Evaluation of Sustained Virologic Response as a Relevant Surrogate Endpoint for Long-term Outcomes of Hepatitis C Virus Infection.

BACKGROUND: The causal link of sustained virologic response (SVR) with outcome has been challenged. With improved SVR rates with direct-acting antivirals (DAAs), the benefit of SVR would be expected to diminish if the association with outcome is not causal. METHODS: Data were collected for patients starting treatment with interferon (IFN) or DAAs between June 2006 and December 2016. To control for disease severity, criteria for the IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial determined IFN-eligibility. Clinical events were decompensation, hepatocellular carcinoma, liver transplantation, and all-cause mortality. RESULTS: In 1078 IDEAL-eligible patients, 1306 treatments occurred (52% IFN, 49% DAAs). Cirrhosis was present in 30% DAAs vs 21% IFN (P < .001). SVR was 97% with DAAs vs 52% with IFN (P < .0001). The 24-month cumulative event-free survival was 99% for IFN and 97% for DAAs with SVR (P = .08) and 96% and 75%, respectively, for non-SVR (P = .01). SVR was associated with improved event-free survival with an adjusted hazard ratio of 0.21 (95% confidence interval, .06-.71; P = .01). Using inverse probability of treatment weighting to match IFN nonresponders with DAA-treated patients, the 24-month event-rate was 1.1% with DAAs compared to 3.4% in IFN nonresponders (P = .005), highlighting the clinical benefit of maximizing SVR. CONCLUSIONS: In IFN-eligible patients, SVR is more commonly achieved with DAAs and confers a similar clinical benefit as in those treated with IFN. The reduced event-rate with DAAs compared to IFN, despite similar disease severity, confirm that SVR alters prognosis leading to improved clinical outcomes.

Maintained virological suppression and renal function with reduced dose tenofovir disoproxil fumarate in renally impaired chronic hepatitis B patients.

Tenofovir disoproxil fumarate (TDF) effectively suppresses viral replication in chronic hepatitis B (CHB), but occasionally leads to renal impairment. We evaluated the prevalence of viral and biochemical breakthrough and renal function kinetics in renally impaired patients with CHB on reduced and on full-dose TDF. This clinic-based longitudinal cohort study included patients receiving full and reduced dose TDF (due to eGFR [Cockcroft-Gault] <60 mL/min/1.73 m2 ). Viral and biochemical breakthroughs were assessed 1 month after starting full and reduced TDF dose until the end-of-follow-up. Breakthroughs were studied in full and reduced dose TDF, and renal function (MDRD) longitudinally before and after dose reduction within patients starting on full-dose TDF. Of 750 patients on TDF, 78 (10%) had reduced dose and 672 (90%) full dose. At the time of dose reduction, 36 (46%) patients had chronic kidney disease stage G3B. A viral breakthrough occurred in one cirrhotic dialysis-dependent patient (dosed 300 mg weekly) which resolved without signs of decompensation, and in one patient on full dose which resolved spontaneously. One biochemical breakthrough occurred during dose reduction and resolved naturally without viral breakthrough. The MDRD improved within the first year of dose reduction (+3.0 [2.5] mL/min per year; P < .005) and remained stable thereafter. Fifty-three (79%) patients reached an MDRD >50 mL/min during dose reduction. Low dose TDF maintains renal function and viral suppression in most renally impaired patients with CHB, even in those with advanced liver disease. This useful, yet simple strategy could be particularly viable in resource-constrained settings.

Prevalence and predictors of complementary and alternative medicine modalities in patients with chronic hepatitis B.

BACKGROUND & AIMS: The use of complementary and alternative medicine (CAM) in patients with chronic hepatitis B (CHB) can interact with antiviral treatment or influence health-seeking behaviour. We aimed to study the use of individual CAM modalities in CHB and explore determinants of use, particularly migration-related, socio-economic and clinical factors. METHODS: A total of 436 CHB outpatients who attended the Toronto Centre for Liver Disease in 2015-2016 were included in this cross-sectional study. Using the comprehensive I-CAM questionnaire and health records, data were collected on socio-demographic and clinical variables and on usage of 16 CAM modalities in the last year. RESULTS: Sixty percent of patients were male, 74% were Asian and 46% were using antiviral treatment. Three-hundred and nine (71%) patients used CAM. Vitamin/mineral preparations (45% of patients) were most commonly used. Overall CAM use and the specific use of potentially injurious CAM, such as green tea extract (9.2%) and St. John's wort (0.2%), were not associated with liver disease severity. Female sex, family history of CHB, lower serum HBV DNA, and higher socio-economic status were independently associated with bio-holistic CAM use, the clinically most-relevant CAM group (P < 0.05); ethnicity, antiviral therapy use and liver disease severity were not. CONCLUSIONS: CAM use among CHB patients was extensive, especially use of vitamin and mineral preparations, but without direct influence on liver disease severity. Bio-holistic CAM use appeared to be associated with socio-economic status rather than with ethnicity or liver disease severity. Despite the rare use of hepatotoxins, physicians should actively inquire about it.