Hepatocellular carcinoma and oral contraceptives.
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Biomedical subjects
Publications and source records attributed to R L Peters.
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Proliferation of bile ductules is commonly seen in expanded portal tracts and periportal areas in many conditions, including advanced alcoholic liver disease. Such ductules are usually tortuous and irregular and composed of cuboidal cells. They frequently have poorly defined lumens. The epithelial cells are similar to those of normal bile ductules and small bile ducts; however, cells that appear intermediate between duct epithelial cells and hepatocytes are frequently identified by light and electron microscopy. The origin of the ductular cells from hepatocytes may be confirmed by the demonstration of the markers of hepatocytes, such as glycogen and glucose-6-phosphatase activity in some proliferated bile ductules. In addition, alcoholic hyalin is occasionally recognizable in the epithelial cells of bile ductules. The majority of periportal bile ductules appears to have been derived from transformation of hepatic cords rather than multiplication of preexisting bile ducts. The proliferated bile ductules seem to communicate between the bile canaliculi and the interlobular bile ducts.
The lymphocytic infiltrates were examined in 10 liver biopsy cores taken from nine cases of acute viral hepatitis (AVH), using cryostat sections. The cells were identified and characterized, using the monoclonal antibodies to T lymphocytes (OKT3), T helper cells (OKT4), and T suppressor/cytotoxic cells (OKT8) in an indirect immunofluorescence technique. Of the nine cases of AVH, three were type B, one was acute type A, with underlying chronic hepatitis type B, and the remaining five were non-A, non-B, with no serological markers. One of the patients with acute non-A, non-B hepatitis was biopsied twice with a 2-month interval due to clinical relapse. Both these biopsies were included in the study. The cellular infiltrates, both lobular and portal, were graded from 1 + to 4 + and evaluated by examining the histological sections stained with hematoxylin and eosin. The approximate percentage of each set of cells staining with different antibodies was estimated in each case. The predominant cells were found to be T lymphocytes in all nine cases of AVH; of the two subsets, T suppressor/cytotoxic cells formed the majority in all except one patient who had AVH type A superimposed on chronic B hepatitis.
Seventy-eight black patients and white patients with primary hepatocellular carcinoma (PHC), 70 years or younger at diagnosis, and 78 age-, sex-, and race-matched neighborhood controls were interviewed. Information sought included usual dietary and drinking habits, cigarette smoking habits, prior medical conditions including a history of hepatitis, prior exposure to blood products, and occupational history. Cigarette smoking was a risk factor for PHC; the relative risk (RR) for current smokers of more than one pack/day compared to nonsmokers was 2.6. Alcohol consumption was also a significant risk factor for PHC; individuals who drank 80 g or more of ethanol per day had a RR of 4.2 compared to those drinking less than 10 g/day. In addition, a history of hepatitis (RR = 13.0) and a history of blood transfusions (RR = 7.0) were significant risk factors for PHC. Each of these factors remained significant after adjustment was made for the others.
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A newly recognized clinical and morphologic pattern of acute alcoholic liver disease is described. Twenty-one patients, having the hepatic morphologic features of alcoholic foamy degeneration, were retrospectively analyzed. All patients had a significant history of chronic alcoholism. Jaundice and hepatomegaly were usually present. Hepatic encephalopathy, ascites, bleeding esophageal varices, or functional renal failure occurred in less than 10%. Usually this was the first episode of decompensation. Laboratory studies revealed a pattern of very transiently marked elevation of serum aminotransferase and more prolonged elevation of alkaline phosphatase activity and bilirubin levels. In the majority of cases, leukocytosis was absent, and serum cholesterol was elevated. The laboratory profile differed significantly from that of acute sclerosing hyaline necrosis. Serologic markers of acute viral hepatitis A and B were absent. Needle biopsy specimens of the liver revealed intact lobular architecture except for 1 case of cirrhosis. The perivenular hepatocytes revealed foamy fatty change characterized by striking cell swelling with massive accumulation of microvesicular fat, bile pigment deposition in the cytoplasm, and no displacement of the nucleus to the periphery of the cell. Megamitochondria were frequently identified. Multiple foci of hepatocyte dropout without significant parenchymal neutrophilic exudation and delicate intrasinusoidal collagen fibers were present in the perivenular area. Macrovesicular fatty change coexisted to a variable degree. The affected hepatocytes had extensive disorganization of the organelles by electron microscopy and decreased or absent functional activity by enzyme histochemical staining. These changes appear to be a purely degenerative process without inflammatory reaction. All patients in the present series showed a rapid recovery upon abstaining from alcohol.
The overall prevalence of delta-antibody among 80 patients with chronic infection of hepatitis B virus in the Los Angeles area was found to be 24%. Twenty-three patients had a histologic diagnosis of persistent hepatitis and 57 had chronic active hepatitis with or without cirrhosis. Only 1 patient among those with persistent viral hepatitis had delta-antibody, whereas 18 with chronic active hepatitis had delta-antibody in their sera (p less than 0.05).
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A series of 30 patients is reported whose primary hepatic tumors had a distinctive histologic pattern that we have called "sclerosing hepatic carcinoma" (SHC). Sixty-nine percent of those tested had hypercalcemia and low levels of serum phosphate. As comparison, 38 control patients who had either classical peripheral cholangiocarcinoma or typical hepatocellular carcinoma were studied. In the control group, only two patients, who also had bone metastases, had hypercalcemia. Sclerosing hepatic carcinoma is characterized by intense fibrosis in which the tubular neoplastic structures are embedded. Although the tumor in each patient superficially resembled peripheral cholangiocarcinoma, on close inspection 63% were found to be of apparent hepatocyte origin, 20% were apparently ductal, and 13% were mixed or not distinguishable. One patient's tumor had the pattern of the rare cholangiolocellular carcinoma. The difficulty of histological diagnosis was well illustrated by the fact that none of premortem biopsies in 16 patients was correctly interpreted unequivocally as primary carcinoma of the liver. Many were misinterpreted as metastatic adenocarcinomas, most frequently of pancreatic origin. We believe that, by describing clinicopathological features, more attention will be drawn to this unique carcinoma of liver origin.
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Clinical and pathologic features of 23 patients with a distinctive histologic and clinical variant of hepatocellular carcinoma are summarized. The variant pattern of hepatocellular carcinoma is most common in the age group 5--35 years and occurs equally in either sex. The distinctive histologic features include 1) deeply eosinophilic neoplastic hepatocytes, many of which contain intracytoplasmic hyaline globules and distinct pale bodies and 2) fibrosis arranged in a lamellar fashion around the neoplastic hepatocytes. The histologic and gross features of the tumor have been confused both with focal nodular hyperplasia and with hepatocellular adenoma. The average survival of 32 months and the high operability rate of 48% far exceed the survival or operability for ordinary hepatocellular carcinoma. Thus, this tumor type must be recognized and considered separately when evaluating therapeutic results in large series of patients with hepatocellular carcinoma.
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In the process of establishing the specificity of direct immunoperoxidase staining of liver tissue for hepatitis B surface antigen (HBsAg), an affinity of free horseradish peroxidase (HRP) for HBsAg in hepatocytes (ground-glass cells) was found. Of 95 patients, the horseradish peroxidase reaction was only positive in the livers of the 35 who were chronically HBsAg seropositive and not in the livers from 60 control patients with alcoholic cirrhosis who were HBsAg seronegative. Comparison studies using the orcein technic and immunoperoxidase methods confirmed the observation that both free horseradish peroxidase (not conjugated to an antibody) and HRP conjugated to an antibody unrelated to HBsAg had an affinity to the cytoplasm of hepatocytes containing HBsAg. The precise nature of this affinity is not known, but it is probably due to a reaction between an activated carbohydrate moiety of horseradish peroxidase and the free amino group of HBsAG.
Plasma, serum, and a concentrate of factor VIII, implicated in human cases of non-A, non-B (NANB) hepatitis, were inoculated into four chimpanzees. All four animals demonstrated significant elevations of alanine aminotransferase levels within five weeks. After recovery from these NANB hepatitis episodes, the chimpanzees were cross-challenged with different inocula. A second episode of NANB hepatitis occurred after challenge in three animals. Reproducibility of the results was established by reversing the sequence of inoculation in two of the animals. A known infectious concentrate of factor VIII failed to induce hepatitis in a previously infected chimpanzee although the animal remained susceptible to a third inoculum, an event suggesting that the first inoculum might contain the same NANB hepatitis agent as the concentrate of factor VIII, which was supported by results of a subsequent cross-challenge experiment. Reinfection did not occur in two chimpanzees injected with their initial challenge strain of NANB hepatitis virus, providing evidence that strain-specific immunity had been established. Thus, experimental evidence is provided for the presence of two NANB hepatitis agents, supporting clinical and epidemiologic studies that favor the existence of more than one etiologic agent.
A patient is described who developed acute hepatic failure two and one-half years following a jejunoileal by-pass. Autopsy revealed advanced micronodular cirrhosis. This case is reported to stress that the development of liver disease following jejunoileal by-pass may be extremely subtle. Hepatic failure may occur as a late complication as well as an early one.
A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HBsAg), was treated with an orthotopic liver allograft. The HBs antigenemia, as measured with several precipitation tests and by complement fixation, became negative after transplantation and remained so for about 2 1/2 months. During the interval, very low titers of the antigen were detectable by radioimmunoassay. At about three months after transplantation, she had an attack of acute hepatitis, at which time HBsAg became detectable by all tests. She recovered, but progressive liver disease developed during the remaining 1 1/2 years of her life. She died of disseminated nocardiosis and candidiasis with deteriorating hepatic function. The homograft at autopsy showed no evidence of rejection, but was the site of chronic active liver disease, although of a different pathologic pattern than that affecting her native liver. The differences in histology may reflect the influence of chronic immunosuppression on the features of chronic active hepatitis.
An enzyme-linked immunosorbent assay was developed for the detection of antibodies to murine hepatitis virus. A high prevalence of antibody to murine hepatitis virus was found by the enzyme-linked immunosorbent assay in colonies with a low prevalence of complement-fixing antibodies. Murine hepatitis virus strain A59 was found to be broadly reactive as an enzyme-linked immunosorbent assay antigen.