Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Does dual infection by hepatitis B and C viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan?

BACKGROUND: There are contradictory data concerning the synergistic effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the progression from chronic hepatitis to hepatocellular carcinoma (HCC). METHODS: To clarify the role of coinfection with HBV and HCV in the progression and pathogenesis of HCC, viral and clinicopathologic features were studied in 368 consecutive HCC patients at the University of Tokyo from 1991-1995. RESULTS: Approximately 83% of patients (305 patients) were seropositive for the HCV antibody ("C-viral") and approximately 10% (37 patients) were positive for the hepatitis B surface antigen ("B-viral"). Positivity for both (dual infection) was found in only 2% of patients, and negativity for both in 5%. The incidence of dual infection in HCC patients was Similar to that in 549 patients with chronic hepatitis (1%) and 119 patients with cirrhosis (1%). Of the six HCC patients with dual infection, five patients were positive for the HBV early antigen and HBV DNA was less than measurable, whereas HCV RNA was detected and ranged from 10(3)-10(6) copies/50 microL of serum by competitive reverse transcriptase-polymerase chain reaction, and the clinical features resembled those of "C-viral" HCC. The remaining patient was early antigen positive and had HBV DNA by slot blot analysis, but the serum HCV RNA level was less than measurable. These data indicate that mutually exclusive viral replication occurred in patients with persistent coinfection. To further clarify further the possible involvement of HBV infection in "C-viral" HCC, HBV core antibody (HBcAb) was tested in 192 patients and was found to be positive in 111 and negative in 81. The serum HCV RNA level and clinicopathologic features (such as age and the severity of liver disease) were similar among the "C-viral" HCC patients irrespective of the presence or absence of HBcAb. CONCLUSIONS: Based on these results, coinfection was found to be much less prevalent than generally is claimed, and even in a few HCC patients with the coinfection the mutually exclusive viral replication was noted, suggesting that coinfection plays little if any role in the development of HCC.

[Percutaneous ethanol injection therapy for small hepatocellular carcinoma].

Hepatocellular carcinoma is different from other solid tumors. Because of concomitant cirrhosis or multiple lesions, most hepatocellular carcinoma is unresectable. Still worse, hepatocellular carcinoma frequently recurs after surgical resection; the 5-year cumulative recurrence rate is 70-90% even after curative hepatectomy. The situation is similar in small hepatocellular carcinoma 2 cm or less in diameter. Thus, non-surgical treatment plays an important role. At present, we think that percutaneous ethanol injection therapy (PEIT) is best for the treatment of hepatocellular carcinoma because of its local curativity, minimal adverse effect on liver function, and the easy feasibility of repeated treatment for recurrence. We have recently treated about 85% of hepatocellular carcinoma cases by PEIT and have achieved satisfactory long-term results. Here we describe our results in PEIT for small hepatocellular carcinoma. By the end of December 1995, we performed PEIT on 410 patients with hepatocellular carcinoma. Among them, 140 patients were diagnosed as having small hepatocellular carcinoma 2 cm or less in diameter. The 1-, 3-, 5-, 7-, and 10-year survival rates of the 140 patients were 93%, 73%, 55%, 51%, and 32%, respectively. Furthermore, in 83 patients who had a single, small hepatocellular carcinoma 2 cm or less in diameter, the 1-, 3-, 5-, 7-, and 10-year survival rates were 92%, 82%, 72%, 66%, and 66%, respectively. Thus PEIT achieved satisfactory long-term survival rates in the treatment of small hepatocellular carcinoma.