Histological benefits of virological response to peginterferon alfa-2a monotherapy in patients with hepatitis C and advanced fibrosis or compensated cirrhosis

Background  Patients with chronic hepatitis C virus and advanced fibrosis or cirrhosis are at risk for disease progression and hepatic decompensation.
Aim  To determine the effects on hepatic histology of treatment with peginterferon alfa-2a (90 or 180 μg/week) or interferon alfa-2a (3 million units three times weekly) for 48 weeks in patients with paired biopsies.
Methods  Liver biopsies were obtained at baseline and 6 months after end of treatment. Histological and virological responses were compared.
Results  Patients attaining sustained virological response ( n  = 40) demonstrated the greatest improvements in fibrosis (−1.0, P  < 0.0001) and inflammation (−0.65, P  < 0.0001). Patients who cleared hepatitis C virus during treatment, but later relapsed ( n  = 59), experienced less improvement in fibrosis (−0.04, P  < 0.0001) and inflammation (−0.14, P  = 0.0768). Nonresponders ( n  = 85) showed no significant improvement in inflammation or fibrosis. Multiple regression analysis showed that the only factors contributing to improvement in fibrosis were sustained virological response (vs. nonresponder, P  = 0.0005; vs. relapse, P  = 0.7525) and body mass index ≤30 kg/m² ( P  = 0.0995).
Conclusions  These findings indicate that virological response to peginterferon alfa-2a improves inflammation and fibrosis in hepatitis C virus patients with advanced fibrosis or cirrhosis. Improving virological response and maintaining ideal body weight are critical for achieving optimal histological outcomes in hepatitis C virus patients.     

De novo depression and anxiety disorders and influence on adherence during peginterferon-alpha-2a and ribavirin treatment in patients with hepatitis C

Background  Depression and anxiety have been associated with interferon treatment and low treatment adherence.
Aim  To study the incidence and associated risk factors of depressive and anxiety disorders during pegylated interferon plus ribavirin and treatment adherence in a prospective cohort of 176 patients with chronic hepatitis C patients.
Methods  Patients were interviewed at baseline using the Structured Clinical Interview for DSM-IV Mental Disorders and the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale were completed. Both questionnaires were completed also after 4, 12 and 24 weeks of treatment.
Results  De novo depressive and/or anxiety disorders were diagnosed in 53 (36%) patients, in whom antidepressants and/or anxiolytics were administered. Higher baseline depression-subscale score (OR = 27.8, 95% CI = 2.82–333), primary education level (OR = 3.1, 95% CI = 1.40–7.03) and being an immigrant (OR = 3.2, 95% CI = 1.12–9.47) were predictors of psychiatric disorders during anti-viral therapy. The percentage of patients with good adherence was lower in those with depression and/or anxiety (79% vs. 90%, P  <   0.04). Only one patient (1%) discontinued treatment because of a major depressive episode. Depression and/or anxiety disorders had no effect on attainment of sustained virological response.
Conclusion  Early detection and treatment of depressive and anxiety disorders favours good adherence to anti-viral treatment in hepatitis C.     

Long-term outcomes of thymosin-alpha 1 and interferon alpha-2b combination therapy in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B

Hepatitis B e antibody (HbeAb) and hepatitis B virus (HBV) DNA positive chronic hepatitis is a clinical entity, distinct from classical hepatitis B e antigen (HbeAg) positive chronic hepatitis B. Our aim was to evaluate the long-term therapeutic efficacy of the combination of interferon alpha-2b and thymosin-alpha1 compared with lamivudine plus interferon alpha-2b and interferon alpha-2b alone. Fifty-two patients with HbeAg-negative chronic hepatitis B were assigned to three different groups in a nonrandomized manner. Group 1 (n = 27) received thymosin-alpha1 [1.6 mg subcutaneously (sc), twice a week] and interferon alpha-2b (10 MIU sc, three times per week) for 26 weeks, subsequently followed by interferon alpha-2b monotherapy at the same dosage for an additional 26 weeks. Group 2 (n = 10) received interferon alpha-2b (10 MIU sc, three times per week) for 52 weeks. Group 3 (n = 15) received interferon alpha-2b (10 MIU sc, three times per week) and lamivudine [100 mg orally (po), q.d.] for 52 weeks, followed by continuous lamivudine (100 mg po, q.d.) therapy. By the end of 78 weeks, a sustained response (SR-6 mo) was seen in 74% (20/27) of the patients within Group 1. On the contrary, Groups 2 and 3 had sustained response rates of 40 (4/10) and 53.3% (8/15), respectively (p = 0.13). At the end of 12 months post-treatment in Group 1, a virological and biochemical response rate was seen in 70.3% of patients (19/27); in contrast, Groups 2 and 3 had response rates of 20 (2/10) and 26.6% (4/15), respectively (p = 0036). At the end of the 18-month post-treatment follow-up period, 71.4% (19/27) of patients in Group 1, 10% of patients in Group 2 (1/10), and 20% of patients in Group 3(3/15) preserved their sustained response (p = 0.0003). Interferon alpha-2b and thymosin-alpha1 combination therapy results in significant virological and biochemical response rates compared with standard therapeutic regimens and is well tolerated.     

Effectiveness of pegylated interferon/ribavirin combination in 'real world' patients with chronic hepatitis C virus infection

Background  Clinical trials have shown that the combination of pegylated interferon/ribavirin induces a sustained virological response in 54–63% of patients with chronic hepatitis C virus infection, but its effectiveness in day-to-day clinical practice is less clear.
Aim  To verify if the efficacy of pegylated interferon/ribavirin combination in 'real world' patients is comparable to that observed in trials.
Methods  The medical records of 397 consecutive naïve patients with chronic hepatitis C virus infection treated with pegylated interferon/ribavirin combination in nontertiary hospital settings were reviewed in order to assess the response to anti-viral treatment.
Results  The sustained virological response rate achieved in this population was similar to that recorded in registration trials (total population: 64%; genotype 1: 46%; genotypes 2–3: 84%). Also, the premature discontinuation rate (15%) was similar to that observed in registration trials, but there were fewer dose reductions in one or both medications (26%). We confirmed the association between adherence and sustained virological response among the patients infected with hepatitis C virus genotype 1 who were treated for ≥80% of the planned duration of treatment.
Conclusion  The effectiveness of pegylated interferon/ribavirin therapy and factors predicting an sustained virological response in everyday clinical practice mirror those reported in randomized-controlled studies.     

Efficacy and safety of antiviral therapy in patients with Crohn's disease and chronic hepatitis C

Background  Efficacy and safety of antiviral combination therapy in patients with Crohn's disease (CD) and chronic hepatitis C (CHC) is presently not established and consequently CHC is rarely treated in CD patients.
Aim  To analyse the efficacy and tolerability of antiviral interferon/ribavirin therapy in patients with CHC and CD.
Methods  Eleven HCV-infected CD patients received either 3 × 1.5 μg/kg/week interferon-α-2b or 180 μg/week peginterferon-α-2a (PEGASYS; Roche, Basel, Switzerland) as monotherapy ( n  = 1) or in combination with 800–1200 mg/day ribavirin (COPEGUS; Roche) ( n  = 10) for 24–54 weeks according to HCV-genotype and initial response respectively. Eight patients were under CD-specific therapy.
Results  Five (46%) patients (HCV-1: n  = 3; HCV-2: n  = 0; HCV-3: n  = 1; unknown: n  = 1) achieved a sustained virological response, three (27%) patients relapsed, three (27%) were nonresponders (all GT 1b). At baseline, the Harvey–Bradshaw Index was 0 (0–8) [median (range)], increased on antiviral therapy to 4 (1–15) ( P  = 0.005) and decreased to baseline level 0 (0–6) after 6-month follow-up.
Conclusions  This preliminary experience demonstrates that treatment of CHC in patients with CD is comparable to the treatment of CHC in those without CD. However, gastrointestinal symptoms may be temporarily exacerbated and haemopoietic growth factors may be required.     

Clinical trial: individualized treatment duration for hepatitis C virus genotype 1 with peginterferon-alpha 2a plus ribavirin

Background  Individualized treatment regimens, taking into account the heterogeneity of patients with chronic hepatitis C, are needed to improve treatment outcomes.
Aim  To investigate prospectively the period of undetectable viraemia required for a high rate of sustained virological response in patients with chronic hepatitis C genotype 1 and the relationship to early viral kinetics.
Methods  Forty-five chronic hepatitis C genotype 1 patients were given peginterferon-alpha 2a plus ribavirin. Viraemia and hepatocyte HCV-RNA levels were quantified using a TaqMan assay. Beyond the first time point of undetectable viraemia (<20 IU/mL) between baseline and treatment week 12, 32 of 45 (71%) patients were randomized to additional 12 weeks (G12); 24 weeks (G24) or 36 weeks therapy (G36). The remaining 13 patients received 48 weeks' treatment (G48).
Results  The sustained virological response rates were: G12 – five of 11 (45%); G24 – eight of 10 (80%); G36 – eight of 11 (73%); G48 – four of 13 (31%). The anti-viral efficacy (ε) and treatment-induced loss of infected hepatocytes ( M δ), were significantly higher in patients with early viral clearance. In G12, patients with sustained virological response had lower baseline viraemia than those who relapsed.
Conclusions  Early viraemia clearance is a better marker than baseline viral load and differentiates chronic hepatitis C genotype 1 with high or low probability of sustained virological response. In patients with viraemia clearance within 12 weeks of starting peg-interferon/ribavirin therapy, an additional period of undetectable viraemia of minimum 24 weeks is required for high sustained virological response.     

Clinical trial: a randomized trial of pegylated-interferon-α-2a plus ribavirin with or without amantadine in treatment-naïve or relapsing chronic hepatitis C patients

Background  The combination therapy of pegylated-interferon-α2a plus ribavirin is considered as the standard of care for patients with chronic hepatitis C. A sustained viral response is obtained in 40–50% of naïve patients with genotype 1 and in around 80% of naïve patients with genotype 2 or 3.
Aim  To assess whether amantadine, added to the conventional combination therapy, could improve the treatment efficacy.
Methods  In all, 630 patients (intent-to-treat population) with chronic hepatitis C were randomized into two groups: 316 patients (treatment group) received pegylated-interferon-α2a (180 μg once weekly) plus ribavirin (1000–1200 mg/daily) with amantadine (200 mg/daily); 314 patients (control group) received pegylated-interferon-α2a (180 μg once weekly) plus ribavirin (1000–1200 mg/daily) without amantadine. The duration of the treatment was 48 weeks for genotypes 1, 4, 5 and 6, and 24 weeks for genotypes 2 and 3.
Results  There was no statistically significant difference between treatments groups for any of the variables tested for. Subgroups of patients likely to take advantage of the addition of amantadine were not identified.
Conclusions  This large study definitely excludes the role of amantadine in addition of conventional combination therapy in the treatment of chronic hepatitis C patients.     

Impact of ribavirin plasma level on sustained virological response in patients treated with pegylated interferon and ribavirin for chronic hepatitis C

Background  The main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). However, the impact of the pharmacological properties of ribavirin on the SVR has not been fully investigated.
Aim  To evaluate, through a prospective study, the association between ribavirin plasma level and SVR response in HCV patients treated with pegylated interferon (PEG-IFN) and ribavirin.
Patients and methods  Patients treated with PEG-IFN and ribavirin had plasmatic ribavirin dosage at weeks 4 and 12. SVR was evaluated 6 months after the end of treatment.
Results  At week 4, a strong correlation was found between HCV-RNA and C _min of ribavirin plasma level ( r  = −0.376, P  = 0.002) and AUC _0→12h of ribavirin plasma level ( r  = −0.277, P  = 0.018). At week 12, a strong correlation was found between HCV-RNA and C _min of ribavirin plasma level ( r  = −0.384, P  < 0.0001) and AUC _0→12h of ribavirin plasma level ( r  = −0.257, P  = 0.002). In genotype 1 patients, AUC _0→12h ribavirin and C _min were significantly correlated with negative HCV-RNA at week 12 and SVR. In the multiple logistic regression model, the only factor independently associated with SVR in genotype 1 patients was negative HCV-RNA at week 12.
Conclusion  C_min of ribavirin at weeks 4 and 12 was significantly higher in sustained virological responders compared with relapser or nonresponder patients. However, in genotype 1 patients, plasma ribavirin level at weeks 4 and 2 was not associated with SVR.     

Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascites

Background  In patients with cirrhosis, ascites is defined as refractory when it cannot be mobilized or recurs early in standard diuretic therapy.
Aim  To compare the safety and efficacy of intravenous high-dose furosemide + hypertonic saline solutions (HSS) with repeated paracentesis in patients with cirrhosis and refractory ascites.
Patients and methods  Eighty-four subjects (59/25 M/F) with cirrhosis, mostly of viral aetiology, admitted for refractory ascites, were randomly assigned to receive furosemide (250–1000 mg/bid i.v.) plus HSS (150 mL H₂O with NaCl 1.4–4.6% or 239–187 mEq/L) (60 patients, Group A) or to repeated paracentesis and a standard diuretic schedule (24 patients, Group B).
Results  During hospitalization, Group A patients had more diuresis (1605 ± 131 mL vs. 532 ± 124 mL than Group B patients; P  < 0.001) and a greater loss of weight at discharge (−8.8 ± 4.8 kg vs. −4.5 ± 3.8 kg, P  < 0.00). Control of ascites, pleural effusions and/or leg oedema was deemed significantly better in Group A.
Conclusions  This randomized pilot study suggests that HHS plus high-dose furosemide is a safe and effective alternative to repeated paracentesis when treating hospitalized patients with cirrhosis and refractory ascites. Larger studies will be needed to evaluate long-term outcomes such as readmission and mortality.     

48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection

BACKGROUND/AIM: Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown. METHOD: We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72. RESULTS: Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37). CONCLUSION: Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.     

Interferon alfacon-1: a review of its pharmacology and therapeutic efficacy in the treatment of chronic hepatitis C

Interferon alfacon-1 (consensus interferon) is a non-naturally occurring, synthetic, type 1 interferon (IFN)alpha that is used for the treatment of patients with chronic hepatitis C. The efficacy of subcutaneously administered interferon alfacon-1 has been demonstrated in clinical trials during the treatment of LFN-naive patients (interferon alfacon-1 9microg 3 times a week for 24 weeks) and retreatment of nonresponders and relapsers to previous interferon therapy (interferon alfacon1 15 microg 3 times a week for up to 48 weeks). Higher and more frequent interferon alfacon-1 dosages have also been investigated. Results from a pivotal double-blind randomised trial in 704 patients with chronic hepatitis C showed that interferon alfacon-19 microg 3 times a week achieved virological and biochemical response rates of 34.9 and 42.2%, respectively, at treatment end-point (week 24). Sustained virological and biochemical responses (week 48) were reported in 12.1 and 20.3% of the patients, respectively. In general, response rates in recipients of interferon alfacon-1 9 microg 3 times a week were similar to those achieved with IFN-alpha2b 3 MIU 3 times a week. However, interferon alfacon-1 was more effective in the subgroup of patients infected with hepatitis C virus (HCV) genotype 1 at end-point (virological response, 24 vs 15%; p < 0.05) and post-treatment observation period (8 vs 4%) although the difference between treatment groups was statistically significant only at treatment end-point. The sustained virological response rate achieved in patients with high baseline levels of serum HCV RNA receiving interferon alfacon-1 was statistically superior to that exhibited in the IFN-alpha2b treatment group (7 vs 0%; p < Interferon alfacon-1 also showed efficacy during the retreatment of non-responders and relapsers to previous IFN therapy in a large nonblind multicentre trial. Sustained virological response (week 72) was observed among 13 and 58% of nonresponders and relapsers, respectively, after 48 weeks of treatment with interferon alfacon-1 15 microg 3 times a week. Interferon alfacon-1 has been generally well tolerated in clinical trials. As with other IFNs, adverse events were reported frequently but were usually considered of mild to moderate severity, decreased with time and caused a small percentage of patients to withdraw from the treatment. Fever, fatigue, arthralgia, myalgia, headache and rigors were the most frequently reported adverse events. Psychiatric adverse events appeared to be dose-related and caused the majority of treatment withdrawals. CONCLUSION: Interferon alfacon-1 is generally well tolerated and is an effective agent in the treatment of patients with chronic hepatitis C. Comparative data from a pivotal randomised trial indicate that the drug has at least equivalent efficacy to IFNalpha-2b, and a statistically significant advantage was demonstrated at treatment end-point in patients infected with HCV genotype 1. A number of ongoing trials with interferon alfacon-1 are evaluating issues such as the optimal dosage regimen and duration of therapy in an effort to improve sustained virological response to therapy, a goal for IFNs in general.     

Clinical trial: randomized, double-blind, placebo-controlled study of nitazoxanide monotherapy for the treatment of patients with chronic hepatitis C genotype 4

Background  Nitazoxanide, licensed in the US for treatment of Cryptosporidium parvum and Giardia lamblia , inhibits hepatitis C virus replication in replicon systems.
Aim  To evaluate the safety and efficacy of nitazoxanide monotherapy for the treatment of chronic hepatitis C.
Methods  This multicentre, randomized, double-blind, placebo-controlled study randomized 50 adult patients with chronic hepatitis C genotype 4 at three centres in Egypt to nitazoxanide 500 mg tablet or placebo twice daily for 24 weeks. Patients were followed up every 4 weeks during treatment and for 24 weeks after therapy.
Results  Seven of 23 patients (30.4%) in the nitazoxanide group achieved undetectable serum HCV RNA compared to 0 of 24 in the placebo group during therapy ( P =  0.004). Each of the seven responders had baseline HCV RNA levels ≤400 000 IU/mL. Six of the seven virological responders were followed up for 24 weeks after the end of treatment, and four patients (17.4% of 23 treated) had a sustained virological response. Adverse events were similar in the nitazoxanide and placebo groups.
Conclusion  Nitazoxanide monotherapy is safe and effective in achieving sustained virological response in a modest number of patients with chronic hepatitis C genotype 4, particularly in patients with low baseline serum HCV RNA levels.     

Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine

Background  The efficacy of long-term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe-Ag)-negative lamivudine-resistant chronic hepatitis B (CHB) patients is still under investigation.
Aim  To assess the safety and efficacy of the long-term adefovir treatment alone or in combination with lamivudine in HBe-Ag-negative CHB patients who had developed breakthrough because of lamivudine-resistant mutants.
Methods  Fifty-nine patients received combination therapy, while 23 switched to adefovir alone after a 3-month course of combination therapy.
Results  The median follow-up after adefovir's onset was 31 (18–40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV-DNA <10⁴ copies/mL ( P  > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively ( P  > 0.50). Virological breakthroughs because of adefovir-resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy ( P  = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow-up. Re-introduction of lamivudine in adefovir-resistant patients achieved reduction in HBV-DNA and biochemical remission, but re-emergence of lamivudine mutants was observed in one patient after 7.5 months.
Conclusion  In HBe-Ag-negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti-viral efficacy because of absence of viral resistance.     

Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitis

Background  In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM.
Aims  To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis.
Methods  Nondiabetic patients with genotype 1 CHC ( n  = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemical and metabolic features including IR. Furthermore, all subjects underwent LSM by TE.
Results  Severe fibrosis (F3–F4) was associated with LSM (OR 1.291; 95%CI 1.106–1.508). LSM was also independently correlated with low platelets ( P  =   0.03), high γGT ( P  <   0.001) and high HOMA ( P  =   0.004) levels. A stiffness value ≥8 KPa was identified as the best cut-off for predicting severe fibrosis ( AUC 0.870); yet this cut-off still failed to rule out F3–F4 fibrosis in 22.7% of patients (false-negative rate) or rule in F3–F4 in 19.6% (false-positive rate). Platelets <200 × 10³/mmc and a HOMA of >2.7 were the major determinants of these diagnostic errors in predicting severe fibrosis.
Conclusions  In nondiabetic patients with genotype 1 CHC, insulin resistance, γGT and platelet levels contribute to LSM independently of liver fibrosis. The identification of these three factors contributes to a more correct interpretation of LSM.     

Prospective evaluation of transient elastography for the diagnosis of hepatic fibrosis in Asians: comparison with liver biopsy and aspartate transaminase platelet ratio index

Background  Transient elastography (TE) is a reliable non-invasive predictor of hepatic fibrosis, but data on TE in Asians are limited.
Aim  To evaluate prospectively the accuracy of TE for diagnosis of hepatic fibrosis in Asians compared with APRI (aspartate transaminase to platelet ratio index).
Methods  One hundred and twenty consecutive patients who underwent liver biopsy were enrolled. TE (Fibroscan) was performed by two independent operators. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) were used to evaluate the accuracy of TE and APRI in diagnosing significant fibrosis (F ≥ 2) and cirrhosis (F4).
Results  Predominant aetiologies were hepatitis B (48%), non-alcoholic steatohepatitis (14%) and hepatitis C (8%). TE was unsuccessful in five patients (4.2%) because of small inter-costal space (three patients), obesity and ascites. There was good correlation between TE and fibrosis ( r  = 0.606). AUROC for diagnosis of significant fibrosis was 0.856 (95% CI 0.779–0.932) for TE and 0.673 (95% CI 0.568–0.777) for APRI. AUROC for diagnosis of cirrhosis was 0.924 (95% CI 0.857–0.990) for TE and 0.626 (95% CI 0.437–0.815) for APRI. Optimal TE value was 9.0 kPa for diagnosis of significant fibrosis and 16.0 kPa for cirrhosis with specificity/sensitivity/PPV/NPV/accuracy of 82.6%/85.2%/80.9%/86.7%/84.1% and 88.9%/82.7%/32.0%/98.8%/83.2%, respectively.
Conclusions  Transient elastography is a reliable predictor of hepatic fibrosis in Asians. Failure of TE in Asians is commonly because of small inter-costal space. TE is superior to APRI for non-invasive diagnosis of hepatic fibrosis and cirrhosis.     

Significant psychological morbidity occurs in irritable bowel syndrome: a case-control study using a pharmacy reimbursement database

Background  Psychological problems are associated with IBS but the strength of this association is unclear.
Aim  To assess co-prescribing of antispasmodic and CNS-acting drugs through a nested case-control study.
Methods  A national dispensing database identified patients who were first dispensed antispasmodic medicines for a continuous 3-month period or more during 2006, using 2005 as a run-in period. Each patient was matched with four control patients and excluded if they received drugs indicated for IBD.
Results  Four hundred and seven patients commenced antispasmodic drugs during 2006. These patients were matched with 1628 controls. In 2005, patients subsequently prescribed antispasmodics were 2–3 times more likely to receive CNS-acting drugs than controls. In the year following commencement of IBS therapy, patients were 2–4 times more likely than controls to be prescribed CNS-acting drugs including antidepressants (35.4% vs. 9.3%), anxiolytics (27.8% vs. 8.8%), antipsychotics (9.8% vs. 3.3%) and hypno-sedatives (32.7% vs. 11.3%; P  < 0.0001). The adjusted OR (95% CI) for antidepressant, anxiolytic, hypnosedative and antipsychotic prescribing in IBS patients were 3.81 (2.79–5.20), 2.84 (2.12–3.81), 2.62 (1.91–3.60) and 2.58 (1.80–3.66), respectively.
Conclusions  Patients prescribed ongoing therapy for presumed IBS are 2–4 times more likely to be prescribed CNS-acting drugs than controls, providing evidence of psychological comorbidity in IBS.     

Clinical trial: peg-interferon alfa-2b and ribavirin for the treatment of genotype-1 hepatitis C recurrence after liver transplantation

Background  Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates.
Aim  To assess the safety and efficacy of pegylated-interferon (PEG-IFN) alfa-2b + ribavirin (RBV) in patients with post-LT recurrent genotype-1 HCV and to establish stopping rules according to response.
Methods  Fifty-three patients with post-LT HCV recurrence were enrolled. Patients received PEG-IFN alfa-2b 1.0 μ/kg/week plus RBV 8–10 mg/kg/day for 24 weeks. Those with 'early virological response at week 24' (EVR24) continued treatment for 24 weeks (group A). Patients without EVR24 were randomized to continue (group B) or to discontinue (group C).
Results  Overall sustained virological response (SVR) was 26% (14/53). Alanine aminotransferase, rapid virological response, EVR12, EVR24, undetectable serum HCV-RNA at weeks 12 (cEVR12) and 24 (cEVR24) were related to SVR. cEVR12 and cEVR24 (OR: 14.7; 95% CI: 2.02–106.4) were independent predictors of SVR. All patients with SVR, had cEVR12. No patient in groups B and C achieved end-of-treatment response. One patient in group B had SVR.
Conclusions  Pegylated-interferon alfa-2b was effective in one of four of patients with HCV genotype 1 after LT. Treatment should be discontinued in patients with no virological response at week 12. Further studies are needed to evaluate whether a longer treatment period may be beneficial in patients with ≥2 log₁₀ drop in HCV-RNA at week 24.     

Supervised conventional interferon α2a in combination with ribavirin therapy is the preferred alternative for treatment of chronic hepatitis C

Objective:

To document the significant sustained virological response with supervised conventional interferon α and ribavirin therapy in hepatitis C virus (HCV)-infected patients, this study was planned.

Materials and Methods:

Sixty chronic hepatitis C naive patients were included in this study. Complete blood counts, prothrombin time, ALT, AST, and qualitative HCV RNA were done. Conventional interferon (INF) α2a, 3MIU, S.C and ribavirin 1000 mg PO was given as supervised therapy for 24 weeks in genotype 3 and 48 weeks in genotype 1 and 4 HCV patients. Qualitative HCV RNA was repeated at 12 weeks, 24 weeks for HCV infections with genotype 1, 2, 3 and 4, at 48 weeks for genotype 1 and 4, and thereafter 6 months after completion of treatment. End virological and sustained virological responses were observed.

Results:

Out of 60 patients, 55 completed the study. Five patients were lost to follow-up. Overall SVR was seen in 47 patients (85.4%) and 4 patients had relapses.

Conclusion:

Significant sustained virological response rates were seen in patients with supervised conventional INF α2a and ribavirin therapy.KEY WORDS: Conventional interferon, hepatitis C, ribavirin, supervised     

Interferon alfacon-1 (Advaferon): a novel synthetic interferon for the treatment of hepatitis C,its pharmacological and clinical profile

Interferon alfacon-1 (Advaferon, also referred to as consensus interferon) is a novel synthetic recombinant type-I interferon (IFN) developed by comparing the amino acid sequences of several natural IFN-alpha subtypes and assigning the most frequently observed amino acid in each corresponding position to generate a consensus molecule. Interferon alfacon-1 binds with high affinity to type-I IFN receptors and has greater biological activity than naturally occurring IFN-alpha as assessed by its increased antiviral, anti-proliferative, and natural killer cell activities, as well as its stronger IFN-stimulated gene induction. In a multicenter, randomized, controlled study, the safety and efficacy of interferon alfacon-1 in comparison with lymphoblastoid interferon-alpha [IFN-alpha (NAMALWA)] was evaluated in patients infected with high-titer chronic hepatitis C virus (HCV). Interferon alfacon-1 (18 MIU) was superior in efficacy without additional toxicity to IFN-alpha (NAMALWA) (9 MIU) in high-titer chronic HCV patients, particularly those infected with genotype 1b. A multicenter open-label study showed that treatment with interferon alfacon-1 (12 MIU) was an effective and tolerable therapy in chronic HCV patients with low viral titers. Another multicenter open-label study showed that re-treatment with interferon alfacon-1 (18 MIU) was an effective and tolerable therapy in chronic HCV patients who relapsed after traditional IFN therapy. Collectively, these clinical studies indicate that interferon alfacon-1, as a novel synthetic interferon, may be a useful therapeutic alternative for the effective treatment of hepatitis C.     

Optimized stepwise combination algorithms of non-invasive liver fibrosis scores including Hepascore in hepatitis C virus patients

Background  Non-invasive liver fibrosis scores such as Hepascore (HS) have been proposed as an alternative to liver biopsy in hepatitis C virus (HCV)-infected patients.
Aim  To validate HS as an alternative to liver biopsy and Fibrotest (FT) and propose five optimized combination algorithms to improve diagnostic accuracy.
Methods  The cohort included 467 patients with HCV. There were 274/467 (59%) men, and mean age was 47 ± 12 years.
Results  Hepascore area under ROC curves (AUC) for ≥F2, F3F4 and F4 diagnosis were 0.82, 0.84 and 0.90 respectively, in the same range as FT. HS and FT were concordant in 387/467 (82%) for fibrosis staging. Among these patients, 342/387 (88%) were concordant with liver biopsy. AUCs of aspartate aminotransferase (AST) to Platelets Ratio Index (APRI) and Forns for ≥F2 were 0.76 and 0.73 (0.65–0.79) respectively. The algorithm combining APRI and HS had the highest rate of avoided liver biopsies (45%) with a high diagnostic accuracy (91%).
Conclusions  Hepascore is an accurate non-invasive marker for ≥F2 and F4 diagnosis in HCV patients. In a pragmatic approach, a stepwise optimized algorithm combining APRI and FT or HS considerably increases diagnostic accuracy and avoided liver biopsies.