Human liver regeneration after major hepatic resection. A study of normal liver and livers with chronic hepatitis and cirrhosis

Abstract

The regenerative process was evaluated in terms of liver size, function, and histology in 28 adults who had major hepatic resection: hepatocellular carcinoma (HCC) in 21, secondary liver cancer from colorectum in four, carcinoma of the gallbladder in one, Klatskin tumor in one, and Caroli's disease in one. There were 22 men and six women. Ages ranged from 17 to 74 years with a mean age of 56.7. All patients with HCC had underlying liver disease: liver cirrhosis in 14 and chronic hepatitis in seven. Extended right lobectomy was done on 10 patients, right lobectomy on 16 patients, and left lobectomy on two patients. The residual liver size was serially estimated with computed tomography (CT) in 15 patients: six with normal liver, five with chronic hepatitis, and four with cirrhosis. A complete restoration of the residual liver size was found within 3 months in 3 and 6 months, respectively, in two patients with normal livers. The liver was enlarged in all patients with the parenchymal diseases but obviously more slowly compared with normal liver. Liver functions were restored normally within 2-3 weeks in patients with normal livers, but hyperbilirubinemia persisted longer in those with chronic hepatitis and cirrhosis. A continuous rise of bilirubin was an ominous sign of liver failure and subsequent death, which occurred in five patients with cirrhosis. Serum alpha-fetoprotein did not rise in accordance with the regeneration. Histologically, evidence of active regeneration with increased mitotic activity was found at 10 and 35 days in those patients with normal livers. Mitosis was not seen in a specimen taken at 7 days. Enlarged cuboidal hepatocytes and cells with basophilic cytoplasm or two nuclei were observed more or less in all specimens. The livers with cirrhosis or hepatitis also showed histologic evidence of regeneration during the first 2 months but substantially less compared with normal liver, which was well supported by the volumetric study of the liver remnants with CT.