Prevalence of different LI-RADS v2018 categories in high-risk patients undergoing CT- or MRI-based screening for hepatocellular carcinoma.

PURPOSE: To estimate the prevalence of Liver Imaging Reporting and Data System (LI-RADS, LR) v2018 categories reported on CT or MRI performed for hepatocellular carcinoma (HCC) screening. MATERIALS AND METHODS: This retrospective study included all reports for CT and MRI exams performed for HCC screening patients between 8/2018 and 4/2020. Patients with ultrasound, CT, or MRI of the abdomen within two years of the index exam were excluded. From each radiology report, we extracted number of reported liver observations, and LI-RADS v2018 category for each observation. RESULTS: There were 329 patients (170 [52%] male, mean age 59 years [SD 12]), of whom 177 (54%) had MRI with gadoxetate, 72 (22%) had MRI with extracellular contrast, 7 (2%) had MRI with unspecified contrast, and 73 (22%) had CT. Of 329 patients, 199 (60%) had no reported observations; 130 patients had 166 reported observations: 114 (68.7%) LR-1, 8 (4.8%) LR-2, 21 (12.6%) LR-3, 6 (3.6%) LR-4, 13 (7.8%) LR-5, 3 (1.8%) LR-M, and 1 (0.6%) LR-TIV. Of 114 LR-1 observations, 78 (68%) were cysts, 17 (15%) were hemangiomas, 12 (11%) were vascular shunts, 3 (3%) were focal nodular hyperplasia, 2 (2%) were siderotic nodules, 1 (1%) was a lipoma, and 1 (1%) was biliary hamartoma. There were 23 observations with probably or definitely malignant categories (LR-4, LR-5, LR-M or LR- TIV), reported in 20/329 (6%) of patients. CONCLUSION: In a cohort of at-risk patients undergoing contrast-enhanced CT/MRI for HCC screening, 60% of had no liver observations, and 6 % had probably or definitely malignant observations. IMPLICATIONS FOR PATIENT CARE: The prevalence of LI-RADS v2018 categories on CT or MR exams used for HCC screening can help develop screening criteria and assess cost-effectiveness of surveillance strategies with CT and MRI.

Comparison of 1-Year Morbidity Following Liver Transplant for Acute Alcoholic Hepatitis Versus Alcoholic Cirrhosis.

OBJECTIVES: With limited data on the morbidity profile of liver transplant as therapy for alcoholic hepatitis, we compared 30-day and 1-year morbidity in liver transplant recipients with alcoholic hepatitis versus alcoholic cirrhosis. MATERIALS AND METHODS: We retrospectively reviewed 38 perioperative variables in patients with alcoholic hepatitis (n = 15) and with alcoholic cirrhosis (n = 46). Multivariable analysis was performed to identify factors independently associated with outcomes. RESULTS: Patients with alcoholic hepatitis were younger (43 vs 58 years; P = .001), with higher pretransplant Model for End-Stage Liver Disease scores (36 vs 29; P = .009) and worse Karnofsky scores (20 vs 50; P < .001). All patients with alcoholic hepatitis received standard criteria deceased donor grafts; however, in the alcoholic cirrhosis group, 64% received standard criteria deceased, 11% living, 11% after cardiac death, 9% extended criteria, and 2% split graft donor organ donations (P > .05). The alcoholic hepatitis group had higher degree of steatosis on explant (P < .005), and the alcoholic cirrhosis group had higher 30-day reoperation rate (P = .001); however, 1-year interventions, vascular and biliary complications, graft and patient survival, and all other variables were similar (P > .05). Rates of alcohol relapse, 1-year infection, and 1-year rejection were higher but not significant (P > .05) in the alcoholic hepatitis group. Thirty-day reoperation (odds ratio of 82.63; 95% CI, 8.02-3338.96; P = .002) and Karnofsky scores (odds ratio of 1.18; 95% CI, 1.08-1.36; P = .006) remained significant on multivariate analysis. CONCLUSIONS: Our results showed significant differences between our patient groups, including worse functional status in the alcoholic hepatitis group but significantly higher 30-day reoperation rates and more variable grafts in the alcoholic cirrhosis group, although both groups had similar overall 1-year complication and survival rates. Although not significant, patients with alcoholic hepatitis had higher alcohol relapse and 1-year infection and rejection rates. A larger cohort is necessary to confirm the strength of these findings.

Commercial insurance delays direct-acting antiviral treatment for hepatitis C kidney transplantation into uninfected recipients.

INTRODUCTION: The advent of direct-acting antivirals (DAAs) has created an avenue for transplantation of hepatitis C virus (HCV)-infected donors into uninfected recipients (D+/R-). The donor transmission of HCV is then countered by DAA administration during the post-operative period. However, initiation of DAA treatment is ultimately dictated by insurance companies. METHODS: A retrospective chart review of 52 D+/R- kidney recipients who underwent DAA treatment post-transplant was performed. Patients were grouped according to their prescription coverage plans, managed by either commercial or government pharmacy benefit managers (PBMs). RESULTS: Thirty-nine patients had government PBMs and 13 had commercial PBMs. Demographics were similar between the two groups. All patients developed HCV viremia, but cleared the virus after treatment with DAA. Patients with government PBMs were treated earlier compared to those with commercial PBMs (11 days vs 26 days, P = .01). Longer time to DAA initiation resulted in higher peak viral loads (ß = 0.39, R2  = .15, P = .01) and longer time to HCV viral load clearance (ß = 0.41, R2  = .17, P = .01). CONCLUSIONS: D+/R- transplantation offers patients an alternative strategy to increase access. However, treatment can be profoundly delayed by a third-party payer authorization process that may be subjecting patients to unnecessary risks and worsened outcomes.

Transplantation of viral-positive hepatitis C-positive kidneys into uninfected recipients offers an opportunity to increase organ access.

The advent of direct-acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus-positive donors into uninfected recipients (D+/R-). Thirty D+/R- patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12 weeks after treatment. An age-matched cohort of uninfected donor and recipient pairs (D-/R-) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R- patients was 100%. The initial median viral load was 531 copies/µL (range: 10-1 × 108 copies/µL) with a median peak viral load of 3.4 × 105 copies/µL (range: 804-1.0 × 108 copies/µL). DAAs were initiated on median POD 9 (range: 5-41 days). All 30 patients had confirmed SVR12. During a median follow-up of 10 months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R- patients as compared to the age-matched cohort (27% vs 60%; P = .01). D+/R- transplantation offers patients an alternative strategy to increase access.

Ineffective Absorption? Failure of Direct-Acting Therapy for Chronic Hepatitis C in Cirrhotic Patients With Roux-en-Y Gastric Bypass.

In this era of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection, treated patients have extremely high rates of sustained virologic response to short courses of therapy regardless of stage of fibrosis. Treatment failure is uncommon and often attributed to medication noncompliance or viral resistance to drug. This report describes 2 Child-Pugh-A cirrhotic patients who failed to clear HCV in response to therapy with DAAs. Each patient had Roux-en-Y gastric bypass (RYGB) surgery preceding DAA therapy. RYGB may create multiple barriers to adequate DAA absorption as a result of changes in gastrointestinal physiology. Treatment monitoring and duration should be carefully considered in this unique patient population.

Cardiac transplantation from non-viremic hepatitis C donors.

BACKGROUND: Hepatitis C (HCV) donors are rarely used for cardiac transplantation due to historically poor outcomes. In 2015, nucleic acid testing (NAT) for viral load was added to the routine work-up of organ donors, allowing for the distinction between subjects who remain viremic (HCV Ab+/NAT+) and those who have cleared HCV and are no longer viremic (HCV Ab+/NAT-). The American Society of Transplantation recently recommended that HCV Ab+/NAT- donors be considered non-infectious and safe for transplantation. We present our initial experience with such donors. METHODS: All patients were counseled regarding donor HCV antibody (Ab) and NAT. Transplant recipients were tested post-transplant at 1 week and at 1, 3, and 6 months for HCV seropositivity and viremia. We also analyzed the UNOS database to determine the potential impact of widespread acceptance of HCV Ab+/NAT- organs. RESULTS: Fourteen HCV Ab‒ subjects received hearts from HCV Ab+/NAT- donors in 2017. Over a median follow-up of 256 (192 to 377) days, 3 patients developed a reactive HCV Ab, yet none had a detectable HCV viral load during prospective monitoring at any time. Analysis of the UNOS database for the calendar year 2016 revealed that only 7 (3%) of 220 HCV Ab+/NAT- donors were accepted for heart transplantation. CONCLUSIONS: We have demonstrated the feasibility of utilizing HCV Ab+/NAT- donors for cardiac transplantation without recipient infection. A small percentage of recipients developed HCV Ab without evidence of viremia, possibly consistent with a biological false reactive test, as has been seen in other settings. Large-scale validation of our data may have a significant impact on transplantation rates.

Sinusoidal Obstruction Syndrome (SOS) in Multiple Myeloma with Renal Failure.

SOS is a rare complication of stem cell transplantation and has significant morbidity and mortality. We present three cases of SOS and highlight underlying risk factors for its development, such as impaired clearance of alkylating agents (especially melphalan) in patients with renal failure and prolonged infection. Although, melphalan and cyclophosphamide cause SOS less commonly than alkylating agents such as busulfan, physicians must use caution when administering these drugs to patients with underlying comorbidities such as renal failure that may increase the likelihood of development of SOS. This is due to unpredictable pharmacokinetics in patients with renal failure and therefore close drug monitoring is required. With the recent FDA approval of defibrotide in 2016, outcomes of SOS have improved and physician awareness is important for prompt diagnosis and treatment.

Bridging therapy effectiveness in the treatment of hepatocellular carcinoma prior to orthotopic liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective treatment for hepatocellular carcinoma (HCC) in patients with underlying cirrhosis and portal hypertension. Availability of OLT is limited by donor-organ shortages, which increase patient waiting time until OLT. A variety of bridging therapies (BT) have been used to halt tumor progression in patients on the OLT waiting list. Despite complete radiologic responses following BT, viable tumor is often present in explants. METHODS: Treatment outcomes were evaluated in 50 patients who had a total of 125 BT for treatment of 93 nodules. Success of BT was assessed by radiologic response compared to histopathological examination of explanted livers. RESULTS: Pre-transplant treatments included: transcatheter arterial chemoembolization (TACE), alcohol ablation (ETOH), radiofrequency ablation (RFA), microwave ablation (MWA), selective internal radiation therapy (SIRT) and stereotactic body radiation therapy (SBRT). Fifty-nine (64%) nodules had a complete radiographic response to therapy; however, only 28 nodules (30%) had complete tumor necrosis (CTN) on explant examination. Ten nodules with CTN were treated with TACE alone. Seven of the 28 nodules with CTN were treated with TACE and RFA. Three of seven nodules treated with TACE and SIRT had CTN. Patients underwent a mean of 2.5 BTs. Six of 50 patients (12%) had no residual HCC in their explants. Five of those six patients (83%) had complete response (CR) on pre-transplant imaging. CONCLUSIONS: Although favorable radiologic responses are seen following BT, viable HCC is seen in the majority of liver explants and radiographic imaging cannot always accurately predict pathological response. This underscores the need for aggressive treatment of patients who otherwise may not be eligible for OLT.

Limited Fibrosis Progression but Significant Mortality in Patients Ineligible for Interferon-Based Hepatitis C Therapy.

BACKGROUND: Individuals ineligible for interferon-based hepatitis C therapy may have a worse prognosis than patients who have failed or not received treatment. AIMS: To provide information about the limitations of medical treatment of hepatitis C in real-world patients. METHODS: We studied 969 treatment-ineligible patients and 403 treated patients enrolled between 1/1/01 and 6/30/06; data were collected until 3/31/13. Treatment barriers were grouped into five categories and classified as health-related or health-unrelated. Fibrosis stage was assessed initially and at the end of follow-up. Mortality was determined by search of the Social Security database. Death certificates of treatment-ineligible patients were reviewed. RESULTS: Initially, 288 individuals had advanced fibrosis and compensated disease; 87 untreated patients developed advanced fibrosis during follow-up. Health-related treatment barriers were more commonly associated with fibrosis progression and worse survival. During follow-up, 247 untreated patients died: 47% of liver-related and 53% of liver-unrelated causes. Patients with significant comorbid illness had the worst five- (70%) and ten-year (50.5%) survival. Despite high mortality (47%) in persons with decompensated liver disease, no treatment barrier was associated with a greater incidence of liver-related death. Only significant comorbid medical illness was an independent predictor of disease progression; however, it was not associated with a greater incidence of liver-related death. Furthermore, treated patients had better 10-year survival than untreated patients on Kaplan-Meier analysis (80.3% vs. 74.5%, P = 0.005). CONCLUSION: Many patients with hepatitis C will die of non-liver-related causes and may not be helped by anti-viral treatment.

Spectrum of Alcoholic Liver Disease.

Liver disease from excessive alcohol consumption is an important cause of morbidity and mortality worldwide. There is a clear relationship between alcohol and a variety of health and socioeconomic problems. According to the World Health Organization, 3.3 million people die of alcohol-related causes annually. Despite public knowledge of its potential adverse effects, alcohol consumption and the morbidity and mortality from alcoholic liver disease (ALD) have increased. ALD comprises a spectrum of injury, including simple steatosis, acute alcoholic hepatitis, and cirrhosis. Rather than being distinct disease entities, these pathologic processes frequently overlap.

Extrahepatic Complications of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver disease that is often associated with the metabolic syndrome. There is a growing awareness that extrahepatic complications occur in individuals with NAFLD, especially an increased risk of cardiovascular disease. Development of diabetes mellitus, chronic kidney disease, colorectal cancer, and endocrinopathies has been linked to NAFLD. This article reviews the extrahepatic complications affecting individuals with NAFLD and the pathogenesis underlying their development.

Expedited liver allocation in the United States: a critical analysis.

The fate of donor livers allocated via an out-of-sequence expedited placement (EP) pathway has not been previously examined. We determined the originating and receiving United Network for Organ Sharing (UNOS) regions of all donor livers procured between January 1, 2010 and October 31, 2012 and placed out of sequence with UNOS bypass code 863 (EP attempt) or 898 (miscellaneous). We reviewed the early function of these liver grafts and assessed the effect of EP allocation on wait-listed patients at our center. Registrants at our center were eligible to receive 1298 liver offers during the interval studied: 218 (16.8%) of these liver offers bypassed our center and were allocated to other centers and used in patients lower on the match-run list. During the study interval, 560 livers were allocated in the United States by EP. Regions 1, 5, 7, 9, and 10 used the greatest number of EP-placed grafts. Region 1 (New England) used the greatest proportion of all EP livers (33% of all imported EP livers in the United States, P < 0.001 versus all other regions). Graft function data were available for 560 livers placed by EP: 491 (88%) of these grafts were functioning at a mean of 399.5 days after transplantation. In conclusion, the transplantation of livers allocated by means of an expedited refusal code is asymmetric across regions and, in some instances, results in the bypassing of patients with higher wait-list priority but without notification of the bypassed center. Short-term graft function after EP allocation is excellent. Policies governing EP allocation should be created in order to improve access to available organs.

Prevalence and natural history of alcoholic liver disease.

Alcoholic liver disease is a major cause of morbidity and mortality among people who drink excessive amounts of alcohol. There is a spectrum of liver injury that ranges from steatosis to varying stages of hepatic fibrosis and cirrhosis, with subsequent risk for hepatocellular carcinoma. Steatohepatitis can occur at any stage of disease.

Value of noncontrast CT immediately after transarterial chemoembolization of hepatocellular carcinoma with drug-eluting beads.

PURPOSE: To retrospectively evaluate the presence and distribution patterns of contrast agent retention in the liver on noncontrast computed tomography (CT) immediately following chemoembolization with drug-eluting beads (DEBs). MATERIALS AND METHODS: From 2008 to 2010, 95 patients with 224 liver lesions had chemoembolization performed with DEBs and a noncontrast CT examination of the liver performed immediately after embolization. Of these, 85 patients with 193 lesions were included. The postembolization CT scan was reviewed by a diagnostic radiologist, and the presence of contrast agent retention within the lesion was assessed. Varying patterns of contrast agent retention were defined. RESULTS: Of the 193 lesions included, 146 (76%) retained contrast medium. Aside from some contrast medium in vessels, very little if any contrast medium was seen in the surrounding liver. Various patterns of contrast agent retention were noted within lesions. In a single case, repeat imaging was obtained 6 hours later, which demonstrated washout of contrast agent in a lesion that had retained contrast agent on the postprocedure CT scan. Of significance, 13 additional foci of contrast agent retention were identified on postchemoembolization CT scans that, on retrospective review of preprocedure imaging, represented enhancing lesions not previously identified. CONCLUSIONS: Noncontrast CT after chemoembolization with DEBs demonstrates contrast agent retention in 76% of cases, without significant contrast medium seen in the adjacent liver parenchyma. The presence or absence of contrast agent retention may prove to be useful in evaluating accurate targeting of a lesion.

Social barriers to listing for adult liver transplantation: their prevalence and association with program characteristics.

Social barriers to effective medical care are mandated to be routinely assessed as part of an evaluation for liver transplantation. This study explores how frequently liver transplant programs encounter these barriers in patients undergoing an evaluation and whether programs with higher proportions of Medicaid patients, historically disadvantaged minority patients, and rural patients encounter social barriers more frequently. A survey for assessing patient demographics and social barriers was electronically completed by representatives of 61 of 104 eligible US adult liver transplant programs (59%). Fifty-eight of the 61 programs identified themselves, and their characteristics were similar to those of all 104 US programs according to publicly available data from the Organ Procurement and Transplantation Network. Social barriers were reported to be encountered sometimes (10%-30%) or frequently (>30%) by the 61 programs as follows: inadequate or unstable health insurance (68.9% of the programs), a chaotic social environment (63.9%), a lack of a care partner (60.7%), an inability to obtain transportation (49.2%), a low educational level (36.1%), inadequate housing (23.0%), a language barrier (19.7%), no reliable way of contacting the patient (16.4%), difficulty in obtaining child care (11.5%), and food insecurity (8.2%). The frequencies of perceived social barriers did not differ significantly between programs reporting higher or lower proportions of Medicaid, minority, or rural patients. Our analysis suggests that program-level operational planning for addressing social barriers to transplant listing should be considered regardless of the proportions of Medicaid-insured, racial or ethnic minority, and rural patients in the population.

Direct-acting antiviral therapy for hepatitis C: attitudes regarding future use.

INTRODUCTION: Response to current therapy of hepatitis C virus (HCV) is suboptimal. Direct-acting antiviral therapies (DAA) are expected to improve treatment outcomes. Additional treatments for HCV will invariably make therapeutic choices and patient management more complex. We hypothesize that current perceptions regarding the complexity of DAA therapy will influence attitudes towards future use by practitioners who are currently treating HCV. METHODS: An Internet-based survey was sent to 10,082 AASLD and AGA members to determine if they treat HCV infection, their knowledge of DAA therapies, attitudes towards current and future HCV treatments, and if they participated in clinical trials using DAA agents. RESULTS: Out of a total of 1,757 individuals responding to the survey, 75% treat HCV; 79% were MDs, 67% were Gastroenterologists, and 24% were Hepatologists. Of the respondents, 77% indicated they were "very aware" or "aware" of DAA therapies, 20% participated in clinical trials, and 3% had minimal knowledge of DAA agents. Comparing treatment "today" versus in the future when DAAs were available, 85 vs. 81% would treat (p = 0.0054), 6 vs. 10% would refer to an "HCV expert" (p = 0.016), and 1% would refer to an ID specialist. Of respondents with "minimal knowledge" of DAA, 52% stated that they would use them in the future. CONCLUSIONS: Although the majority of respondents appear ready to utilize DAA agents in the future, referrals to "hepatitis C experts" will increase. More than half of respondents with "minimal knowledge" of DAA therapies also appear to be willing to utilize these compounds, raising concerns regarding their inappropriate use. Broad education of healthcare providers to prevent inappropriate use of these agents will be critical.

Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients.

Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin have demonstrated sustained viral response rates (SVRs) of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may not be equivalent. The goal of this study was to assess the effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naïve, human immunodeficiency virus (HIV)-negative, United States urban population with many ethnic minority patients. We evaluated 2,370 outpatients for HCV therapy from 2001 to 2006 in the Faculty Practice of the Albert Einstein College of Medicine or the attending-supervised Montefiore Medical Center Liver Clinic. Care was supervised by one experienced physician under conditions of everyday clinical practice, and appropriate ancillary resources were made available to all patients. Two hundred fifty-five patients were treated with a mean age of 50 years (60% male, 40% female; 58% Hispanic, 20% African American, 9% Caucasian, 13% other; 68% genotype 1, the remainder genotypes 2 or 3). Patients had at least one liver biopsy. Intention-to-treat analysis (ITT) showed SVR in 14% of genotype 1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly higher in faculty practice (27%) than in clinic patients (15%) by intention-to-treat (P = 0.01) but not per-protocol analysis (46% faculty practice, 34% clinic). 3.3% of 1,656 treatment-naïve, HIV antibody-negative individuals ultimately achieved SVR. Current hepatitis C therapies may sometimes be unavailable to, inappropriate for, and ineffective in United States urban patients. Treatment with pegylated interferon and ribavirin was less effective in this population than is implied by multinational phase III controlled trials. New strategies are needed to care for such patients.

Entry of hepatitis C virus and human immunodeficiency virus is selectively inhibited by carbohydrate-binding agents but not by polyanions.

We studied the antiviral activity of carbohydrate-binding agents (CBAs), including several plant lectins and the non-peptidic small-molecular-weight antibiotic pradimicin A (PRM-A). These agents efficiently prevented hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infection of target cells by inhibiting the viral entry. CBAs were also shown to prevent HIV and HCV capture by DC-SIGN-expressing cells. Surprisingly, infection by other enveloped viruses such as herpes simplex viruses, respiratory syncytial virus and parainfluenza-3 virus was not inhibited by these agents pointing to a high degree of specificity. Mannan reversed the antiviral activity of CBAs, confirming their association with viral envelope-associated glycans. In contrast, polyanions such as dextran sulfate-5000 and sulfated polyvinylalcohol inhibited HIV entry but were devoid of any activity against HCV infection, indicating that they act through a different mechanism. CBAs could be considered as prime drug leads for the treatment of chronic viral infections such as HCV by preventing viral entry into target cells. They may represent an attractive new option for therapy of HCV/HIV coinfections. CBAs may also have the potential to prevent HCV/HIV transmission.