Introduction: Despite its limitations, alpha-fetoprotein (AFP) is still the most common used serum marker for hepatocellular carcinoma (HCC). Alpha-fetoprotein-L3 (AFP-L3), protein induced by vitamin K absence (PIVKA-II) and Glypican-3 (GPC-3) have been proposed as complementary biomarkers but their role is still controversial. Aims and Methods: We prospectively included 101 patients with HCC and 52 control patients with liver cirrhosis with the aim to investigate the diagnostic performance of AFP, AFP-L3 PIVKA-II, and GPC-3 as single markers or in combination for HCC diagnosis. To compare the diagnostic value in distinguishing the presence of HCC from chronic nonmalignant liver disease, receiver operating characteristic (ROC) curves were constructed for each marker and for every combination of markers. Results: When all biomarkers were individually analyzed, AFP-L3 had the highest area under the curve (AUC) (0.84), followed by AFP (0.79), PIVKA-II (0.75) and GPC-3 (0.73) for HCC diagnosis. The best sensitivity (84.7%) was for AFP L3 at a cut-off >13.5ng/mL and the best specificity (93.9%) was for AFP at a cut-off >18.9 ng/mL. For combinations of two biomarkers, the AUC was highest (0.87) for AFP and AFP-L3. The combination of all four biomarkers resulted in a much better sensitivity (88.1%) and specificity (93.9%) than each of the markers individually (p = 0.01). Conclusion: AFP-L3 was the most useful single marker for HCC diagnosis, and the combination of AFP, AFP-L3 and PIVKA-II could maximize the diagnostic performance. Efforts to seek novel combination of biomarkers for HCC should be continued.
Hepatitis C viral (HCV) treatment has rapidly advanced with the use of direct-acting antivirals (DAA), and many patients achieve sustained virological response (SVR). Although the risk of liver tumors is greatly reduced, there are still patients who achieve SVR but will progress to hepatocellular carcinoma (HCC). HCV infection is also a known risk for cholangiocellular carcinoma (CLC), although it is considered a relative infrequent liver malignancy. We report a series of five cases of CLC in patients that achieved SVR after HCV treatment with DAA. There were three women and two males with a median age of 62 years (range 49 to 77 years). Four patients had liver cirrhosis at the time of their HCV treatment. The interval from achieving SVR until CLC diagnosis varied, ranging from 4 to 36 months (median=12). Three patients presented with advanced disease and had extrahepatic spread at the time of their diagnosis. One patient had a resectable tumor, with no recurrence 4 years later. In one case, the tumor was initially considered an atypical HCC and was treated by radiofrequency ablation. Three years later, she was diagnosed with a large tumor recurrence that was demonstrated to be a CLC on liver biopsy. The last two patients were older males with HCV compensated cirrhosis diagnosed with CLC more than two years after achieving SVR. Palliative chemotherapy was started in both. Only a handful of CLC cases have been reported in HCV patients after SVR. Clinicians should take into account the possible development of an aggressive CLC.
Acute on chronic liver failure (ACLF) is a dynamic syndrome, but frequently associated with a high 1 month mortality rate. This is the first study applying the new European Association for the Study of the Liver- chronic liver failure consortium criteria to explore mortality on the waiting list (WL) and early after liver transplantation (LT) in a cohort of Romanian cirrhotic patients that improved or recovered after an episode of ACLF. To assess frequency and waitlist mortality for different grades of ACLF. An observational study was conducted; 257 patients with liver cirrhosis included on the WL between 2015 and 2017 were analyzed. The cumulative incidence of waitlist mortality or removal was calculated for combination of competing events using multivariable competing risks regression. ACLF-1 occurred in 12.07%, ACLF-2 in 7.39% and ACLF-3 in 8.56% of patients. Median Model for End Stage Liver Diseases (MELD) score at the moment of ACLF was 29. The main event while on the WL was death, followed by ACLF; patients with ACLF-3 had a significantly greater subhazard ratio for mortality of 2.25 (1.55–3.26) compared to patients with ACLF-1 or 2. LT proved to be associated with a significantly lower risk of death on the WL at 6 months after inclusion. One and 12 months post-transplant survival of patients with or without ACLF was similar ( P = .77). Occurrence of an ACLF episode while on the WL is associated with a significantly high mortality rate, as well as MELD score at inclusion on the WL, renal and liver failure, presence of hepatic encephalopathy. Overall patient short and long term survival after LT is similar to non-ACLF patients in good selected cases.
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