Improvement in Chronic Hepatocerebral Degeneration Following Liver Transplantation

Chronic progressive hepatocerebral degeneration with spastic paraparesis, dementia, dysarthria, ataxia, tremor, and neuropsychiatric symptoms follows long-standing portal-systemic shunting, is associated with structural changes in the central nervous system, and does not respond to conventional therapy for hepatic encephalopathy. A case of advanced chronic liver disease with severe, progressive hepatocerebral degeneration after 23 yr of portal-systemic shunting is reported in whom there was significant objective improvement in intellectual function and in the chronic neurological signs 3 mo after orthotopic liver transplantation and further improvement 12 mo after transplantation

Peginterferon Alfa-2a, Lamivudine, and the Combination for HBeAg-Positive Chronic Hepatitis B

Background: Current treatments for chronic hepatitis B are suboptimal. In the search for improved therapies, we compared the efficacy and safety of pegylated interferon alfa plus lamivudine, pegylated interferon alfa without lamivudine, and lamivudine alone for the treatment of hepatitis B e antigen (HBeAg)–positive chronic hepatitis B. Methods: A total of 814 patients with HBeAg-positive chronic hepatitis B received either peginterferon alfa-2a (180 µg once weekly) plus oral placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), or lamivudine alone. The majority of patients in the study were Asian (87 percent). Most patients were infected with hepatitis B virus (HBV) genotype B or C. Patients were treated for 48 weeks and followed for an additional 24 weeks. Results: After 24 weeks of follow-up, significantly more patients who received peginterferon alfa-2a monotherapy or peginterferon alfa-2a plus lamivudine than those who received lamivudine monotherapy had HBeAg seroconversion (32 percent vs. 19 percent [

Treatment with interferons (including pegylated interferons) in patients with hepatitis B

Studies of 4 to 6 months of treatment with interferon for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection have shown clearance of HBeAg to be higher in treated patients than it is in controls by approximately 25%. These results are considerably better than those with antiviral agents. Therefore, the recent European Association for the Study of the Liver (EASL) Consensus Committee recommended the use of interferon alpha for this condition. Treatment with pegylated interferons in several trials has shown better results still. Lamivudine in combination with interferon, however, did not improve the results at 6 months after the end of therapy. In HBeAg-negative chronic HBV infection, pegylated interferon alpha is superior to lamivudine, and, again, combination with lamivudine does not improve the results. Side effects in all studies have been tolerable. Thus, these observations in chronic HBV infection, whether HBeAg-positive or HBeAg-negative, suggest an important, even primary, role for pegylated interferon therapy

The Role of Interferon Therapy in Hepatitis B

W. Graham E. Cooksley, MD, explores the place that interferon currently holds in the therapeutic armamentarium against hepatitis B

Discordance of hepatitis B e antigen and hepatitis B viral deoxyribonucleic acid

Sera from 899 hepatitis B surface antigen (HBsAg) carriers from four separate ethnic groups (Caucasian, Australian Aboriginal, Melanesian, and Asian) were studied for their correlation for hepatitis B virus deoxyribonucleic acid (HBV DNA) and hepatitis B e antigen (HBeAg). Discordance, as signified by the absence of HBV DNA despite the presence of HBeAg, was unusual in Caucasians but frequently occurred in the other three ethnic groups (11–25%). Analysis by age showed that it occurred occasionally during childhood and, in this age group, may simply be part of the process of seroconversion with impending loss of HBeAg, whereas its greater prevalence in patients with liver disease may have a different mechanism. In sera obtained from Melanesians with hepatocellular carcinoma and Asians with chronic hepatitis, discordance was a common feature with HBV DNA being undetectable in those with HBeAg in 87% and 72%, respectively. A number of important implications flow from these observations pertinent to the use of HBeAg to detect replicating virus and the prognostic significance of HBeAg in HBsAg carriers when HBV DNA is undetectable

Discordance of hepatitis B e antigen and hepatitis B viral deoxyribonucleic acid

Sera from 899 hepatitis B surface antigen (HBsAg) carriers from four separate ethnic groups (Caucasian, Australian Aboriginal, Melanesian, and Asian) were studied for their correlation for hepatitis B virus deoxyribonucleic acid (HBV DNA) and hepatitis B e antigen (HBeAg). Discordance, as signified by the absence of HBV DNA despite the presence of HBeAg, was unusual in Caucasians but frequently occurred in the other three ethnic groups (11–25%). Analysis by age showed that it occurred occasionally during childhood and, in this age group, may simply be part of the process of seroconversion with impending loss of HBeAg, whereas its greater prevalence in patients with liver disease may have a different mechanism. In sera obtained from Melanesians with hepatocellular carcinoma and Asians with chronic hepatitis, discordance was a common feature with HBV DNA being undetectable in those with HBeAg in 87% and 72%, respectively. A number of important implications flow from these observations pertinent to the use of HBeAg to detect replicating virus and the prognostic significance of HBeAg in HBsAg carriers when HBV DNA is undetectable

The absence of hepatitis B virus DNA in hepatitis B e antigen positive sera from chronic hepatitis B surface antigen carriers in China

Sera from 20 Chinese patients with chronic hepatitis B were examined for hepatitis B e antigen and hepatitis B virus (HBV) DNA. There was considerable discordance with HBV DNA not being detectable in 10 out of 13 (77%) patients who were hepatitis B e antigen positive. Further testing for anti‐HBe and HBV‐DNA polymerase activity confirmed the results. Possible reasons for this discordance are discussed but neither hepatitis D (delta) infection nor the acquired immunodeficiency syndrome (AIDS) could be implicated

Symptom prevalence and clustering of symptoms in people living with chronic hepatitis C infection

Quality of life has been shown to be poor among people living with chronic hepatitis C. However, it is not clear how this relates to the presence of symptoms and their severity. The aim of this study was to describe the typology of a broad array of symptoms that were attributed to hepatitis C virus (HCV) infection. Phase 1 used qualitative methods to identify symptoms. In Phase 2, 188 treatment-naïve people living with HCV participated in a quantitative survey. The most prevalent symptom was physical tiredness (86%) followed by irritability (75%), depression (70%), mental tiredness (70%), and abdominal pain (68%). Temporal clustering of symptoms was reported in 62% of participants. Principal components analysis identified four symptom clusters: neuropsychiatric (mental tiredness, poor concentration, forgetfulness, depression, irritability, physical tiredness, and sleep problems); gastrointestinal (day sweats, nausea, food intolerance, night sweats, abdominal pain, poor appetite, and diarrhea); algesic (joint pain, muscle pain, and general body pain); and dysesthetic (noise sensitivity, light sensitivity, skin problems, and headaches). These data demonstrate that symptoms are prevalent in treatment-naïve people with HCV and support the hypothesis that symptom clustering occurs

Establishment of a cell line from a hepatocellular carcinoma from a patient with hemochromatosis

We describe the establishment and characterization of a novel hepatoma cell line. This cell line, designated RBHF‐1, was established from a hepatocellular carcinoma of a 67‐yr‐old man with a history of genetic hemochromatosis. At this writing, the cells have been maintained in RPMI‐1640 tissue‐culture medium and fetal calf serum without any additional supplements for 30 mo. The cells form colonies on soft agar and are not tumorigenic in nude mice. The cell line is polymorphic and displays characteristics of mature hepatocytes by synthesizing albumin, α2‐macroglobulin, fibronectin and α‐fetoprotein. Cytogenetic analysis shows multiple chromosomal aberrations, with a consistent deletion in the long arm and deletions or rearrangements in the short arm of chromosome 1. There is no evidence for hepatitis B or hepatitis C virus infection of the cell line. The cells contain no detectable intracellular iron after staining with Perls' stain. Unlike other hepatoma cell lines, there is no detectable binding of epidermal growth factor to RBHF‐1 cells. This is the first cell line to be established from a patient with hemochromatosis, and it provides a potentially important model for the study of hepatocyte transformation in association with iron overload. (Hepatology 1994;20:74–81.)</p