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The purpose of this study was to clarify the factors linked to recurrence of small hepatocellular carcinomas, up to 3 cm in diameter, after hepatectomy. Fifty patients with small hepatocellular carcinomas who underwent hepatectomy between 1976 and 1988 were observed for possible recurrence for at least 2 yr. These patients were divided into two groups: 20 patients who had recurrence within 2 yr and 30 patients who had no recurrence within 2 yr. The recurrence pattern was analyzed by hepatic angiography. Statistical analysis by the chi 2 test and stepwise logistic regression showed that the risk factors linked to recurrence were (a) tumor diameter greater than 2.2 cm, (b) intracapsular infiltration of tumor cells, (c) tumor location deep in the liver, (d) macroscopical and microscopical tumor invasion into the portal vein and (e) tumor invasion into the portal vein or intrahepatic metastasis. When patients diagnosed with small hepatocellular carcinomas have any of these risk factors, postoperative adjuvant therapy and follow-up should be particularly carefully considered, since these patients are at high risk for early recurrence.

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The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies and antiviral drugs for COVID-19 against these variants 1,2 . The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries 3 . Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone 4 , we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants.The Omicron variant of SARS-CoV-2, the virus responsible for COVID-19, was first detected in late November 2021 and has spread rapidly around the world. Omicron variants have been classified into four different sublineages: BA.1, BA.1.1, BA.2 and BA.3. The original Omicron lineage, BA.1, rapidly became the prevailing variant circulating in many countries; however, BA.2 variants have become dominant in at least 68 countries 3 . Moreover, the prevalence of BA.2 is increasing rapidly in several other countries including South Africa, Sweden, Austria, Singapore, Georgia and Sri Lanka (https://covariants.org/per-variant). Preliminary data indicate that the BA.2 variant may be more transmissible than the BA.1 variant 5,6 .Recently, we and others have shown that BA.1 variants are less pathogenic in animal models than previously circulating variants of concern 7-9 (VOC), consistent with preliminary clinical data in humans 10 . Moreover, other studies have reported that BA.1 variants show reduced sensitivity to vaccine-or infection-induced antibodies, as well as some therapeutic monoclonal antibodies [11][12][13][14][15] . The spike (S) protein of SARS-CoV-2 mediates viral receptor binding and membrane fusion, both of which are essential for viral infection of host cells. The S protein is also the principal antigen targeted by the host neutralizing antibody response 16 . Notably, mutations in the S protein, such as E484K, N501Y, D614G and P681H/R, have ...