Effects of Food Insecurity on Hepatic Steatosis and Fibrosis in People With HIV.

BACKGROUND & AIMS: Food insecurity (FI) is a risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis in the general population, but its impact on liver disease in people with HIV (PWH) is unknown. METHODS: We examined the association of FI with prevalence of NAFLD and fibrosis in a diverse cohort of PWH. PWH aged ≥ 18 years on antiretroviral therapy, HIV RNA <200 copies/mL, and without other known liver diseases were screened for NAFLD (controlled attenuated parameter ≥263 decibels/meter) and advanced fibrosis (liver stiffness measurement ≥11 kilopascals) by vibration controlled transient elastography at 8 U.S. CENTERS: Participants were categorized as food insecure using the Six-Item Short Form Household Food Security Survey. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of NAFLD and advanced fibrosis by FI status. RESULTS: Among 654 PWH, NAFLD was present in 348 (53%) and advanced fibrosis in 41 (6%). FI was present in 203 of participants (31%), including 97/348 with NAFLD (28%) and 18/41 with advanced fibrosis (44%). In multivariable analysis, FI was associated with lower odds of NAFLD (OR, 0.57; 95% CI, 0.37-0.88) and a greater, but nonsignificant, odds of advanced fibrosis (OR, 1.38; 95% CI, 0.65-2.90). We identified a significant interaction between FI and diabetes (P = .02) on fibrosis risk, with greater odds of fibrosis among food insecure PWH and diabetes (OR, 3.83; 95% CI, 1.15-12.73) but not among food insecure nondiabetics (OR, 1.12; 95% CI, 0.47-2.98). CONCLUSIONS: FI is highly prevalent among PWH and associated with lower odds of NAFLD, and among PWH with diabetes, there is greater odds of advanced fibrosis. FI may contribute to hepatic fibrosis through mechanisms other than steatosis in PWH.

Hepatitis B e Antigen-Negative Single Hepatocyte Analysis Shows Transcriptional Silencing and Slow Decay of Infected Cells With Treatment.

BACKGROUND: Nucleos(t)ide analogues (NUCs) rarely cure chronic hepatitis B (CHB) because they do not eliminate covalently closed circular deoxyribonucleic acid, the stable replication template. In hepatitis B e antigen (HBeAg)-positive CHB during NUCs, HBV-infected cells decline slowly and are transcriptionally silenced. Whether these occur in HBeAg-negative CHB is unknown. METHODS: Using paired liver biopsies separated by 2.7-3.7 years in 4 males with HIV and HBeAg-negative CHB at both biopsies and 1 male with HIV who underwent HBeAg seroconversion between biopsies, we quantified amounts of viral nucleic acids in hundreds of individual hepatocytes. RESULTS: In the 4 persistently HBeAg-negative participants, HBV-infected hepatocytes ranged from 6.2% to 17.7% (biopsy 1) and significantly declined in 3 of 4 by biopsy 2. In the HBeAg seroconverter, the proportion was 97.4% (biopsy 1) and declined to 81.9% at biopsy 2 (P < .05). We extrapolated that HBV eradication with NUCs would take >100 years. At biopsy 1 in the persistently HBeAg-negative participants, 23%-56.8% of infected hepatocytes were transcriptionally inactive-higher than we observed in HBeAg-positive CHB-and significantly declined in 1 of 4 at biopsy 2. CONCLUSIONS: In HBeAg-negative CHB on NUCs, the negligible decline in infected hepatocytes is similar to HBeAg-positive CHB, supporting the need for more potent therapeutics to achieve functional cure.

Chronic Hepatitis C: Advances in Therapy and the Remaining Challenges.

Hepatitis C virus (HCV) infection contributes significantly to liver cirrhosis and hepatocellular carcinoma (HCC), often requiring liver transplantation. Introducing direct-acting antiviral agents (DAAs) has radically changed HCV treatment. DAAs achieve high rates of sustained virological response (>98%). Even then, resistant-associated substitution and HCC during or after treatment have become prominent clinical concerns. Further, several clinically significant issues remain unresolved after successful HCV eradication by DAAs, including treating patients with chronic kidney disease or decompensated liver cirrhosis. Extensive and large-scale screening and treatment implementation programs are needed to make DAA therapies effective at the population level.

Evaluation of a pilot emergency department linkage to care program for patients previously diagnosed with Hepatitis C.

There is a significant number of Emergency Department (ED) patients with known chronic hepatitis C virus (HCV) infection who have not been treated with directly acting antivirals. We implemented a pilot ED-based linkage-to-care program to address this need and evaluated the impact of the program using the HCV Care Continuum metrics. Between March 2015 and May 2016, dedicated patient care navigators identified HCV RNA-positive patients in an urban ED and offered expedited appointments with the on-site viral hepatitis clinic. Patient demographics and care continuum outcomes were abstracted from the EMR and analysed to determine significant factors influencing linkage-to-care (LTC) and treatment initiation rates. The ED linkage-to-care program achieved a 43% linkage-to-care rate (165/384), 22% treatment rate (84/384) and 16% sustained virologic response rate (63/384). Significant associations were found between linkage-to-care and increasing age (OR = 1.03), Medicare insurance (OR = 2.21) and having a primary care physician (PCP) (OR = 4.03). For patients who were linked, the odds of initiating treatment were also positively significantly associated with increasing age (OR = 1.04) and having a PCP (OR = 2.77). For patients who initiated treatment, the odds of sustained virologic response were marginally associated with having a PCP (OR = 4.92).Our ED linkage-to-care program utilized care coordination to successfully link nearly half of approached HCV RNA-positive patients to care. This design can be feasibly replicated by other EDs given limited non-clinical training required for linkage-to-care staff. Adoption of similar programs in other EDs may improve the rates of LTC and treatment initiation for previously diagnosed HCV patients.

Nonadherence to Ledipasvir/Sofosbuvir Did Not Predict Sustained Virologic Response in a Randomized Controlled Trial of Human Immunodeficiency Virus/Hepatitis C Virus Coinfected Persons Who Use Drugs.

BACKGROUND: Eliminating hepatitis C virus (HCV) will require effective treatment delivery to persons with substance use disorders (SUDs). We evaluated the relationship between ledipasvir/sofosbuvir treatment persistence (receiving 84 tablets), adherence, and sustained virologic response (SVR) in persons with human immunodeficiency virus (HIV)/HCV coinfection. METHODS: Of the 144 participants with HIV/HCV and SUDs, 110 initiated a 12-week treatment course under 1 of 3 conditions (usual care, peer mentors, and cash incentives). We used self-report, pharmacy pill counts, and expected date of refill to examine adherence. Persistent participants were categorized as high adherence (taking ≥90% of doses) or low adherence (taking <90% of doses). RESULTS: Most participants persisted on treatment after initiation (n = 105), with 95% (n = 100) achieving SVR. One third (34%) of participants had moderate/heavy alcohol use by the biomarker phosphatidylethanol ([Peth] ≥50 ng/mL), and 44% had urine toxicology positive for cocaine or heroin at enrollment. The proportion of persons with high adherence was 72% (n = 76), and the proportion of persons with low adherence was 28%. Although low adherence was associated with moderate/heavy alcohol use by PEth (relative risk = 2.77; 95% confidence interval, 1.50-5.12), SVR did not vary according to adherence (P = .702), and most participants (97%) with low adherence achieved SVR. CONCLUSIONS: Treatment persistence led to high SVR rates among persons with HIV/HCV, despite imperfect adherence and SUDs.

Evolution of Fatty Liver Disease and Relationship With Lipoproteins and Clinical Outcomes in Hepatitis B/Human Immunodeficiency Virus Coinfection.

BACKGROUND: Fatty liver disease (FLD) and hepatitis B virus (HBV) infection occur commonly in human immunodeficiency virus (HIV). FLD resolution is associated with improvement in lipoproteins in HIV-uninfected patients. We evaluated changes in FLD in an HBV/HIV-coinfected cohort. METHODS: One hundred eight HBV/HIV-coinfected adults with baseline liver biopsies were followed every 24 weeks (median, 166 weeks) and 60 had follow-up biopsies. Baseline FLD categories (none, ≥5% steatosis, steatohepatitis), their change, and relationships with clinical and lipid/lipoprotein parameters were explored using multivariable modeling. RESULTS: Median age was 50 years, and 93% were male. At baseline 30% had FLD. With control for lipid-lowering medications and body mass index, low-density lipoprotein (LDL) cholesterol (LDL-C), LDL particle concentration (LDL-P), and apolipoprotein B (apoB) decreased and adiponectin increased over time (all P < .05); On follow-up (vs baseline), there was no significant difference in FLD category (P = .85); 60% remained without FLD, 17% had unchanged, 12% worsening, and 12% improved FLD. Baseline low-density lipoproteins (LDL-C, LDL-P, small LDL-P) and apoB appeared highest in those with unchanged FLD status (all P < .05). No associations between changes in FLD across follow-up (worsening/improvement vs unchanged) and lipid/lipoproteins changes were identified. CONCLUSIONS: In this cohort, there was no significant change in FLD prevalence over a relatively short timeframe. Baseline atherogenic lipids appeared highest in those with persistent steatosis or steatohepatitis, suggesting potentially increased cardiovascular risk in this group, but an independent relationship between individual-level change in FLD status and lipid/lipoprotein levels across follow-up was not observed.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4 years and post-LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.

Single hepatocytes show persistence and transcriptional inactivity of hepatitis B.

There is no cure for the more than 270 million people chronically infected with HBV. Nucleos(t)ide analogs (NUCs), the mainstay of anti-HBV treatment, block HBV reverse transcription. NUCs do not eliminate the intranuclear covalently closed circular DNA (cccDNA), from which viral RNAs, including pregenomic RNA (pgRNA), are transcribed. A key gap in designing a cure is understanding how NUCs affect HBV replication and transcription because serum markers yield an incomplete view of intrahepatic HBV. We applied single-cell laser capture microdissection and droplet digital PCR to paired liver biopsies collected from 5 HBV/HIV-coinfected persons who took NUCs over 2-4 years. From biopsy 1 to 2, proportions of HBV-infected hepatocytes declined with adherence to NUC treatment (P < 0.05); we extrapolated that eradication of HBV will take over 10 decades with NUCs in these participants. In individual hepatocytes, pgRNA levels diminished 28- to 73-fold during NUC treatment, corresponding with decreased tissue HBV core antigen staining (P < 0.01). In 4 out of 5 participants, hepatocytes with cccDNA but undetectable pgRNA (transcriptionally inactive) were present, and these were enriched in 3 participants during NUC treatment. Further work to unravel mechanisms of cccDNA transcriptional inactivation may lead to therapies that can achieve this in all hepatocytes, resulting in a functional cure.

Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.

BACKGROUND: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection. METHODS: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S. RESULTS: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10 IU/mL and changed by -4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%-42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%-1.7%) (P < .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = -160 pg/mL per day at 24 hours, but no further after Day 4. CONCLUSIONS: We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection.

Single Hepatocyte Hepatitis B Virus Transcriptional Landscape in HIV Coinfection.

BACKGROUND: Hepatitis B virus (HBV) is a leading cause of liver failure and hepatocellular carcinoma. Approximately 10% of people with HIV also have HBV and are at higher risk of liver disease progression than in HBV monoinfection. Antivirals, common to HIV and HBV, suppress HBV DNA levels but do not eradicate virus because the transcriptional template, covalently closed circular DNA (cccDNA), is long lived in infected hepatocytes. METHODS: Using single-cell laser capture microdissection, we isolated >1100 hepatocytes from 5 HIV/HBV coinfected persons with increasing exposure to HBV antivirals (HB1-HB5; no exposure to >7 years exposure), quantifying cccDNA and pregenomic RNA (pgRNA) in each cell using droplet digital polymerase chain reaction. RESULTS: The proportion of infected hepatocytes decreased with antiviral exposure from 96.4% (HB1) to 29.8% (HB5). Upper cccDNA range and median pgRNA decreased from HB1 to HB5 (P < .05 for both). The amount of pgRNA transcribed per cccDNA also decreased from HB1 to HB5 (P < .05). Cells with inactive pgRNA transcription were enriched from 0% (HB1) to 14.3% (HB5) of infected hepatocytes. CONCLUSIONS: cccDNA transcription is reduced in HIV/HBV coinfected people with longer antiviral duration. Understanding HBV transcriptional regulation may be critical to develop a functional cure.

Overlapping epidemics of alcohol and illicit drug use among HCV-infected persons who inject drugs.

BACKGROUND: Alcohol use in people who inject drugs (PWID) with hepatitis C virus (HCV) infection accelerates liver disease progression. This paper describes the prevalence and associated correlates of alcohol use among HCV antibody positive PWID. METHODS: In a large cohort of HCV antibody positive PWID (N = 1623) followed from 2005 to 2013, we characterized alcohol use using the AUDIT-C. We used multivariable logistic regression with generalized estimated equations to examine socio-demographic, clinical, and substance use correlates of alcohol use. RESULTS: At their initial visit, 41% reported no, 21% reported moderate, and 38% reported heavy alcohol use. The odds of moderate and heavy alcohol use increased with greater intensity of substance use represented by a composite summary variable which ranged from 0 to 3 substances (street-acquired prescription drugs, non-injection cocaine/heroin, and injection drugs) used. Compared to those who used no drugs, those who used 3 substances had 3.71 odds (95% CI: 3.07-4.48) of moderate alcohol use and 3.65 odds (95% CI: 3.20-4.16) of heavy alcohol use. CONCLUSIONS: The prevalence of moderate/heavy alcohol use is high among HCV antibody positive PWID and occurs frequently in combination with other drug use. This may contribute to progressive liver fibrosis thus limiting the gains achieved from HCV cure. Public health interventions need to address the overlapping epidemics of HCV, alcohol use, and other substance use in this population.

Changes in practice and perception of hepatitis C and liver transplantation: Results of a national survey.

With new practice guidelines, it is important to understand how liver transplant (LT) centers have incorporated direct-acting antivirals (DAAs) into the management of hepatitis C virus-infected (HCV+) candidates and recipients. To explore how DAAs have affected LT centers' willingness to treat HCV+ candidates and recipients and to use HCV+ donors, we surveyed high volume US LT centers (11/2014-12/2015) regarding practices for HCV+ candidates, recipients, and donors, before vs after DAAs. We used the Scientific Registry of Transplant Recipients to compare centers' number of LTs, HCV+ recipients, and HCV+ donors in the years before (1/1/2012-12/31/2013) and after (1/1/2016-12/31/2017) survey administration. Of 80 centers contacted, 57 (71.3%) responded, representing 69.0% of the total volume of LTs in 2013. After DAAs, most centers increased treating candidates with low (≤15) model for end-stage liver disease (MELD) (85.2%), intermediate/high (>15) MELD (92.6%), and hepatocellular carcinoma (79.6%). There was consensus to treat low MELD candidates (90.8% "most of the time/always"), but less certainty for intermediate/high MELD candidates (48.2% "sometimes"). Universal post-LT HCV treatment increased (7.4% vs 57.4%). After DAAs, 42.6% were more willing to use HCV+ donors for HCV+ candidates, and 38.9% were willing to consider using HCV+ donors for HCV- candidates. Overall, with DAAs, centers were more willing to treat HCV+ candidates and recipients and to use HCV+ donors; recent recommendations may help to guide treatment decisions for intermediate/high MELD candidates.

An Education and Field Experience Program to Increase Detection of Human Immunodeficiency Virus and Hepatitis C Virus.

BACKGROUND: Baltimore is an urban center that has been highly impacted by human immunodeficiency virus (HIV) and hepatitis C virus (HCV); however, many individuals are unaware of their HIV and/or HCV status. In 2013, the Johns Hopkins Center for AIDS Research (CFAR) developed Generation Tomorrow, an HIV and HCV education, testing, and counseling program with community input and collaboration. OBJECTIVES: The aims of Generation Tomorrow are to increase HIV and HCV awareness and detection in Baltimore and engage the next generation of health professionals (students) and community members (peers) in HIV and HCV outreach services. METHODS: The Generation Tomorrow educational component includes formal HIV and HCV testing and counselling training, and a lecture series for students and peers. The participants then engage in field assignments and outreach events with Johns Hopkins associated programs or community-based organizations. RESULTS: Generation Tomorrow trained 71 students and peers in three cohorts, 70% of whom reported that they planned to stay in HIV- and/or HCV-related work. From October 2014 to May 2015, which represents the first year that Generation Tomorrow ran with the full academic calendar, Generation Tomorrow students and peers worked with partner organizations to conduct 1,104 HIV rapid antibody tests and found 19 individuals (1.72%) to be HIV positive. Additionally, 778 HCV rapid antibody tests were conducted and 175 individuals (22.5%) were HCV antibody positive. CONCLUSIONS: Generation Tomorrow has been successful in engaging students and community peers in HIV and HCV education, testing, and counseling, and has documented HIV and HCV positivity rates well above general community prevalence.

Cigarette Smoking in Persons Living with Hepatitis C: The National Health and Nutrition Examination Survey (NHANES), 1999-2014.

BACKGROUND: Cigarette smoking is common in persons living with hepatitis C (hepatitis C+), but national statistics on this harmful practice are lacking. A better understanding of smoking behaviors in hepatitis C+ individuals may help in the development of targeted treatment strategies. METHODS: We extracted data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2014. Hepatitis C+ were compared with hepatitis C- adults in the entire sample and in the subset of current smokers. Measures included demographics, current smoking, cigarettes/day, nicotine dependence, other tobacco use, substance use, and medical and psychiatric comorbidities. RESULTS: Complete smoking and hepatitis C virus (HCV) data were available for 39,472 (90.1%) of 43,793 adult participants in NHANES during the study years. Hepatitis C+ smoked at almost triple the rate of hepatitis C- adults (62.4% vs 22.9%), with no significant difference between hepatitis C+ men and women (64.5% vs 58.2%). Hepatitis C+ smokers were more likely to smoke daily than hepatitis C- smokers (87.5% vs 80.0%), but had similar levels of nicotine dependence. Hepatitis C+ smokers were more likely to be older (mean age: 47.1 vs 41.5 years), male (69.4% vs 54.4%), Black (21.2% vs 12.1%), less educated (any college: 31.8% vs 42.9%), poor (mean family monthly poverty index: 1.80 vs 2.47), uninsured (43.9% vs 30.4%), use drugs (cocaine: 11.1% vs 3.2%; heroin: 4.0% vs 0.6%), and be depressed (33.2% vs 13.5%). Multivariate analyses revealed significant associations of both hepatitis C infection and cigarette smoking with current depression and hypertension. CONCLUSIONS: There is a cigarette smoking epidemic embedded within the hepatitis C epidemic in the United States. The sociodemographic profile of hepatitis C+ smokers suggests that the implementation of effective tobacco treatment will be challenging. Thoughtful treatment strategies that are mindful of the unique characteristics of this group are needed.

Increased Mortality Among Persons With Chronic Hepatitis C With Moderate or Severe Liver Disease: A Cohort Study.

BACKGROUND: Despite the availability of curative treatment for hepatitis C virus (HCV) infection, because of cost, treatment is often denied until liver fibrosis has progressed to at least moderate fibrosis and, in some cases, cirrhosis. That practice is justified on assumptions that there are no medical consequences to having moderate disease and that disease stage transitions can be anticipated. METHODS: We performed transient elastography on 964 people chronically infected with HCV with a history of injection drug use living in Baltimore, Maryland. Liver stiffness was evaluated semiannually from 2006 to 2014 using validated cutoffs for moderate fibrosis (8.0-12.3 kPa) and severe fibrosis/cirrhosis (>12.3 kPa). RESULTS: Among 964 persons, 62%, 23% and 15% had baseline measurements suggestive of no/mild fibrosis, moderate fibrosis, and severe fibrosis/cirrhosis, respectively. All-cause and nonaccidental mortality were elevated in persons with moderate fibrosis (adjusted hazard ratio [aHR], 1.42 [95% confidence interval {CI}, .96-2.11]; aHR, 1.66 [95% CI, 1.06-2.59], respectively) after adjustment for sociodemographics, substance use, and human immunodeficiency virus status. Despite the increased risk of mortality among those with moderate fibrosis, no combination of demographic, behavioral, and clinical factors, nor changes in stiffness measurements themselves could predict the transition from mild to moderate fibrosis with sufficiently high diagnostic accuracy (C-statistic = 0.72 for best-performing model). CONCLUSIONS: Delaying treatment for anyone chronically infected with HCV regardless of fibrosis stage may be detrimental given the increased risk of mortality even for those with moderate disease and the inability to predict the transition from mild to moderate disease.

Cigarette Smoking Behaviors and Beliefs in Persons Living With Hepatitis C.

BACKGROUND AND RATIONALE: Tobacco use is common among persons living with hepatitis C (PLHC), yet little is known about their smoking behaviors and beliefs. Modern hepatitis C treatment offers a unique opportunity to intensively engage this population about other health risks, including smoking. MAIN RESULTS: Seventy-seven tobacco users (40 hepatitis C virus [HCV] seropositive and 37 HCV seronegative) enrolled in an interview study in a New York City clinic. The mean age was 51.6, 57.1% were male, 40.3% Latino, and 49.4% black. 67.5% were single and 18.2% were employed. HCV+ smokers differed from HCV- smokers in having a higher prevalence of illicit substance use, depression, and hypertension. PLHC smokers were highly motivated to quit, with 52.5% stating an intention to quit within 30 days. Most of the PLHC smokers had used cessation-directed pharmacotherapy, but almost none had tried a quitline or a quit smoking website. PLHC smokers scored higher on the intrapersonal locus of control subscale. Almost a quarter (22.5%) believed that smoking "helped fight the HCV." CONCLUSIONS: PLHC smokers have a high burden of psychiatric and substance use comorbidity. They exhibit characteristics that distinguish them from uninfected smokers, and many harbor false beliefs about imagined benefits of smoking. They are highly motivated to quit but underutilize cessation aids. Without aggressive intervention, smoking-related morbidity will likely mute the health benefits and longevity gains associated with hepatitis C treatment. Research such as this may prove useful in guiding the development of future tobacco treatment strategies. IMPLICATIONS: This is the first paper to examine, in detail, sociobehavioral correlates of tobacco use in PLHC. PLHC are recognized by the Department of Health and Human Services as a high-priority health disparities population. We are not aware of any tobacco treatment services designed specifically for PLHC. The first step in designing an intervention is defining the characteristics of the target group. Our findings will begin to address this need, and may prove useful in optimizing tobacco treatment strategies for smokers living with hepatitis C.

Hepatitis C Virus Postexposure Prophylaxis in the Healthcare Worker: Why Direct-Acting Antivirals Don't Change a Thing.

Currently, 380 000-400 000 occupational exposures to blood-borne pathogens occur annually in the United States. The management for occupational HIV or hepatitis B virus exposures includes postexposure prophylaxis (PEP) when necessary; however, PEP is not recommended for hepatitis C virus (HCV) exposures. Recent approval of HCV direct-acting antivirals (DAAs) has renewed discussions as to whether these therapies could be used to prevent infection after exposure. There are no published studies addressing this question, but the prescribing of DAAs for PEP has been reported. We will discuss the differences in transmission of the 3 most common blood-borne pathogens, the natural history of early HCV infection, and the scientific rationale for PEP. In particular, we will discuss how the low feasibility of conducting an adequately powered clinical trial of DAA use for PEP and the low cost-effectiveness of such an intervention is not supportive of targeting limited resources for such use.

Extrahepatic morbidity and mortality of chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.