patients aged 1.8–21.8 years (median 14.0 years) with alanine aminotransferase (ALT)>80 IU/L at entry were enrolled for IFN-α therapy. They received IFN-α therapy with a dose of 3 MU/m2/day three times a week for 24 weeks. A control group included untreated 21 CHB patients closely matched for gender, age, duration of ALT >80 IU/L and HBeAg status. All 42 patients were prospectively followed for 6.5–12.5 years after the end of therapy. Results: The cumulative rate of virological response [anti-HBe seroconversion and serum hepatitis B virus (HBV)-DNA <105 copies/ml] was not different between the IFN-treated patients and control patients at 1 year (41 vs 44%) and at 6 years (88 vs 89%) after stopping treatment. Serum hepatitis B surface antigen loss occurred in two (9.5%) treated patients and in one (4.8%) control patient. Patients with a successful treatment response (anti-HBe seroconversion, HBV-DNA <102 copies/ml and ALT normalization at 1 year after stopping treatment) were younger than those without a successful response ( P=0.03). A lower pretreatment serum HBV-DNA level (<2 × 108 copies/ml) is not only a significant factor to predict successful treatment response ( P=0.008) but also has a beneficial effect on the long-term cumulative rate of virological response in IFN-treated patients ( P=0.021), but not in control patients. Genotype difference or emergence of a precore stop codon mutant before treatment was not predictive for HBeAg clearance. Conclusion: For young CHB patients in Taiwan with infection occurring perinatally or in early childhood, the real advantage of IFN-α therapy was not observed. IFN-α therapy showed a beneficial effect on short- and long-term virological outcomes only in those with a lower pretreatment serum HBV-DNA level. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)-positive ( n=271) and HBeAg-negative ( n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 μg peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88–89 vs 96–100%), serious AEs (4–5 vs 7–16%) and treatment withdrawals (6–8 vs 17–33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression. [ABSTRACT FROM AUTHOR]

The clinical usefulness of hepatitis B virus core-related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B. Patients: Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow-up period of 19.3 months. Results: The pretreatment positive rate of HBe antigen, or pretreatment levels of HBVcrAg or HBV DNA did not differ between patients with and without lamivudine resistance. Levels of both HBVcrAg and HBV DNA decreased after the initiation of lamivudine administration; however, the level of HBVcrAg decreased significantly more slowly than that of HBV DNA. The occurrence of lamivudine resistance was significantly less frequent in the 56 patients whose HBV DNA level was less than 2.6 log copy/ml at 6 months of treatment than in the remaining 25 patients. The cumulative rate of lamivudine resistance was as high as 70% within 2 years in the latter group, while it was only 28% in the former group. Lamivudine resistance did not occur during the follow-up period in the 19 patients whose HBVcrAg level was less than 4.6 log U/ml at 6 months of treatment, while it did occur in 50% of the remaining patients within 2 years. Conclusion: These results suggest that measurement of HBV DNA is valuable for identifying patients who are at high risk of developing lamivudine resistance, and that, conversely, measurement of HBVcrAg is valuable for identifying those who are at low risk of lamivudine resistance. [ABSTRACT FROM AUTHOR]

Lu J-Y, Chuang L-M, Yang W-S, Tai T-Y, Lai M-Y, Chen P-J, Kao J-H, Lee C-Z, Lee H-S. Adiponectin levels among patients with chronic hepatitis B and C infections and in response to IFN-α therapy. Liver International 2005: DOI: 10.1111/j.1478-3231.2005.0. © Blackwell Munksgaard 2005 The study was designed to survey the change of adiponectin levels before and after interferon-α (IFN-α) therapy in patients with chronic hepatitis B and C infections. Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-α for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-α therapy. Insulin suppression test was conducted before and within 1 week after IFN-α therapy. The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-α treatment (−4.8±2.2 vs. 0.5±1.0 μg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-α ( P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9±3.2 vs. 10.8±3.0 μg/ml, P=0.02, n=4) and HBV responders (17.7±4.1 vs. 9.2±1.0 μg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6±1.8–11.7±1.2 mmol/l, P=0.03), but not in non-responders (12.3±1.1–11.0±1.0 mmol/l, P=0.20), after IFN-α therapy. IFN-α resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-α treatment, contributes to the lowering of adiponectin levels needs to be further investigated. [ABSTRACT FROM AUTHOR]

Lin C-L, Liao L-Y, Wang C-S, Chen P-J, Lai M-Y, Chen D-S, Kao J-H. Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B.Liver International: 2005: 25: 564–570.© Blackwell Munksgaard 2005The long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B are distinct from those in HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in this special clinical setting remain largely unknown. We thus investigated the association of hepatitis B virus (HBV) genotypes as well as precore/basal core-promoter mutations with the clinical and virological characteristics of patients with HBeAg-negative chronic hepatitis B in Taiwan.HBV genotypes and sequences of precore and basal core-promoter regions of the HBV genome were determined in 174 HBeAg-negative chronic HBV infection patients including 62 inactive carriers and 112 with different stages of liver disease.HBV carriers with older age (>50 years) (odds ratio, 9.09; 95% confidence interval (CI), 3.22–25,P<0.001) and basal core-promoter mutant of HBV (odds ratio, 4.12; 95% CI, 1.41–12.03,P=0.01) were associated with the development of liver cirrhosis and hepatocellular carcinoma (HCC). The gender-related risk factors associated with the development of liver cirrhosis and HCC were further analyzed, and basal core-promoter mutant was only associated with the development of liver cirrhosis and HCC in male carriers (odds ratio, 4.35; 95% CI, 1.30–14.52,P=0.02).The risk of development of liver cirrhosis and HCC is significantly increased in patients with advanced age as well as with basal core-promoter mutant of HBV. In addition, basal core-promoter mutant might contribute to the gender difference of the progression of liver disease in HBeAg-negative chronic hepatitis B in Taiwan. [ABSTRACT FROM AUTHOR]

Liaw Y-F, Leung N, Guan R, Lau GKK, Merican I, McCaughan G, Gane E, Kao J-H, Omata M for the Asian-Pacific consensus update working party on chronic hepatitis B. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update.Liver International 2005: 25: 472–489.© Blackwell Munksgaard 2005.A large amount of new data on the treatment of chronic hepatitis B has become available such that the 2003 consensus statement requires revision and update.New data were presented, discussed and debated in an expert pre-meeting to draft a revision. The revised contents were finalized after discussion in a general meeting of APASL.Conceptual background, including the efficacy and safety profile of currently available and emerging drugs, was reviewed. Nineteen recommendations were formed and unresolved issues and areas for further study were suggested.The current therapy of chronic hepatitis B is modestly effective but not satisfactory. The development of new drugs and new strategies is required to further improve the outcomes of treatment. [ABSTRACT FROM AUTHOR]

Mah Y-H, Kao J-H, Liu C-J, Chen C-L, Chen P-J, Lai M-Y, Chen D-S. Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan.Liver International DOI: 10.1111/j.1478-3231.2005.01055.x.© Blackwell Munksgaard 2005The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. We therefore studied the prevalence of HFE mutations and their impact on the progression of chronic viral hepatitis in Taiwan.H63D and C282Y mutations were screened by using polymerase chain reaction followed by restriction fragment length polymorphism in 152 chronic hepatitis B patients with various stages of liver disease, 87 chronic hepatitis C patients with various stages of liver disease, and 49 healthy controls. The distribution of each allele frequency was then compared among different groups of patients and in various stages of liver disease.All three groups of patients were C282Y wild type and the majority of H63D mutations were heterozygotes. Although statistically not significant, allele frequencies of H63D mutation in hepatitis B-related liver cirrhosis (6%) and hepatitis C-related liver cirrhosis (9.1%) were higher than those in healthy control (2%). After adjustment for age and sex, hepatitis B patients with H63D heterozygosity had a higher likelihood of cirrhosis than those with H63D wild type (odds ratios (OR): 3.2, confidence interval (CI): 0.49–20.5,P=0.22). Similarly, hepatitis C patients with H63D homozygosity had a higher likelihood of cirrhosis compared with those with H63D wild type (OR: 2.35, CI : 0.19–28.5,P=0.52).Almost all Taiwanese are C282Y wild type. H63D heterozygote and homozygote, occurring in less than 5% of the subjects, tended to be associated with the development of liver cirrhosis, irrespective of viral etiology. Screening for H63D mutation might be considered in patients with chronic viral hepatitis in Taiwan. [ABSTRACT FROM AUTHOR]

Background/aim: Accurate histological assessment of liver fibrosis is essential in the management of chronic hepatitis B (CHB). Although semi- quantitative scoring systems describe well the pathological patterns of hepatic structure, they produce fibrosis evaluation that is not very precise. Image analysis or morphornetry has the theoretical advantage of providing truly quantitative data. Patients and methods: The present study aimed at validating a new image analysis system, Bioquant Nova Prime, in estimating collagen content in liver biopsy samples from patients with CHB. The biopsies were stained with picrosirius red and the areas of collagen were measured. The results were correlated with laboratory parameters and Ishak modified histological scores. Discriminative reliability of morphornetry was determined using receiver operating characteristics (ROC) analysis. Results: There was excellent interobserver agreement (r = 0.84-0.94, P< 0.01) in the morphornetric analysis. Significant correlations between the quantitative m orphornetric data and the semi-quantitative score (Spearman' s r = 0.68-0.78, P<0.001) were also demonstrated. Excellent discriminative power of morphornetry in differentiating mild from advanced fibrosis and cirrhosis from absence of cirrhosis was shown by the ROC analysis. Conclusions: Our results validated the use of Bioquant Nova Prime in estimating collagen content in liver biopsies. We showed that morphometry is a sensitive method of liver fibrosis quantification in CHB and complements semi-quantitative histological scoring system. This tool, with its reliable intraassay variability, could be of special value in assessing histological response to treatment after anti-viral or anti-fibrotic therapy. [ABSTRACT FROM AUTHOR]

Fotiadu A, Tzioufa V, Vrettou E, Koufogiannis D, Papadimitriou CS, Hytiroglou P. Progenitor cell activation in chronic viral hepatitis. Liver International 2004: 24: 268–274. © Blackwell Munksgaard 2004 Oval cell proliferation is known to occur in experimental models of hepatic regeneration and carcinogenesis. Recent studies have suggested that activation of progenitor cells, representing the human counterpart of oval cells, may play a role in hepatic diseases. Therefore, we evaluated putative progenitor cells in chronic viral hepatitis. Forty-one needle liver biopsy specimens from patients with chronic hepatitis B and 43 specimens from patients with chronic hepatitis C were examined histologically. The grade (histological activity index (HAI)) and stage (degree of fibrosis) were determined on routinely stained sections. The number of progenitor cells was assessed semiquantitatively on cytokeratin 7- (CK 7-) stained sections. In both aetiological categories of chronic viral hepatitis, progenitor cell numbers were found to increase in parallel to the HAI, as well as to the stage of disease. Features suggestive of hepatocytic differentiation of progenitor cells were also noted on immunohistochemical stains for CK 7 and ‘hepatocyte-specific’ antigen. In chronic hepatitis B and chronic hepatitis C, progenitor cell activation is correlated with the grade and stage of disease. Proliferating progenitor cells may play a role in hepatic regeneration occurring in this setting. [ABSTRACT FROM AUTHOR]