Myron J. Tong

Hepatocellular carcinoma. Diagnostic and prognostic features in North American patients.

Diagnostic and prognostic characteristics of 121 North American patients with hepatocellular carcinoma seen in one metropolitan area over a 6‐year period were assessed using multivariate analysis. Presenting symptoms commonly included abdominal pain (53%) or mass (34%), anorexia (31%), and ascites (20%); however, the ability to make an early diagnosis was complicated by a variety of unusual symptoms accounting for 25% of presentations. While cirrhosis (63%) and hepatitis B surface antigen (HBsAg) positivity (52%) were common associated findings, the majority of patients (67%) had no prior diagnosis of liver disease. Despite the vascular nature of these malignancies, percutaneous biopsy procedures performed in 66 patients provided diagnostic material in over 85% of cases with little morbidity. Histologic diagnosis was made by blind percutaneous biopsy (41 done, 83% positive), peritoneoscopy with directed percutaneous biopsy (25 done, 88% positive), laparotomy (42 done, 98% positive), or autopsy (19). Percutaneous hepatic biopsy procedures were associated with no mortality and rare bleeding (three cases). Overall median survival was only 18 weeks; multivariate analysis indicated increased bilirubin or presence of pulmonary metastases adversely influenced outcome. Unexpectedly, patients younger than 45 years of age had a significantly (P < 0.01) greater survival (median, 40 versus 9 weeks) than did older patients with this disease. We conclude: (1) hepatocellular carcinoma can be rapidly and safely diagnosed using percutaneous biopsy procedures; (2) North American patients with hepatocellular carcinoma younger than 45 years of age have a more favorable prognosis.

Pathological spectrum of liver diseases in sickle cell disease

Most pathologic studies of liver disease in sickle cell anemia and its variants were performed retrospectively on autopsy specimens, and, because of the prominent histologic features of intrasinusoidal sickling and Kupffer cell erythrophagocytosis, hepatic dysfunction was attributed to the intrahepatic sickling of erythrocytes in this hemoglobinopathy. We compared the liver histology from 19 patients who had liver biopsies to the autopsy specimens from 32 patients who succumbed to the complications of the hemoglobinopathy. In the former, nine patients had histological evidence of viral hepatitis. Four of these patients had both serological and immunohistochemical evidence of hepatitis B surface antigen. The features of biliary tree obstruction were found in two cases and alcoholic cirrhosis and sarcoid granuloma in one case each. Only one patient, who had recovered from septic shock, showed ischemic necrosis. In five patients incidentally biopsied during cholecystectomy, no significant lesions were found. Fourteen of the autopsy specimens showed ischemic necrosis, a result which was significantly different from the biopsy group. Ten cases had no significant morphologic changes other than heavy iron deposits. There were two cases with chronic active hepatitis, two with diffuse fibrosis, and one case each of cirrhosis, acute viral hepatitis, cholestasis, and giant cell hepatitis. Intrahepatic sickling and erythrophagocytosis were seen in almost all specimens and did not correlate with liver disease or transaminase elevation. Other than the patient with septic shock, ischemic necrosis was found only in postmortem material. These histological features may represent red cell destruction rather than the etiology of liver disease in these patients.

A predictive model for the development of hepatocellular carcinoma, liver failure, or liver transplantation for patients presenting to clinic with chronic hepatitis C.

ObjectiveChronic infection with hepatitis C may lead to the development of cirrhosis, liver failure, and hepatocellular carcinoma. However, not all patients progress to these endpoints. Ideally, clinicians could improve their capability of stratifying the risk and the time frame within which their patients will progress to these endpoints. The purpose of the present study was to construct statistical models predicting disease progression for individual patients.MethodsStudy endpoints were the development of hepatocellular carcinoma, liver transplantation, or death due to liver disease. The study cohort was 256 patients with hepatitis C acquired from either blood transfusion or use of intravenous drugs. During follow-up, 17 patients developed hepatocellular carcinoma, seven received liver transplantation, and 12 died from liver disease.ResultsOn multivariate analysis a history of decompensation (relative risk [RR] 4.321, 95% confidence interval [CI] 1.777–10.511) and the serum albumin (RR 0.253, 95% CI 0.136–0.474) were independently associated with the study endpoints. Patients without a history of decompensation and with a serum albumin ≥4.1 mg/dl had a 3.2% chance of developing the study endpoints within 5 yr. Patients with a history of decompensation and a serum albumin <4.1 mg/dl had a 40% chance of developing a study endpoint within 5 yr. Baseline genotype and quantitative RNA were not associated with development of the clinical endpoints, with the exception of patients coinfected with two or more genotypes.ConclusionsThus, the serum albumin and a history of decompensation are useful for predicting the development of hepatocellular carcinoma, liver transplantation, and death due to liver disease among patients with hepatitis C.

Evidence for clustering of hepatitis B virus infection in families of patients with primary hepatocellular carcinoma

Family members of 13 patients with hepatitis B surface antigen (HBsAg) positive primary hepatocellular carcinoma (PHC) were tested for the presence of hepatitis B virus‐associated antigens and antibodies. Of the 122 members examined, circulating HBsAg was detected in 47 (39%), antibody to HBsAg (anti‐HBs) was found in 37 (30%), and antibody to hepatitis B core antigen (anti‐HBc) alone was present in 13 (11%). The relatives with the highest frequency of HBsAg positivity were the offspring of the propositus, followed by the nieces and nephews and the grandchildren. Anti‐HBs and anti‐HBc were detected most often in the spouses and non‐blood relatives. Evidence for past and present hepatitis B virus (HBV) infection was more frequently found in the Asian family members when compared to the non‐Asians. The e antigen (HBeAg) was present in 38% of the HBsAg positive individuals, including four with PHC; antibody to HBeAg (anti‐HBe) was rarely detected. These results indicate that clustering of HBV infection was commonly present in family members of patients with PHC. The HBsAg positive individuals may be major contributors to the endemic pool of the virus, and may themselves be potential cases of chronic active type B hepatitis, cirrhosis, and PHC.

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir

AbstractIntroductionnLoss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos(t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied.MethodsnWe retrospectively studied the outcomes of 54 HBeAg-positive CHB patients who were treated with either ETV (nxa0=xa030) or TDF (23) or both (nxa0=xa01) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment.ResultsOnly 4 (7xa0%) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24xa0%) continued to have HBV DNA levels below 2000xa0IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69xa0%) developed HBV DNA >2000xa0IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62xa0%) remained HBeAg negative/anti-HBe positive, 12 (32xa0%) became HBeAg positive, and 2 (5xa0%) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse.ConclusionsDurability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy.

Hepatitis B Vaccination of Neonates and Children

Perinatal transmission of the hepatitis B virus (HBV) occurs in a high percentage of infants born to mothers who are acutely infected with the virus at the time of delivery or who are chronic carriers of the hepatitis B surface antigen (HBsAg). The majority of infants who acquire the virus during the perinatal period and become HBV carriers have no clinical symptoms. However, there are reports of acute and fulminant hepatitis and even primary liver cancer occurring in a few HBsAg-positive infants. Immunoprophylaxis given to infants born to HBsAg-positive mothers at birth with a combination of hepatitis B immunoglobulin and hepatitis B vaccine is the most effective means of preventing the chronic HBV carrier state and its potential complications. In a multicenter trial in the United States, 85 to 90 percent of the children of HBsAg-positive mothers remained HBsAg-negative when treated with this combination regimen. Studies conducted outside the United States have yielded similar results. Other investigations indicate that the hepatitis B vaccine alone may be of value in preventing perinatal transmission of HBV in developing countries that are unable to afford hepatitis B immunoglobulin.

Immunologic studies and clinical follow-up HBsAg-positive polyarteritis nodosa

Three patients with hepatitis B surface antigen (HBsAg)-positive polyarteritis nodosa (PAN) who are clinically well 41/2–51/2 years after their initial illnesses are described. In each case electron microscopic studies demonstrated the presence of aggregates of HBsAg in both acute and quiescent phase sera. One patient had a lower circulating HBsAg titer during the acute illness, while no change in serial HBsAg titers was observed in the other two patients. Two of the three patients showed lymphocyte transformation to purified HBsAg during the quiescent phase of the PAN. The role of immune complexes in the pathogenesis of HBsAg-positive PAN is discussed.

Lack of supportive evidence for an autosomal recessive inheritance in chronic hepatitis B infections.

Two families with persistent hepatitis B infections are described. The patterns of HBsAg positivity in the parents and offspring are not compatible with the theory that susceptibility to chronic hepatitis B infection is inherited as an autosomal recessive trait.Two families with persistent hepatitis B infections are described. The patterns of HBsAg positivity in the parents and offspring are not compatible with the theory that susceptibility to chronic hepatitis B infection is inherited as an autosomal recessive trait.

T and B Lymphocytes in Uremic Patients with Type B Hepatitis Infection

Peripheral T and B lymphocytes were measured in (1) hepatitis B surface antigen (HBsAg)-positive, (2) HBsAg-negative uremic patients on chronic hemodialysis (CHD) therapy, and (3) patients with type B chronic active viral hepatitis (CAVH). When compared to normals, a decrease in the absolute number of T and B lymphocytes was detected in both CHD groups. CAVH patients had a decrease in the total number of T lymphocytes. When expressed as percentage of T lymphocytes, normals and HBsAg-negative CHD patients had similar values, while a decrease was detected in both HBsAg-positive CHD and CAVH patients. Also, in the latter two groups, hepatitis B virus infection resulted in an increase in the total number and percentage of null cells.