Erratum to: Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study.

[This corrects the article DOI: 10.1093/ofid/ofab006.].

Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study.

BACKGROUND: The majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands. METHODS: We performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions (RAS) evaluation. RESULTS: We included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with available SVR-12 data. Only 73% (8/11) genotype 3-infected patients achieved SVR-12, the majority being genotype 3b patients with 63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS. CONCLUSIONS: The DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However, the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes.

Comparison of interobserver agreement of magnetic resonance elastography with histopathological staging of liver fibrosis.

PURPOSE: MR elastography (MRE) can serve as an accurate surrogate marker of liver fibrosis. For any diagnostic test that is to replace the current reference standard, interobserver agreement should be at least as good and preferably better. The objective of this study was to perform a head-to-head comparison of the interobserver agreements of MRE and liver fibrosis staging on biopsy in a single cohort of hepatitis patients. METHODS: One hundred and three patients with viral hepatitis B or C who had a liver biopsy underwent MRE. Two readers independently selected a region-of-interest (ROI) in the liver to derive elasticity values. Two pathologists first independently staged fibrosis on biopsies using the METAVIR classification and subsequently held a consensus meeting. Interobserver agreements of elasticity values and fibrosis stages were assessed with intraclass correlation coefficients (ICC). RESULTS: MRE and biopsy data were available for 85/103 patients. ICC of pathologists staging fibrosis was almost perfect at 0.91 (95% CI 0.86-0.94). ICC for MRE readers was significantly (P < 0.0001) higher at 0.99 (95% CI 0.98-1.00). CONCLUSIONS: Interobserver agreement for liver fibrosis staging was almost perfect for both histopathology and MRE, with a significant higher agreement for MRE. Its high interobserver agreement and reliable accuracy support the use of MRE as a non-invasive screening tool for liver fibrosis.

Non-invasive evaluation of liver fibrosis: a comparison of ultrasound-based transient elastography and MR elastography in patients with viral hepatitis B and C.

OBJECTIVE: To compare the diagnostic accuracy of TE and MRE and establish cutoff levels and diagnostic strategies for both techniques, enabling selection of patients for liver biopsy. METHODS: One hundred three patients with chronic hepatitis B or C and liver biopsy were prospectively included. Areas under curves (AUROC) were compared for TE and MRE for METAVIR fibrosis grade ≥ F2 and ≥F3. We defined cutoff values for selection of patients with F0-F1 (sensitivity >95%) and for significant fibrosis F2-F4 (specificity >95%). RESULTS: Following exclusions, 85 patients were analysed (65 CHB, 19 CHC, 1 co-infected). Fibrosis stages were F0 (n = 3), F1 (n = 53), F2 (n = 15), F3 (n = 8) and F4 (n = 6). TE and MRE accuracy were comparable [AUROCTE ≥ F2: 0.914 (95% CI: 0.857-0.972) vs. AUROCMRE ≥ F2: 0.909 (0.840-0.977), P = 0.89; AUROCTE ≥ F3: 0.895 (0.816-0.974) vs. AUROCMRE ≥ F3: 0.928 (0.874-0.982), P = 0.42]. Cutoff values of <5.2 and ≥8.9 kPa (TE) and <1.66 and ≥2.18 kPa (MRE) diagnosed 64% and 66% of patients correctly as F0-F1 or F2-F4. A conditional strategy in inconclusive test results increased diagnostic yield to 80%. CONCLUSION: TE and MRE have comparable accuracy for detecting significant fibrosis, which was reliably detected or excluded in two-thirds of patients. A conditional strategy further increased diagnostic yield to 80%. KEY POINTS: • Both ultrasound-based transient elastography and magnetic resonance elastography can assess hepatic fibrosis. • Both have comparable accuracy for detecting liver fibrosis in viral hepatitis. • The individual techniques reliably detect or exclude significant liver fibrosis in 66 %. • A conditional strategy for inconclusive findings increases the number of correct diagnoses.

Reassessment of the predictive value of the Forrest classification for peptic ulcer rebleeding and mortality: can classification be simplified?

BACKGROUND AND STUDY AIMS: This study aimed to reassess whether the Forrest classification is still useful for the prediction of rebleeding and mortality in peptic ulcer bleedings and, based on this, whether the classification could be simplified. PATIENTS AND METHODS: Prospective registry data on peptic ulcer bleedings were collected and categorized according to the Forrest classification. The primary outcomes were 30-day rebleeding and all-cause mortality rates. Receiver operating characteristic curves were used to test whether simplification of the Forrest classification into high risk (Forrest Ia), increased risk (Forrest Ib-IIc), and low risk (Forrest III) classes could be an alternative to the original classification. RESULTS: In total, 397 patients were included, with 18 bleedings (4.5%) being classified as Forrest Ia, 73 (18.4%) as Forrest Ib, 86 (21.7%) as Forrest IIa, 32 (8.1%) as Forrest IIb, 59 (14.9%) as Forrest IIc, and 129 (32.5%) as Forrest III. Rebleeding occurred in 74 patients (18.6%). Rebleeding rates were highest in Forrest Ia peptic ulcers (59%). The odds ratios for rebleeding among Forrest Ib-IIc ulcers were similar. In subgroup analysis, predicting rebleeding using the Forrest classification was more reliable for gastric ulcers than for duodenal ulcers. The simplified Forrest classification had similar test characteristics to the original Forrest classification. CONCLUSION: The Forrest classification still has predictive value for rebleeding of peptic ulcers, especially for gastric ulcers; however, it does not predict mortality. Based on these results, a simplified Forrest classification is proposed. However, further studies are needed to validate these findings.

T-cell responses at baseline and during therapy with peginterferon-alpha and ribavirin are not associated with outcome in chronic hepatitis C infected patients.

BACKGROUND: Since the association between hepatitis C virus (HCV)-specific T-cell responses both pre-treatment and during interferon-alpha based therapy and viral clearance is unresolved, a combined analysis of distinctive T-cell characteristics (proliferation and interferon-gamma production) is important to clarify this issue. METHODS: Peripheral blood mononuclear cells (PBMC) collected in 22 chronic HCV infected patients at pre-treatment and at week 4 during pegIFN-alpha/ribavirin therapy, were stimulated with overlapping peptide pools in a [3H]-thymidine assay, an interferon-gamma-ELISA, and a sensitive 12-day T-cell expansion assay. RESULTS: Compared to the [3H]-thymidine proliferation and interferon-gamma secretion assays, the 12-day T-cell expansion assay was more sensitive in detecting T-cell responses. No significant association was demonstrated between pre-treatment HCV-specific CD4+ or CD8+ T-cell responses and either a sustained virological response (SVR) or a rapid virological response (RVR). However, a skewing of individual responses towards the non-structural antigens was observed. During pegIFN-alpha/ribavirin therapy, HCV-specific CD4+ and CD8+ T-cells declined similarly in both SVR/RVR and non-SVR/non-RVR patients. CONCLUSION: No correlation was found between the magnitude of pre-treatment HCV-specific T-cell responses and the outcome of pegIFN-alpha/ribavirin therapy in terms of SVR and RVR. Moreover, the magnitude of HCV-specific T-cell responses declined in all patients early during treatment.