Although liver transplantation (LT) yields survival benefit for patients with acute‐on‐chronic liver failure grade 3 (ACLF‐3), knowledge gaps remain regarding risk factors for post‐LT mortality. We retrospectively reviewed data from 10 centers in the United States and Canada for patients transplanted between 2018 and 2019 and who required care in the intensive care unit prior to LT. ACLF was identified using the European Association for the Study of the Liver‐Chronic Liver Failure (EASL‐CLIF) criteria. A total of 318 patients were studied, of whom 106 (33.3%) had no ACLF, 61 (19.1%) had ACLF‐1, 74 (23.2%) had ACLF‐2, and 77 (24.2%) had ACLF‐3 at transplantation. Survival probability 1 year after LT was significantly higher in patients without ACLF (94.3%) compared with patients with ACLF (87.3%; P = 0.02), but similar between ACLF‐1 (88.5%), ACLF‐2 (87.8%), and ACLF‐3 (85.7%; P = 0.26). Recipients with ACLF‐3 and circulatory failure (n = 29) had similar 1‐year post‐LT survival (82.3%) compared with patients with ACLF‐3 without circulatory failure (89.6%; P = 0.32), including those requiring multiple vasopressors. For patients transplanted with ACLF‐3 including respiratory failure (n = 20), there was a trend toward significantly lower post‐LT survival (P = 0.07) among those with respiratory failure (74.1%) compared with those without (91.0%). The presence of portal vein thrombosis (PVT) at LT for patients with ACLF‐3 (n = 15), however, yielded significantly lower survival (91.9% versus 57.1%; P < 0.001). Multivariable logistic regression analysis revealed that PVT was significantly associated with post‐LT mortality within 1 year (odds ratio, 7.3; 95% confidence interval, 1.9‐28.3). No correlation was found between survival after LT and the location or extent of PVT, presence of transjugular intrahepatic portosystemic shunt, or anticoagulation. LT in patients with ACLF‐3 requiring vasopressors yields excellent 1‐year survival. LT should be approached cautiously among candidates with ACLF‐3 and PVT.

To compare the all-cause survival, cancer-specific survival and progression-free survival of surgical resection (SR) versus ablation (AB) for small hepatocellular carcinoma. Our sample consisted of treatment-naïve patients who underwent AB or SR for small HCC (≤5 cm) from 2009-2016 in the SEER-Medicare database. Patients who had a non-HCC malignancy diagnosis within 5 years, lost entitlement 1 year prior to treatment or underwent liver transplant were excluded. Unadjusted and Cox regression model analysis of all-cause survival, cancer-specific survival and progression-free survival were compared. Cox regression model included basic demographic factors, socioeconomic factors, medical comorbidities, and liver disease prognostic indicators. A total of 767 patients who received AB and 214 who received SR met our study inclusion criteria. There were no significant differences between groups for age, gender, socioeconomic factors or the number of medical comorbidities. However, there were significant differences in prognostic indicators for and etiology of liver disease (all P values < 0.05). Unadjusted and adjusted all-cause survival, cancer-specific survival and progression-free survival were all superior in the SR group with all P values <0.001. With SR as a reference group, the unadjusted HRs (95% CI) for all cause survival, cancer-specific survival and disease-specific survival following AB were 2.32 (1.82-2.94), 2.45 (1.70-3.53), and 2.48 (2.01-3.06), respectively. The fully adjusted HRs (95% CI) for all cause survival, cancer-specific survival and disease-specific survival following AB were 1.83 (1.41-2.36), 2.28 (1.54-3.38) and 2.08 (1.65-2.62), respectively. In this national sample of patients with small hepatocellular carcinoma, compared to AB, SR is associated with better all cause survival, cancer-specific survival, and disease-specific survival. After adjusting for known socioeconomic factors, medical comorbidities and liver disease prognostic indicators, the differences between groups decreased. Unmeasured and unaccounted for confounders may account for at least part of the remaining differences between these groups.

To compare the hospitalization and complication rates following microwave ablation (MWA) versus radiation segmentectomy (RS) in treatment of small hepatocellular carcinoma (HCC). Following local IRB approval, HCC patients who underwent treatment with MWA or RS for solitary HCC within Milan criteria between 2005-2018 at a single institution were reviewed. Patients who had prior HCC treatment, multifocal HCC or HCC larger than 5 cm were excluded. Basic demographics, presence and etiology of liver disease, medical comorbidities, type of initial LRT, pretreatment tumor size, postprocedural admission and complication rates were compared using Chi-squared test or Student's t-test. The Society of Interventional Radiology (SIR)-adverse event classification system was utilized in evaluating complications. Postprocedural admission rates and complications within 30 days of the procedure were recorded and compared between the two groups using Chi-squared tests. 30 small HCC patients were included in this study. 18/30 (60%) underwent MWA and 12/30 (40%) underwent RS. There was no statistically significant difference between the groups in age (71 vs. 73 years, P = 0.53), gender (64% vs. 72% male, P = 0.49), liver disease etiology, presence of major medical comorbidities (DM, CAD, COPD), or pretreatment tumor size (1.7 vs. 2.4 cm, P = 0.50). All 12 patients who underwent RS were discharged following a short stay in the recovery room, and did not experience complications attributable to the procedure within 30 days. However, 14/18 (78%) patients were admitted following MWA for a median of 1 day (range, 0-6). For those who underwent MWA, 5/18 (27.8%) experienced a complication within 30 days, including two patients with perilesional hematomas who were admitted for pain control (SIR Class B), and one patient with a pneumothorax requiring chest tube placement and prolonged hospital stay (SIR Class D). Complication rates between groups are not statistically significant (P = 0.125). Although complication and hospitalization rates following RS were lower, no significant difference was found between groups in this small study. Larger studies are needed to further explore these results.

To evaluate thrombotic and clinical outcomes for TIPS patients treated with controlled expansion (CE) or constrained VIATORR stents based on balloon dilation to various diameters. We reviewed all outcomes for TIPS patients treated with CE or constrained VIATORR stents at a large academic interventional radiology service between January 2015 to September 2019. All case reports, follow-up imaging, and follow-up procedures were reviewed. Information collected includes initial balloon dilatation diameter, average time of patency, the percent of patients whose TIPS became occluded, the portosystemic gradients pre and post-TIPS and the percent of patients who underwent TIPS revision. A total of 75 patients met criteria and were divided into three subgroups based on initial TIPS dilatation size: 6-7 mm, 8 mm, and 10 mm. There were 12 patients in the 6- to 7-mm group with 2 occlusions (16.7%) and 8 revisions (66.7%). There were 48 patients in the 8-mm group with 2 occlusions (4.3%) and 10 revisions (21.7%), and 17 patients in the 10-mm group with 2 occlusions (15.4%) and 5 revisions (29.4%). Analysis of the data showed that there was a statistically significant difference in revision rates between the three groups (P = 0.01). However, no significant difference was found in occlusion rates (P = 0.13). Post-TIPS gradients for patients in all three groups was < 10 mm Hg. Our data provides occlusion and revision rates and other key outcomes for TIPS procedures performed with VIATORR stents at a large tertiary care interventional radiology service with a complex patient population. We found that there was a significant difference in revision rates for TIPS based on initial dilatation diameter which suggests that narrower TIPS are more likely to require revision. However, we found that there was no statistically significant difference in occlusion rates, suggesting that wider TIPS are no less likely to become occluded than narrower TIPS.Tabled 1TIPS Size (mm)Patients (n)Average Time of Patency (days)Occlusions (n)Occluded (%)RevisionsRevisions (%)Post-TIPS Gradient (mm Hg)6-71279216.7866.79.184631524.31021.76.81017192215.4529.48.4 Open table in a new tab

To compare time to retreatment of transarterial monotherapy versus combination therapy in conjunction with ablation for hepatocellular carcinoma (HCC) with tumor size 3-5 cm. Following institutional review board approval, we retrospectively reviewed all hepatocellular carcinoma (HCC) patients with solitary tumors 3 to 5 cm in size, who received locoregional therapy at a single institution between 2006 and 2018. Patients who had undergone prior locoregional therapy or prior surgical resection were excluded. Those who underwent liver transplant or surgical resection following locoregional therapy were censored at time of surgery. Baseline patient demographics, and comorbidities were compared using Chi-squared test. Time to retreatment and overall survival were assessed compared between groups using log-rank test. A total of 29 HCC patients met our study inclusion criteria. 24/29 (83%) had bland embolization or chemoembolization monotherapy, while the other five underwent combination therapy consisting of transarterial therapy plus ablation. There were no significant differences between the monotherapy and combination therapy groups in mean age (65.8 vs. 73.3 years, P = 0.13), gender (25% vs. 20% female, P = 1.00), and medical comorbidities (diabetes mellitus (41.7% vs. 60%, P = 0.64), heart disease (33.3% vs. 20%, P = 0.65), chronic kidney disease (12.5% vs. 20%, P = 1) or history of other malignancy (8.3% vs. 0%, P = 1)), respectively. The median time to retreatment following monotherapy was 41 days compared to 105 days in the combination therapy group (P = 0.06). Overall survival could not be accurately compared between groups due to too few events during median study follow-up time of 482 days. In this comparative study, although there was no significant difference in time to retreatment between the monotherapy and combination therapy groups, there was clearly a trend towards improved time to retreatment with combination therapy. Additional larger, prospective studies are needed to further assess the potential survival benefit of combination therapy over monotherapy for this group whom have several treatment options available.

To compare the efficacy and complication rates of locoregional therapies (LRT) versus systemic therapy (ST) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Following local institutional review board approval, we reviewed all HCC patients with PVTT treated at a single institution between 2005 and 2018. Baseline patient demographics, comorbidities, severity of liver disease, as well as tumor and treatment characteristics were compared between groups using Chi-squared or Student’s t-test. Overall survival (OS) and progression-free survival (PFS) were compared between groups using the log-rank test. Complications were assessed and graded per Society of Interventional Radiology (SIR) guidelines and compared using Chi-squared test. 17 HCC patients with PVTT were identified, 10 of whom received LRT and 7 who received ST. LRT patients received transarterial chemoembolization (TACE, 20%), transarterial radioembolization (TARE, 30%), and bland transarterial embolization (TAE, 50%). ST patients all received sorafenib. There were no significant differences between the LRT and ST groups in basic demographics, medical comorbidities, history of other malignancy, tumor characteristics, liver disease or performance status (table). Median OS was 444 days for the LRT group and 1147 days for the ST group (P = 0.7). Median PFS was 83 days following LRT and 67 days following ST (P = 0.3). Complication rates did not differ significantly between LRT and ST groups (50% vs. 28.6%, P = 0.62). In this comparative study, there were no significant differences in OS, PFS, or complications for HCC patients with PVTT receiving LRT versus ST. Additional larger, prospective studies are needed to further assess survival benefit and complication rates between these treatment modalities for this difficult-to-treat population.Tabled 1LRTSTP valueAge (yrs)63.5620.53Gender (% female)4028.61.00Diabetes Mellitus (%)1042.90.25Heart Disease (%)3000.23Other Malignancy History (%)2000.49Largest Tumor Diameter (cm)5.98.20.35Extrahepatic Disease (%)2028.61.00Child-Pugh Score (% C)028.60.28ECOG Performance Score (% stage 0)6028.60.53 Open table in a new tab

BACKGROUND:Recurrence of hepatitis C virus (HCV) following liver transplantation (LT) is universal for those with ongoing viraemia and is associated with higher rates of allograft failure and death. However, the optimal timing of HCV treatment for patients awaiting transplant remains unclear.AIM:To evaluate the comparative cost-effectiveness of treating HCV pre-LT vs. post-LT (pre-emptive or after HCV recurrence).METHODS:A Markov state-transition model was created to simulate the progression of a cohort of HCV-genotype 1 or 4 cirrhotic patients from the time of transplant listing until death. We then used this model to study the cost-effectiveness of ledipasvir-sofosbuvir (LDV/SOF) with ribavirin for 12 weeks, administered for three separate treatment strategies: (i) pre-LT; (ii) post-LT preemptively prior to HCV recurrence; or (iii) post-LT after HCV recurrence.RESULTS:In the base-case analysis using a median model for end-stage liver disease (MELD) score <25 at the time of transplant, we found that pre-LT treatment of HCV led to more QALYs for fewer dollars compared to other strategies. Analysis limited to living donor LT recipients revealed that pre-LT treatment was also the most cost-effective strategy. When the analysis was repeated for MELD ≥25, decompensated disease (Child-Pugh class B or C), and hepatocellular carcinoma cases, preemptive post-LT strategy was more cost-effective.CONCLUSIONS:Treatment of HCV prior to liver transplantation appears to be the most cost-effective strategy for patients with a MELD score <25. For patients with a MELD ≥25 or decompensated cirrhosis, preemptive post-liver transplantation treatment before HCV recurrence is the most cost-effective strategy.

Watch a video presentation of this article Watch the interview with the author Elevation in serum creatinine is a common laboratory finding for patients with cirrhosis and can indicate the presence of either an acute kidney injury (AKI) or chronic kidney disease (CKD). However, creatinine may underestimate the actual extent of renal impairment, and both serum creatinine and creatinine-based equations for glomerular filtration rate estimation have been proven to be inaccurate for cirrhotic patients.1 Therefore, clinicians should have a low threshold for diagnosis and treatment of kidney injury among patients with cirrhosis. Providers should be cognizant that cirrhotic patients often have lower baseline creatinine levels because of the presence of protein–calorie malnutrition, reduced muscle mass, impaired creatinine production from the liver, and increased renal tubular creatinine excretion.1 Thus, the clinical relevance of a single creatinine value requires a comparison with prior laboratory values and interpretation within clinical context. For purposes of this focused review, we will concentrate on the diagnosis and management of AKI, which is the most common cause of elevated creatinine in cirrhotic patients, occurring in nearly 20% of all cirrhotic hospitalizations.2 Early recognition of AKI is critical because it is associated with other complications of cirrhosis, such as spontaneous bacterial peritonitis (SBP) and variceal hemorrhage, and it is an independent predictor of mortality.3 Patients with a history of persistently elevated creatinine values or low glomerular filtration rate estimation likely have CKD and will not be addressed in this review. According to the Acute Kidney Injury Network (AKIN), the definition of AKI is an abrupt (within 48 hours) reduction in kidney function, seen by an increase in serum creatinine by at least 0.3 mg/dL or increase of at least 50% (1.5-fold) from baseline, or a reduction in urine output to less than 0.5 mL/kg/hour for more than 6 hours.4 There are three stages of AKI severity according to the AKIN criteria classification (Table 1). Clinicians must also be aware that patients with CKD are susceptible to a superimposed acute injury. Initial workup includes a full assessment of renal and liver functions, as well as excluding common clinical precipitants, especially infections such as SBP (Table 2). • Urinalysis, including urine microscopy and sediment • Urine tests: electrolytes, osmolality, protein, albumin • Urine output • Renal ultrasound • Consider echocardiogram if concerned for cardiorenal process • Liver tests: AST, ALT, Tbili, Dbili, Alk Phos, INR, albumin • Liver ultrasound with Doppler • Diagnostic paracentesis (including total protein, albumin, cell count) • Cultures: urine, blood • Diagnostic paracentesis (peritoneal fluid Gram stain and culture) • Chest X-ray To diagnose the type of AKI, one must analyze the clinical scenario and the results of the initial evaluation. Postrenal failure is quickly identified by the presence of hydronephrosis on renal ultrasound or by resolution of urinary obstruction with placement of a urinary catheter. It is, however, more challenging to distinguish among PRA, HRS, and ATN. Table 3 outlines the key diagnostic findings as a general guideline. Dependent on the clinical setting, the use of urine electrolytes as well as the urinary sediment can potentially elucidate the diagnosis. PRA is typically responsive to volume repletion, whereas HRS is a functional type of prerenal kidney injury due to renal vasoconstriction that persists after volume challenge.2 Although a type of prerenal AKI, cardiorenal syndrome (or congestive nephropathy) may worsen with volume expansion and requires evaluation with an echocardiogram to determine the presence of a decreased ejection fraction. ATN can typically be distinguished by clinical scenario and urine studies, notably with granular casts in the urine sediment; however, this finding may be nonspecific in advanced cirrhosis. It is essential to determine the presence of HRS. There are two types of HRS (types 1 and 2), which are differentiated by timing and patient characteristics. HRS-1 is a type of AKI with sudden decline in renal function (within 2 weeks), often developing after a precipitating event such as SBP and it is associated with poor short-term prognosis. Whereas HRS-2 is more indolent, occurring slowly over time (weeks to months), and it usually presents in the outpatient setting as refractory ascites.2 HRS is only considered as a possible diagnosis in patients with cirrhosis and ascites after other causative factors have been excluded, such as ATN, decreased cardiac outflow, shock, nephrotoxins, and parenchymal kidney disease. If there is no improvement in creatinine after at least 2 days of volume expansion (albumin 1 g/kg body weight/day), HRS is the most likely cause.2, 5 HRS accounts for about one-sixth (17%) of all AKI cases among hospitalized cirrhotic patients and about one-fourth (25%) of cases determined to be prerenal AKI.2 The pathophysiology of HRS is illustrated in Figure 1.2 The initial step in the treatment of an elevated creatinine concentration and concern for AKI in any cirrhotic patient is to discontinue potential offending agents such as diuretics, lactulose, NSAIDs, vasodilators, and other nephrotoxins. Concurrently, the patient should be evaluated for any underlying precipitants such as gastrointestinal bleeding or infection (ie, SBP). If renal function does not improve after 24 hours, patients should then be given intravascular volume repletion using albumin as the preferred agent.2, 5 The diagnosis is likely PRA if the creatinine responds to volume. However, if the patient is unresponsive after at least 2 days of diuretic withdrawal and expansion of volume with albumin, then HRS should be strongly considered. If there is clinical suspicion for HRS (ie, ascites, low mean arterial pressure, hyponatremia), the diagnosis of HRS is assumed and the combination of albumin plus vasoconstrictors should be started immediately. According to AASLD practice guidelines, if the patient is on a medical floor, an oral vasoconstrictor, midodrine, can be combined with octreotide, a somatostatin analogue, and albumin to initially treat HRS6; although recent literature has shown that this regimen is not as effective as more potent vasoconstrictors.7 However, when in the intensive care unit, albumin plus norepinephrine (or terlipressin if outside the United States) should be considered. All patients with HRS should be immediately referred to a liver transplant center for transplant evaluation.6 Refer to Figure 2 for a proposed algorithm on the treatment of AKI in hospitalized patients with cirrhosis. Patients with cirrhosis and renal failure have a poor prognosis. For all causes of renal failure, the 1-month mortality rate is near 50%, whereas the 6-month mortality rate approaches 80%.8 Prognosis is markedly dependent on the cause of renal injury. According to a large, single-center, prospective cohort, 3-month survival rates ranged from 73% for parenchymal disease, 46% for hypovolemia, 31% for infection-associated renal failure, and only 15% for HRS.9 Furthermore, type 1 HRS has a worse prognosis compared with type 2 HRS, with a median survival of only 1.0 month compared with 6.7 months, respectively.10 Given the poor short-term survival in HRS, it is crucial for these patients to be evaluated for liver transplantation, because this remains the only curative option.2, 6, 9