Hepatitis C: Current Controversies and Future Potential in Solid Organ Transplantation

Purpose of Review

To highlight the changing landscape of hepatitis C virus (HCV) infection in the context of organ transplantation. This focuses on areas of controversy and future potential in the era of highly effective direct-acting antiviral (DAA) agents.

Recent Findings

Since the advent of safe and highly effective DAA therapy, HCV infection is now curable in virtually all cases, including organ transplant recipients. Excellent drug tolerability and safety combined with high cure rates across all organ groups means that HCV is no longer a barrier to transplantation or its outcomes. Mounting data demonstrate the safety of using organs from HCV-infected donors with subsequent treatment of HCV in the recipient and a potential to expand the donor pool.

Summary

Historical data demonstrating inferior survival in transplant recipients with HCV is of limited relevance in the DAA era. Virtually all transplant recipients with HCV infection can be cured, while early data also suggest excellent outcomes in recipients of organs from HCV viremic donors. The optimal timing of HCV therapy in relation to transplantation and the optimal use of organs from HCV viremic donors remain areas of controversy and ongoing research efforts.

     

Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure

Background

Introduced in 2013–2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90–95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients.

Methods

The Medline was searched for “HCV infection”, “HCV treatment”, “Directly acting antivirals”,“HCV resistance”.

Results

Most patients who did not achieve an SVR have been found to be infected with HCV mutant strains with a reduced susceptibility to these drugs. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A regions and rarely in the NS5B region. Treatment-induced mutants resistant to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration.

Conclusions

Patients who have failed HCV treatment with DAA agents have several re-treatment options, but re-treatment selection may be intricate and resistance testing is recommended to optimize this choice. It is, therefore, important to bear in mind that the correct determination of HCV genotype and subtype and the identification of RASs are essential elements for choosing the optimal re-treatment. It is supposed that it is useful to give readers some other suggestions regarding therapeutic reprocessing.

     

Non-tuberculous Mycobacterial Infections in Thoracic Transplant Candidates and Recipients

Purpose of Review

To review and discuss the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of non-tuberculous mycobacteria (NTM) in thoracic transplantation.

Recent Findings

Non-tuberculous mycobacteria are ubiquitous but are an uncommon cause of disease after solid organ transplantation. The incidence of infection is higher in thoracic transplant recipients than in abdominal transplant recipients, with most cases seen after lung transplantation. It is associated with increased morbidity and, occasionally, mortality. Infection in the pre-transplant setting can occur in lung transplant candidates, often posing a dilemma regarding transplant listing. Disease manifestations are diverse, and pulmonary disease is the most common. Diagnosis requires a high index of suspicion. Treatment requires a multiple-drug combination and is limited by drug-drug interactions and tolerability. Mycobacterium abscessus is a challenge in lung transplant recipients, due to its intrinsic resistance and propensity to relapse even after prolonged therapy. Mycobacterium chimaera is an emerging pathogen associated with contamination of heater-cooler units and is described to cause disease months after cardiothoracic surgery.

Summary

NTM infections in thoracic organ transplant recipients are uncommon but are associated with substantial morbidity and mortality. Data from larger multicenter studies is needed to better define the epidemiology of NTM in thoracic transplantation, best treatment options, and the management of infected transplant candidates.

     

Effects of a Video on Organ Donation Consent Among Primary Care Patients: A Randomized Controlled Trial

BACKGROUND

Low organ donation rates remain a major barrier to organ transplantation.

OBJECTIVE

We aimed to determine the effect of a video and patient cueing on organ donation consent among patients meeting with their primary care provider.

DESIGN

This was a randomized controlled trial between February 2013 and May 2014.

SETTING

The waiting rooms of 18 primary care clinics of a medical system in Cuyahoga County, Ohio.

PATIENTS

The study included 915 patients over 15.5 years of age who had not previously consented to organ donation.

INTERVENTIONS

Just prior to their clinical encounter, intervention patients (n?=?456) watched a 5-minute organ donation video on iPads and then choose a question regarding organ donation to ask their provider. Control patients (n?=?459) visited their provider per usual routine.

MAIN MEASURES

The primary outcome was the proportion of patients who consented for organ donation. Secondary outcomes included the proportion of patients who discussed organ donation with their provider and the proportion who were satisfied with the time spent with their provider during the clinical encounter.

KEY RESULTS

Intervention patients were more likely than control patients to consent to donate organs (22 % vs. 15 %, OR 1.50, 95%CI 1.10–2.13). Intervention patients were also more likely to have donation discussions with their provider (77 % vs. 18 %, OR 15.1, 95%CI 11.1–20.6). Intervention and control patients were similarly satisfied with the time they spent with their provider (83 % vs. 86 %, OR 0.87, 95%CI 0.61–1.25).

LIMITATION

How the observed increases in organ donation consent might translate into a greater organ supply is unclear.

CONCLUSION

Watching a brief video regarding organ donation and being cued to ask a primary care provider a question about donation resulted in more organ donation discussions and an increase in organ donation consent. Satisfaction with the time spent during the clinical encounter was not affected.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01697137

     

Current and future challenges in HCV: insights from an Italian experts panel

Background

The recent availability of direct acting antiviral drugs (DAAs) has drastically changed hepatitis C virus (HCV) treatment scenarios, due to the exceedingly high rates of sustained virological response (SVR) and excellent tolerability allowing for treatment at all disease stages.

Methods

A panel of Italian experts was convened twice, in November 2016 and January 2017, to provide further support on some open issues and provide guidance for personalized HCV care, also in light of forthcoming regimens.

Results and conclusions

Treatment recommendations issued by international and national liver societies to guide clinicians in the management of HCV infection are constantly updated due to accumulating new data. Such recommendations may not be applicable to all healthcare settings for a variety of reasons. Moreover, some gaps still remain and the spectrum of patients to be treated is also evolving.

     

Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients

Background and Aims

The prevalence of naturally occurring HCV-NS5A resistance-associated substitutions (RAS) to DAA drugs might affect the response to treatment in HCV/HIV coinfected subjects. There are limited data on the frequency of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected patients when ultra-deep sequencing methodologies are applied.

Methods

HCV-NS5A-RAS were evaluated among 25 subjects in each group. Patients were matched by age, gender, and hepatic fibrosis stage category to control for selection bias.

Results

Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48% of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had clinically relevant mutations to DAA directed at NS5A.

Conclusion

While the clinical significance of this observation may be limited in highly drug adherent populations, some HCV/HIV coinfected persons may be at greater risk of viral resistance if suboptimal dosing occurs.

     

Treatment of chronic genotype-3 hepatitis C virus infection using direct-acting antiviral agents: An Indian experience

Background

Direct-acting antiviral drugs (DAAs) are favored for the treatment of hepatitis C virus (HCV) infection. However, the experience with the DAAs currently available in India in the treatment of genotype-3 HCV is limited. We therefore reviewed our experience with these drugs in treating patients with chronic genotype-3 HCV infection, including those with cirrhosis.

Methods

We prospectively followed adult patients with genotype-3 HCV infection who had received treatment regimens containing sofosbuvir with/without daclatasvir. Patients were categorized as chronic hepatitis C (CHC), compensated cirrhosis (CC), and decompensated cirrhosis (DC). They received either (i) sofosbuvir and ribavirin, with or without pegylated interferon (Peg-IFN) for 12 or 24 weeks, or (ii) sofosbuvir and daclatasvir, with or without ribavirin for 12 or 24 weeks. Response was assessed using HCV RNA testing after 2 or 4 weeks of treatment (rapid virological response [RVR]), at treatment completion (end-of-treatment response [ETR]) or 12 weeks after treatment completion (sustained virological response [SVR12]).

Results

Of the 160 patients (90% treatment-naïve; CHC 49%, CC 32%, and DC 19%), 39 (24%) received Peg-IFN, sofosbuvir and ribavirin, 21 (13%) received sofosbuvir and ribavirin, and 100 (63%) received sofosbuvir and daclatasvir, with or without ribavirin. On intention-to-treat basis, RVR, ETR, and SVR12 in the entire cohort were 146/160 (91.3%), 151/160 (94.4%), and 147/160 (91.9%), respectively. Seven patients died (CC 2, DC 5) during treatment; four (2 CHC, 2 DC) patients discontinued treatment; and two patients with CC relapsed.

Conclusions

Dual-DAA-based regimens were safe and highly effective in treating genotype-3 HCV infection in CHC and CC patients.

     

Should Sarcopenia Increase Priority for Transplant or Is It a Contraindication?

Purpose of Review

The purpose of this review is to discuss the current evidence regarding the impact of sarcopenia on patients with cirrhosis awaiting liver transplantation and to determine if its presence should be considered a criterion for expedited transplantation or a contraindication for transplantation.

Recent Findings

Sarcopenia is a negative predictor of survival in patients on a waiting list and after liver transplant. The gut-liver axis and the liver-muscle axis have been explored to understand the complex pathophysiology of sarcopenia.

Summary

Sarcopenia is a frequent finding in patients with cirrhosis. The diagnosis is ideally based on cross-sectional image analysis (CT or MRI) and treatment consists of optimization of caloric and protein intake. To date, prioritizing tools for liver transplantation have not included nutrition or sarcopenia parameters. Patients with a low Model for End-Stage Liver Disease (MELD) or MELD-Na score and sarcopenia would benefit from prioritization for transplant in order to reduce time on waiting list and therefore mortality.

     

Donor Diabetes Mellitus Is an Independent Risk Factor for Graft Loss in HCV Positive but Not HCV Negative Liver Transplant Recipients

Background and Aims

Graft survival in HCV (hepatitis C virus) infected recipients is worse than those transplanted for other liver diseases. We studied whether several donor cardiovascular risk factors (including advanced age, smoking, hypertension, and diabetes mellitus) contribute to worse outcomes for HCV positive and HCV negative liver transplant recipients.

Methods

We obtained data from the United Network for Organ Sharing on all adult liver transplants performed in the United States between January 1, 1998 and December 31, 2003. In total, 27,033 transplant cases were evaluated. Independent predictors of graft survival were determined using Cox proportional hazards regression analysis after controlling for factors previously found to be associated with differences in transplant outcomes.

Results

Donor diabetes was a strong independent risk factor for graft failure [hazard ratio (HR) = 1.20, p = 0.006] only in HCV positive recipients. Neither donor smoking status nor hypertension predicted graft loss in either cohort. Consistent with previous studies, advanced donor age, donation after cardiac death, height, and African American donor all predicted graft loss amongst both cohorts.

Conclusion

Accounting for donor diabetes in relation to recipient HCV status in the selection of liver recipients may result in improved graft survival.

     

Interaction Between Hepatocellular Carcinoma and Hepatitis C Eradication With Direct-acting Antiviral Therapy

Purpose of review

The approval of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment. However, the publication of a study from Barcelona in 2016 raised concern for an increased risk of recurrence of hepatocellular carcinoma (HCC) after potentially curative therapy in patients receiving DAAs. This article reviews the current literature on the interaction between HCC and hepatitis C eradication with DAAs.

Recent findings

Following publication of the initial observation in 2016, a number of studies have looked at the impact of active HCC on the success of antiviral therapy, as well as that of treatment with DAAs on both the occurrence and recurrence of HCC. The presence of active HCC decreases sustained virologic response (SVR) rates with DAAs. However, SVR rates improve in patients who have achieved complete radiological response or are treated post transplantation. With respect to occurrence of HCC after DAAs, many small single-center studies without a control group have documented high incidence. The rates are also higher when compared to those of historical controls treated with interferon, but these patients are not comparable because DAA-treated population is more likely to have advanced fibrosis or decompensation. In large studies that have included a control group (patients treated concurrently who did not achieve SVR), a decrease in the occurrence of HCC has been demonstrated. With regard to recurrence of HCC, while smaller single-center studies have shown an increase, larger studies with control group have not replicated those findings. However, methodological limitations in the published studies limit our ability to make a firm conclusion on both the occurrence and recurrence of HCC after DAA therapy.

Summary

The presence of active HCC decreases treatment success rates with DAAs. Therefore, it is recommended that treatment of HCV in patients with HCC be deferred till there is complete radiological response. Though there are major limitations with the currently published studies, the data does not support an increase in the occurrence or recurrence of HCC after DAA therapy.

     

Intragastric balloon as a novel modality for weight loss in patients with cirrhosis and morbid obesity awaiting liver transplantation

Introduction

In extreme obesity, bariatric surgery or weight loss by lifestyle modification is often not possible because of presence of decompensated cirrhosis. Endoscopic intragastric balloon placement may be used as minimal invasive technique to promote weight loss and make them better candidates for liver transplantation surgery; however, there is no literature in this regard.

Methods

Patients with body mass index (BMI) >40 kg/m² or BMI between 35 and 40 (with a low graft to recipient weight ratio) were considered for weight reduction modalities including dietary counseling and intragastric balloon placement when feasible.

Results

Intragastric balloon placement was done in six males and two females, age 46?±?5 years, BMI 43.5?±?6.9 kg/m². All patients (except one with hepatocellular carcinoma) had decompensated liver disease, mean Child score was 8.5?±?1.6. Five of them had successful liver transplantation (three deceased and two living donor liver transplantation) after weight loss, while three are waiting. All these five patients had uneventful post-transplant course. All patients had transient vomiting except one, in whom volume of balloon was decreased due to persistent vomiting. All patients except one had weight loss. None of patients had any serious complications. Three of five patients maintained weight loss post-transplant also.

Conclusion

Intragastric balloon placement is a useful modality for promoting short-term weight loss and thereby making morbidly obese recipients fit for liver transplantation surgery.

     

Zytomegalievirus nach Nierentransplantation

Background

Despite widespread use of antiviral cytomegalovirus (CMV) prophylaxis, active CMV infections with progression to CMV disease remain of paramount importance after renal transplantation, which can lead to severe complications particularly in CMV seronegative recipients of a CMV seropositive donor kidney.

Objective

Risk stratification of active CMV infections and CMV disease, immune reactivity, clinical challenges, and development of approaches to disease management.

Methods

Discussion of recent developments and expert recommendations.

Results

There is a particularly high risk for the development of active CMV infections and CMV disease in CMV seronegative recipients of a CMV seropositive donor kidney. In this case CMV prophylaxis followed by preemptive therapy is recommended. The focus of this combined strategy is to prevent severe tissue-invasive CMV disease and to reduce the indirect effects of active CMV infections with inferior patient and transplant survival. Patients at increased risk who do not generate adequate CMV-specific cellular immunity after transplantation, nevertheless develop severe and occasionally recurrent active CMV infections after termination of prophylactic measures. In the case of life-threatening therapy-resistant CMV disease, adoptive transfer of CMV-specific T?cells has been proven to be a safe and effective therapy option.

Conclusion

Clinically problematic courses of active CMV infections are limited to those patients with severely impaired CMV-specific immunity. The quantification of CMV-specific cellular immunity represents an appropriate instrument to achieve a better stratification of the risk of active CMV infections in patients at increased risk and is the subject of current research studies.

     

Update on Current Evidence for Hepatitis C Therapeutic Options in HCV Mono-infected Patients

Purpose of Review

Therapies for hepatitis C (HCV) are evolving rapidly with the advent of novel direct-acting antiviral agents (DAAs). We review evidence for currently or imminently available regimens to aide clinicians in understanding current therapeutic options.

Recent Findings

A number of DAA combinations have completed clinical trials and are available for use. Current combinations are often genotype-specific, and combine HCV protease inhibitors, NS5A inhibitors and/or NS5B inhibitors to suppress HCV replication, leading to eradication. Current potential combinations for genotype 1 infection include sofosbuvir-ledipasvir, paritaprevir/ritonavir-ombitasvir-dasabuvir, sofosbuvir with daclatasvir, and grazoprevir-elbasvir. These regimens have been associated with sustained virologic response (SVR) rates of over 95 % for treatment naïve individuals after 12 weeks of therapy regardless of cirrhosis, and some sub-groups of patients may be successfully treated with just 8 weeks of sofosbuvir-ledipasvir. Regimens for genotype 2 and 3 include sofosbuvir with ribavirin, sofosbuvir with daclatasvir, or with velpatasvir, which may offer highest SVR rates when available. The development of HCV drug resistance, particularly against NS5A agents, may impact subsequent regimens. The need for baseline screening for resistant variants is unclear for most regimens, but likely would affect only a minority of patients.

Summary

All-oral curative regimens for HCV are now possible for most patients.

     

Impact of endoscopic ultrasound-guided fine-needle aspiration in prospective liver transplant recipients with hepatocellular carcinoma and lymphadenopathy

Background

Diagnosis of metastatic disease is important in patients with cirrhosis and hepatocellular carcinoma (HCC) to prevent futile liver transplantation. Some of these patients have metastatic lymphadenopathy; however, it is difficult to perform percutaneous fine-needle aspiration due to presence of collateral and anatomic location. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of lymph nodes offers several advantages like real-time vision, proximity to target, and avoidance of collaterals.

Aim

The aim of this study was to look for metastatic lymphadenopathy by EUS-guided FNA (EUS-FNA) in prospective liver transplant recipients with HCC.

Methods

A prospective study was conducted from January 2013 to January 2016 at a tertiary care center. All prospective liver transplant recipients with HCC had PET-CT and bone scan to look for metastatic disease. EUS-FNA was done in patients with abdominal or mediastinal lymphadenopathy and no evidence of extrahepatic disease. Data is shown as median (25–75 interquartile range).

Results

EUS-guided FNA was done for 50 patients (42 abdominal and 8 mediastinal lymph nodes), age 57 (53–62) years, Child-Turcotte-Pugh 7 (6–9), and model for end-stage liver disease 10 (7–16). FNA material was adequate in 92% patients, metastasis in 15 (30%), granulomatous lymphadenopathy in 4 (8%), and reactive change in 27 patients (54%). The material was inadequate for diagnosis in 4 (8%) patients. Thus, EUS-guided FNA precluded transplantation in 30% of patients with lymphadenopathy, and 4 (8%) patients received anti-tubercular therapy before liver transplantation.

Conclusion

In patients with HCC and lymphadenopathy, EUS-guided FNA detected metastatic disease and precluded liver transplantation in approximately one third of patients.

     

Three months of weekly rifapentine plus isoniazid for latent tuberculosis treatment in solid organ transplant candidates

Background

Isoniazid daily for 9 months is the recommended regimen for latent tuberculosis infection (LTBI) in solid organ transplant (SOT) candidates, but its use is controversial, due to reports of hepatotoxicity and low treatment completion rates. A 12-week course of once weekly directly observed therapy (DOT) with isoniazid plus rifapentine (3HP) is a new LTBI treatment regimen. Tolerability and safety data of 3HP LTBI treatment in SOT candidates are limited.

Methods

Twelve consecutive SOT candidates who underwent DOT with 3HP for LTBI at Westchester Medical Center, Valhalla, New York, USA, between January 2013 and August 2016 were prospectively evaluated for tolerability and safety of 3HP. The diagnosis of LTBI was made in a person with a positive interferon-gamma release test, without a history of previously treated active or latent tuberculosis infection, and without signs, symptoms, or radiographic evidence of active tuberculosis. Patients were followed up 1 month after treatment completion and at routine follow-up visits with their transplant providers.

Results

Eleven patients were men, and the median age was 60 years (range 44–72). Eight patients were liver, and four kidney transplant candidates. The median Model for End-Stage Liver Disease (MELD score) was 17 (range 10–31). All patients completed treatment. Only a single patient developed transaminitis greater than twice the baseline value. Three patients underwent liver transplantation. None of them developed tuberculosis at 9, 22, or 40 months following transplantation.

Conclusion

Directly observed 3HP LTBI treatment was not associated with hepatotoxicity, even in patients with higher MELD scores. Further studies are needed to confirm the safety and efficacy of this LTBI treatment regimen in the SOT population.

     

Similar Sustained Virologic Response in Real-World and Clinical Trial Studies of Hepatitis C/Human Immunodeficiency Virus Coinfection

Background

Clinical trials evaluating efficacy of direct-acting antiviral (DAA) therapies demonstrate sustained virologic response (SVR) rates greater than 90% in patients infected with hepatitis C (HCV) and human immunodeficiency virus (HIV). However, generalizability of this data to real-world coinfected populations is unknown.

Aim

We aim to compare efficacy data from clinical trials to effectiveness data of real-world observational studies that evaluate oral interferon-free HCV treatment regimens in patients infected with HIV and HCV.

Methods

We included English-language studies on PubMed and MEDLINE databases from inception until October 2017. Eight clinical trials and 11 observational studies reporting on efficacy data and effectiveness data, respectively, of interferon-free oral DAA regimens in HCV/HIV coinfected patients, were included.

Results

Of patients in the eight clinical trials evaluated, 93.1% (1218/1308) achieved SVR12; of the 11 real-world observational studies, 90.8% (2269/2499) achieved SVR12. Relative risk between those treated in clinical trials versus observational studies was 0.98. Patients with genotype 1 infection, African-American patients, cirrhotic patients, and patients with prior HCV treatment experience had similar rates of SVR in real-world and clinical trial cohorts.

Conclusion

SVR among real-world HCV/HIV coinfected populations treated with DAA regimens is similar to SVR of patients studied in clinical trials. Historically negative predictors of achieving SVR during the era of interferon-based treatments, such as those with cirrhosis, prior HCV treatment failure, GT1 infection, and African-American race, are not associated with a significantly lower SVR in real-world populations treated with various DAA regimens.

     

High sustained virological response to pegylated interferon and ribavirin for recurrent genotype 3 hepatitis C infection post-liver transplantation

Introduction

Treatment outcomes of recurrent HCV genotype 3 (GT-3) after liver transplantation (LT) are ill-defined.

Aims

To determine efficacy, predictors, and long-term survival after treatment of recurrent HCV GT-3 infection, post-LT, with a combination of pegylated interferon (PEG) and ribavirin (RBV).

Methods

We studied all LT recipients (LTR) in our program treated with PEG and RBV for recurrent HCV GT-3 between Jan 1st 2002 and Dec 31st 2013. Antiviral therapy (AVT) was started if histology showed recurrent HCV with ≥stage2 fibrosis. Treatment was intended for 24 or 36 weeks, depending on early virologic response, and/or 24 weeks consolidation. Primary endpoint was sustained virological response (SVR). We also studied predictors of SVR and long-term patient survival.

Results

Among 492 LT for HCV-related cirrhosis and/or hepatocellular carcinoma performed during the study period, 110 (22 %) had HCV GT-3 infection. Fifty-two (10.5 %) HCV GT-3 patients had indications for AVT. Six were unable to complete the AVT, three because of clinical decompensation and one each because of metastatic disease involving the brain, lung cancer, and ductopenic rejection. Forty-seven (90 %) patients achieved early virological response (EVR) and 37 (71 %) achieved SVR. Predictors of SVR were EVR (p < 0.001), stage ≤3 fibrosis (p = 0.008), and 36 weeks treatment duration (p < 0.001). Less advanced fibrosis ≤3 was independent predictor of SVR (OR 0.18, 95 % CI 0.05–0.67). SVR patients had actuarial (Kaplan–Meier) 1, 3, and 10 year post-treatment survival of 100, 100, and 95 %, compared with 87, 78, and 20 % for non-SVR patients (p < 0.001, log rank test).

Conclusion

Efficacy of AVT for recurrent HCV GT-3 post-LT is high, and comparable with that for non-transplant patients. Less advanced fibrosis is an independent predictor of SVR. SVR improves long-term survival.

     

Ledipasvir/Sofosbuvir Effectively Treats Hepatitis C Virus Infections in an Underserved Population

Background

Underserved populations have an unequal burden of HCV infections and poor outcomes with interferon-based treatments. Direct-acting antivirals have the potential to reduce these inequalities.

Aims

We aimed to estimate sustained virologic response (SVR) following treatment with sofosbuvir-based regimens for HCV infections among underserved individuals and summarize the frequency of SVR across published studies of underserved populations.

Methods

We used data from a clinical cohort of patients aged ≥?18 years who initiated sofosbuvir-based regimens for HCV infection between February 2014 and June 2016 at an urban public hospital network that serves as the healthcare safety-net for Tarrant County, Texas. We estimated SVR with corresponding 95% confidence limits (CL). In addition, we systematically reviewed the evidence to identify other studies of direct-acting antivirals among underserved populations.

Results

Our study population comprised 435 patients. The majority of patients were aged ≥?50 years (76%), male (52%), non-Hispanic White (54%), HCV genotype 1 (79%) and treated with ledipasvir/sofosbuvir (69%). Overall SVR was 89% (95% CL 86, 92%) and highest for ledipasvir/sofosbuvir (SVR?=?95%, 95% CL 92, 97%). The reported SVR following direct-acting antivirals among 837 underserved patients from three other studies ranged between 90 and 99%.

Conclusions

Our results suggest that direct-acting antivirals, particularly ledipasvir/sofosbuvir, are generally effective for achieving SVR among underserved patients with HCV infections and may help reduce inequalities in HCV prevalence and outcomes for this vulnerable population.

     

Beware of HCV and HEV in Patients with Suspected Drug-Induced Liver Injury

Purpose of Review

Without a specific biomarker, the diagnosis of drug-induced liver injury (DILI) relies on exclusion of other causes of liver injury. This review examines the importance of testing for hepatitis C (HCV) and hepatitis E (HEV) in patients with suspected DILI.

Recent Findings

Several national DILI registries have reported HCV and HEV infection in patients initially diagnosed with DILI. Particularly in patients with suspected DILI who have acute hepatocellular liver injury, acute HCV and acute HEV infection should be considered even in the absence of traditional risk factors. For HCV infection, testing for HCV RNA and HCV antibody are recommended. For HEV, the high prevalence of HEV IgG antibody means that HEV IgM antibody testing is suggested to exclude this infection.

Summary

There should be a high clinical suspicion for acute HCV and HEV infection in patients with acute hepatocellular liver injury suspected of being due to DILI.