Treatment Of Acute Hepatitis C Virus Research Articles

2395 Treating Acute Hepatitis C Virus Infections: Is It Cost Effective?

INTRODUCTION: One- fourth of acute HCV patients spontaneously clear the virus. Direct antiviral agents(DAA) decreased the duration of treatment, cost-effective, and reduce the transmission risk. Of 2 cases we present here, one achieved SVR with DAA and another cleared the virus spontaneously. CASE DESCRIPTION/METHODS: 1) 51 y/o F presented with RUQ pain & jaundice. Labs: AST 1633, ALT 2214, ALP 345, T.bili 6.4. Imaging: no biliary obstruction. Acute hepatitis panel was positive for HCV antibodies. These were negative 3 months ago. Genotype was 1a and viral load was 1,000,000. Biopsy showed acute hepatitis with lobular and portal inflammation. She was treated with ledipasvir 90 mg/sofosbuvir 400 mg daily for 12 weeks and SVR was achieved. 2) 29 y/o M presented with RUQ and jaundice. He is an IVDU. Labs: AST 1338, ALT 2921 T bili at 14.8 and ALP 244. Imaging: negative for biliary obstruction. He was tested positive for HCV RNA titers . His prior HCV Ab was negative 2 weeks ago.Genotype was 1a and viral titers were1,894,692. He was given Oxcarbazapine recently. Biopsy showed lobular inflammation with hepatocyte necrosis, eosinophils, granulomas and portal inflammation consistent with acute hepatitis. Though the presence of the eosinophils and granulomas suggest Oxcarbazepine induced liver injury, the marked hepatocyte injury coincides with acute HCV. He cleared the HCV spontaneously after 4 months. DISCUSSION: Liver tests and HCV RNA monitoring for 6 months is recommended for acute HCV treatment. when the quality adjusted life years (QALY) and costs were measured in a microsimulation model, treatment of acute HCV,when compared to chronic HCV in non- high-risk behaviors, QALY increased by 0.02. The increased cost was 483 dollars with a resulted incremental cost effectiveness ratio (ICER) of $19,9991 per QALY, demonstrating that this treatment is cost effective. In high risk patients the QALY increased by 0.03 and decreased costs up to $3,655, substantiating this as a cost saving outcome. Although more studies are needed to demonstrate the effectiveness of DAAS,this particular study seemed to be promising.

Acute HCV Treatment: What Should We Do in the DAA Era?

Acute hepatitis C infection is a growing concern in the USA, especially in light of the opioid epidemic. Prior treatment data consisted of trials in patients receiving interferon-based regimens. There is now emerging evidence regarding the safety and efficacy of direct-acting antivirals for the treatment of acute hepatitis C. This review summarizes the current evidence on the treatment of acute HCV in the DAA era. Certain populations, such as people who inject drugs, or HIV-positive men who have sex with men, may benefit from early treatment of acute HCV. As compared with chronic hepatitis C, shorter durations of treatment appear highly effective in acute infection, resulting in reduced viral transmission, as well as potentially reduced overall costs of care related to this disease. Further studies are needed to clarify the optimal drug combinations and treatment durations to achieve sustained virologic response in these patients.

Should we treat acute hepatitis C? A decision and cost-effectiveness analysis.

Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost-effective or cost-saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6-week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. (Hepatology 2018;67:837-846).

Direct-acting antiviral-based therapy for acute hepatitis C coinfection.

Modern interferon (IFN)-free, and potentially also ribavirin-free, combinations consisting of two or three direct-acting antivirals (DAAs) are highly efficacious in treating chronic hepatitis C virus (HCV) infection with treatment durations being much shorter and with much more favorable toxicity profiles. With the acute HCV (AHC) epidemic among men who have sex with men (MSM) still ongoing, the question remains should we be using DAAs in the acute phase of the infection? To date, none of the currently available DAAs has been licensed for use in the setting of AHC infection. Thus, the current gold standard of treatment still is a combination of pegylated interferon (pegIFN) and weight-adapted ribavirin (RBV). However, with less patients being treated in the acute phase, the current epidemic of AHC in HIV-positive MSM will continue. A decision to treat AHC with pegIFN and RBV can currently only be made on an individual basis in an open discussion between patient and physician which will need to weigh up the risk and benefits of a rather toxic and lengthy treatment now versus the likely available options in the chronic phase. Therefore, studies with IFN-free DAA combinations remain of great urgency to further evaluate the role of DAAs in the treatment of AHC.

A Randomized Clinical Trial of Pegylated Interferon for Acute Hepatitis C Virus Infection in Active Injection Drug Users

Background: Treatment of acute HCV is more effective than treatment of chronic HCV, but physicians are often reluctant to treat people who inject drugs (PWID). Methods: HIV seronegative PWID with acute hepatitis C infection were randomized to receive 24 weeks of pegylated interferon (Peg-IFN) or to observation. Serum HCV RNA was measured every 4 weeks. After 24 weeks, control subjects with persistent viremia were offered treatment with Peg-IFN and ribavirin. The primary endpoint of the trial was likelihood of achieving a sustained virologic response (SVR).Secondary endpoints included time to viral clearance, treatment adherence and incidence of depression. Results: 24 patients were randomized to treatment vs. control; 1 was lost to follow-up before the baseline visit. Of the 9 patients who received >1 injection of Peg-IFN, 55% had an SVR; three became re-infected. Among controls, 14% cleared virus, 79% became chronically infected. Treated participants were more likely to clear HCV than controls (HR (95% CI) =15.34 (3.08-76.40), p=0.001).Additionally, for the univariate analysis, participants with more recent PWID (5.00 (1.23 – 20.00)), a baseline viremia< 5 log IU/mL (3.57 (0.94 – 14.28)), and an ALT level ≤ to 450 IU/mL (6.67 (0.83 – 50.00)) were more likely to clear virus. Sixty-seven percent of participants received at least 80% of scheduled injections and the incidence of severe depression was low. Conclusions: We found that treatment of HCV in active PWID was effective and safe, though re-infections occurred. Adherence rates in this cohort were excellent, supporting the idea that this difficult-to-treat population benefits from medically supervised injections.

The Spectrum of Undiagnosed Hepatitis C Virus Infection in a US HIV Clinic

United States guidelines endorse one-time HCV antibody screening at HIV diagnosis. Rescreening HCV-seronegative patients on a regular basis is still not policy, although HIV-infected persons have reasonably substantial HCV incidence. We evaluated routine risk factor-independent HCV antibody re-testing in a Rhode Island HIV clinic. We instituted annual HCV antibody testing for HCV-seronegative patients who had not been rescreened in a year or more. Testing based on clinical suspicion continued. We conducted a chart review of new antibody-positive cases in the first year of rescreening, July 2006 to June 2007. Of 245 rescreened patients, 11 (4.5%) seroconverted. Five (45%) were female. Median time between last negative and first positive result was 32 months (range 8-98 months). Six (55%) had documented risk factors and 6 (55%) elevated ALT (> 45 IU/L) between antibody tests; none prompted re-testing. One seroconverter died of hepatocellular carcinoma 3.7 years after HCV diagnosis. A twelfth was rescreened for suspected acute HCV based on ALT of 515 IU/L. He had newly detectable HCV RNA then seroconversion, and achieved SVR following 6 months of treatment in the acute phase for genotype 1 infection. Incident HCV is not uncommon among HIV-infected patients in care. Rescreening identified undiagnosed HCV in this population. HCV RNA should be checked promptly in HCV-seronegative persons with ALT elevation. We observed consequences of late diagnosis (hepatocellular carcinoma) and benefits of early diagnosis (cure with treatment of acute HCV). Adding annual rescreening to the Ryan White Program would facilitate earlier identification of undiagnosed HCV and create an instant widespread surveillance system, providing HCV incidence data.

Reply:

We acknowledge the letter of Dr. Wedemeyer and colleagues and will happily respond to both their questions and also their not so subtle insinuations. It is well known that Egypt has the highest prevalence (15%) and incidence of HCV in the world. The Egyptian program for the screening, identification and treatment of acute HCV has enabled large scale studies of acute HCV with documented seroconversion in predominantly healthcare workers. Directly observed therapy and the almost universal inclusion of healthcare workers and their families has led to clinical trials with large numbers of highly motivated patients. These studies have in fact enrolled approximately 250 patients over a period of 3 years. Additional patients were screened or followed, but these patients were not treated because they either refused therapy or did not meet inclusion criteria. There were 3 clinical trials undertaken between 2002 and 2005, of which two have been published in addition to a 3rd small trial comparing Interferon and ribavirin to PEG-Interferon monotherapy. Interim analysis and some data from the above mentioned articles, as well as a study comparing PEG-IFN and conventional IFN in a small cohort, were presented in part during AASLD, EASL and DDW meetings in 2004 and 2005. Randomization was centralized for these trials and all trials ran in tandem with patients randomly being offered entry into a trial — a common practice at many large academic centers, where at any one time 10 to 15 therapeutic HCV trials may be ongoing. The comment that the control groups in the HEPATOLOGY1 and Gastroenterology papers2 are the same is incorrect as they differ with respect to nearly all demographic criteria and are different patients. However, the most disturbing aspect of this letter and the prior letter from the same group to Gastroenterology,3 is the insinuation that this research could not be done as described in Egypt. We have voluntarily provided the independent DSMB reports for this trial to the Editorial Board at Gastroenterology outlining the recruitment strategies, patient enrollment and validating the data and study design and we have offered to provide the independent DSMB report to the Editors of HEPATOLOGY. Competition between groups is healthy but we consider this a series of unprecedented attacks by an established leading European Investigator on an Egyptian/US consortium doing very important, validated and meaningful studies. We congratulate the HepNet group on doing acute HCV studies in a country with a prevalence of HCV of 0.5%, needle free hospitals, needle exchange programs and with the lowest incidence of acute HCV worldwide.4 In spite of several inconsistencies in the HepNet study, we rely on the principle of truth in scientific communication. Acute HCV research is moving east where there is a real clinical problem with the disease and the ability to perform larger, equally well-run clinical trials with all HCV genotypes included. Finally, an erratum with correction missed in the proofs had already been submitted to HEPATOLOGY prior to receipt of the letter from Wedemeyer and we are sorry for the confusion on the part of the readers. Sanaa Kamal*, Khalifa Khalifa , Khairy Moustafa , Margaret Koziel , Leila El Gohary , Amr Ramy , Nezan Afdhal§, * Harvard Institutes of Medicine, Department of Infectious Diseases, Boston, MA, Ain Shams University, Liver Disease Center, Cairo, Egypt, Beth Israel Deaconess Medical Center, Boston, MA, § Director, Liver Center Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA

Chronic Hepatitis C: Updated Swedish Consensus

In 1999 a Swedish national expert panel published recommendations for the treatment of chronic hepatitis C (HCV) infection. Recently, pegylated interferon (peg-IFN) products have been introduced, and an increased knowledge concerning treatment of acute HCV and HCV-human immunodeficiency virus (HIV) coinfection has been gained. As a result of this, an update of the Swedish recommendations was developed following an expert meeting in October 2002. The panel now recommends the use of peg-IFN together with ribavirin as the standard treatment. Owing to the excellent response rates in HCV genotype 2 and 3 infections, these patients can be treated for 24 weeks without preceding liver biopsy. For patients with genotype 1 infection (with a slightly below 50% sustained response rate after 48 weeks treatment) and only mild histological disease, treatment can be postponed until future better treatment options become available. In patients who fail to achieve a 99% reduction (2 log drop) in viral titre after 12 weeks of treatment, discontinuation of therapy is recommended. Patients previously treated with IFN monotherapy and not having achieved a sustained virological response are recommended the same combination treatment as treatment-naive patients. IFN monotherapy is recommended in patients with acute hepatitis C. For children with chronic HCV infection, combination treatment is mainly recommended in clinical trials. For HCV-HIV coinfected patients, combination treatment is recommended and preferably given when blood CD4 counts are above 350/ml and before antiretroviral treatment (ART) is needed. Concurrent ART or prominent liver fibrosis requires frequent monitoring because of the increased risk for mitochondrial toxicity and liver failure.