Treatment-naive Chronic Hepatitis Research Articles

Fibrosis progression in interferon treatment-naive Chinese plasma donors with chronic hepatitis C for 20 years: a cohort study

To evaluate the progression of fibrosis and factors influencing this in interferon (IFN) treatment-naive Chinese plasma donors infected with hepatitis C virus (HCV) for approximately 20 years. From July 2010 to June 2011, we investigated 122 IFN treatment-naive chronic hepatitis C (CHC) patients infected by plasma donation in 1992-1995. Liver fibrosis stage and inflammation grade were evaluated by Metavir and Scheuer scoring systems, respectively. One hundred and twenty patients underwent liver biopsy. Liver biopsy was not performed in one patient with cirrhosis due to ascites, and another patient was excluded because of an invalid biopsy specimen. Cirrhosis was observed in three patients (fibrosis stage F4 in two patients revealed by biopsy, and one patient with ascites confirmed by physical and Doppler ultrasound examination). Fibrosis stages F1 and F2 were present in 55 and 50 patients, respectively. The severity of liver inflammation was independently related to moderate to severe fibrosis (F ≥2). Older age and male sex showed an increasing tendency for more severe fibrosis (F3/F4) in the present cohort. Based on histopathology results, the progression of fibrosis in patients with CHC infected by repeated plasma donation is slow after HCV infection of approximately 20 years. Liver inflammation is closely related to the development of moderate to severe liver fibrosis.

Apolipoprotein J, a glucose-upregulated molecular chaperone, stabilizes core and NS5A to promote infectious hepatitis C virus virion production

Hepatitis C virus (HCV) infection leads to glucose abnormality. HCV depends on lipid droplets (LDs) and very-low density lipoproteins for assembly/releasing; however, the components and locations for this process remain unidentified. Apolipoprotein J (ApoJ), upregulated by glucose, functions as Golgi chaperone of secreted proteins and resides abundantly in very-low density lipoproteins. This study investigates the interplay between glucose, ApoJ and HCV virion production. The effects of high glucose on ApoJ expression and HCV production were evaluated with cultivated HuH7.5, primary human hepatocytes, and in treatment naive chronic hepatitis C patients. How ApoJ affects HCV lifecycle was assessed using siRNA knockdown strategy in JFH1 infected and subgenomic replicon cells. The interactions and locations of ApoJ with viral and host components were examined by immunoprecipitation, immunofluorescence and subcellular fractionation experiments. HCV infection increased ApoJ expression, which in parallel with HCV infectivity was additionally elevated with high glucose treatment. Serum ApoJ correlated positively with fasting blood glucose concentration and HCV-RNA titre in patients. ApoJ silencing reduced intracellular and extracellular HCV infectivity and extracellular HCV-RNA, but accumulated intracellular HCV-RNA in HCV-infected cells. ApoJ interacted with HCV core and NS5A and stabilized the dual protein complex. HCV infection dispersed cytoplasmic ApoJ from the compact zones of the Golgi to encircle LDs, where co-localization of the core, NS5A, HCV-RNA, subcellular markers for LDs, endoplasmic reticulum (ER), Golgi, and membrane contact sites occurred. ApoJ facilitates infectious HCV particle production via stabilization of core/NS5A, which might surround LDs at the ER-Golgi membrane contact site.

Correlation between Serum Quantitative HBsAG Levels, Quantitative HBV-DNA Levels, Histological Activity Index and Hepatic HBsAG Expression in Patients with Treatment Naive Chronic Hepatitis B Virus Infection

Background and objectives: To date little is known about the role of HBsAg quantification in HBV infection. The current study aims at assessing the correlation between serum quantitative HBsAg levels, quantitative HBVDNA levels, hepatic immuno-histochemical expression of HBsAg and histological activity of disease in chronic HBV infection.

Impact of Support with EPO and GCSF on Outcome of Antiviral Therapy in Treatment-Naive Chronic Hepatitis C Patients from Northern India

Impact of Support with EPO and GCSF on Outcome of Antiviral Therapy in Treatment-Naive Chronic Hepatitis C Patients from Northern India

Correlation between Serum Quantitative HBsAG and HBV-DNA Levels with Histological Activity Index and Hepatic HBsAG Expression in Liver Biopsy Specimens of Patients with Treatment Naive Chronic Viral Hepatitis B Infection

Background and objectives: Chronic viral hepatitis B is a leading cause of chronic liver disease in the south-east Asia region. Various surrogate markers have been evaluated for correlation with severity of liver disease, includes aminotransferase levels, HBV surface and envelope antigens and HBV-DNA levels. Qualitative and quantitative estimation of tissue expression of viral antigens have been evaluated for correlation with severity of liver disease only in a few studies till date. The current study aims at assessing the correlation between serological markers and hepatic immuno-histochemical expression of HBsAg with histological activity of the disease in patients with treatment naïve chronic viral hepatitis B infection.

Lamivudine and Adefovir Motif Variants Detected in chronic Hepatıtıs B patients.

Chronic hepatitis B is an important health problem worldwide. Lamivudine, adefovir, entecavir and telbivudine are the oral drugs licensed for the treatment of patients with chronic hepatitis B. Implementation of antiviral therapy leads to the emergence of mutant strains during the treatment in chronic hepatitis B. Primary antiviral resistance may be rarely encountered. The aims of this study were to detect the resistance patterns of Hepatit B Virus strains in treatment-naive chronic hepatitis B patients. A total of 147 CHB patients were included to this study which was carried on between January 2007- December 2010. HBV DNA levels were detected by using the Real time PCR (COBAS Ampli- Prep/COBAS TaqMan HBV Test). HBV-DNA was extracted from the sera of the patients by using extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line prob assay (Inno-Lipa HBV DR v2, Innogenetics N.V, Ghent, Belgium) was used to determine motif variants at viral polymerase gene fragment in HBV-DNA samples of these patients and evaluated colorimetrically. In 147 patients antiviral resistance rate was found 17% (25/147) for lamivudin, 5.44% (8/147) adefovir, 0.68%(1/147) lamivudin and adefovir. Various mutations were detected. This mutations; responsible for lamivudine resistance YMDD+YVDD (n=10), YMDD+YIDD (n=12), YIDD (n=2), YVDD (=1); responsible for adefovir resistance N236T (n=3), A181T (n=5); responsible for lamivudine and adefovir resistance YMDD+YIDD+N236T (n=1). As a conclusion, it is thought that drug resistance should be followed up regularly, the determination of HBV drug resistance as immediate as possible period may be instructive for the treatment and follow-up in CHB patients. Although determination of known mutations with Inno Lipa DR v2 method is disadvantage, because of ease of application and the determination of both lamivudin-adefovir resistance in a short time, it can be used for the treatment and follow-up in CHB patients.

Evaluation of 48-week response of treatment-naive chronic hepatitis B patients to 0.5 mg/day entecavir

The hepatitis B virus (HBV) is an important healthcare problem. Chronic hepatitis B infection may present with a wide range of manifestations from inactive carrier state to cirrhosis and hepatocellular cancer. Therefore, treatment is very important in chronic hepatitis B. In this study, the treatment results of 199 chronic hepatitis B patients taking entecavir 0.5 mg/day for 48 weeks were evaluated. This study retrospectively evaluated data of 199 treatment-naive chronic hepatitis B patients who were treated with entecavir. Of the 199 treatment-naive chronic hepatitis B patients, 141 (70.9%) were males and 58 (29.1%) were females, and mean age of the whole group was 37.5 ± 12.1 years. HBeAg was positive in 91 (45.7%) and antiHBe was positive in 108 (54.3%) patients. Mean HBV DNA value was 666,449,365.5 ± 2,759,013,996.9 IU/mL, mean ALT value was 112.1 ± 95.7 U/L, and mean AST value was 95.3 _ 71.2 U/L. At week 24 of the treatment, HBV DNA levels were below 50 IU/mL in 56% of the HBeAg-positive and 76% of the HBeAg-negative patients. At week 48 of the treatment, HBV DNA levels were below 50 IU/mL in 79% of the HBeAg-positive and 87% of the HBeAg- negative patients. At week 24, ALT had normalized in 72% of the HBeAg-positive and 79% of the HBeAg-negative patients. At week 48, ALT had normalized in 89% of the HBeAg-positive and 88% of the HBeAg-negative patients. AntiHBe seroconversion was seen in 2 of 91 patients (2.2%), but the loss of HBsAg was never observed. The 48-week entecavir treatment at a dose of 0.5 mg/day was shown to be effective both for HBeAg-positive and negative patients.

Early termination of immune tolerance state of hepatitis B virus infection explains liver damage.

To assess an early termination of immune tolerance state of chronic hepatitis B virus infection in Bangladesh and its clinical significance. From a series of 167 treatment-naive chronic hepatitis B patients aged between 12 to 20 years (mean ± SD; 17.5 ± 2.8 years), percutaneous liver biopsies of 89 patients who were all hepatitis B e antigen negative at presentation were done. Of them, 81 were included in the study. They had persistently normal or raised serum alanine aminotransferase (ALT) values. A precore mutation (PCM) study was accomplished in 8 patients who were randomly selected. Forty-four (53.7%) patients had significant necroinflammation (HAI-NI > 7), while significant fibrosis (HAI-F ≥ 3) was seen in 15 (18.5%) patients. Serum ALT (cut off 42 U/L) was raised in 29 (35.8%) patients, while low HBV DNA load (< 10(5) copies/mL) was observed in 57 (70.4%) patients. PCM was negative in all 8 patients. This study indicates that the current concept of age-related immune tolerance state of HBV infection deserves further analyses in different population groups.

Efficacy of Tenofovir in Adefovir-Experienced Patients Compared with Treatment-Naive Patients with Chronic Hepatitis B

Tenofovir (TDF) has similar antiviral efficacy in both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients. Data on TDF use in patients with adefovir (ADV) resistance is inconsistent. The aim of our study was to assess antiviral efficacy of TDF against nucleoside analogue-naive (NN) and ADV-resistant (ADV-R) CHB and suboptimal responders to ADV (ADV-S). A database of 135 CHB patients treated with TDF was analysed. A total of 37 patients with incomplete data were excluded and analysis was performed in 98 (44 NN, 30 ADV-R and 24 ADV-S). Patients with primary ADV-R mutations had either A181T/V or N236T mutations or both. HBV DNA was measured at 3-month intervals until month 24. Primary outcome measures were comparison of the decline of HBV DNA between the three treatment groups. NN patients had higher baseline HBV DNA compared with ADV-R and ADV-S patients (6.08 log10 IU/ml versus 5.53 and 4.88, respectively; P=0.002). By exponential regression analysis, HBV DNA decline kinetics differed between the three groups. HBV DNA decline was faster in NN patients compared to ADV-R and ADV-S CHB patients (P=0.002 and P=0.004, respectively). Undetectable HBV DNA was achieved in 77.2%, 60% and 75% of NN, ADV-R and ADV-S CHB patients, respectively, at month 12 (P= not significant). HBV DNA decline is slower in ADV-experienced patients compared with treatment-naive patients. The clinical significance of this slow response may be important in patients with critical liver reserve and high viral load. Optimal combination treatment (TDF+ entecavir) could be considered in these patients.

Durability of a sustained virological response, late clinical sequelae, and long-term changes in aspartate aminotransferase to the platelet ratio index after successful treatment with peginterferon/ribavirin for chronic hepatitis C

Previous studies, mostly retrospective using conventional interferon, have suggested a favorable prognosis for patients with chronic hepatitis C and a sustained virological response (SVR). However, long-term outcome, including changes in the degree of hepatic fibrosis, of SVR patients in the era of pegylated interferon (PegIFN) remains underdefined. We prospectively evaluated the long-term virological, clinical, and biochemical outcomes, including aspartate aminotransferase-to-platelet ratio index (APRI), in chronic hepatitis C patients with an SVR. We included 145 consecutive, treatment-naive chronic hepatitis C patients (mean age 47.3±9.1 years; 87 men; 42.1% genotype 1; 36.6% genotype 2/3) who achieved an SVR after combination therapy with PegIFN-α/ribavirin. The mean follow-up time was 68.8±35 months. The overall incidence of hepatocellular carcinoma (HCC) and liver-related death was 1.4 and 0.7%, respectively. Among nine (7.6%) patients with pretreatment cirrhosis, two (22.2%) developed HCC and one of them (11.1%) died. No patient had conclusive evidence of late virological relapse. All patients retained normal liver biochemistry, except for five of 145 (3.5%), who had persistently elevated transaminase levels, all of whom were diagnosed with new liver disease. APRI values improved significantly with treatment (0.95±1.09 vs. 0.66±0.64, P<0.001) and continued to improve after a mean of 61.4±45.5 months from an SVR in patients (n=54; 37.2%) with significant (Metavir ≥F2) pretreatment fibrosis (1.13±0.66 vs. 0.67±0.45, P<0.001). The long-term outcome, including APRI, of chronic hepatitis C patients treated successfully with PegIFN/ribavirin and followed for a mean of 5.7 years is favorable. However, a high risk of progression to HCC and liver-related death remains for patients with pretreatment cirrhosis, in our setting, as high as 22.2 and 11.1%, respectively.

Sa1006 Effectiveness of Oral Antiviral Therapy for Treatment-Naive Chronic Hepatitis B (CHB) in Routine Clinical Practice

Background: Liver cirrhosis is inevitable outcome triggered by consistent chronic inflammation. Recent studies have implied that liver cirrhosis accompanied with angiogenesis. Our previous studies demonstrated that celecoxib could reduce angiogenesis in hepatocellular carcinoma and gastric adenocarcinoma. However, the effect of celecoxib on the antiangiogenesis of cirrhotic liver is still controversial. Objective: To investigate the effect of celecoxib on angiogenesis of cirrhotic liver. Methods: Peritoneal injection of thiacetamide (TAA) was employed to induce liver cirrhosis (200 mg/kg every three days × 16 weeks). 36 male Sprague-Dawley rats were assigned to three groups: group 1 (TAA + celecoxib, n = 12) received TAA plus celecoxib (20 mg/kg/day) by gavage from the initiation of TAA administration on, group 2 (TAA, n = 12) received TAA plus placebo and group 3 (Control, n = 12) received injections of 0.9% saline (1mL i.p., every three days). Serum biochemistry for liver and kidney function parameters and serum prostaglandin E2 (PGE2) were determined. Portal pressure and mean artery pressure were also measured. Histopathological study and vascular casting by scanning electron microscope (SEM) of liver vascular were performed. Additionally, immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and western blot for CD31, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2), and Cyclooxygenase-2 (COX-2) were determined. Results: Compared with TAA group, the fibrotic areas of liver tissues in TAA+celecoxib group were significantly decreased by one fold (20.8 ± 1.5% vs. 10.6 ± 0.9%, p , 0.001). Histological sections, vascular casts of hepatic portal vein by SEM, IHC and qRT-PCR for CD31 showed that hepatic fibrosis was accompanied with significant neoangiogenesis in TAA group when compared with Control group (0.1502 ± 0.0143 vs. 0.0325 ± 0.0086 mm2, p , 0.001). Impressively, the increased vascular areas were greatly reduced after celecoxib treatment (0.0485 ± 0.0097 vs. 0.1502 ± 0.0143 mm2, p , 0.001). The up-regulation of VEGF and VEGFR-2, COX-2 and PGE2 induced by TAA administration were significantly inhibited after celecoxib treatment. Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8% (14.88 ± 0.84 vs. 12.23 ± 1.09 mmHg, p , 0.001). No significant differences in arterial pressure, heart rate and liver and kidney function parameters were observed among three groups (p . 0.05). Conclusions: Anti-angiogenesis therapy with celecoxib ameliorated hepatic angiogenesis, portal pressure as well as fibrosis. This result suggested that celecoxib would be beneficial for the treatment of liver cirrhosis.

Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy: Homology modeling and molecular docking studies.

Adefovir is an adenosine analogue approved by the Food and Drug Administration for the treatment of chronic hepatitis B. Mutations occurring in the hepatitis B virus (HBV) reverse transcriptase (rt) domains are shown to confer resistance to antiviral drugs. The role of the rtI233V mutation and adefovir resistance remains contradictory. In this study, it was attempted to evaluate the impact of putative rtI233V substitution on adefovir action by homology modeling and docking studies. The HBVrt nucleotide sequence containing rtI233V mutation was obtained from the treatment-naive chronic hepatitis B subject. The three dimensional model of HBV polymerase/rt was constructed using the HIV-1rt template (PDB code: 1RTD A) and the model was evaluated by the Ramachandran plot. Autodock was employed to dock the HBV polymerase/rt and adefovir. The modelled structure showed the amino acid rtI233 to be located away from the drug interactory site. The substitution of isoleucine to valine did not appear to affect the catalytic sites of the protein. In addition, it does not alter the conformation of bent structure formed by residues 235 to 240 that stabilizes the binding of dNTPs. Therefore, it was predicted that rtI233V substitution may not independently affect the antiviral action of adefovir and incoming dNTP binding.

Effect of Entecavir in Patients Who Lack Lamivudine Resistance after Lamivudine Treatment for Chronic Hepatitis B

Background/Aims: The effect of entecavir (ETV) in treatment-naive chronic hepatitis B (CHB) is well established. This study aimed to assess the efficacy of ETV treatment at 0.5 mg/day in ETV-switch and ETV-retreatment groups of CHB patients without lamivudine (LMV)-resistance from LMV monotherapy. Methods: Study subjects included 350 CHB patients who had been treated with 0.5 mg/day of ETV for at least 6 months. Patients were divided into two groups: an LMV-naive group (n = 263) and an LMV-experienced group (n = 87). The LMV-experienced group was further subdivided into an ETV-switch group (n = 43) and an ETV-retreatment group (n = 44) defined by the period between stopping LMV and restarting ETV. Results: There were no significant differences in mean age, sex ratio, prevalence of liver cirrhosis and hepatitis B e antigen (HBeAg) positivity between the LMV-naive and -experienced groups. However, the LMV-naive group had higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and a shorter ETV treatment duration than the LMV-experienced group. There were also distributional differences in the hepatitis B virus (HBV) DNA levels of LMV-naive and -experienced patients prior to ETV treatment. After ETV treatment, there were no significant differences between the two groups in the rates of undetectable HBV DNA at 6, 12 and 18 months; HBeAg loss and seroconversion; normalization of ALT; virologic breakthrough; and ETV-genotypic resistance. Lastly, the effect of ETV did not differ between the ETV-switch and -retreatment groups. Conclusions: The effect of ETV in the LMV-experienced group without LMV-resistance did not differ from that in the LMV-naive group. Furthermore, there was no difference in the effect of ETV between the ETV-switch and -retreatment groups. (Korean J Med 2013;84:810-817)

AST-platelet ratio index in the prediction of significant fibrosis and cirrhosis in patients with chronic hepatitis B

We aimed to evaluate the diagnostic accuracy of AST-platelet ratio index in the prediction of significant fibrosis and cirrhosis in chronic hepatitis B patients by comparison with liver biopsy. We retrospectively reviewed our computerized data of chronic hepatitis B patients who attended the Gastroenterology Clinic from 2004-2009. Treatment-naive chronic hepatitis B patients who had undergone liver biopsy were included in this study. The degree of fibrosis was scored according to the Ishak staging system. Significant fibrosis was defined as F3-6 and cirrhosis as F5-6. AST-platelet ratio index was calculated based on the original studies. Tests results were compared between the groups F0-2 versus F3-6 and F0-4 versus F5-6. Two hundred and fifty consecutive patients with chronic hepatitis B were included in this study. The area under the ROC curves of AST-platelet ratio index to predict significant fibrosis and cirrhosis were 0.779 and 0.781, respectively. Using cut-off values ≤0.5 and >1.5, significant fibrosis was excluded with a negative predictive value of 91.30% and sensitivity of 87.69% and predicted with a positive predictive value of 59.52% and specificity of 90.81% in 53.60% of patients. Using cut-off values ≤1 and >2, cirrhosis was excluded with a negative predictive value of 92.09% and sensitivity of 64.10% and predicted with a positive predictive value of 33.33% and specificity of 91.47% in 81.60% of patients. AST-platelet ratio index may be a useful noninvasive marker in the exclusion of both significant fibrosis and cirrhosis in patients with chronic hepatitis B. However, it is not accurate in the prediction of either significant fibrosis or cirrhosis.

Efficacy and safety of entecavir in clinical practice in treatment-naive Caucasian chronic hepatitis B patients

Efficacy and safety of entecavir in clinical practice in treatment-naive Caucasian chronic hepatitis B patients

Diagnostic potential of serum direct markers and non‐invasive fibrosis models in patients with chronic hepatitis B

Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the disadvantages of liver biopsy, many studies related to non-invasive biomarkers and scores have been performed. In this study, we aimed to assess the diagnostic value of serum direct markers and non-invasive fibrosis models to predict liver fibrosis in the treatment-naive chronic hepatitis B (CHB) patients and to compare their diagnostic performance. This study included 58 patients with a diagnosis of CHB virus infection and 30 healthy controls. Hyaluronic acid, tissue inhibitor of matrix metalloproteinase 1 and amino-terminal propeptide of type III procollagen were measured by enzyme-linked immunosorbent assay; and the Original European Liver Fibrosis panel, the Enhanced Liver Fibrosis (ELF) panel, PP score, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 indexes were calculated using the formulas taken from previous publications. Fibrosis stage was determined using Ishak's scoring system. The fibrosis stages identified upon liver biopsy was F0 in 12 patients (20.7%), F1-2 in 36 (62.1%) and F3-5 in 10 (17.2%). The diagnostic value of all the non-invasive indices was low to detect mild fibrosis. We demonstrated that the diagnostic accuracy of HA is the best for predicting fibrosis of F3 or more (area under the receiver-operator curve, 0.902). In our study, the results from a combination of tests showed that ELF and APRI had the highest diagnostic value sensitivity of 90%, specificity of 100%, positive predictive value of 100% and negative predictive value of 96.4% for detection of fibrosis of F3 or more. In CHB patients, combination of ELF and APRI has a better diagnostic value in predicting fibrosis of F3 or more.

520 RESPONSE TO TENOFOVIR TREATMENT OF TREATMENT-NAIVE VS ADEFOVIR-RESISTANT VS SUBOPTIMAL RESPONDER PATIENTS WITH CHRONIC HEPATITIS B

Tenofovir (TVF) is known to possess potent and similar antiviral efficacy against treatment-naive and lamivudine-resistant chronic hepatitis B (CHB). TVF may be less effective against adefovir (ADV)resistant CHB (van Bommel et al, Hepatology 2010). These data need confirmation. Aim:We aimed to assess antiviral efficacy of TVF against treatmentnaive (TN) and ADV-resistant (ADV-R) CHB and suboptimal ADV (ADV-S) responders. Methods: The database of 2 tertiary referral centers was analyzed. HBV DNA had been measured with Cobas Taqman (Roche Diagnostics; detection limit 20 IU/mL) at 3-monthly intervals in the first year and then every 6 months. Data of 24 months of treatment were analyzed in a total of 135 patients (52 TN, 55 ADV-R, 28 AD-S). HBV DNA measurements were available at months 3, 6, 9, 12, 18 and 24 in 49, 43, 39, 40, 32 and 23 TN; 37, 49, 38, 41, 33 and 23 ADV-R and 26, 28, 26, 25, 24 and 21 ADV-S patients, respectively. Results: The 3 groups were similar with regard to age, sex and HBeAg-status. T-N patients had higher baseline HBV DNA compared to ADV-R and ADV-S groups (6.7 log10 IU/mL vs. 5.9 and 5.6, p = 0.004, respectively). Cirrhosis was present in 11, 21 and 29% of TN, ADV-R and ADV-S patients (p = 0.033). By exponential regression analysis, no difference between HBV DNA decline kinetics between the 3 groups was observed. However, by linear regression analysis of the first 3 months data HBV DNA decline was faster in TN patients compared to ADV-R CHB. Undetectable HBV DNA was achieved in 63%, 60% and 76% of TN, ADV-R and ADV-S CHB patients at week 48 (p =NS). Corresponding figures were 70%, 80% and 86% (p =NS). Conclusion: Over a 24 month period, HBV DNA decline kinetics were similar in TN CHB and patients with ADV-R and ADV-S CHB. Only in the first 3 months, HBV DNA decline was slower in ADV-R patients suggesting that in AD-R patients with critical liver reserve combination treatment could be considered (Peterson et al, J Hepatol 2011-in press).

Hungarian consensus guideline for the diagnosis and treatment of B, C, and D viral hepatitis

More than 1% of the Hungarian population is infected with hepatitis B, C, or D viruses. Since 2006 the diagnostics and therapy of these infections are carried out in treatment centers according to national guidelines - since 2010 according to financial protocols. The consensus-based guidelines for 2012 are published in this paper. The guidelines stress the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection is pegylated interferon for 48 weeks or continuous entecavir therapy. The later must be continued for at least 6 months after hepatitis B surface antigen (HBsAg) seroconversion. Tenofovir disoproxil fumarat is not yet reimbursed by the National Health Insurance Fund. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Treatment naive chronic hepatitis C patients should initially receive pegylated interferon and ribavirin dual combination therapy. In genotype 1 infection if response is insufficient at 4 or 12 weeks one of the two new direct acting antivirals (boceprevir or telaprevir) should be added. The length of treatment is usually 48 weeks; in cases of extended early viral response shorter courses are recommended. Previous treatment failure patients with genotype 1 infection should receive a protease inhibitor backed triple combination therapy, mostly for 48 weeks. However, relapsers without cirrhosis and with extended rapid viral response, shorter telaprevir based combination therapy is sufficient. Drug-drug interactions as well as emergence of viral resistance are of particular importance. For genotype 2 or 3 HCV infections 24 weeks, for genotype 4 infections 24, 48 or 72 weeks of pegylated interferon plus ribavirin therapy is recommended in general. The guidelines published here become protocols when published as official publications of the Hungarian Health Authority.

Efficacy and safety of peginterferon α-2a (40 KD) plus ribavirin in treatment-naive chronic hepatitis C patients in Central and Eastern Europe

Assess the safety and efficacy of 24 or 48 weeks of treatment with peginterferon α-2a (40 KD) plus ribavirin in treatment-naive patients with chronic hepatitis C. All patients in this open-label multinational study were assigned at the investigator's discretion to receive peginterferon α-2a (40 KD) 180 µg/week plus ribavirin (800 mg/day) for a total of 24 weeks or peginterferon α-2a (40 KD) 180 µg/week plus ribavirin (1000/1200 mg/day) for a total of 48 weeks. Treatment success was defined as sustained virological response [sustained virological response (SVR); hepatitis C virus RNA less than 50 IU/ml after completion of untreated follow-up]. A total of 789 treatment-naive patients were enrolled, of whom 91% (138 of 152) of nongenotype 1 patients and 77% (490 of 637) of genotype 1 patients completed 24 and 48 weeks of treatment, respectively. The overall SVR rate was 58% (459 of 789), and was 70 and 55% in nongenotype 1 and genotype 1 patients, respectively. Age (per 10-year decrement) and baseline hepatitis C virus RNA level (≤ 400 000 vs. >4 00 000 IU/ml) were significantly associated with SVR by multiple logistic regression analysis. The safety profile of peginterferon α-2a (40 KD) plus ribavirin was similar to that reported in pivotal trials, with no new or unexpected safety signals. The combination of peginterferon α-2a (40 KD) plus ribavirin was well tolerated and produced an overall SVR rate of 58% in treatment-naive patients. This study confirms that SVR rates achieved in pivotal clinical trials in Western Europe and the USA can be achieved in routine clinical practice in Central and Eastern Europe.

AST-platelet ratio index, Forns index and FIB-4 in the prediction of significant fibrosis and cirrhosis in patients with chronic hepatitis C

The aim of this study was to evaluate the diagnostic accuracy of aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 for the assessment of hepatic fibrosis in chronic hepatitis C patients by comparison with liver biopsy. We retrospectively reviewed our computerized data of chronic hepatitis C patients who admitted to the Gastroenterology Clinic between 2004 and 2008. Treatment-naive chronic hepatitis C patients who had undergone liver biopsy and had laboratory test results allowing the calculation of aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 were included in this study. The degree of fibrosis was scored according to the METAVIR staging system. Significant fibrosis was defined as F2-4 and cirrhosis as F4. Aspartate aminotransferase-platelet ratio index, the Forns index and FIB-4 were calculated based on the original studies. Tests results were compared between groups F0-1 (no or mild fibrosis) versus F2-4 (significant fibrosis) and F03 (no cirrhosis) versus F4 (cirrhosis). One hundred and fifty patients with chronic hepatitis C were included in this study. The areas under the ROC curves of the Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 to predict significant fibrosis were 0.795, 0.774 and 0.764, respectively. The area under the ROC curves of the Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 to predict cirrhosis were 0.879, 0.839 and 0.874, respectively. The Forns index, aspartate aminotransferase-platelet ratio index and FIB-4 were accurate noninvasive blood tests to predict the presence or absence of significant fibrosis and cirrhosis in half of the chronic hepatitis C patients. The Forns index was slightly better than the aspartate aminotransferase-platelet ratio index and FIB-4 in the prediction of significant fibrosis and cirrhosis.