Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Severe Mononeuritis Multiplex Associated with Peginterferon-Ribavirin Therapy of Chronic Hepatitis C

Vasculitis is a common extrahepatic manifestation of chronic hepatitis C virus infection and could be either associated with cryoglobulinemia or not. The mechanism of peripheral neuropathy seems to be vasculitic in both cryoglobulinemic and non-cryoglobulinemic patients. Antiviral therapy with peginterferon and ribavirin usually improves symptoms of virus-induced neuropathy. Herein, we reported on a rare case of hard mononeuritis multiplex triggered by antiviral therapy in a patient without neurological symptoms before the treatment

Severe Mononeuritis Multiplex Associated with Peginterferon-Ribavirin Therapy of Chronic Hepatitis C

Vasculitis is a common extrahepatic manifestation of chronic hepatitis C virus infection and could be either associated with cryoglobulinemia or not. The mechanism of peripheral neuropathy seems to be vasculitic in both cryoglobulinemic and non-cryoglobulinemic patients. Antiviral therapy with peginterferon and ribavirin usually improves symptoms of virus-induced neuropathy. Herein, we reported on a rare case of hard mononeuritis multiplex triggered by antiviral therapy in a patient without neurological symptoms before the treatment

Extreme gastric dilation caused by chronic lead poisoning: A case report

Lead is a toxic metal that affects many organ systems and functions in humans. In the majority of adults, chronic lead poisoning comes from exposures to work places and can occur in numerous work settings, such as manufacturing, lead smelting and refinement, or due to use of batteries, pigments, solder, ammunitions, paint, car radiators, cable and wires, certain cosmetics. In some countries, lead is added to petrol. We present a rare case of gastric dilation caused by long-term petrol ingestion. A 16-year-old young man was admitted to our hospital due to a 6-mo history of exhaustion, dizziness, nausea, abdominal cramps and constipation. X-ray examination revealed dilated stomach descending into the pelvis and small bowel distension. After a long clinical observation, we found that the reason for the chronic lead poisoning of the patient was due to a 3-year history of petrol ingestion. The patient spontaneously recovered and stomach returned to its normal position and size. Lead poisoning should be taken into consideration in all unexplained cases of gastric dilation

The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia

The goal of this study was to identify host and viral factors affecting the response to pegylated interferon/ribavirin (PEG-IFN/RBV) treatment in patients with chronic hepatitis C genotype 1b. Baseline characteristics of the patients and sequences within the p7 region were analyzed in pre-treatment serum samples from 53 individuals with chronic hepatitis C genotype 1b and related to the outcome of therapy. We found a significant correlation between age and response to therapy (p LT 0.001). Furthermore, the pre-treatment viral load was closely associated with the stage of liver fibrosis (p LT 0.001). The presence of fewer than 4 mutations and age above 40 were significantly associated with non-response (NR) (p LT 0.001). Our findings may be useful for estimating the likelihood of achieving a sustained virologic response (SVR) in patients who are chronically infected with hepatitis C virus genotype 1b

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin