Adverse events associated with ribavirin in sofosbuvir-based therapies for patients with chronic hepatitis C: A community practice experience.

OBJECTIVE: Due to high sustained virological response (SVR) rates, sofosbuvir-based regimens are currently a mainstay for hepatitis C virus (HCV) therapies. The addition of pegylated interferon (PEG-IFN) and ribavirin impacts patients' quality of life during treatment. This study aimed to compare severe adverse events (SAEs) amongst therapeutic combinations for HCV in a community clinic setting. METHODS: From December 2013 to July 2014, 128 chronic HCV-infected patients were treated with sofosbuvir, ribavirin and weekly PEG-IFN for 12 weeks (cohort 1), 12 or 24 weeks of sofosbuvir and ribavirin (cohorts 2 and 3) or sofosbuvir plus simeprevir for 12 weeks (cohort 4). Adverse events were recorded from baseline to 12 or 24 weeks of treatment. RESULTS: SAEs appeared in 15.6-53.8% of ribavirin-inclusive treated patients compared to 4.8% of the ribavirin-free regimen. PEG-IFN, sofosbuvir plus ribavirin had the highest frequencies of fatigue, headache and rash compared to either 12 or 24 weeks of ribavirin and sofosbuvir. However, sofosbuvir and ribavirin regimens led to significant increases in dyspnea, need for ribavirin dose reductions and withdrawal from treatment due to SAEs. Anemia was also more frequent in ribavirin-inclusive combinations (P < 0.001). Conversely, sofosbuvir plus simeprevir reached similar SVR rates at week 12 post-treatment compared to all ribavirin-containing regimens, but with significantly fewer adverse events (P = 0.006). At week 12 post-treatment, cirrhotic patients experienced a higher virological relapse rate than non-cirrhotic patients (P = 0.019). CONCLUSIONS: Ribavirin-inclusive HCV therapies increased the frequencies of SAEs, had higher dropout rates and increased patient morbidity.

Predicting clinical outcomes in patients with HBsAg-positive chronic hepatitis.

BACKGROUND AND AIMS: The progression of HBsAg-positive chronic hepatitis is insidious and unpredictable. Identification of factors leading to either a benign or more serious clinical outcome may assist in decision making for antiviral therapy. METHODS: From 1989 to 1998, 130 untreated patients with chronic hepatitis were enrolled in a prospective study and followed every 3-6 months with liver and virologic tests, platelet counts and alpha-fetoprotein (AFP) measurements. RESULTS: During a mean follow-up of 107 ± 86 months, 16 (12.3 %) chronic hepatitis patients progressed to cirrhosis (annual rate 1.4 %), and 23 (17.7 %) reverted to being inactive carriers (annual rate 2.1 %). Compared to baseline values, chronic hepatitis patients who progressed to cirrhosis exhibited declines in mean platelet counts (225.7-195.2 mm(3), p = 0.008-0.04) during the first 4 years of follow-up, while those who reverted to being inactive carriers had substantial reductions in mean levels of AST (83.5-27.2 u/l, p < 0.001-0.002) and ALT (100.2-29.2 u/l, p < 0.001-0.007). In addition, during spontaneous alanine aminotransferase (ALT) flares, patients progressing to cirrhosis had concomitant elevations of AFP levels, while patients who became inactive carriers maintained normal AFP values during ALT flares (13.45 vs. 4.65 ng/ml, p = 0.001). These AFP differences during episodes of ALT flares were similarly observed when analyzed in two separate cohorts of cirrhosis and inactive carrier patients. CONCLUSION: Patients with chronic hepatitis who progressed to cirrhosis exhibited declines in platelet counts and had AFP elevations during ALT flares. To prevent progression, serial measurements of these parameters during the chronic hepatitis stage will assist in identifying patients requiring antiviral therapy.

Tumor factors associated with clinical outcomes in patients with hepatitis B virus infection and hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection is a common cause of hepatocellular carcinoma (HCC) in the United States. This study evaluated the impact of surveillance and treatment on HBV-infected HCC patients and identified factors associated with survival. METHODS: From 1981 to 2010, 166 hepatitis B surface antigen (HBsAg)-positive HCC patients were evaluated. Fifty-eight patients had HCC detected by surveillance, while 108 patients presented with HCC. RESULTS: Compared to patients detected by surveillance, those presenting with HCC had more symptoms (65.7% vs 41.4%; P=.002), were more frequently outside of Milan criteria (73.7% vs 29.6%; P<.001), more often presented with diffuse tumors (23.2% vs 1.9%; P<.001), and had a shortened median survival time (9.5 months vs 18.7 months; P=.003). Patients who presented with diffuse tumors were younger and more often male (P=.002-.007), had a higher alpha-fetoprotein (AFP) level (P=.023), and had a median survival time of only 1.68 months. By multivariate analysis, factors that were significantly associated with mortality included diffuse tumors (hazard ratio [HR], 6.30; 95% confidence interval [CI], 3.14-12.66; P<.001), being outside of Milan criteria (HR, 2.02; 95% CI, 1.26-3.23; P=.005), albumin level (HR per 1 standard deviation decrease, 1.4; 95% CI, 1.15-1.72; P=.001), AFP level (HR per 1 log standard deviation increase, 1.38; 95% CI, 1.13-1.67; P=.001), and receiving liver transplantation versus other treatments (HR, 0.08-0.38; 95% CI, 0.03-0.87; P<.001 to P=.022). CONCLUSION: In the United States, HBV-related HCC is a common malignancy, especially among Asian immigrants. Identification of HBsAgpositive subjects and routine HCC surveillance are essential for improving survival in these patients.