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Background and Aims Hepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120. Methods In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed. Results Rates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group B (3.5%), group C (0%), and group D (3.5%). Rates of HBsAg loss and HBsAg seroconversion in group A were significantly higher than rates in group C (P

Hepatitis B surface antigen (HBsAg) loss is the ideal clinical endpoint but is achieved rarely during oral antiviral treatment. A current unmet need in CHB management is achievement of HBsAg loss with a finite course of oral antiviral therapy, thereby allowing discontinuation of treatment. Significantly higher rates of HBsAg loss at 72 weeks post-treatment have been demonstrated when tenofovir disoproxil fumarate (TDF) was combined with pegylated interferon (PEG-IFN) for 48 weeks compared with either monotherapy. This analysis provides follow-up data at week 120.In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus PEG-IFN for 48 weeks (group A), TDF plus PEG-IFN for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or PEG-IFN for 48 weeks (group D). Efficacy and safety at week 120 were assessed.Rates of HBsAg loss at week 120 were significantly higher in group A (10.4%) than in group B (3.5%), group C (0%), and group D (3.5%). Rates of HBsAg loss and HBsAg seroconversion in group A were significantly higher than rates in group C (P 0.001 for both) or group D (HBsAg loss: P = 0.002; HBsAg seroconversion: P 0.001).The results of this analysis confirm the results from earlier time points which demonstrate the increased rate of HBsAg loss in patients treated with a finite course of PEG-IFN plus TDF compared with the rates in patients receiving either monotherapy.

Treatment of chronic hepatitis B (CHB) is difficult. The response rate to interferon (IFN) as well as nucleoside analogs is not more than 30% in general. While interferon has many side effects, development of resistance in most of the nucleoside analogs precludes long-term use. Both groups of drugs are most efficacious in patients who already had or develop strong cellular immunity with treatment. A pre-S2-containing vaccine was shown to enhance cellular immunity and suppress hepatitis B virus (HBV)-DNA in subjects with chronic hepatitis B. We aimed to test the efficacy of short-term use of a nucleoside analog in combination with a pre-S2-containing vaccine in patients with CHB. In this open study, 48 consecutive patients (32 males and 16 females, mean age +/- SD: 33 +/- 12 years) with CHB without cirrhosis were treated with 100 mg/day lamivudine and four weekly intramuscular injections of Genhevac B 20 mcg (six doses) for 24 weeks. While 19 patients were hepatitis B e antigen (HBeAg) positive (+ve), 29 patients were Anti-HBe/HBV-DNA +ve at the outset. Response was defined as seroconversion to anti-HBe in HBeAg +ve subjects and normalization of alanine aminotransferase (ALT) with loss of HBV-DNA in anti-HBe/HBV-DNA +ve subjects. HBeAg seroconversion occurred in 5/19 subjects (26%). Eighteen of 29 anti-HBe/HBV-DNA +ves responded. In the follow-up, while relapse was not observed in any of the patients who seroconverted, 11/18 from the anti-HBe/HBV-DNA +ve group relapsed, resulting in a sustained response (SR) rate of 24% in this group. All the relapses happened in the first 48 weeks of follow-up, with no relapse thereafter. Pretreatment high serum HBV-DNA was a strong negative predictor of sustained response (SR) in HBeAg +ve group. Pretreatment serum ALT over 2 x upper limit of normal and HBV-DNA less than 200 pg/ml appeared positive predictors. None of HBeAg +ve previous interferon failures responded. Twenty-four weeks of lamivudine and hepatitis B vaccine treatment induces SR in around 1/4 of the patients with CHB. Most of the responders had high ALT and relatively low DNA.

Background and aim Viral load is used for the diagnosis and monitoring the treatment of chronic hepatitis B (CHB). These methods are molecular-based and are expensive. Previous studies suggest that quantitative hepatitis B surface antigen (HBsAg) studied by automated chemiluminescent microparticle immunoassay can be a surrogate marker. In this study, we aimed to investigate whether quantitative HBsAg correlates hepatitis B virus (HBV) DNA levels during CHB treatment. Methods The study included 18 patients (13 male, 5 female, mean age: 33 ± 9 years) with CHB. They were given pegylated interferon ± lamivudine for 52 months and serum samples were obtained in weeks 0, 4, 8, 24, 48, 52, and 76. HBV DNA was measured by TaqMan polymerase chain reaction (PCR; Erasmus MC, University Medical Center, Rotterdam, The Netherlands). Quantitative HBsAg was studied by automated chemiluminescent microparticle immunoassay (Architect HBsAg, Abbott, IL). Results HBV DNA levels were measured as follows: 9.66, 7.69, 7.06, 5.93, 5.89, 5.88, and 7.27 logarithmic genome equivalent/ml, respectively. The corresponding HBsAg quantitation results were 42,888, 31,176, 37,882, 27,277, 28,279, 29,471, and 31,535 IU/ml, respectively. They showed a significant correlation (canonical correlation = 0.85). Conclusions HBsAg studied by automated chemiluminescent microparticle immunoassay correlates with HBV DNA and can be a surrogate marker during the monitoring of the efficacy of HBV treatment.

Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the worldwide. This infection is often insidious and one-half of infected patients are asymptomatic. Determination of risk factors for HCV transmission is very important. The aim of this study was to assess the risk factors, transmission to spouses and children for HCV infection in Turkish population. One hundred and fifty-one patients with chronic hepatitis C and 151 control cases were investigated for the probable risk factors of HCV infection. Complete blood count, ALT, AST, albumin, prothrombin time, upper abdomen ultrasonography assessment and percutaneous liver biopsy (not for cirrhotics) were performed in all patients with chronic hepatitis C. Anti-HCV testing was done by using second-generation ELISA in 302 cases. Minor surgical operation (p < 0.001), major surgical operation (p = 0.001), blood transfusion (p < 0.001), multi-partner sex (p < 0.05), frequent dental therapy (p < 0.05), and dental extraction (p < 0.001) in patients with a chronic HCV infection were found to be higher than the control group. No significant difference was found in other risk factors. The rate of hepatitis C virus in index cases was found to be 1.8% in their spouses and 1.2% in their children. Our study showed that surgical operation, frequent dental therapy, dental extraction, multi-partner sex, and blood transmission are the main risk factors for HCV infection in Turkish community.

We aimed to compare the efficacy of interferon-α2b (IFN) induction treatment in combination with ribavirin to IFN induction alone in chronic hepatitis C. In total, 125 patients (66 male, 59 female, mean age: 48 ± 9, range: 21–70) were enrolled and randomized into two arms: In the first, patients received 5 MU/day of IFN for 4 weeks followed by 3 MU/day for the next 4 weeks. Treatment was continued with 3 MU three times a week IFN for an additional 40 weeks. Ribavirin was administered 1000–1200 mg/day according to the body weight for the entire 48-week period. In the second arm, patients received placebo in addition to IFN. Fifty-nine patients were placed in the ribavirin arm and 66 in placebo arm. All patients were genotype 1. At week 48, 24/66 (36%) from the placebo and 31/59 (52%) from the ribavirin group responded (P < 0.05). However, during the 24-week untreated follow-up period, 13/24 (54%) from the placebo, and 8/31 (26%) from the ribavirin group relapsed (P = 0.002.), resulting in a sustained virologic response (SVR) rate of 17% in the placebo and 39% in the ribavirin group (P = 0.005.) In conclusion, IFN induction treatment in combination with ribavirin is superior to IFN induction treatment alone in genotype 1 patients, and the SVR rate of 39% is encouraging.

Sertraline is a commonly prescribed selective serotonin reuptake inhibitor drug. Hepatotoxicity caused by sertraline is rare. Asymptomatic elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels have been rarely reported and shortly normalize after discontinuation of the agent. We present a case of severe drug-induced hepatitis in a patient receiving sertraline. To our knowledge, this is the seventh case in the medical literature as being associated with severe hepatotoxicity. Since it is extremely rare, we do not suggest a strict laboratory monitoring. However, sertraline should be discontinued in cases with symptoms implying hepatotoxicity and the patients should be informed of the potential of this side effect.

Interferon-alpha (IFN) and ursodeoxycholic acid (UDCA) combined have a controversial role in the treatment of chronic type C hepatitis. We studied the long-term efficacy of both drugs alone or in combination. In a three-year period, 108 patients were randomized into three treatment arms: (1) IFN alone 3 MU three times a week (N = 49), (2) IFN 3 MU three times a week + UDCA 250 mg twice a day (N = 45), and (3) UDCA alone 250 mg twice a day (N = 14). Response was defined as complete normalization of serum ALT. For the responders at the end of six months, the treatment was run to 12 months. Nonresponders (NRs) of the first group were crossed over to combination and NRs of the combination received 6 MU three times a week IFN+UDCA for the next six months. The enrollment to the UDCA alone arm was stopped early, since only 1/14 normalized serum ALT at the end of third month. However, 12/14 completed six months and 11 NRs received IFN 3 MU three times a week alone for the next six months. Twelve discontinued treatment due to side effects. Responders were followed-up untreated for 18 months. Sustained response (SR) was defined as persistence of normal serum ALT levels in this period. At the end of six months, 22/45 (48%) from the IFN-alone and 23/39 (58%) from the combination group responded. Twenty NRs from former and 15 of latter group were crossed over. While none of the 20 from the IFN-alone group responded to the combination, 1/15 NRs of the combination group responded to dose escalation. SR was achieved in 9/45 (20%) of the IFN alone and 7/39 (18%) of the combination group. The mean time form the end of the treatment to the relapse was not different between the groups. Five of 11 UDCA NRs responded to IFN with SR in 2. It was concluded that UDCA as a single agent is ineffective in achieving response in the treatment of chronic type C hepatitis. Combined with IFN, it increases response rate insignificantly although this is not sustained.

An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C patients is reported, and their presence is considered to be a predictor of treatment success. However, there is only one prevalence study on granuloma in chronic hepatitis B, and its significance for treatment outcome is unknown. We aimed to determine the prevalence of hepatic granulomas in a larger group of chronic hepatitis B patients and to compare their presence with the response to interferon therapy. Biopsy specimens of chronic hepatitis B patients were reevaluated for the presence of hepatic granulomas. All patients with hepatic granuloma were screened for other granulomatous diseases by tuberculin skin test, chest X-ray and computed tomography, venereal disease research laboratory, Brucella agglutination tests, and exposure to hepatotoxic agents. We screened 663 cases of chronic hepatitis B. Hepatic granulomas were found in 10 cases (1.5%). The granulomas could not be ascribed to any other reason. Of the 10 patients with hepatic granulomas, 4 responded to interferon therapy, 2 dropped out, and 4 were nonresponders. We conclude that hepatic granuloma is a rare finding in chronic hepatitis B and its presence does not seem to predict the response to interferon therapy.

Several studies have reported that interferon therapy increases elimination rate of HBeAg and anti-HBe seroconversion in chronic hepatitis B (CHB) patients. We aimed to evaluate long-term results of interferon-α treatment in HBeAg positive CHB patients in a country with exclusively D genotype. Seventy-one naive CHB patients (M/F 61/10, mean age 29 ± 12 years, range 16–62) treated with 6 months of interferon-α 2b, 10 MU tiw and had a consequent untreated follow-up period of at least 10 years with positive response were identified and their data were reviewed. The therapy response was defined as HBeAg seroconversion with undetectable HBV-DNA. The responders were followed-up at 3–6-month intervals. Twenty-eight (39%) patients achieved HBeAg seroconversion (25 within the therapy, 3 within the consequent 12 months off-treatment follow-up). The responders were followed-up with a mean period of 152 months (range 123–181). In the follow-up period, 21/25 (84%) initial responders relapsed. On the other hand, 3 patients who did not respond at the end of therapy sustained the response during follow-up. Hence 21/28 total responders relapsed (75%), either with HBeAg reversion (3, 14.3%) or HBV-DNA elevation over 2000 IU/ml (or its equivalent in other types of definitions) and ALT elevation (18, 85.7%). The sustained response was present in 7 patients (9.8%). Serious side effects precluding completion of treatment occurred in three patients (4.2%). In multivariate analysis none of the pre-treatment parameters appeared to be significant in predicting response. Sustained response to interferon treatment is low in HBeAg positive CHB patients with genotype D.

We aimed to compare the efficacy of interferon-alpha2b (IFN) induction treatment in combination with ribavirin to IFN induction alone in chronic hepatitis C. In total, 125 patients (66 male, 59 female, mean age: 48 +/- 9, range: 21-70) were enrolled and randomized into two arms: In the first, patients received 5 MU/day of IFN for 4 weeks followed by 3 MU/day for the next 4 weeks. Treatment was continued with 3 MU three times a week IFN for an additional 40 weeks. Ribavirin was administered 1000-1200 mg/day according to the body weight for the entire 48-week period. In the second arm, patients received placebo in addition to IFN. Fifty-nine patients were placed in the ribavirin arm and 66 in placebo arm. All patients were genotype 1. At week 48, 24/66 (36%) from the placebo and 31/59 (52%) from the ribavirin group responded (P0.05). However, during the 24-week untreated follow-up period, 13/24 (54%) from the placebo, and 8/31 (26%) from the ribavirin group relapsed (P = 0.002.), resulting in a sustained virologic response (SVR) rate of 17% in the placebo and 39% in the ribavirin group (P = 0.005.) In conclusion, IFN induction treatment in combination with ribavirin is superior to IFN induction treatment alone in genotype 1 patients, and the SVR rate of 39% is encouraging.