Hepatitis C virus (HCV) causes chronic infection accompanied by a high risk of liver failure and hepatocellular carcinoma. CD8؉ T cell responses are important in the control of viremia. However, the T cell response in chronic infection is weak both in absolute numbers and in the range of epitopes targeted. In order to explore the biology of this response further, we analyzed expression of a panel of natural killer cell markers in HCV compared with other virus-specific T cell populations as defined by major histocompatibility complex class I tetramers. We found that CD161 was significantly expressed on HCV-specific cells (median 16.8%) but not on CD8؉ T cells specific for human immunodeficiency virus (3.3%), cytomegalovirus (3.4%), or influenza (3.4%). Expression was seen in acute, chronic, and resolved disease and was greatest on intrahepatic HCV-specific T cells (median 57.6%; P < 0.05). Expression of CD161 was also found on hepatitis B virus-specific CD8؉ T cells. In general, CD161؉CD8؉ T cells were found to be CCR7؊ "effector memory" T cells that could produce proinflammatory cytokines (interferon-␥ and tumor necrosis factor-␣) but contained scanty amounts of cytolytic molecules (granzyme B and perforin) and proliferated poorly in vitro. Expression of CD161 on CD8؉ T cells was tightly linked to that of CXCR6, a chemokine with a major role in liver homing. Conclusion: We propose that expression of CD161 indicates a unique pattern of T cell differentiation that might help elucidate the mechanisms of HCV immunity and pathogenesis. (HEPATOLOGY 2008;47:396-406.)

The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which 14 HCV-negative patients underwent successful liver transplantation from HCVpositive donors. Nine patients received viremic (nucleic acid testing [NAT]-positive) livers and started a 12-week course of oral glecaprevir-pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody-positive nonviremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.

Coronavirus disease 2019 (COVID‐19) is associated with adverse outcomes, including need for invasive mechanical ventilation and death in people with risk factors. Liver enzyme elevation is commonly seen in this group, but its clinical significance remains elusive. In this study, we calculated the Fibrosis‐4 (FIB‐4) score for a cohort of hospitalized patients with COVID‐19 and assessed its association with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA, inflammatory cytokine levels, and clinical outcome. A total of 202 hospitalized participants who tested positive for SARS‐CoV‐2 by nasopharyngeal sampling were included in this analysis. FIB‐4 was calculated for each participant using the alanine aminotransferase, aspartate aminotransferase, age, and platelet count. We evaluated the association between FIB‐4 and mortality using both multivariate logistic regression and Cox proportional hazards model. Correlations between FIB‐4 and SARS‐CoV‐2 RNA and cytokine levels were evaluated using the Spearman test. Among the 202 participants, 22 died. The median FIB‐4 in participants who survived and died were 1.91 and 3.98 ( P < 0.001 by Mann‐Whitney U test), respectively. Each one‐unit increment in FIB‐4 was associated with an increased odds of death (odds ratio, 1.79; 95% confidence interval, 1.36, 2.35; P < 0.001) after adjusting for baseline characteristics including sex, body mass index, hypertension, diabetes, and history of liver diseases. During hospitalization, FIB‐4 peaked and then normalized in the survival group but failed to normalize in the death group. FIB‐4 was positively correlated with the level of SARS‐CoV‐2 viral load and monocyte‐associated cytokines, especially interleukin‐6 and interferon gamma–induced protein 10. Conclusion: FIB‐4 is associated with mortality in COVID‐19, independent of underlying conditions including liver diseases. FIB‐4 may be a simple and inexpensive approach to risk‐stratify individuals with COVID‐19.