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Hepatocellular carcinoma is a rising indication for liver transplantation in the United States. Downstaging, defined as the reduction of tumor burden using local-regional therapy into Milan criteria, opens an avenue to access cure through transplant for patients who traditionally would not qualify. Approaching the selection of downstaging candidates through an assessment of hepatic function, staying within a modest expansion of tumor burden, and incorporation of serologic/imaging markers for tumor biology provide the best chance for successful downstaging. Following well-defined downstaging protocols with built-in failure criteria ensures excellent post-transplant outcomes.

Background & Aims Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). Methods We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. Results Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29–4.55), decompensated cirrhosis (HR 2.91 [1.70–5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53–7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47–3.70]) and decompensated cirrhosis (OR 2.50 [1.20–5.21]) were independently associated with risk for severe COVID-19. Conclusions The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. Clinicaltrials.gov number NCT04439084

Background Crowdsourcing may be an effective strategy to develop test promotion materials. We conducted an online randomized controlled trial (RCT) to evaluate a crowdsourced intervention to promote hepatitis B virus (HBV) and hepatitis C virus (HCV) testing among men who have sex with men (MSM) in China. Methods MSM never previously tested for hepatitis were recruited through social media. Eligible men were randomized to receive an online crowdsourced intervention or no testing promotion materials. Outcomes including self-reported and confirmed HBV and HCV test uptake were assessed after four weeks. Odds ratios (OR) with 95% confidence intervals (95% CI) of men achieving primary and secondary outcomes between the intervention and control arms were calculated. Findings 556 eligible men were enrolled. Overall, 17•4% (97/556) of men self-reported HBV and HCV testing and 7•9% (44/556) confirmed HBV and HCV test uptake. The intervention was seen by 72•1% and 29•0% of men in the intervention and control arms, respectively. In intention-to-treat analysis, confirmed HBV and HCV test uptake was similar between the two arms, both when using a missing=failure approach (OR 0•98, 95% CI 0•53–1•82) or multiple imputation (OR 1•46, 95% CI 0•72–2•95). Interpretation This RCT extends the literature by developing and evaluating an intervention to spur hepatitis testing in a middle-income country with a high burden of hepatitis. Overall test uptake among MSM in China was similar to previous interventions promoting hepatitis testing in high-income countries. We found frequent intervention sharing, complicating interpretation of the results, and the role of crowdsourcing to promote hepatitis testing remains unclear.

In the United States, hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related deaths and was the 5th most common cause in 2020.1 One in 5 Americans lives in a rural area,2 yet little is known about temporal changes in HCC incidence by rural-urban residence. Area-specific data are critical to guide public health strategies and clinical interventions. Our study compared the overall and subgroup incidence trends for HCC across rural and urban communities in the United States over the past 20 years using the North American Association of Central Cancer Registries database, which covers 93% of the United States and well-represents the rural United States (North American Association of Central Cancer Registries 14.6% rural vs United States 14.8% rural).3.

Summary Background Advances in therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) have ushered in a new era in chronic hepatitis treatment. To maximise the effectiveness of these medicines, individuals must be engaged and retained in care. We analysed operational interventions to enhance chronic viral hepatitis testing, linkage to care, treatment uptake, adherence, and viral suppression or cure. Methods We did a systematic review of operational interventions, and did meta-analyses for sufficiently comparable data. We searched PubMed, Embase, WHO library, International Clinical Trials Registry Platform, PsycINFO, and CINAHL for randomised controlled trials and controlled non-randomised studies that examined operational interventions along the chronic viral hepatitis care continuum, published in English up to Dec 31, 2014. We included non-pharmaceutical intervention studies with primary or secondary outcomes of testing, linkage to care, treatment uptake, treatment adherence, treatment completion, treatment outcome, or viral endpoints. We excluded dissertations and studies of children only. Data were extracted by two independent reviewers, with disagreements resolved by a third reviewer. Studies were assessed for bias. Data from similar interventions were pooled and quality of evidence was assessed using GRADE. This study was registered in PROSPERO (42014015094). Findings We identified 7583 unduplicated studies, and included 56 studies that reported outcomes along the care continuum (41 for HCV and 18 for HBV). All studies except one were from high-income countries. Lay health worker HBV test promotion interventions increased HBV testing rates (relative risk [RR] 2·68, 95% CI 1·82–3·93). Clinician reminders to prompt HCV testing during clinical visits increased HCV testing rates (3·70, 1·81–7·57). Nurse-led educational interventions improved HCV treatment completion (1·14, 1·05–1·23) and cure (odds ratio [OR] 1·93, 95% CI 1·44–2·59). Coordinated mental health, substance misuse, and hepatitis treatment services increased HCV treatment uptake (OR 3·03, 1·24–7·37), adherence (RR 1·22, 1·05–1·41), and cure (RR 1·21, 1·07–1·38) compared with usual care. Interpretation Several simple, inexpensive operational interventions can substantially improve engagement and retention along the chronic viral hepatitis care continuum. Further operational research to inform scale-up of hepatitis services is needed in low-income and middle-income countries. Funding World Health Organization and US Fulbright Program.

Tests to detect the presence and activity of hepatitis B virus (HBV) are the cornerstones of diagnosis and management. Assays that detect or measure serum levels of HB surface antigen, HB surface antibody, and HB core antibody are used to identify patients with exposure to HBV, whereas other tests provide information on the level of virus replication, the presence of specific variants, and presence of virus reservoirs. Newer diagnostic tests, used only in research settings so far, aim to quantify levels of intrahepatic HBV replication. Other tests have been developed to detect HBV infection in resource-limited settings. We review point of care tests (essential in global screening efforts), standard diagnostic tests used in routine clinical management, and newer tests that might be used in clinical trials of agents designed to cure HBV infection.

Background End-stage liver disease and hepatocellular carcinoma due to hepatitis C virus (HCV) co-infection are increasingly common causes of death among HIV-infected individuals. However, there are few clinical investigations of HIV/HCV co-infected individuals from low and middle-income nations. Here, we compare the epidemiology of HCV-infected and HIV/HCV co-infected individuals in Southern China and examine hepatic fibrosis scores in co-infected individuals. Methods We conducted a retrospective cross-sectional study of treatment-naïve HIV/HCV co-infected and HCV mono-infected subjects. Bivariate and multivariate models were used to examine the association between demographics and HCV genotype. Among co-infected individuals, we also studied the relationship between fibrosis scores derived from non-invasive studies and HCV genotype. Results Data were collected from 175 HCV-infected individuals, including 89 (51 %) HIV/HCV co-infected individuals. HIV/HCV co-infection was correlated with intravenous drug use (AOR 46.25, p

Hepatitis C virus (HCV) infection continues to be a significant contributor to morbidity and mortality in the United States and throughout the world. Due to latency of infection, HCV is expected to cause an increasing number of liver-related deaths over the next 10 years despite a dramatic drop in incidence over the last 20 years. The present recommended treatment for patients with chronic HCV infection is triple therapy with pegylated interferon α, ribavirin and a protease inhibitor (PI). There are no guidelines for treatment in the elderly (defined as 65 years and older). As the largest cohort with HCV ages, it has become critical to evaluate the effect of treatment on life expectancy in elderly patients. We used a simple decision analysis model to simulate the impact of HCV treatment on life expectancy. Cohorts separated by gender entered the model at five age groups (60 to 80) and at the five stages of liver fibrosis (F0 to F4). The primary outcome was mean life expectancy and number of life years gained. Hazard ratios for all-cause mortality in cirrhosis before and after achieving sustained virologic response (SVR) were applied to baseline annual mortality rates to obtain F4-specific mortality rates. Sensitivity analysis was performed to ensure results were robust over a wide range of values. Our model demonstrated that the greatest life expectancy benefit of treatment was derived from treatment of younger patients with higher levels of fibrosis. Overall, men benefitted more than woman, with equalization of this benefit in cirrhosis. In our base-case scenario with a SVR rate of 70%, the mean years of life expectancy gained across all ages and stages of fibrosis were 2.18 years for women and 2.95 years for men. Based on a treatment threshold of 6 months of life expectancy gained, only men between 60 and 70 should be treated in the F0 cohort. From F2 and above, all cohorts reached our threshold value. The rate of SVR affected number of life years gained but did not substantially alter treatment decisions. Elderly patients have higher rates of progression of liver fibrosis and are more likely to present with complications of liver disease. Although prior studies on treatment of patients older on 65 are limited, data exists that these patients respond with similar rates of SVR as younger patients. Furthermore, recent studies have shown a clear decrease in liver-related morbidity and mortality if SVR is achieved. Given our findings of improved survival, this study highlights the importance of treatment in this at-risk cohort especially as shorter regimens and higher SVR rates are anticipated with upcoming PIs. Our results provide evidence for consideration of HCV treatment in clinical practice for all men between 60and 70-years of age and any patient of either gender with advanced fibrosis or cirrhosis. Life expectancy gains and treatment recommendations stratified by age, gender and fibrosis