Serum angiotensin converting enzyme activity in evaluation of patients with liver disease.

This study was undertaken to evaluate angiotensin converting enzyme activity in patients with liver disease, and to explore its relationship to thyroid function in patients with liver disease. Serum angiotensin converting enzyme activity and thyroid hormone levels, determined in 79 patients with intrahepatic-type liver disease and 18 patients with extrahepatic biliary obstruction, were compared with values in 129 euthyroid controls. Serum angiotensin converting enzyme activity was higher in intrahepatic disease than in extrahepatic obstruction, but statistically significant only for acute intrahepatic disease. In the patients studied, high serum angiotensin converting enzyme activity (22 units/ml or more) virtually excluded extrahepatic biliary obstruction, with a negative predictive value of 94 percent. Low serum angiotensin converting enzyme activity had a positive predictive value for extrahepatic obstruction of only 67 percent. Increased angiotensin converting enzyme activity could not be explained as a function of enhanced thyroid activity. Serum angiotensin converting enzyme activity may be useful in separating patients with intrahepatic liver disease from those with extrahepatic obstruction.

Hepatitis B virus infection and hepatocellular carcinoma: correlation between IgM antibody to hepatitis B core antigen, hepatitis B e antigen, and hepatitis B DNA.

Sera from 102 black patients with primary hepatocellular carcinoma (PHC) and hepatitis B surface antigenemia were tested for immunoglobulin M antibody against hepatitis B core (IgM anti-HBc), hepatitis B e antigen (HBeAg), and hepatitis B viral (HBV) DNA. Their prevalences were compared to those of a control group of 124 age and sex matched black HBV carriers without tumor. IgM anti-HBc was present in 68.6%, HBeAg in 32.3%, and HBV-DNA in 26.7% of the patients. In the control population, IgM anti-HBc was present in 45%, HBeAg was detected in 3.2%, and HBV-DNA in 25.8%. We conclude that IgM anti-HBc is present appreciably more often than either HBeAg or HBV-DNA in patients with PHC. HBeAg or IgM anti-HBc in serum of HBsAg positive carriers may predict an added risk of PHC development in South African blacks.

Hepatitis C in Peru: risk factors for infection, potential iatrogenic transmission, and genotype distribution.

A large seroepidemiologic and genotyping study of hepatitis C virus (HCV) was conducted in Lima, Peru, during the periods of 1986 to 1993 (cohort A) and 1994 (cohort B). Anti-HCV seroprevalence rates were 15.6% (216 of 1,389) and 11.7% (168 of 1,438), respectively. Low rates were seen among volunteer blood donors (1.1% and 0.8%). Anti-HCV rates were much higher among patients undergoing hemodialysis (43.7% and 59.3%), hemophiliacs (60.0% and 83.3%), in those more than 39 years old (18.2% and 26.0%), in females (25.0% and 27.4%), and in less-educated persons (16.9%). Age- and gender-adjusted risk factors in cohort B included blood transfusion history (adjusted odds ratio [AOR] = 29.8), prior organ transplantation (AOR = 9.1) or a history of hepatitis (AOR = 4.9), previous hospitalization (AOR = 3.7), a history of intravenous drug use (AOR = 3.5), prior major surgery (AOR = 2.6), a history of acupuncture (AOR = 2.1), previous dental procedures (AOR = 1.2), and prior medical injections (AOR = 1.04). The most prevalent HCV genotype was type 1 (86%), followed by type 3 (10%) and type 2 (2%). Transmission through unsafe injection-related and medical/dental procedures appears to play an important role in HCV infection among Peruvians.

Hepatic emergencies in pregnancy.

Although liver disease during pregnancy is a rare event, it can have devastating effects on the mother and the child. This article reviews diseases uniquely associated to pregnancy, such as fatty liver of pregnancy, toxemia, and others. It also details new advances in diseases such as viral hepatitis and pregnancy and intrahepatic cholestasis of pregnancy.

Serologic diagnosis of viral hepatitis.

Viral hepatitis has become a difficult field in which clinical and laboratory skills are needed to establish the correct diagnosis and plan for the appropriate therapy. For example, it is no longer enough to diagnose chronic hepatitis B or C. Now, the viral titer or viral genotype must be known. The laboratory test then must be understood in the context of the clinical presentation. This article helps the clinician to acquire such working knowledge. It summarizes available data for hepatitis A, B, C, D, and E. It also includes the recently discovered viral agents, hepatitis G and the hepatitis GB agents.

Initial report of a hepatitis investigation in rural Belize.

In spring 1991, Belizian health officials expressed concern about a possible hepatitis outbreak in a banana farming district. A study was designed to identify cases and to address the serological prevalence of hepatitis virus markers. Three populations were studied: (i) persons meeting a clinical case definition for hepatitis; (ii) designated banana workers; and (iii) people in a random sample of households in the community. Information was collected using questionnaires and sera were collected for laboratory testing. This report presents the preliminary results of a study conducted in June 1991. Among people who met the clinical case definition, 24% of 42 tested had immunoglobulin M antibody to hepatitis B virus (HBV) core antigen (anti-HBc IgM). In the worker and household survey populations, 284 and 280 people, respectively, were tested for anti-HBc IgM. In each group, 4% were positive. HBV surface antigen was found in 37% of 43 clinical cases, 18% of workers, and 13% of people in the household survey. Among the 3 study populations, the prevalence of HBV core antibody (anti-HBc) ranged from 73% to 81%. Almost all tested persons had evidence of prior hepatitis A virus infection. Evidence of prior infection with hepatitis viruses A and B was widespread, but an aetiology could not be established for most of the clinical cases. However, the prevalence of hepatitis B markers in this population was very high compared to other reports from the Caribbean.

Serologic markers of hepatitis B virus (HBV) and hepatitis D virus infection in carriers of hepatitis B surface antigen who are frequently exposed to HBV.

Serum hepatitis B e antigen (HBeAg) and HBV DNA are indicators of active replication of HBV, whereas IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to chronic HBV infection. Fifty-eight carriers of hepatitis B surface antigen (HBsAg) who had frequent parenteral exposures were studied for the presence of HBeAg, HBV DNA, IgM anti-HBc and hepatitis delta virus (HDV) serologic markers. Active replication of HBV was detected in 36.2% (25% of drug addicts, 16.7% of thalassemia patients, and 46.9% of hemodialysis patients) and seropositivity for IgM anti-HBc in 55.2% of the HBsAg carriers. Among the 39 HBsAg carriers who were negative for HBeAg, IgM anti-HBc was detected significantly more frequently than HBV DNA (46.1% vs. 5.1%, p less than 0.001). Serologic evidence of HDV infection was detected in 35% of drug addicts, 50% of thalassemia patients and in 9.4% of hemodialysis patients. These data revealed that continued replication of HBV was more frequent in hemodialysis patients than in drug addicts and thalassemia patients who are HBsAg carriers and the opposite was true for the prevalence of HDV infection.

Serologic diagnosis of viral hepatitis.

The diagnosis of viral hepatitis is complex, particularly when the five leading causative agents belong to different virus families and evoke distinct immunologic response. This article connects known serologic markers to new methods and guides the ordering and interpretation of contemporary laboratory tests.

Low-molecular-weight IgM antibody to hepatitis B core antigen in chronic infections with hepatitis B virus.

IgM antibody to hepatitis B virus core antigen (IgM anti-HBc) develops during acute hepatitis B but frequently persists in chronic infections. To characterize persistent IgM anti-HBc better, 7-8S and 19S immunoglobulin fractions were prepared by rate-zonal centrifugation of sera from 17 patients with persistent hepatitis B (chronic active hepatitis) and were tested for IgM anti-HBc by a specific radioimmunoassay. In 16 sera peak activity was found in 7-8S fractions, although in 11 sera a minor peak was also present in 19S fractions. The low molecular weight of the predominant IgM anti-HBc was confirmed by gel filtration. In competition experiments, the binding of 7-8S antibody to an anti-IgM-coated solid phase was blocked more effectively by purified IgM than by purified IgG. These findings indicate that hepatitis B carriers with chronic active hepatitis have predominantly 7-8S IgM anti-HBc and represent a novel demonstration of naturally occurring 7-8S IgM with defined antiviral specificity.

A 22-year-old man with a liver mass and markedly elevated serum alpha fetoprotein.

Our patient presented with a large liver mass, an extremely elevated AFP level, and an almost certain diagnosis of HCC. However, extensive evaluation and biopsies failed to demonstrate malignancy, and the available evidence strongly suggests that the patient has an adult polycystic disease without renal involvement, and that the mass was the result of hemorrhage and degenerative changes in one of his cysts. Polycystic diseases can involve only one lobe, as it appears in this case. Only about 10-15% of patients with polycystic disease have symptoms due to the liver disease, while 30-50% have associated renal disease. Thus, our patient is unusual in several respects. However, his liver mass has decreased in size, he feels well, and his biochemical abnormalities have returned to normal. Despite a classic presentation for HCC, this case underscores the necessity for a thorough evaluation, especially for patients without major risk factors for hepatocellular carcinoma.

Effect of corticosteroid therapy on levels of antibody to hepatitis B core antigen in patients with chronic type B hepatitis.

Serum levels of antibody to hepatitis B core antigen and IgM antibody to hepatitis B core antigen were tested in 15 patients who participated in a randomized, placebo-controlled trial of a 28-day course of prednisolone therapy. During treatment, serum levels of antibody to hepatitis B core antigen and IgM antibody to hepatitis B core antigen decreased in all 10 treated patients, but in none of five controls (p less than 0.05). Also during therapy, ALT activity decreased by an average of 50% and serum IgG levels by 30% (both p less than 0.05). Serum levels of hepatitis B virus DNA and DNA polymerase activity did not change significantly. Four to 10 weeks after discontinuation of prednisolone, a rebound of serum ALT and IgM antibody to hepatitis B core antigen levels occurred, which usually resolved within the subsequent months of follow-up evaluation. In three patients, however, there was a prolonged exacerbation of the disease following prednisolone withdrawal; in these three, levels of IgM antibody to hepatitis B core antigen and ALT remained elevated above pretreatment values. The close correlation between changes in serum ALT activity and IgM antibody to hepatitis B core antigen levels suggests that corticosteroids can modulate disease activity in chronic type B hepatitis by suppression of the host-immune response to hepatitis B virus antigens.

19S and 7-8S forms of IgM antibody to hepatitis B core antigen in acute icteric hepatitis superimposed on hepatitis B surface antigen carriage.

The 19S and 7-8S forms of IgM antibody to hepatitis B core antigen (IgM anti-HBc) were separated by rate-zonal centrifugation from the serum of 20 Greek hepatitis B surface antigen (HBsAg) carriers with a superimposed acute icteric hepatitis positive for IgM anti-HBc by a radioimmunoassay. Serological markers of hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis D virus (HDV) infections were detected with radioimmunoassays and serum HBV DNA was detected with molecular hybridization techniques. Eighteen of the 20 carriers showed a predominance of one or the other form of IgM anti-HBc. Low molecular weight (7-8S) IgM anti-HBc was observed more frequently in HDV superinfection (5/9) and was related to a low mortality (1/9). In contrast, 19S IgM anti-HBc was observed more frequently in reactivation of chronic hepatitis B (6/9) and was related to a high mortality (5/9). These preliminary data show that in HBsAg carriers with a superimposed acute icteric hepatitis, predominance of 19S IgM anti-HBc is frequently associated with a severe clinical course; the opposite is true for predominance of 7-8S IgM anti-HBc.

Recurrent clinical exacerbations of liver disease during the course of infection with hepatitis C virus.

Symptomatic clinical relapses during the course of chronic hepatitis C virus (HCV) infection are uncommon. Furthermore, acute liver dysfunction with elevated bilirubin during alpha-interferon therapy without other apparent coexisting diagnoses is rare. The case of a 31-yr-old man with three clinical exacerbations of HCV infection over an 18-month period is described. The third episode was characterized by rising serum aminotransferase levels on alpha-interferon therapy. The precise cause of this patient's flares is unknown. An immunologically mediated clearance of the hepatitis C virus, mutation of HCV, or infection with different HCV viral strains are the leading possibilities.

Serological markers of hepatitis B virus and hepatitis D virus infections in Greek adults with primary hepatocellular carcinoma.

Primary hepatocellular carcinoma (PHC) has been linked etiologically to chronic hepatitis B virus (HBV) infection by epidemiologic and molecular lines of evidence. Serologic evidence of HBV and hepatitis delta virus (HDV) infection was assessed in sera from 47 Greek patients with PHC. Radioimmunoassays for the detection of serological markers of HBV and HDV infections and molecular hybridization techniques for the detection of HBV DNA sequences were used. Serological evidence of HBV infection was found in 93.6% of PHC patients. Of the 47 patients, 20 (42.6%) were positive for HBsAg, 43 (91.5%) were positive for anti-HBc and 21 (44.7%) were positive for anti-HBs. Anti-HBe was detected in a high percentage (90%) of HBsAg positive PHC patients. Anti-HBc IgM was also detected in 90% of HBsAg positive PHC patients; in contrast, HBV DNA was detected only in 5% of them. None of the 47 patients had serological evidence of HDV infection. These data show that HBV appears to be the principal etiological agent of PHC in Greece.

Low-dose intradermal and intramuscular vaccination against hepatitis B.

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Evaluation of liver histology, ALT elevation, and HCV RNA titer in patients with chronic hepatitis C.

OBJECTIVE: Hepatic histological evaluation is currently the gold standard to determine the degree of liver injury in chronic hepatitis C. It is unclear whether degree of serum ALT elevation or quantitative hepatitis C virus (HCV) RNA can predict level of histological damage. METHODS: Fifty nine biopsies from 44 patients with chronic hepatitis C were reviewed. The amount of liver damage was quantified using the Histology Activity Index (HAI) and was compared with serum ALT and, in 26 biopsies, quantitative HCV RNA (branched DNA amplification, Quantiplex, Chiron). RESULTS: A statistically significant linear relationship was noted between degree of ALT elevation and amount of liver injury based on HAI score (p < 0.05) although this relationship was not statistically strong (rs = 0.4900). No significant correlation was noted between serum ALT and HCV RNA titer (rs = 0.4044) or between quantitative HCV RNA titer and HAI score (rs = 0.3506). No individual component of the HAI correlated with ALT or HCV RNA. CONCLUSIONS: Although there is a correlation between serum ALT and degree of hepatic injury based on HAI score, this relationship is weak and probably of no clinical use. There is no significant correlation between HCV RNA and serum ALT or HCV RNA and degree of hepatic injury in individual patients. Hepatic histological evaluation continues to be required for clinical assessment of patients with chronic hepatitis C.

Small bile duct abnormalities in sarcoidosis.

We report four patients with hepatic involvement of sarcoidosis manifested primarily by bile duct depletion. The patients developed fever, weight loss, anorexia, a markedly elevated alkaline phosphatase, and mildly abnormal serum levels of aspartate aminotransferase. Endoscopic retrograde cholangiopancreatography showed slight intrahepatic irregularities but were not diagnostic of sclerosing cholangitis. Liver biopsy showed predominantly bile duct depletion, ranging from an estimated 10-100% absence of bile ducts in portal areas, which correlated with the degree of fibrosis. The degree of bile duct depletion is useful as a histological marker in patients with sarcoid liver disease. Steroids improve symptoms, but do not inhibit the development of "ductopenia."

Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection.

A newly developed assay for IgA class antibody to hepatitis E virus (IgA anti-HEV) was used to study 145 serum samples collected during an outbreak of an enterically transmitted hepatitis that occurred in 3 villages in the lower Shebeli region of Southern Somalia between January, 1988 and November, 1989. A total of 52.4% of the afflicted patients were found positive for IgA anti-HEV, and 73.1% of these were also positive for IgM. Both antibodies disappeared during the convalescence period. Similar results were also seen in serum obtained from sporadic cases of acute waterborne hepatitis in Pakistan.