Safety and efficacy of simeprevir plus sofosbuvir with or without ribavirin in patients with decompensated genotype 1 hepatitis C cirrhosis.

Combination antiviral therapy involving sofosbuvir (SOF) and simeprevir (SIM) is a treatment option in patients with genotype 1 chronic hepatitis C; however, the safety of this regimen in patients with decompensated cirrhosis is not established. Data from a combined treatment cohort of 2 large hepatology referral centers were evaluated to assess for safety and efficacy of SIM plus SOF with or without ribavirin (RBV) in patients with Child B or C cirrhosis. All (n = 42) patients included in the analysis had Child B (n = 35) or C (n = 7) cirrhosis and received 400 mg daily of SOF plus 150 mg daily of SIM, with (n = 7) or without (n = 35) RBV, for 12 weeks. Of the 42 patients in this cohort, 31 (74%) were male, 22 (52%) had failed prior treatments, and 28 (67%) were genotype 1a. Prior decompensating events included encephalopathy (57%), fluid overload (88%), or variceal hemorrhage (24%). Median Model for End-Stage Liver Disease score was 12 (range, 6-25). Treatment was well tolerated overall with more than one-half (57%) reporting no adverse events. In those reporting adverse events, the most common were fatigue (n = 6), insomnia (n = 4), headache (n = 5), nausea (n = 4), and grade 1 rash (n = 1). One patient developed chemical pancreatitis that did not require treatment discontinuation. Three of 7 patients who received RBV developed anemia, with 2 requiring blood transfusions and 1 requiring a dose reduction. No episodes of decompensation requiring hospitalization or deaths occurred on treatment. Of 42 patients, 38 (90%) patients had negative viral load at end of treatment (EOT), and 31 of 42 patients (74%) achieved sustained virological response 12 weeks after EOT; 10 of 10 patients (100%) with HCV genotype 1b achieved sustained virological response for 12 weeks (SVR12). In conclusion, SOF plus SIM was very well tolerated in patients with advanced Child B/C decompensated cirrhosis. Overall, 74% of patients achieved SVR12; 100% of patients with genotype 1b decompensated cirrhosis achieved SVR12.

Sofosbuvir and simeprevir in hepatitis C genotype 1-patients with end-stage renal disease on haemodialysis or GFR <30 ml/min.

BACKGROUND & AIMS: Treating chronic hepatitis C (CHC) in patients with end-stage renal disease (ESRD) has suboptimal tolerability and cure rates. Safety and efficacy of sofosbuvir plus simeprevir regimen in CHC-infected patients with ESRD on haemodialysis (HD) or glomerular filtration rate (GFR) <30 ml/min is unknown. We evaluated the safety and efficacy of sofosbuvir and simeprevir in this special patient population. METHODS: All (n = 17) patients in the analysis had ESRD on HD or GFR <30 ml/min. All received sofosbuvir 400 mg daily and simeprevir 150 mg daily, without ribavirin for 12 weeks. Safety and efficacy data were collected; including SVR4 and SVR12 data for all patients after completing therapy. RESULTS: In this 17 patient cohort, eight (47%) were cirrhotic, four (24%) had stage three liver fibrosis and 13 (76%) were genotype 1A. All 17 have completed 12 weeks of therapy. Treatment was overall well tolerated with no treatment discontinuations reported. Four (24%) patients reported mild adverse events (AE). These AEs were insomnia (n = 2), headache (n = 1), nausea (n = 1) and worsening anaemia requiring blood transfusion (n = 1). All 17 patients reached post-treatment week-12 follow-up, and achieved SVR12 or virological cure (100% SVR12). CONCLUSIONS: Daily, full dose of sofosbuvir plus simeprevir for 12 weeks of therapy appears to be well tolerated in patients with ESRD on HD or GFR <30 ml/min. Most common AEs resembled those of healthier CHC patients without significant renal impairment. The cure rates obtained in this cohort treated with sofosbuvir and simeprevir are dramatically superior to any previous treatment regimen studied & published in this special patient population.

S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders.

BACKGROUND & AIMS: Less than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after pegylated interferon (peginterferon) and ribavirin therapy. S-adenosyl methionine (SAMe) improves interferon signaling in cell culture. We assessed the effect of SAMe on the kinetics of the early antiviral response and interferon signaling in nonresponders to previous antiviral therapy and investigated the mechanisms involved. METHODS: Nonresponders with HCV genotype 1 were given peginterferon alfa-2a and ribavirin for 2 weeks (course A, baseline/control). After 1 month, patients received SAMe (1600 mg daily) for 2 weeks and then peginterferon and ribavirin for 48 weeks (course B; completed by 21 of 24 patients). Viral kinetics and interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells (PBMCs) were compared between courses. RESULTS: The decrease in HCV RNA from 0 to 48 hours (phase 1) was similar with and without SAMe. However, the second phase slope of viral decline was improved with SAMe (course A, 0.11 ± 0.04 log(10) IU/mL/wk; course B, 0.27 ± 0.06; P = .009); 11 patients (53%) achieved an early virological response, and 10 (48%) had undetectable HCV RNA by week 24. Induction of ISGs in PBMCs was significantly greater during course B. In cultured cells, SAMe increased induction of ISGs and the antiviral effects of interferon by increasing STAT1 methylation, possibly affecting STAT1-DNA binding. CONCLUSIONS: The addition of SAMe to peginterferon and ribavirin improves the early viral kinetics and increases ISG induction in nonresponders to previous therapy. SAMe might be a useful adjunct to peginterferon-based therapies in chronic HCV infection.

Increased caffeine consumption is associated with reduced hepatic fibrosis.

Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. This study was undertaken to use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Patients undergoing liver biopsy completed a detailed caffeine questionnaire on three occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. One hundred seventy-seven patients (99 male, 104 white, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75(th) percentile for the cohort (308 mg = approximately 2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.80; P = 0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index, and alcohol intake in all patients (OR, 0.25; 95% CI, 0.09-0.67; P = 0.006), as well as the subset with HCV infection (OR, 0.19; 95% CI, 0.05-0.66; P = 0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis.

Effect of Low Positive End of Treatment Viral Load with Direct-Acting Antiviral Therapy on Sustained Virologic Response.

Background: Direct-acting antivirals (DAAs) are highly effective treatments against hepatitis C virus (HCV), with sustained virologic response (SVR) rates of 93-100% against all genotypes. In most patients, viral load (VL) becomes undetectable four weeks into treatment, but rarely a low positive VL may be observed at the end of treatment (EOT). This study was conducted to determine the effect of low positive EOT VLs with DAA therapies on SVR at 12 and 24 weeks. Methods: A retrospective chart review was conducted from January 2014 to December 2018 on 1256 HCV patients of all genotypes (1-6) who had received DAA therapy at two large hepatology referral centers. Baseline demographic data, along with VL at week four, EOT, and SVR12/24 time points were collected for patients that had positive EOT VL. Treatment outcome for any patient with positive EOT VL was noted. Results: Eight out of 1256 patients treated with varying DAA therapies were observed to have low positive EOT VLs ranging from <15 to 235 IU/mL. One patient had a negative EOT VL, but 23 IU/mL at week four after EOT. All eight patients who had low positive EOT VLs and one patient who had a low positive VL at four weeks after EOT achieved SVR at weeks 12 and 24. One of the eight patients had cirrhosis. The majority of patients were genotype 1a. Conclusion: In the DAA treatment era, low levels of detectable HCV RNA at EOT does not predict treatment failure.

Viral hepatitis and HIV in Africa.

With increasing access to antiretroviral therapy across sub-Saharan Africa, progress is finally being made in combating the devastating HIV epidemic. As HIV-infected individuals live longer, the effects of coinfection with chronic hepatitis B and C will likely become an increasingly relevant issue. Indeed, HIV adversely affects the natural history of HBV and HCV, both of which are endemic across the African continent, Issues ranging from appropriate diagnostic testing to prevention and treatment are affected by HIV coinfection, particularly in resource-limited settings. In addition, some of the more complex problems such as occult infection, immune reconstitution, and antiretroviral hepatotoxicity are becoming increasingly important considerations. In this review, we present the available data on coinfection in Africa with a major emphasis on prevalence, routes of transmission, prevention and treatment strategies.

Complementary and alternative medicine (CAM) for the treatment of chronic hepatitis B and C: a review.

Complementary and alternative medicine (CAM) has been used for centuries in China and Japan to treat various illnesses, including viral hepatitis. Several therapeutic approaches constitute CAM, the most relevant for this review being the use of herbals. However, profound disagreements exist between conventional and alternative medicine practitioners regarding their value. Western medical advocates cite deep concerns about the purity of most herbals because of lack of standardized production, the paucity of pharmacokinetic data, the fact that few well-designed randomized, controlled trials of these products have been performed and the evidence that some herbals have been responsible for severe adverse effects. Nevertheless, many in the public, even in western countries, turn to the use of herbals, believing that they must be safe and effective because they are 'natural' and have been used for centuries, and because of dissatisfaction with conventional medicine. Accordingly, their use in western countries and the costs incurred have increased each year. While there is evidence that some herbals have physiological effects, there still is insufficient evidence to recommend their use. This paper reviews the classification, epidemiology and philosophy of CAM, and the reasons advanced for herbal use to treat viral hepatitis. The criteria necessary to develop a potential pharmacological agent are presented, as well as the requirements for conducting a scientifically valid treatment trial of herbals. Five herbals used in the past to treat viral hepatitis are reviewed and evaluated for the quality of their studies and mention is made of herbals known to have adverse effects.