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Phillip J Buckhurst,1 George Lau,2 Jon I Williams,2 Mark Packer3 1School of Health Professions, University of Plymouth, Plymouth, UK; 2Bausch and Lomb Surgical, Bausch and Lomb Bridgewater, New Jersey, NJ, USA; 3Mark Packer Consulting, Boulder, CO, USACorrespondence: Phillip J Buckhurst, School of Health Professions, University of Plymouth, Plymouth, UK, Tel +44 1752 588884, Email Phillip.buckhurst@plymouth.ac.ukPurpose: To assess the refractive outcomes, intraocular centration and rotational stability of the enVista toric intraocular lens (IOL).Patients and Methods: This study was a prospective, multi-centre, double-masked, partially randomized and partially controlled clinical trial. A total of 191 participants were implanted with toric IOL (1.25, 2.00, or 2.75D) or non-toric IOL (control). The lowest range of corneal astigmatic eyes were randomized to 1.25D toric or control. Higher astigmatic powers were allocated to the treatment arm. Subjects were assessed immediately postoperatively, 1– 2 (V1), 7– 14 (V2), 30– 60 (V3) and 120– 180 (V4) days postoperatively. Unaided (UDVA) and distance corrected visual acuity (CDVA), manifest refraction and corneal curvature were assessed. Vector analysis was used to calculate surgically induced refractive correction (SIRC), correction ratio (CR), error magnitude (EM) and error vector (EV). Slit-lamp photography was used to measure centration and rotational stability.Results: UDVA was better in the low toric IOL group in comparison with the control group at V4 (p< 0.001). There was an undercorrection in the control group, whereas the average CR for all toric subjects was 1.00 ± 0.32: V2, 0.98 ± 0.34: V3 and 0.98 ± 0.35: V4. The absolute IOL rotational stability in comparison to the position of the IOL at V1 was 1.35° ± 0.97°: V2, 1.35° ± 1.07°: V3 and 1.38° ± 1.25°: V4. Decentration was generally inferior (V1: 0.04 ± 0.22mm, V2: 0.05± 0.20mm, V3: 0.08 ± 0.22mm, V4: 0.04 ± 0.21mm) and nasal (V1: 0.19 ± 0.23mm, V2: 0.20 ± 0.20mm, V3: 0.20 ± 0.21mm, V4: 0.17 ± 0.22mm).Conclusion: Participants with low levels of corneal astigmatism achieved superior vision and refractive outcomes in the low toric group over the control. Moderate and high levels of astigmatism achieved excellent refractive outcomes. The toric IOL demonstrated high levels of both rotational and centrational stability.Keywords: IOL, astigmatism, cataract, enVista, toric

Post the coronavirus disease 2019 (COVID-19) pandemic, there arises the concern of a new epidemic as cases of monkeypox are being confirmed, globally. With the initial clinical manifestation of monkeypox resembling that of the common cold or seasonal flu, recognizing alternative differential diagnoses is imperative as a medical health practitioner. The characteristic monkeypox maculopapular rash with the progression to vesicles and pustules before scabbing can be described in several other infections. Understanding the disease progression and distinct clinical presentation of monkeypox in its various stages may allow for a more expedient diagnosis among healthcare providers. Though eradicated, the clinical presentation of smallpox is the most similar to that of monkeypox; however, smallpox is no longer a concern for the general population. Other conditions such as molluscum contagiosum, syphilis, varicella zoster, measles, rickettsialpox, and scabies can present with rashes that may resemble singular or multiple states of the monkeypox rash progression. The ability to correctly diagnose an individual's condition promptly may allow healthcare providers to provide correct supportive therapies or treatments.

Background & Aim Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. Methods All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. Recommendations We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

BackgroundCOVID-19 has been giving the devastating impact on the current medical care system. There are quite many guidelines on COVID-19, but only a few on the management of hepatocellular carcinoma (HCC) during COVID-19 pandemic.AimsWe develop these recommendations to preserve adequate clinical practice for the management of HCC.MethodsExperts of HCC in the Asia–Pacific region exchanged opinions via webinar, and these recommendations were formed.ResultsClose contact should be minimized to reduce possible exposure of both medical staff and patients to the novel coronavirus. To prevent transmission of the virus, meticulous hygiene measures are important. With the decrease in regular medical service, the medical staff may be mobilized to provide COVID-19-related patient care. However, diagnosis and treatment of HCC should not be delayed because of COVID-19 pandemic. The management of HCC should be the same as in non-pandemic circumstances. HCC is highly malignant, thus it is recommended not to delay curative treatment such as surgery and ablation. However, a kind of triage is necessary even among patients with HCC when resources are insufficient for all to be treated. Curative treatments should be periodized and cytoreductive or non-curative treatment such as vascular interventions and systemic therapy may be postponed until it can be performed safely with sufficient resources. For patients with confirmed or suspected to be infected with the novel coronavirus, diagnosis and treatment should be postponed until the virus is eliminated or they are confirmed as not being infected with it.ConclusionsThese are collection of measures implemented by front-line medical professionals. We would evolve these recommendations over time as more real-world data becomes available.

Background Confronting a once-in-a-century pandemic with COVID-19, tremendous stress has been placed in all walks of life worldwide. Aims In order to enhance scientific information interflow in the arena of liver diseases in Asia–Pacific region during this difficult time, Asian-Pacific Association for the Study of the Liver (APASL) has taken the initiative to form the APASL COVID-19 Taskforce to formulate a clinical practice guidance in Hepatology, liver-related oncology, transplantation and conduct of clinical trials. Methods A taskforce with 22 key opinion leaders in Hepatology from 16 countries or administration regions in Asia–Pacific regions was formed and through intense interaction via webinar, this guidance was formulated. Based on scientific data and experiences, recommendations were made in the management of liver injury, liver transplantation, autoimmune diseases, chronic liver diseases, delivery of elective and emergency services and conduct of clinical trials. Conclusions This is the first consensus clinical guidance synthesized by APASL for our hepatologist and their allied medical personal.

To evaluate the safety and effectiveness of a new dispersive ophthalmic viscosurgical device (OVD) (ClearVisc) compared with an approved dispersive OVD (Viscoat) when used in cataract surgery.16 clinics in the United States.Prospective multicenter controlled randomized 1:1 (ClearVisc:Viscoat; stratified by site, age group, and cataract severity). Patients and examiners masked.Patients aged 45 years or older with age-related noncomplicated cataract considered amenable to treatment with standard phacoemulsification cataract extraction and intraocular lens (IOL) implantation were included. Patients were randomized to receive either ClearVisc or Viscoat using standard techniques. 5 postoperative visits occurred at 6 hours, 24 hours, 7 days, 1 month, and 3 months. The primary effectiveness outcome was the change in endothelial cell density (ECD) from baseline to 3 months. The primary safety end point was the proportion of patients who experienced at least 1 intraocular pressure (IOP) measurement ≥30 mm Hg at any follow-up visit. Noninferiority was tested. Inflammation and adverse events were evaluated.372 patients were randomized: 184 patients in the ClearVisc group and 188 patients in the Viscoat group. ClearVisc was noninferior to Viscoat in mean percentage of ECD loss from baseline to 3 months (8.4% and 6.8%, respectively). ClearVisc was significantly noninferior to Viscoat in the proportion of patients with postoperative IOP ≥30 mm Hg at any follow-up visit (17.4% and 20.3%, respectively, P = .0002).ClearVisc dispersive OVD provides surgeons with a new option in the continuum of approved dispersive OVDs with beneficial properties as a surgical aid in cataract extraction and IOL implantation.

Background Drug-induced liver injury (DILI) is one of the most serious adverse drug reactions and the incidence has been increasing rapidly. Accumulating evidence suggested that the immune activation and systemic inflammatory responses play a significant role in the progression of DILI. Corticosteroids are often used in DILI, but clinical usefulness remain controversial. We therefore conducted a prospective randomized controlled study to investigate whether corticosteroid therapy can accelerate recovery and reduce mortality in severe DILI (SDILI).Methods SDILI patients with total bilirubin (TBIL) ≥171 μmol/L presented to Fifth Medical Center of PLA General Hospital, Beijing from 1/1/2015 to 31/12/2019 were randomized into prednisolone group and control group. The primary endpoints were proportion of subjects with resolution of SDILI defined as decrease in TBIL by at least 35 μmol/L to below 171 μmol/L and overall survival at 6 months. Patients in prednisolone group received prednisolone 60 mg/day therapy for the first 7 days. Patients reaching the primary endpoint or achieved decrease in TBIL by more than 35 umol/L on day 8 would continue on tapering doses of prednisolone, otherwise prednisolone would be discontinued.Results On day 8, 50.7% (34/67) and 26.5% (18/68) of the subjects in the prednisolone group and control group achieved the primary endpoint respectively, p=0.002. However, there was no significant difference in overall survival at 6 months, 95.52% (64/67) vs 91.2% (62/68), p= 0.2. All deaths in both groups occurred in patients who failed to achieve SDILI resolution on day 8.Conclusions Prednisolone therapy may accelerate recovery of SDILI and shorten hospitalization.

With the introduction of effective directly acting antiviral agents (DAAs) therapy, control and elimination of hepatitis C virus (HCV) infection is becoming a feasible goal. In Hong Kong, HCV prevalence in general population is 0.3%-0.5% over the past decades. However, like other high-income areas/countries, high prevalence of HCV infection has been found in several population groups, such as people who inject drugs (PWID), patients undergoing dialysis, and human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/ AIDS) patients. Based on the epidemiological study using data retrieved from the Hong Kong HCV Registry from January 2005 to March 2017, the estimated territory-wide diagnosis rate and treatment rate of HCV infection were only 50.9% and 12.4%, respectively. Although these rates was comparable to many developed countries/areas, the performances remained substantially below 90% and 80%, the 2030 targets proposed by World Health Organization (WHO). In recognition of the challenges, the Hong Kong Government set up the Steering Committee on Prevention and Control of Viral Hepatitis (SCVH) which formulated the Hong Kong Viral Hepatitis Action Plan 2020-2024. The Action Plan adopts four key strategies, as described in the WHO framework for global action, namely, awareness, surveillance, prevention and treatment. With the effective implementation of the Action Plan, especially in targeted screening of high-risk populations and more generalized use of the highly efficacious DAAs for all diagnosed HCV subjects, the goals of reducing HCV transmission and HCV-related morbidity and mortality can be achieved in Hong Kong by 2030.

Copyright © 2019 John Wiley & Sons Ltd., © 2019 John Wiley & Sons Ltd, The decay rate of hepatitis C virus (HCV)-infected cells during therapy has been used to determine the duration of treatment needed to attain a sustained virologic response, but with direct-acting anti-virals (DAA), this rate has been difficult to estimate. Here, we show that it is possible to estimate it, by simultaneously analysing the viral load and alanine aminotransferase (ALT) kinetics during combination DAA therapy. We modelled the HCV RNA and ALT serum kinetics in 26 patients with chronic HCV genotype 1b infection, under four different sofosbuvir-based combination treatments. In all patients, ALT decayed exponentially to a set point in the normal range by 1-3 weeks after initiation of therapy. The model indicates that the ALT decay rate during the first few weeks after initiation of therapy reflects the death rate of infected cells, with an estimated median half-life of 2.5 days in this patient population. This information allows independent estimation of the rate of loss of intracellular replication complexes during therapy. Our model also predicts that the final ALT set point is not related to the release of ALT by dying HCV-infected cells. Using ALT data, one can separately obtain information about the rate of 'cure' of HCV-infected cells versus their rate of death, something not possible when analysing only HCV RNA data. This information can be used to compare the effects of different DAA combinations and to rationally evaluate their anti-viral effects., Portions of this work were done under the auspices of the US Department of Energy under contract 89233218CNA000001. This research was supported by the National Science Foundation under grant no. NSF PHY11-25915; by NIH grants R25GM067110, R01AI028433, R01OD011095, R01AI078881, R01AI116868, and P30AI050409; Gordon and Betty Moore Foundation Grant no. 2919.01; Cheng Si-yuan (China-international) Hepatitis Research Foundation and Humanity & Health Medical group.

Historical and archaeological records help shed light on the production, ritual practices, and personhood of cult objects characterizing the central Peruvian highlands after ca. AD 200. Colonial accounts indicate that descendant groups made and venerated stone images of esteemed forebears as part of small-scale local funerary cults. Prayers and supplications help illuminate how different artifact forms were seen as honored family members (forebears, elders, parents, siblings). Archaeology, meanwhile, shows the close associations between carved monoliths, tomb repositories, and restricted cult spaces. The converging lines of evidence are consistent with the hypothesis that production of stone images was the purview of family/lineage groups. As the cynosures of cult activity and devotion, the physical forms of ancestor effigies enabled continued physical engagements, which vitalized both the idol and descendant group.

An epidemic of acute respiratory syndrome (Covid-19) started in humans in Wuhan in 2019, and became a pandemic. Groups from China Identified and sequenced the virus responsible for COVID-19, named SARS-CoV-2, and determined that it was a novel coronavirus (CoV) that shared high sequence identity with bat- and pangolin-derived SARS-like CoVs, suggesting a zoonotic origin. SARS-CoV-2 is a member of Coronaviridae, a family of enveloped, positive-sense, single-stranded RNA viruses that infect a broad range of vertebrates. The rapid release of the sequence of the virus has allowed the development of diagnostic tools (e.g., RT-PCR). Additionally, serological tests can allow identification of persons who have been infected. In humans, CoVs tend to cause mild to moderate upper respiratory tract infections. The fatality rate is around 1-3% for infected persons. An acute respiratory distress syndrome (ARDS) likely due to an uncontrolled immune activation (“cytokine storm”) occurs in patients with severe disease and poor prognosis. Risk factors for mortality include: advanced age, obesity, diabetes, hypertension and other comorbidities. Drug repurposing has been used to rapidly identify potential treatment for COVID-19, which could move quickly to phase-3. Better knowledge of the virus, its enzymes, will be mandatory to develop more potent and specific direct-acting antiviral agents (DAA). In the long term, a vaccine to prevent infection would be crucial; however even if successful it might not be available before 2021-22. To date, with the exception of intravenous Remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy and safety of any other drugs against SARS-CoV-2. The aim of this review is to provide insights on the discovery of SARS-CoV-2, its virology, the diagnostic tools, and the ongoing drug discovery effort.

Camelids have long played a key role in assessing the economies of Andean groups, not least in discussions of key anthropological themes such as domestication, diet, exchange, and verticality. Most discussions have focused on human intervention in animal use—most commonly how animals are incorporated and used by humans in their economic worlds. In this paper, I want to shift emphasis and examine how camelids came to be part of a mutually constitutive socio-cultural system. Two faunal assemblages (one from a small village and the other a major fortified center) and art imagery are assessed to describe the uptake of intensive camelid herding/consumption practices in the Recuay culture (c. AD 1-700) and the dramatic cultural transformations that ensued. At the same time that hunting diminished greatly, the faunal materials indicate increasing reliance on camelids in diverse residential food practices, corporate feasts, and fiber production. Just as important, camelids become the signal expression of the emerging wealth and status of nobles, which drive the production of effigy ceramics, figurines, and camelid fiber garments. Rather than being epiphenomenal to social change, camelids were therefore active elements, indeed co-participants, which shaped the look and reproduction of an ancient Andean society.

Background and Aim Cytokine storm has been reported in patients with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We examine the incidence of acute on chronic liver failure (ACLF) in COVID-19 patients with pre-existing compensated chronic liver disease (CLD). Methods From 20 Jan 2020 to 7 Feb 2020, we studied 140 consecutive COVID-19 patients admitted to either Fuyang Second People’s Hospital (FYSPH), Anhui or the Fifth Medical Center of Chinese PLA General Hospital (PLAGH) in Beijing, China. Pre-existing CLD includes those with liver cirrhosis assessed by APRI/FIB-4 score and /or ultrasound; NAFLD as identified by either ultrasound or hepatic steatosis index with significant liver fibrosis and chronic hepatitis B (CHB) or hepatitis C (CHC) infection. The diagnosis, grading of severity and clinical management of COVID-19 patients complied to the guideline and clinical protocol issued by the China National Health Commission. All patients had liver function test at least twice weekly till discharge with full recovery or death. Results In total, 3 had liver cirrhosis, 6 patients had CHB, 13 had NAFLD with significant liver fibrosis (one also had CHB). On admission, none had liver decompensation. COVID-19 disease progression was significantly less frequent in non-CLD patients (10/118 8.5%) than CLD patients (13/22 59.1%, p

Background We aimed to clarify high-risk factors for coronavirus disease 2019 (COVID-19) with multivariate analysis and establish a predictive model of disease progression to help clinicians better choose a therapeutic strategy. Methods All consecutive patients with COVID-19 admitted to Fuyang Second People’s Hospital or the Fifth Medical Center of Chinese PLA General Hospital between 20 January and 22 February 2020 were enrolled and their clinical data were retrospectively collected. Multivariate Cox regression was used to identify risk factors associated with progression, which were then were incorporated into a nomogram to establish a novel prediction scoring model. ROC was used to assess the performance of the model. Results Overall, 208 patients were divided into a stable group (n = 168, 80.8%) and a progressive group (n = 40,19.2%) based on whether their conditions worsened during hospitalization. Univariate and multivariate analyses showed that comorbidity, older age, lower lymphocyte count, and higher lactate dehydrogenase at presentation were independent high-risk factors for COVID-19 progression. Incorporating these 4 factors, the nomogram achieved good concordance indexes of .86 (95% confidence interval [CI], .81–.91) and well-fitted calibration curves. A novel scoring model, named as CALL, was established; its area under the ROC was .91 (95% CI, .86–.94). Using a cutoff of 6 points, the positive and negative predictive values were 50.7% (38.9–62.4%) and 98.5% (94.7–99.8%), respectively. Conclusions Using the CALL score model, clinicians can improve the therapeutic effect and reduce the mortality of COVID-19 with more accurate and efficient use of medical resources.

Summary There are many unanswered questions about the population history of the Central and South Central Andes, particularly regarding the impact of large-scale societies, such as the Moche, Wari, Tiwanaku, and Inca. We assembled genome-wide data on 89 individuals dating from ∼9,000-500 years ago (BP), with a particular focus on the period of the rise and fall of state societies. Today’s genetic structure began to develop by 5,800 BP, followed by bi-directional gene flow between the North and South Highlands, and between the Highlands and Coast. We detect minimal admixture among neighboring groups between ∼2,000–500 BP, although we do detect cosmopolitanism (people of diverse ancestries living side-by-side) in the heartlands of the Tiwanaku and Inca polities. We also highlight cases of long-range mobility connecting the Andes to Argentina and the Northwest Andes to the Amazon Basin. Video Abstract, Graphical Abstract, Highlights • Ancient DNA transect reveals north-south substructure of Andean highlands by 5,800 BP • After 5,800 BP, gene flow mixed highland people with their neighbors • After 2,000 BP, striking genetic continuity through rise and fall of major cultures, Genome-wide data from 89 ancient humans illuminates the changes to the genetic landscape in the Central Andes over 9,000 years, revealing large-scale gene flow and cosmopolitan societies in the Tiwanaku and Inca polities.

379 Background: A single priming dose of T (anti-CTLA-4) added to D (anti-PD-L1) in the STRIDE (Single T Regular Interval D) regimen, formerly T300+D, showed encouraging clinical activity and limited toxicity in a phase 2 uHCC study (Study 22, NCT02519348), suggesting single exposure to T is sufficient to improve upon D activity. HIMALAYA (NCT03298451) evaluated the efficacy and safety of STRIDE or D vs sorafenib (S) in uHCC. Methods: HIMALAYA is an open-label, multicenter, phase 3 study, in which pts with uHCC and no prior systemic therapy were initially randomized to STRIDE (T 300 mg plus D 1500 mg [one dose] plus D 1500 mg every 4 weeks [Q4W]), D (1500 mg Q4W), S (400 mg twice daily), or T 75 mg Q4W (4 doses) plus D 1500 mg Q4W (T75+D). Recruitment to T75+D ceased after a planned analysis of Study 22 showed T75+D did not meaningfully differ from D. The primary objective was overall survival (OS) for STRIDE vs S. The secondary objective was OS noninferiority (NI) of D to S (NI margin: 1.08). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR; RECIST v.1.1), duration of response (DoR), and safety. Results: In total, 1171 pts were randomized to STRIDE (N=393), D (N=389), or S (N=389). At data cutoff (DCO), the primary objective was met: OS was significantly improved for STRIDE vs S (hazard ratio [HR], 0.78; 96% confidence interval [CI], 0.65–0.92; p=0.0035; Table). D met the objective of OS NI to S (HR, 0.86; 96% CI, 0.73–1.03). ORRs were higher for STRIDE (20.1%) and D (17.0%) than for S (5.1%). No new safety signals were identified. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 25.8% (STRIDE), 12.9% (D), and 36.9% (S) of pts. Grade 3/4 hepatic TRAEs occurred in 5.9% (STRIDE), 5.2% (D), and 4.5% (S) of pts. No TRAE of esophageal varices hemorrhage occurred. Rates of TRAEs leading to discontinuation were 8.2% (STRIDE), 4.1% (D), and 11.0% (S). Conclusions: HIMALAYA was the first large phase 3 trial with a diverse, representative uHCC population and extensive long-term follow-up to assess both mono- and combination immunotherapy. D was noninferior to S with favorable safety. The combination of a single priming dose of T plus D in STRIDE displayed superior efficacy and a favorable benefit-risk profile vs S. STRIDE is a proposed, novel, first-line standard of care systemic therapy for uHCC. Clinical trial information: NCT03298451. [Table: see text]

436 Background: The phase 2 Study 22 trial (NCT02519348) investigated durvalumab (anti-programmed cell death ligand-1 [PD-L1] antibody) and tremelimumab (anti-cytotoxic T-lymphocyte associated antigen 4 antibody) as monotherapy, or durvalumab in combination with tremelimumab or bevacizumab (anti-vascular endothelial growth factor [VEGF] antibody), for the treatment of patients with unresectable hepatocellular carcinoma (uHCC). Results of Study 22 that evaluated durvalumab and tremelimumab as monotherapy or in combination were reported previously. PD-L1 inhibition plus VEGF inhibition with bevacizumab may exhibit an additive effect to improve clinical activity. Herein, we report results from a single-arm cohort of Study 22, evaluating durvalumab plus bevacizumab as first-line treatment in patients with uHCC. Methods: Patients with uHCC who had not received any prior systemic therapy were administered durvalumab 1120 mg plus bevacizumab 15 mg/kg once every 3 weeks. Adequate endoscopic therapy according to institutional standards was required for patients with a history of gastrointestinal bleeding for >12 months or those at high risk for esophageal varices. The primary endpoint was safety. Secondary endpoints included confirmed objective response rate (ORR; assessed by blinded independent central review [BICR] according to RECIST v1.1), duration of response (DoR; RECIST v1.1 by BICR) and overall survival (OS). Results: At the data cut-off (November 6, 2020), 47 patients were allocated to receive treatment. Median total treatment duration was 6.2 months (durvalumab) and 4.1 months (bevacizumab). Thirty-three (70.2%) patients experienced an adverse event possibly related to treatment (TRAE). Grade 3 or 4 TRAEs occurred in 4 (8.5%) patients; serious TRAEs occurred in 5 (10.6%) patients, including gastric ulcer perforation, ascites, and liver tumor rupture, possibly related to bevacizumab, and raised creatinine and pneumonitis, possibly related to durvalumab. There were 3 (6.4%) discontinuations and no deaths associated with TRAEs. Objective responses (RECIST 1.1 by BICR) were confirmed in 10 patients (ORR, 21.3%; 95% CI, 10.7–35.7); median DoR (RECIST 1.1 by BICR) was not reached. Median OS was not reached (95% CI, 12.52 months–non-estimable). Conclusions: Durvalumab plus bevacizumab was well tolerated and showed promising clinical activity in patients with uHCC. Durvalumab with or without bevacizumab in combination with transarterial chemoembolization is being investigated as locoregional therapy in patients with HCC not amenable to curative treatment in the phase 3 EMERALD-1 study (NCT03778957), and durvalumab with or without bevacizumab is being investigated in patients with HCC at high risk of recurrence after curative treatment in the phase 3 EMERALD-2 study (NCT03847428). Clinical trial information: NCT02519348.

Background and aim The incidence of hepatocellular carcinoma (HCC) decreases significantly in chronic hepatitis C (CHC) patients with sustained virologic response (SVR) after pegylated-interferon plus ribavirin (PR) or direct-acting antiviral (DAAs) therapy. We follow-up a single cohort of CHC patients to identify risk factors associated with HCC development post-SVR. Method CHC patients with SVR in Beijing/Hong Kong were followed up at 12–24 weekly intervals with surveillance for HCC by ultrasonography and alpha-fetoprotein (AFP). Multivariate Cox proportional hazards regression analysis was used to explore factors associated with HCC occurrence. Results Between October 2015 and May 2017, SVR was observed in 519 and 817 CHC patients after DAAs and PR therapy respectively. After a median post -SVR follow-up of 48 months, HCC developed in 54 (4.4%) SVR subjects. By adjusted Cox analysis, older age (≥55 years) [HR 2.4, 95% CI (1.3–4.3)], non-alcoholic fatty liver diseases [HR 2.4, 95%CI (1.3–4.2), higher AFP level (≥20 ng/ml) [HR 3.4, 95%CI (2.0–5.8)], higher liver stiffness measurement (≥14.6 kPa) [HR 4.2, 95%CI (2.3–7.6)], diabetes mellitus [HR 4.2, 95%CI (2.4–7.4)] at pre-treatment were associated with HCC occurrence. HCC patients in the DAAs induced SVR group had a higher prevalence of NAFLD as compared with those in the PR induced SVR group, 62% (18/29) vs 28% (7/25), p = 0.026. A nomogram formulated with the above six independent variables had a Concordance-Index of 0.835 (95% CI 0.783–0.866). Conclusion Underlying NAFLD is associated with increased incidence of HCC in chronic HCV patients post-SVR, particularly in those treated with DAA., Highlights • Patients with chronic hepatitis C infection are still at risk of HCC after achieving sustained virus clearance (SVR). • Non-alcoholic liver disease (NAFLD) is emerging as an important risk factor for hepatocellular carcinoma. • Underlying NAFLD is associated with increased incidence of HCC in patients with chronic HCV infection after sustained virologic response SVR.

Review of Rosenfeld, Silvana and Bautista, Stefanie (eds.) (2017) Rituals of the Past: Prehispanic and Colonial Case Studies in Andean Archaeology, University Press of Colorado (Boulder, CO), xiii + 321 pp. $81.00 hbk.

While Marcel Mauss's landmark essay onThe Gifthas been vital in social anthropology, inspiring a vast and influential secondary literature, the gift has been much less prominent in archaeological interpretation. This study considers evidence for an ancient Andean gift economy, a system of reciprocal exchanges focused on making people and ensuring group social relations, rather than accumulating wealth/capital. Excavations at Yayno (north highlands, Ancash, Peru) revealed two features dating to the time of the Inkas: 1) a slab-lined cist burial; and 2) an offering deposit containing abundant long-distance trade and sumptuary items. Besides its mountaintop location, the burial's intrusive character and foreign items indicate that the offerings were made to propitiate the place, ruins and their divine aspect. This essay studies the reciprocal acts that led to the offerings, comparing them to gifting patterns in Inka human sacrifices known ascapac hucha.The key actors in the exchange were children, divinities, Inka bureaucrats, local leaders and state subjects.