Patient perspectives and overall satisfaction after liver resection for benign disease.

BACKGROUND: Management of benign liver lesions (BLLs) is still an object of discussion. Frequently, patients receive multiple opinions about their diagnosis and treatment from physicians specialized in different areas, which can be opposite and controversial. This study aimed to understand patients' decision-making process in electing surgery and assess their satisfaction after resection for BLLs. METHODS: A 104-question survey was administered to 98 patients who had a resection for BLLs in 4 different hepatopancreatobiliary and transplant centers in Argentina. The first section included 64 questions regarding the initial discovery of the BLL, the decision-making process, and the understanding of the patient's feelings after surgery. The second section, 42 queries, referred to the quality of life. The patient's final diagnosis and outcome were correlated with the survey results using univariate analysis. RESULTS: Among 97 patients who had undergone liver resection for BLLs, 69 (70%) completed the survey. The median age was 51.71 years (range, 18-75), and 63% of the patients were females. Moreover, 21% of patients received conflicting information from different healthcare providers. Surgeons were the best to describe the BLL to the patient (63%), and 30% of patients obtained opinions from multiple surgeons. The respondents were quite or fully satisfied with their decision to have surgery (90%) and the decision-making process (91%). Only 59% of patients considered their lifestyle better after surgery, and 89% of patients would have retaken the same decision. CONCLUSION: Patients with resected BLLs are delighted with the decision to have surgery, regardless of the final diagnosis and outcome. The role of surgeons is crucial in the decision-making process.

Pre-operative assessment of living liver donors' liver anatomy and volumes.

Decades of experience supports LDLT as a favorable strategy to reduce waitlist mortality. The multiple regenerative pathways of hepatocytes and other hepatic cells justify the rationale behind it. Nonetheless, living liver donation is still underused and its broader implementation is challenging, mostly due to variability in practices leading to concerns related to donor safety. A non-systematic literature search was conducted for peer-reviewed original articles related to pre-operative evaluation of living liver donor candidates. Eligible studies were synthesized upon consensus for discussion in this up-to-date review. Review of the literature demonstrate that the importance of preoperative assessment of vascular, biliary and liver volume to ensure donor safety and adequate surgical planning for graft procurement is widely recognized. Moreover, data indicates that anatomic variants in vascular and biliary systems in healthy donors are common, present in up to 50% of the population. Therefore, comprehensive mapping and visualizations of each component is needed. Different imaging modalities are reported across practices and are discussed in detail. Lastly, assessment of liver volume must take into account several technical and donor factors that increase the chances of errors in volume estimation, which occurs in up to 10% of the cases. Experience suggests that maximizing donor safety and lessening their risks is a result of integrated experience between hepatobiliary and transplant surgery, along with multidisciplinary efforts in performing a comprehensive pre-operative donor assessment. Although technical advances have increased the accuracy of volume estimation, over- or under-estimation remains a challenge that needs further attention.

Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis.

BACKGROUND & AIMS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. METHODS: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. RESULTS: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001). CONCLUSIONS: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. IMPACT AND IMPLICATIONS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

What is the optimal management of thromboprophylaxis after liver transplantation regarding prevention of bleeding, hepatic artery, or portal vein thrombosis? A systematic review of the literature and expert panel recommendations.

BACKGROUND: A key tenet of clinical management of patients post liver transplantation (LT) is the prevention of thrombotic and bleeding complications. This systematic review investigated the optimal management of thromboprophylaxis after LT regarding portal vein thrombosis (PVT) or hepatic artery thrombosis (HAT) and prevention of bleeding. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Seven databases were used to conduct extensive literature searches focusing on the use of anticoagulation in LT and its impact on the following outcomes: PVT, HAT, and bleeding (CRD42021244288). RESULTS: Of the 2478 articles/abstracts screened, 16 studies were included in the final review. All articles were critically appraised by a panel of independent reviewers. There was wide variation regarding the anticoagulation protocols used. Thromboprophylaxis with therapeutic doses of heparin/Vitamin K antagonist combination did not decrease the risk of de novo or the recurrence of PVT but was associated with an increased risk of bleeding in some studies. Only the use of aspirin resulted in a small but significant decrease in the incidence of HAT post-LT, yet it did not increase the risk of bleeding. CONCLUSIONS: Based on existing data and expert opinion, thromboprophylaxis at therapeutic or prophylactic dose is not recommended for prevention of de novo PVT following LT in patients not at high risk. Aspirin should be considered as the standard of care following LT to prevent HAT. Thromboprophylaxis should be strongly considered in recipients at risk of HAT and PVT following LT.

Performance of pre-transplant criteria in prediction of hepatocellular carcinoma progression and waitlist dropout.

BACKGROUND & AIM: Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout because of tumour progression. The aim of this study was to compare the alpha-foetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. METHODS: A multicentre cohort study was conducted in 20 Latin American transplant centres, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumour characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics. RESULTS: HCC dropout rate was significantly higher in patients beyond (24% [95% CI 16-28]) compared to those within Milan criteria (8% [95% IC 5%-12%]; p < .0001), with a SHR of 3.01 [95% CI 2.03-4.47]), adjusted for waiting list time and bridging therapies (c-index 0.63 [95% CI 0.57; 0.69). HCC dropout rates were higher in patients with AFP scores >2 (adjusted SHR of 3.17 [CI 2.13-4.71]), c-index of 0.71 (95% CI 0.65-0.77; p = .09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout (SHR 1.68 [95% CI 1.08-2.61]). CONCLUSIONS: Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.

When Should We Perform Intraoperative Cholangiography? A Prospective Assessment of 1000 Consecutive Laparoscopic Cholecystectomies.

BACKGROUND: Intraoperative cholangiography (IOC) has been historically used to detect common bile duct (CBD) stones, delineate biliary anatomy, and avoid or promptly diagnose bile duct injuries (BDIs) during laparoscopic cholecystectomy (LC). We aimed to determine the usefulness of routine IOC during LC in an urban teaching hospital. METHODS: A consecutive series of patients undergoing LC with routine IOC from 2016 to 2018 was prospectively analyzed. Primary outcomes of interest were: CBD stones, BDI, and anatomical variations of the biliary tract. Secondary outcomes of interest were: IOC success rate, IOC time, and readmission for residual lithiasis. A comparative analysis was performed between patients with and without preoperative suspicion of CBD stones. RESULTS: A total of 1003 LC were analyzed; IOC was successful in 918 (91.5%) patients. Mean IOC time was 10 (4 to 30) minutes. Mean radiation received by the surgeon per procedure was 0.06 millisieverts (mSv). Normal IOC was found in 856 (93.2%) patients. CBD stones and aberrant biliary anatomy were present in 58 (6.3%) and 4 (0.4%) cases, respectively. Two patients (0.2%) underwent unnecessary CBD exploration because of false-positive IOC. Four patients (0.4%) with normal IOC were readmitted for residual CBD stones. Five (0.5%) minor BDI undetected by the IOC were diagnosed. Patients with preoperative suspicion of CBD stones had significantly higher rates of CBD stones detected on IOC as compared with those without suspicion (23.2% vs. 2.1%, P<0.0001). CONCLUSION: Routine use of IOC resulted in low rates of BDI diagnosis, aberrant biliary anatomy identification and/or CBD stones detection. Selection of patients for IOC, rather than routine use of IOC appears a more reasonable approach.

Multifocal Nodular Fatty Infiltration of the Liver: A Rare Benign Disorder That Mimics Metastatic Liver Disease.

Fatty liver disease is a frequent diagnosis. Rarely, it adopts a multifocal nodular pattern mimicking multiple liver metastases. Multifocal nodular fatty infiltration of the liver entails a challenging problem that must be included as a differential diagnosis when dealing with healthy patients with an incidental finding of multiple liver lesions, even in the absence of obesity or metabolic syndrome. A complete clinical examination and high-quality imaging, including magnetic resonance imaging, might help to confirm diagnosis and to avoid unnecessary liver biopsies.

Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort.

BACKGROUND & AIM: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.

Liver transplantation for hepatocellular carcinoma: impact of expansion criteria in a multicenter cohort study from a high waitlist mortality region.

This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).

Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma.

The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.

Parenchyma-sparing liver resections.

Modern liver surgeon must be equipped with excellent theoretical and clinical skills to perform a perfect liver resection. A particular and growing relevance is devoted to parenchyma sparing liver surgery (PSS). Indeed, reducing the sacrifice of functioning parenchyma is one of the keys of a successful surgery, once oncological issues are properly addressed. Intraoperative ultrasound together with oncological and anatomical new insights have enhanced the possibility to offer PSS even in advanced disease usually afforded with major resections or staged procedures or even considered unresectable. These complex hepatectomies are mainly performed with open surgery, while major or staged procedures could be faced with minimal access liver surgery (MALS): that is generating a potential conflict between open PSS and MALS major hepatectomies. An overall evaluation of oncological radicality, safety, salvageability, and quality of life suggest to prioritize PSS, which is always minimal invasive liver surgery in a hepatic-centered perspective, while MALS is not.

Current status of liver transplantation in Latin America.

The lack of adequate financial coverage, education, and the organization has been the main limiting factor for the development of transplantation in Latin America. As occurred worldwide, the number of patients on liver waiting lists in Latin America grows disproportionately compared to the number of liver transplantations (LTs) performed. Although many law modifications have been made in the last year, most countries lack social awareness about the importance of donation and the irreversibility of brain death. The mechanisms and norms for organ procurement and infrastructure development, capable of supporting this high demand, are still in slow progress in most countries. Access to LT in the region is very heterogeneous. While some countries have no active LT programs so far, others are an international model of a public transplantation system (Brazil) or a national information system (Argentina). While some countries have only a few LT centers, others have too many LT centers performing an inadequate low number of LTs. Disparity to access transplantation remains the major challenge in the region. Cultural and educational efforts have to be accompanied by transparent public policies that will likely increase organ donation and activity in transplantation. The purpose of this article is to review the trends and current activity in LT within Latin America, based on prior publications and the information available in each country of the region.

Direct-Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait-List Progression or Posttransplant Recurrence.

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre- or post-LT DAA effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alpha-fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre- or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT.

Surveillance for Hepatocellular Carcinoma: Does the Place Where Ultrasound Is Performed Impact Its Effectiveness?

BACKGROUND: Biannual ultrasound (US) is recommended as the clinical screening tool for hepatocellular carcinoma (HCC). The effectiveness of surveillance according to the place where US is performed has not been previously reported. AIMS: To compare the effectiveness of US performed in the center responsible for follow-up as opposed to US proceeding from centers other than that of follow-up. METHODS: This is a multicenter cohort study from Argentina. The last US was categorized as done in the same center or done in a different center from the institution of the patient's follow-up. Surveillance failure was defined as HCC diagnosis not meeting Barcelona Clinic Liver Cancer (BCLC) stages 0-A or when no nodules were observed at HCC diagnosis. RESULTS: From 533 patients with HCC, 62.4% were under routine surveillance with a surveillance failure of 38.8%. After adjusting for a propensity score matching, BCLC stage and lead-time survival bias, surveillance was associated with a significant survival benefit [HR of 0.51 (CI 0.38; 0.69)]. Among patients under routine surveillance (n = 345), last US was performed in the same center in 51.6% and in a different center in 48.4%. Similar rates of surveillance failure were observed between US done in the same or in a different center (32% vs. 26.3%; P = 0.25). Survival was not significantly different between both surveillance modalities [HR 0.79 (CI 0.53; 1.20)]. CONCLUSIONS: Routine surveillance for HCC in the daily practice improved survival either when performed in the same center or in a different center from that of patient's follow-up.

A changing etiologic scenario in liver transplantation for hepatocellular carcinoma in a multicenter cohort study from Latin America.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trends of liver related HCC etiologies during the last years in Latin America. METHODS: From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005-2006, 2007-2008, 2009-2010 and 2011-2012 were considered. Etiology of liver disease was confirmed in the explant. RESULTS: Participating LT centers per country included 2 from Brazil (n=191), 5 transplant programs from Argentina (n=98), 2 from Colombia (n=65), 4 from Chile (n=49), 2 from Mexico (n=12), and 1 from Peru (n=11) and Uruguay (n=9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis accounted for 6% and 7%, respectively. While HCV decreased from 48% in 2005-06 to 26% in 2011-12, NAFLD increased from 1.8% to 12.8% during the same period, accounting for the third cause of HCC. This represented a 6-fold increase in NAFLD-HCC, whereas HCV had a 2-fold decrease. Patients with NAFLD were older, had lower pre-LT serum AFP values and similar 5-year survival and recurrence rates than non-NAFLD. CONCLUSION: There might be a global changing figure regarding etiologies of HCC in Latin America. This epidemiological change on the incidence of HCC in the world, although it has been reported, should still be confirmed in prospective studies.

Adherence to Barcelona Clinic Liver Cancer therapeutic algorithm for hepatocellular carcinoma in the daily practice: a multicenter cohort study from Argentina.

BACKGROUND AND AIM: Adherence to the Barcelona Clinic Liver Cancer (BCLC) staging algorithm for the treatment of hepatocellular carcinoma is challenging in the daily practice. We aimed to analyze adherence to BCLC along with its effect on patient survival. PATIENTS AND METHODS: A cohort study was conducted in 14 hospitals from Argentina including patients with newly diagnosed hepatocellular carcinoma (2009-2016). Adherence was considered when the first treatment was the one recommended by the BCLC. RESULTS: Overall, 708 patients were included. At diagnosis, BCLC stages were as follows: stage 0 4%, A 43%, B 22%, C 9% and D 22%. Overall, 53% of the patients were treated according to BCLC, 24% were undertreated, and 23% overtreated. Adherence to BCLC increased to 63% in subsequent treatments. Independent factors associated with adherence to BCLC were the presence of portal hypertension [odds ratio: 1.63; 95% confidence interval (CI): 1.11-2.39] and BCLC stage C (odds ratio: 0.32; 95% CI: 0.12-0.72). In a multivariable model adjusting for portal hypertension and BCLC stages, adherence to BCLC showed improved survival (hazard ratio: 0.67; 95% CI: 0.52-0.87). CONCLUSION: Adherence to BCLC represents a challenge in the daily practice, with almost half of the patients being treated accordingly, showing that the decision-making process should be tailored to each individual patient.

Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina.

AIM: To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years. METHODS: A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit. RESULTS: A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers (n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLD-HCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% (P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality. CONCLUSION: The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.