Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis.

Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5 g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.

Increased Mitochondrial Genetic Diversity in Persons Infected With Hepatitis C Virus.

BACKGROUND & AIMS: The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression. METHODS: We evaluated the genetic diversity of 2 mtDNA genomic regions (hypervariable segments 1 and 2) obtained from sera of 116 persons using next-generation sequencing. RESULTS: Results were as follows: (1) the average diversity among cases with seronegative acute HCV infection was 4.2 times higher than among uninfected controls; (2) the diversity level among cases with chronic HCV infection was 96.1 times higher than among uninfected controls; and (3) the diversity was 23.1 times higher among chronic than acute cases. In 2 patients who were followed up during combined interferon and ribavirin therapy, mtDNA nucleotide diversity decreased dramatically after the completion of therapy in both patients: by 100% in patient A after 54 days and by 70.51% in patient B after 76 days. CONCLUSIONS: HCV infection strongly affects mtDNA genetic diversity. A rapid decrease in mtDNA genetic diversity observed after therapy-induced HCV clearance suggests that the effect is reversible, emphasizing dynamic genetic relationships between HCV and mitochondria. The level of mtDNA nucleotide diversity can be used to discriminate recent from past infections, which should facilitate the detection of recent transmission events and thus help identify modes of transmission.

Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more.

Sustained virologic response (SVR) is defined as aviremia 24 weeks after completion of antiviral therapy for chronic hepatitis C virus (HCV) infection. In analyses of SVR durability, the incidence of late relapse is extremely low (<1%). Histologic regression of both necroinflammation and fibrosis has been demonstrated in paired liver biopsy samples in SVR-achieving patients. More noteworthy is the sustained responder's favorable prognosis even with baseline cirrhosis; despite mostly retrospective analyses, relative to nonresponders or to those untreated, patients with SVR have significantly fewer liver-related complications, less hepatocellular carcinoma, and fewer liver-related deaths. Although HCV is associated with insulin resistance, successful eradication of HCV appears to reduce the risk of impaired fasting glucose and diabetes development. In summary, chronic HCV infection is curable with SVR attainment, and with cure comes improved liver histology and more favorable clinical outcomes, in comparison with patients who do not achieve the same therapeutic milestone.

Hepatitis C virus infection in African Americans.

Hepatitis C is more prevalent among African Americans than among persons of any other racial group in the United States. However, comparatively little data are available on the natural history and treatment of hepatitis C in this population. Compared with white persons, African American persons have a lower rate of viral clearance and, consequently, a higher rate of chronic hepatitis C. Nonetheless, African American persons may have a lower rate of fibrosis progression than do white persons. African American persons with hepatitis C-related cirrhosis have higher rates of both hepatocellular carcinoma and liver cancer-related mortality than do white persons with hepatitis C-related cirrhosis. In nearly all treatment trials that enrolled a significant proportion of African American subjects, such patients had inferior treatment responses, compared with those of white subjects. The prevalence of infection with hepatitis C virus genotype 1 is higher among African American patients than white patients, although this difference does not account for a greatly dissimilar response to therapy. Some of the postulated mechanisms for these disparate treatment responses and natural histories of infection are also reviewed.