Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Direct-acting antiviral agents (DAAs) eradicate hepatitis C virus (HCV) infection in the majority of patients. We critically evaluated the impact of DAAs on hepatocellular carcinoma (HCC) risk, a major complication of HCV infection. RECENT FINDINGS/RESULTS:HCC than patients who fail treatment or remain untreated. Furthermore, reduction in HCC risk is similar whether SVR is achieved with DAAs or interferon (IFN). However, DAA-induced SVR does not eliminate HCC risk entirely. Therefore, patients with pre-existing cirrhosis require ongoing surveillance even after SVR is achieved.Early, descriptive, uncontrolled reports suggested that DAAs may increase the risk of recurrent HCC. While studying HCC recurrence presents major methodologic challenges, larger studies containing appropriate comparison control groups largely refuted these concerns. SUMMARY/CONCLUSIONS:Recent studies provide evidence that DAA-induced SVR reduces HCC risk.

BACKGROUND & AIMS:Screening patients with cirrhosis for hepatocellular carcinoma (HCC) has been recommended. We conducted a matched case-control study within the US Veterans Affairs (VA) health care system to determine whether screening by abdominal ultrasonography (USS) and/or by measuring serum level of α-fetoprotein (AFP) was associated with decreased cancer-related mortality in patients with cirrhosis. METHODS:We defined cases (n = 238) as patients with cirrhosis who died of HCC from January 1, 2013 through August 31, 2015 and had been in VA care with a diagnosis of cirrhosis for at least 4 years before the diagnosis of HCC. We matched each case to 1 control (n = 238), defined as a patient with cirrhosis who did not die of HCC and had been in VA care for at least 4 years before the date of the matched case's HCC diagnosis. Controls were matched to cases by year of cirrhosis diagnosis, race and ethnicity, age, sex, etiology of cirrhosis, Model for End-Stage Liver Disease score, and VA medical center. We identified all USS and serum AFP tests performed within 4 years before the date of HCC diagnosis in cases or the equivalent index date in controls and determined by chart extraction (blinded to case or control status) whether these tests were performed for screening. RESULTS:There were no significant differences between cases and controls in the proportions of patients who underwent screening USS (52.9% vs 54.2%), screening measurement of serum AFP (74.8% vs 73.5%), screening USS or measurement of serum AFP (81.1% vs 79.4%), or screening USS and measurement of serum AFP (46.6% vs 48.3%) within 4 years before the index date, with or without adjusting for potential confounders. There also was no difference in receipt of these screening tests within 1, 2, or 3 years before the index date. CONCLUSIONS:In a matched case-control study of the VA health care system, we found that screening patients with cirrhosis for HCC by USS, measurement of serum AFP, either test, or both tests was not associated with decreased HCC-related mortality. We encourage additional case-control studies to evaluate the efficacy of screening for HCC in other health care systems, in which available records are sufficiently detailed to enable identification of the indication for USS and AFP tests.

BACKGROUND:The mean age of patients with chronic hepatitis C virus (HCV) infection in the USA has been increasing. Despite the increasing proportion of HCV-infected elderly patients, this group is under-represented in clinical trials of HCV treatment. AIM/OBJECTIVE:We aimed to describe the real-world effectiveness of direct-acting antivirals (DAAs) among elderly patients. PATIENTS AND METHODS/METHODS:We retrospectively identified 17 487 HCV-infected patients who were started on treatment with sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir-based regimens in the Veterans Affairs Healthcare System between 1 January 2014 and 30 June 2015. We ascertained sustained virologic response (SVR) rates in patients aged below 55, 55-59, 60-64, 65-69, 70-74, and 75 years or older and performed multivariable logistic regression to determine whether age predicted SVR. RESULTS:Overall unadjusted SVR rates were 91.2% [95% confidence interval (CI): 89.7-92.4], 89.8% (95% CI: 88.8-90.7), 90.8% (95% CI: 90.1-91.6), 91.1% (95% CI: 90.1-91.9), 90.0% (95% CI: 86.9-92.4), and 93.8% (95% CI: 88.8-96.7) in patients aged below 55, 55-59, 60-64, 65-69, 70-74, and 75 years or older. Unadjusted SVR rates were similar in all age groups after stratifying by genotype, treatment regimen, stage of liver disease, and treatment experience. In multivariate models, age was not predictive of SVR after adjusting for confounders. CONCLUSION/CONCLUSIONS:DAAs produce high rates of SVR in all age groups, including patients in our oldest age category (≥75 years). Advanced age in and of itself should not be considered a barrier to initiating DAA treatment.

UNLABELLED:Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon-based treatments for chronic hepatitis C virus infection, whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct-acting antiviral regimens in the Veterans Affairs health care system nationally. We identified 21,095 hepatitis C virus-infected patients (11,029 [52%] white, 6,171 [29%] black, 1,187 [6%] Hispanic, 348 [2%] Asian/Pacific Islander/American Indian/Alaska Native, and 2,360 [11%] declined/missing race or ethnicity) who initiated antiviral treatment with regimens containing sofosbuvir, simeprevir + sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir during the 18-month period from January 1, 2014, to June 30, 2015. Overall SVR rates were 89.8% (95% confidence interval [CI] 89.2-90.4) in white, 89.8% (95% CI 89.0-90.6) in black, 86.0% (95% CI 83.7-88.0) in Hispanic, and 90.7% (95% CI 87.0-93.5) in Asian/Pacific Islander/American Indian/Alaska Native patients. However, after adjustment for baseline characteristics, black (adjusted odds ratio = 0.77, P < 0.001) and Hispanic (adjusted odds ratio = 0.76, P = 0.007) patients were less likely to achieve SVR than white patients, a difference that was not explained by early treatment discontinuations. Among genotype 1-infected patients treated with ledipasvir/sofosbuvir monotherapy, black patients had significantly lower SVR than white patients when treated for 8 weeks but not when treated for 12 weeks. CONCLUSION:Direct-acting antivirals produce high SVR rates in white, black, Hispanic, and Asian/Pacific Islander/American Indian/Alaska Native patients; but after adjusting for baseline characteristics, black race and Hispanic ethnicity remain independent predictors of treatment failure. Short 8-week ledipasvir/sofosbuvir monotherapy regimens should perhaps be avoided in black patients with genotype 1 hepatitis C virus. (Hepatology 2017;65:426-438).

BACKGROUND:It is unclear whether alcohol use negatively impacts HCV treatment outcomes in the era of direct antiviral agents (DAAs). We aimed to evaluate the associations between current levels of drinking and treatment response among persons treated for HCV with DAAs in the national Veterans Affairs (VA) healthcare system. METHODS:We identified patients who initiated HCV DAAs over 18 months (1/1/14-6/30/15) and had documented alcohol screening with the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire within one year prior to initiating therapy. DAAs included: sofosbuvir (SOF), ledipasvir/sofosbuvir (LDV/SOF) or ombitasvir-paritaprevir-ritonavir, and dasabuvir (PrOD). AUDIT-C scores were categorized as 0 (abstinence), 1-3 (low-level drinking) and 4-12 (unhealthy drinking) in men or 0, 1-2 and 3-12 in women. RESULTS:Among 17,487 patients who initiated DAAs, 15,151 (87%) completed AUDIT-C screening: 10,387 (68.5%) were categorized as abstinent, 3422 (22.6%) as low-level drinking and 1342 (8.9%) as unhealthy drinking. There were no significant differences in sustained virologic response (SVR) rates between abstinent (SVR 91%; 95% CI: 91-92%), low-level drinking (SVR 93%; 95% CI 92-94%) or unhealthy drinking (SVR 91%; 95% 89-92) categories in univariable analysis or in multivariable logistic regression models. However, after imputing missing SVR data, unhealthy drinkers were less likely to achieve SVR in multivariable analysis (AOR 0.75, 95% CI 0.60-0.92). CONCLUSION:Absolute SVR rates were uniformly high among all persons regardless of alcohol use, with only minor differences in those who report unhealthy drinking, which supports clinical guidelines that do not recommend excluding persons with alcohol use.