Chronic hepatitis C: Treat or wait? Medical decision making in clinical practice

AIM: To analyzes the decision whether patients with chronic hepatitis C virus (HCV) infection are treated or not

Predictive Factors for Sustained Virological Response after Treatment with Pegylated Interferon α-2a and Ribavirin in Patients Infected with HCV Genotypes 2 and 3

<div><p>Background</p><p>Previous trials have often defined genotype 2 and 3 patients as an “easy to treat” group and guidelines recommend similar management.</p><p>Aims</p><p>The present study looks for differences between the two genotypes and analyzes predictive factors for SVR.</p><p>Methods</p><p>Prospective, community-based cohort study involving 421 physicians throughout Germany. The analysis includes 2,347 patients with untreated chronic HCV genotype 2 (n = 391) and 3 (n = 1,956) infection treated with PEG-IFN α-2a plus ribavirin between August 2007 and July 2012.</p><p>Results</p><p>When compared with genotype 2 patients, those with genotype 3 were younger, had a shorter duration of infection, lower values of total cholesterol, LDL cholesterol and BMI, a higher frequency of drug use as infection mode and male gender (p<0.0001, respectively), and a higher APRI score (p<0.005). SVR was higher in genotype 2 when compared with genotype 3 (64.7% vs. 56.9%, p = 0.004). By multivariate analysis of genotype 2 patients, low baseline γ -GT and RVR predicted SVR. In genotype 3 age ≤45 years, cholesterol>130 mg/dl, a low APRI score, and a γ-GT ≥3-times ULN, RVR, and RBV starting dose were associated with SVR by multivariate analysis.</p><p>Conclusions</p><p>The present study corroborates that liver fibrosis is more pronounced in genotype 3 vs. 2. SVR is higher in genotype 2 versus genotype 3 partly because of follow-up problems in genotype 3 patients, in particular in those infected by drug use. Thus, subgroups of genotype 3 patients have adherence problems and need special attention also because they often have significant liver fibrosis.</p><p>Trial Registration</p><p>Verband Forschender Arzneimittelhersteller e.V., Berlin, Germany <a href="http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb" target="_blank">ML21645</a> ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT02106156" target="_blank">NCT02106156</a></p></div

Main characteristics of patients infected with GT2 and GT3 (Mean).

<p>Main characteristics of patients infected with GT2 and GT3 (Mean).</p

Main characteristics of patients infected with GT2 and GT3.

<p># alcohol abuse was assessed by judgement of the physician.</p><p>* only patients who were treated at least for 4 weeks and in whom RVR was correctly determined (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107592#s2" target="_blank">Methods</a> for further details).</p><p>** only patients who were treated at least for 12 weeks and in whom EVR was correctly determined (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107592#s2" target="_blank">Methods</a> for further details).</p><p>Main characteristics of patients infected with GT2 and GT3.</p

SVR versus mode of infection in GT2 and GT3 patients.

<p>(multiple answers allowed; differences between modes of infections in GT2 versus GT3 were tested for significance by Fisher's exact χ²-test without correcting for multiple testing).</p><p>SVR versus mode of infection in GT2 and GT3 patients.</p

Univariate analysis of variables for prediction of SVR in GT2 and GT3.

<p>* OR  =  Odds Ratio; CI  =  Confidence interval.</p><p>** With a planned treatment end or with treatment discontinuation for virological failure or adverse events.</p><p># By univariate analysis baseline thrombocytes and GOT were also significant in GT3 in predicting SVR; in GT2 these variables were not significant. Since the APRI score which combines these two variables had a higher predictive value when compared with the two single variables only the APRI score was used for further analyses.</p><p>Univariate analysis of variables for prediction of SVR in GT2 and GT3.</p

BMI and baseline cholesterol versus gender.

<p>BMI and baseline cholesterol versus gender.</p

Dronedarone, amiodarone and other antiarrhythmic drugs, and acute liver injuries: a case-referent study

International audienceBACKGROUND: Spontaneous reports of acute liver injuries (ALI) in patients taking dronedarone triggered an EMAalert in 2011. This study aimed to assess the risk of ALI for class III antiarrhythmic drugs controlling for the useof other potential ALI-inducing drugs.METHODS: Between 2010 and 2014, consecutive ALI cases (≥50 years-old) were identified across Germany. ALIwas defined as a new increase in at least one of the transaminases≥3 times the upper limit of normal (ULN)or≥2 ULN if alkaline phosphatase, with (“definite”case) or without (“biochemical”case) suggestive signs/symp-toms of ALI, excluding other liver diseases. Recruited community controls were matched to cases on gender, ageand inclusion date. Exposure to antiarrhythmic drugs and co-medication up to 2 years before ALI onset was in-formed by patients and confirmed by physicians' prescriptions. Adjusted Odds Ratios (aOR) were obtained fromconditional multivariable logistic regressions, adjusted for a multivariate disease risk score and co-medication.RESULTS: 252 cases and 1081 matched controls were included (59.1% females; mean age: 64 years). Exposure toclass III antiarrhythmic drugs was 4.0% in cases and 1.5% in controls, aOR = 3.6 (95% CI: 1.6–8.4). Associationswith exposure to dronedarone and amiodarone were respectively 3.1 (95% CI: 0.7–14. 8) and 5.90 (1.7–20.0).Restricting the analysis to definite or severe ALI cases did not change these results.CONCLUSIONS: Class III antiarrhythmic drugs were associated with ALI, amiodarone displaying the highest risk, andresults were robust to case definitions. Continued vigilance is needed for patients taking these drug