Background. Comparable sustained virologic response (SVR) rates have been documented between Asian patients who received 24 weeks of pegylated interferon (IFN) plus ribavirin and white patients who ...received 48 weeks of combination therapy for hepatitis C virus genotype 1 (HCV-1) infection. Whether a 48-week course of combination therapy shows a better SVR rate than a 24-week course of such therapy among Asian patients with HCV-1 infection has not been confirmed in multicenter, randomized studies. Methods. In this multicenter, randomized trial, 308 treatment-naive HCV-1-infected Asian patients were randomly assigned to receive either 24 or 48 weeks of pegylated IFN-α-2a (180 µg per week) plus ribavirin (1000–1200 mg/day) therapy. The primary end point was SVR, defined as an undetectable serum HCV RNA level 24 weeks after discontinuation of therapy. In addition, rapid virologic response (RVR) was defined as an undetectable serum HCV RNA level at week 4 of therapy, and complete early virologic response was defined as an undetectable serum HCV RNA level at 12 weeks of therapy in the absence of RVR. Results. By intention-to-treat analysis, patients who received 48 weeks of therapy had a significantly higher SVR rate than did those who received 24 weeks of therapy (76% vs. 56%; P<.001). Among patients with a baseline serum HCV RNA level <800,000 IU/mL and RVR, SVR rates were comparable between 24- and 48-week courses of therapy (94% vs. 100%; P=.13). In contrast, 48 weeks of therapy was associated with a significantly higher SVR rate than was 24 weeks of therapy among patients without RVR (39% vs.16%; P=.01) and among those who achieved a complete early virologic response (44% vs. 20%; P=.02). Conclusions. In treatment-naive Asian patients with HCV-1 infection, 48 weeks of pegylated IFN-α-2a plus ribavirin therapy is associated with a higher SVR rate, compared with 24 weeks of such therapy. Patients with a baseline serum HCV RNA level <800,000 IU/mL and who have achieved an RVR can receive a 24-week course of therapy without compromising the SVR rates; however, those who have not achieved an RVR but who have achieved a complete early virologic response should receive a 48-week course of therapy. Clinical trials registration. NCT00495131.
Although percutaneous liver biopsy (PLB) is the gold standard for staging hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) before renal transplantation or antiviral therapy, ...concerns exist about serious postbiopsy complications. Using transient elastography (TE, Fibroscan(®)) to predict the severity of hepatic fibrosis has not been prospectively evaluated in these patients.
A total of 284 hemodialysis patients with CHC were enrolled. TE and aspartate aminotransferase-to-platelet ratio index (APRI) were performed before PLB. The severity of hepatic fibrosis was staged by METAVIR scores ranging from F0 to F4. Receiver operating characteristic curves were used to assess the diagnostic accuracy of TE and APRI, taking PLB as the reference standard.
The areas under curves of TE were higher than those of APRI in predicting patients with significant hepatic fibrosis (≥F2) (0.96 versus 0.84, P<0.001), those with advanced hepatic fibrosis (≥F3) (0.98 versus 0.93, P=0.04), and those with cirrhosis (F4) (0.99 versus 0.92, P=0.13). Choosing optimized liver stiffness measurements of 5.3, 8.3, and 9.2 kPa had high sensitivity (93-100%) and specificity (88-99%), and 87, 97, and 93% of the patients with a fibrosis stage of ≥F2, ≥F3, and F4 were correctly diagnosed without PLB, respectively.
TE is superior to APRI in assessing the severity of hepatic fibrosis and can substantially decrease the need of staging PLB in hemodialysis patients with CHC.
Interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and viral factors can predict sustained virological response (SVR) in HCV genotype-1 (HCV-1) patients receiving 48 weeks of ...pegylated interferon and ribavirin. Whether these factors would identify those patients who can benefit from a shorter duration of therapy remains unclear.
Treatment-naive HCV-1 patients (n=662) receiving 24 or 48 weeks of combination therapy were enrolled. Baseline demographic data, HCV viral load, IL28B SNP genotypes (rs8099917), duration of therapy and rapid virological response (RVR) were evaluated to predict SVR. The SVR rates were further stratified by the independent factors and compared.
The IL28B rs8099917 TT genotype, low baseline viral load (HCV RNA≤600,000 IU/ml), RVR and 48-week therapy independently predicted SVR. In RVR patients with the IL28B rs8099917 TT genotype, the SVR rate of 24-week therapy was comparable to 48-week therapy (95% versus 99%; P=0.21) at low baseline viral load, but was inferior to 48-week therapy (70% versus 97%; P<0.001) at high baseline viral load. In non-RVR patients, the SVR rate of 24-week therapy was inferior to 48-week therapy for those with the IL28B rs8099917 TT genotype but high baseline viral load (23% versus 62%; P<0.001), and those with the IL28B rs8099917 GT/GG genotype but low baseline viral load (0% versus 33%; P=0.02).
HCV-1 patients simultaneously bearing the IL28B rs8099917 TT genotype, low baseline viral load and RVR can benefit from a shorter duration of combination therapy.
Percutaneous liver biopsy is the gold standard for staging hepatic fibrosis of hemodialysis patients with chronic hepatitis C before renal transplantation or antiviral therapy. Concerns exist, ...however, about serious post-biopsy complications. To evaluate a more simple approach using standard laboratory tests to predict hepatic fibrosis and its evolution, we studied 279 consecutive hemodialysis patients with chronic hepatitis C and a baseline biopsy. Among them, 175 receiving antiviral therapy underwent follow-up biopsy to evaluate the histological evolution of fibrosis. Multivariate analysis of routine laboratory tests at baseline showed the aspartate aminotransferase-to-platelet ratio index was an independent predictor of significant hepatic fibrosis. The areas under curves of this ratio to predict fibrosis stages F2-4 were 0.83 and 0.71 in the baseline and follow-up sets; and 0.75 and 0.80 respectively, for patients with sustained or non-sustained virological response groups in the follow-up sets. By a judicious setting of cut-off levels for the baseline and non-sustained groups, and the sustained virological response group, almost half and 60 percent of the baseline and follow-up sets could be correctly diagnosed without biopsy. Our study found the aminotransferase-to-platelet ratio index is accurate and reproducible for assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C. Applying this simple index could decrease the need of percutaneous liver biopsy in this clinical setting.
: Background: The diagnostic value of Doppler and various noninvasive indices in predicting significant hepatic fibrosis in hepatitis C virus (HCV) carriers with persistently normal alanine ...aminotransferases (PNALT) is unknown.
Methods: Seventy‐nine treatment‐naïve HCV carriers with PNALT, who received Doppler ultrasonography and percutaneous liver biopsies, were enrolled in the study. Doppler indices, including portal vein velocity (PVV), hepatic arterial resistive index (HARI), hepatic arterial pulsatility index (HAPI), splenic arterial resistive index (SARI), and splenic arterial pulsatility index (SAPI), were compared with known biochemical indices used in HCV carriers with elevated ALT levels, including aspartate aminotransferase (AST) to platelet ratio index (APRI), age‐platelet index (API), and AST to ALT ratio (AAR), for the diagnostic accuracy of significant hepatic fibrosis.
Results: SAPI was the most discriminatory index among the Doppler indices (P<0.001). By comparing areas under the receiver‐operating characteristic (AUROC) of SAPI with various biochemical indices, SAPI was superior to APRI, API, and AAR for predicting significant fibrosis (≥F2) (0.862 vs. 0.673, 0.639, 0.504). SAPI set at 0.85 and 1.10 had a sensitivity of 96.7% and 66.7%, a specificity of 44.6% and 96.0%, a positive predictive value of 41.4% and 87.1%, and an negative predictive value of 97% and 87.7% in predicting significant fibrosis.
Conclusions: This study indicates that SAPI is the most useful index among Doppler and biochemical indices for the detection of significant hepatic fibrosis in HCV carriers with PNALT levels.
The authors report a case of myxoid adrenal cortical carcinoma (ACC) clinically manifesting as primary hyperaldosteronism. The 82-year-old female patient had a history of hypertension and was sent to ...the emergency room because of change in consciousness. Ventricular fibrillation occurred, and severe hypokalemia was found. Increased renal loss of potassium, high serum aldosterone level, low renin activity, and a huge tumor in the left suprarenal area were revealed when tests were conducted to determine the cause of her hypokalemia. Left adrenalectomy was performed. The tumor measured 13 cm in diameter and showed a heterogeneous cut surface with gelatinous material. Microscopically, the lesion was composed of polygonal cells with eosinophilic cytoplasm and arranged in arborizing cords in a myxoid background. Capsular and vascular invasion were observed. The tumor stained positive for synaptophysin, melan-A, vimentin, and α-inhibin but negative for cytokeratin. A primary myxoid ACC was diagnosed, which is a rare histological variant. The authors review 13 other reported cases. Most of these were functional tumors causing Cushing syndrome, and only 2 cases presented as primary hyperaldosteronism. All cases had similar microscopic and immunohistochemical features. Distal metastases and local recurrence were not uncommon. Close clinical follow-up is imperative.
Background & Aims: The value of Doppler ultrasonography to evaluate the severity of hepatic fibrosis in patients with chronic hepatitis C (CHC) remains controversial. Methods: Consecutive ...histologically proven patients with CHC over a 4-year period were divided into training (n = 335) and validation (n = 168) sets. Hepatic Doppler impedance index, splenic Doppler impedance index, and mean portal vein velocity were evaluated for all patients before liver biopsies. Multivariate logistic regression was performed to find the independent factors to predict patients with significant fibrosis (≥F2) and cirrhosis (F4) in the training set. Receiver operating characteristic curves were constructed for these factors to evaluate the diagnostic accuracy of significant hepatic fibrosis and cirrhosis in the training set, and in the validation set to evaluate the reproducibility. Results: Multivariate logistic regression revealed that the splenic arterial pulsatility index (SAPI) and the mean portal vein velocity were predictive of significant fibrosis (≥F2) and cirrhosis (F4). Receiver operating characteristic analysis showed the areas under the curves of regression models and SAPI were comparable in predicting significant fibrosis (0.88 vs 0.87, P = .22) and cirrhosis (0.92 vs 0.90, P = .12) in the training set. Areas under the curves of SAPI were 0.89 and 0.92 in predicting significant hepatic fibrosis and cirrhosis in the validation set. By choosing optimized cut-off levels, 54% and 76% of the patients with significant hepatic fibrosis and cirrhosis could be predicted correctly. Conclusions: SAPI is accurate and reproducible for assessing the severity of hepatic fibrosis in patients with CHC. Applying this simple Doppler index can decrease the need for staging liver biopsy.
Pegylated interferon and ribavirin for 72 weeks improve sustained virological response (SVR) in HCV genotype 1 (HCV-1) slow viral responders. Whether interleukin 28B (IL28B) single nucleotide ...polymorphism (SNP) genotypes and on-treatment viral responses can identify non-rapid virological response (RVR) patients who benefit from 48 or 72 weeks of therapy remains unclear.
Treatment-naive HCV-1 patients who failed to achieve RVR were randomly assigned to receive 48 (n=168) or 72 (n=167) weeks of therapy. Baseline factors and on-treatment virological responses at weeks 8 and 12 were evaluated for SVR in 289 compliant patients who received ≥80% of drug dosages and treatment duration, and had end of follow-up viral response. The stratified SVR rates for independent factors were compared by treatment duration.
Treatment duration, IL28B rs8099917 genotypes, cirrhosis, week-8 viral response (undetectable HCV RNA at treatment week 8) and complete early virological response (cEVR) predicted SVR. In week-8 viral response patients, the SVR rates of 72-week and 48-week treatment were similar (75-88%), regardless of IL28B SNP genotypes or cirrhosis. In non-week-8 viral response patients who achieved cEVR, the SVR rate of 72-week treatment was higher than that of 48-week treatment for non-cirrhotic patients, regardless of IL28B SNP genotypes (91-100% versus 13-44%; P=0.001).
Although IL28B SNP genotypes predict SVR, they play a minor role when on-treatment viral responses are taken into consideration. On-treatment viral responses at weeks 8 and 12 are the key determinants to decide the optimal treatment duration in HCV-1 patients without RVR.
To prospectively develop and evaluate the accuracy of a duplex Doppler ultrasonographic (US) index for predicting the presence or absence of esophageal varices in patients with compensated cirrhosis ...(Child-Pugh class A) by using endoscopy as the reference standard.
The study had institutional review board approval; all participants gave informed consent. Data in a total of 383 prospectively enrolled patients who underwent duplex Doppler US and screening endoscopy were divided into training (n = 240) and validation (n = 143) sets. Duplex Doppler US indexes, including mean portal vein velocity (PVV), hepatic impedance indexes, splenic impedance indexes, and the splenic index were evaluated with univariate and multivariate logistic regression analyses to find the independent factors predictive of the presence of esophageal varices. Receiver operating characteristic (ROC) curves were constructed for these factors to evaluate diagnostic accuracy in the training set and reproducibility in the validation set.
Multivariate logistic regression analysis showed that splenic index and mean PVV were predictive of the presence of esophageal varices in the training set. A splenoportal index (SPI) was calculated as the splenic index divided by mean PVV to amplify the opposite effects on esophageal varices. Areas under ROC curves for SPI were significantly higher than those for the splenic index (0.93 vs 0.90, P = .02) and mean PVV (0.93 vs 0.67, P < .001) in the training set and in the validation set (0.96 vs 0.91 for splenic index, P = .01; 0.93 vs 0.80 for mean PVV, P < .001). An SPI threshold of 3.0 had 92% sensitivity, 93% specificity, 91% positive predictive value, and 94% negative predictive value for esophageal varices. Applying this cutoff value correctly predicted the presence or absence of esophageal varices in 92% of the patients without screening endoscopy.
SPI can serve as a useful noninvasive index to predict the presence or absence of esophageal varices.
Comparable sustained virologic response (SVR) rates have been documented between Asian patients who received 24 weeks of pegylated interferon (IFN) plus ribavirin and white patients who received 48 ...weeks of combination therapy for hepatitis C virus genotype 1 (HCV-1) infection. Whether a 48-week course of combination therapy shows a better SVR rate than a 24-week course of such therapy among Asian patients with HCV-1 infection has not been confirmed in multicenter, randomized studies.
In this multicenter, randomized trial, 308 treatment-naive HCV-1-infected Asian patients were randomly assigned to receive either 24 or 48 weeks of pegylated IFN-alpha-2a (180 microg per week) plus ribavirin (1000-1200 mg/day) therapy. The primary end point was SVR, defined as an undetectable serum HCV RNA level 24 weeks after discontinuation of therapy. In addition, rapid virologic response (RVR) was defined as an undetectable serum HCV RNA level at week 4 of therapy, and complete early virologic response was defined as an undetectable serum HCV RNA level at 12 weeks of therapy in the absence of RVR.
By intention-to-treat analysis, patients who received 48 weeks of therapy had a significantly higher SVR rate than did those who received 24 weeks of therapy (76% vs. 56%; P < .001). Among patients with a baseline serum HCV RNA level <800,000 IU/mL and RVR, SVR rates were comparable between 24- and 48-week courses of therapy (94% vs. 100%; P = .13). In contrast, 48 weeks of therapy was associated with a significantly higher SVR rate than was 24 weeks of therapy among patients without RVR (39% vs.16%; P = .01) and among those who achieved a complete early virologic response (44% vs. 20%; P = .02).
In treatment-naive Asian patients with HCV-1 infection, 48 weeks of pegylated IFN-alpha-2a plus ribavirin therapy is associated with a higher SVR rate, compared with 24 weeks of such therapy. Patients with a baseline serum HCV RNA level <800,000 IU/mL and who have achieved an RVR can receive a 24-week course of therapy without compromising the SVR rates; however, those who have not achieved an RVR but who have achieved a complete early virologic response should receive a 48-week course of therapy.
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