From a theoretical point of view, orthotopic liver transplantation (OLT) should be considered the ideal therapeutic option for patients with hepatocellular carcinoma (HCC).This neoplasm usually appears in the setting of liver cirrhosis, 1,2 and thus, OLT would eliminate the tumor and the oncogenic underlying liver. However, the first series of OLT for HCC showed disappointing results. [3][4][5][6] The inclusion of patients with advanced HCC prompted a high recurrence rate (higher than 50% at 3 years) whereas the survival rate (20%-50% at 5 years) was clearly less than that of non-HCC patients. Subsequent reports showed that HCC stage is a key point in determining the success of OLT in these patients and suggested that patients with early HCC could benefit from OLT both in terms of recurrence and survival. 5,7-10 Thereby, the recurrence rate of patients with incidental tumors which were discovered at the time of the pathological examination of the explanted liver is negligible. 3,7 Finally, two recent studies have shown that if OLT is restricted only to patients with early HCC (some years ago these tumors would have been identified only in the explanted livers), the risk of recurrence is minimal and the survival is identical to that of patients without HCC. 11,12 These encouraging data would favor OLT as the first therapeutic option to be considered in patients with HCC 13 as surgical resection is hampered by a higher recurrence rate during follow up [14][15][16][17] ; however, OLT is a highly invasive procedure with potentially severe complications in the early, medium, and long-term follow up. In addition, it must be stressed that HCC in most of the patients arises on liver cirrhosis caused by infection with HBV or HCV, 2,18 which frequently infects the graft, 19,20 and that the progression of the liver disease may be faster than in immunologically competent individuals. 21 As previously reported, 22-25 the treatment schedule applied in our Liver Unit in patients with HCC considered OLT only for those patients with solitary tumors smaller than 5 cm in whom resection was contraindicated, whereas the stage according to the TNM staging system was not taken into account. The present study analyzes the outcome of the cohort of the first 58 HCC patients submitted to OLT following this pre-established treatment algorithm, describing the accuracy of the preoperative staging, the recurrence and survival data, and also the rate of viral infection of the new liver. PATIENTS AND METHODS PatientsBetween January 1989 and December 1995, 877 patients with HCC were diagnosed, staged, and treated in our Liver Unit according to a previously published schedule. [22][23][24][25] Patients with HCC were Abbreviations: HCC, hepatocellular carcinoma; OLT, orthotopic liver transplantation; TNM, tumor-node-metastasis classification system; pTNM, pathological tumor-nodemetastasis classification.From the

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Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies. Correspondence

BACKGROUND The coronavirus 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). This project has evaluated if the schedule of LC screening or procedures has been interrupted /delayed because of the COVID-19 pandemic. MATERIAL AND METHODS An international survey evaluated the impact of COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia and Africa (73.7%, 17.1%, 5.3%, 2.6% and 1.3% per continent, respectively). Eighty-seven per cent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening program, 50% cancelled curative and/or palliative treatments for LC, and 44.0% cancelled the liver transplantation program. Forty-five out 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service prior to COVID-19 pandemic (n=19/37). CONCLUSION The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with LC. Modifications in screening, diagnostic and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision making.

We investigated the frequency of HBsAg clearance and the possible role of viral superinfection in a long-term follow-up of 184 patients with chronic hepatitis B (CHB). Our subjects were 184 patients with chronic hepatitis B and the follow-up was 12-216 months (mean 66.2 +/- 53.7 months). The investigative methods used were: immunoenzymatic assays for HBV, HCV, HDV, and HIV markers; polymerase chain reaction (PCR) for HBV DNA; and liver biopsy and immunoperoxidase. During the follow-up, 20 of the 184 patients cleared serum HBsAg. A comparison of patients with persistent HBsAg(group I) and of those who cleared this marker (group II) showed a significant difference in mortality (P = 0.002) between the two groups and a tendency to a more severe exacerbation (flare) in group II (P = 0.07). Antibodies to hepatitis C and D virus as well as antibodies to HIV were equally distributed in both groups. Thirteen patients (7.9%) from group I, but none from group II, subsequently developed hepatocellular carcinoma. These results suggest that the frequency of spontaneous clearance of HBsAg during chronic HBV infection is low. No determinant factor for the clearance was found, including the presence of liver cirrhosis. Serum HBV DNA was undetectable by PCR after clearance in 16 out of 17 patients.