Distinguishing between acute and symptomatic chronic hepatitis B virus infection

BACKGROUND/AIMS: Differentiating between an acute hepatitis B (AH-B) infection and an acute exacerbation of a chronic hepatitis B (CH-B) infection can present a problem for the clinician. The only current serological method of distinguishing between acute and symptomatic chronic hepatitis B virus (HBV) infection is the immunoglobulin M antibody to hepatitis B core antigen (anti-HBc) assay, which can be problematic. Therefore, in an attempt to better distinguish between acute and chronic HBV infection, sera from 26 patients with AH-B and 53 patients with CH-B were compared in a variety of experimental immunoassays. METHODS: Experimental assays have been designed to detect free antibody to hepatitis B e antigen (anti-HBe), hepatitis B e antigen (HBeAg)/anti-HBe immune complexes (ICs), and hepatitis B surface antigens (HBsAg)/antibody to hepatitis B surface antigen (anti-HBs) in the presence of excess antigen. An additional assay was developed to detect a novel anti-HBc specificity, designated antibody to woodchuck hepatitis virus (anti-HBcW), which cross-reacts with the core antigen of the woodchuck hepatitis virus. RESULTS: Sera from patients with CH-B showed significantly higher levels of free anti-HBe, HBeAg/anti-HBe ICs, and HBsAg/anti-HBs ICs compared with AH-B patient sera. Furthermore, patients with CH-B consistently produced high titer anti-HBcW, whereas patients with AH-B produced little or no anti-HBcW antibody. CONCLUSIONS: The serology of AH-B infection and symptomatic CH-B infection can be distinguished using a variety of experimental immunoassays in addition to the immunoglobulin M anti-HBc assay.     

Prevention of hepatitis A virus infection

Hepatitis A virus infection is major cause of acute hepatitis in the United States, accounting for approximately 75,000 cases of clinical illness each year. These infections occur among persons in every age group and are associated with a variety of exposures related to fecal-oral transmission. Recently, the U.S. Food and Drug Administration approved licensure of two inactivated hepatitis A vaccines. Both vaccines are highly immunogenic and have been licensed in pediatric and adult formulations. The prevention of hepatitis A virus infection is directly related to many aspects of family practice, and family physicians may see patients in a variety of settings that warrant administration of hepatitis A vaccine. Groups for whom vaccination is currently recommended include international travelers, children in communities with high rates of hepatitis A virus infection, men who have sex with men, Illicit drug users, patients with chronic liver disease and persons with clotting factor disorders.     

A case of vertical transmission of hepatitis A virus infection

We present a case of hepatitis A infection in a 2.5-month-old male who became icteric after 18 d of birth. The diagnosis of hepatitis A was made by compatible clinical symptoms, laboratory results and liver biopsy showing evidence of hepatitis, and confirmed by detection of anti-HAV IgM antibodies. Because the mother had an acute icteric hepatitis A 1 week before delivery, and the viraemic phase of hepatitis A infection is very short, approximately 7 d, we suggest that the infant was infected by his mother, before birth.     

Assisted reproduction and hepatitis C virus infection

Medically assisted procreation poses a difficult problem when one or both partners of couple are infected with HCV. Epidemiologic and fundamental works show a low risk of HCV sexual transmission and no pregnancy complications or fetal abnormalities have been reported. However, the outcome of HCV infected children is unknown. These contrasting findings suggest that medically assisted procreation using sperm of spouse needs to be cautious. Before medically assisted procreation, testing of couples for HCV antibodies must be done and interferon therapy is required for patients with histological chronic active hepatitis and for HCV positive mothers or infected couples. In the absence of specific legislation or consensual recommendations, detailed informations must be given to the couples in order to obtain an informed consent.     

Non-Hodgkin's lymphoma and hepatitis C virus infection

The hepatitis C virus (HCV) is a recently described and important cause of acute and chronic liver disease. A hallmark of HCV is its propensity to become chronic, some patients with chronic HCV progressing to cirrhosis and hepatocellular carcinoma (HCC). HCV is also lymphotrophic and we report 2 patients with HCV cirrhosis who developed non-Hodgkins lymphoma (NHL). These cases raise the possibility that chronic HCV infection of lymphocytes plays an aetiological role in this malignancy. However screening of a further 63 consecutive patients over the age of 50 years with NHL for HCV antibody by second generation enzyme linked immunoassay (ELISA) failed to identify any patients with evidence of HCV infection. This suggests that HCV is an uncommon contributory factor for the development of non-Hodgkins lymphoma in the United Kingdom.     

The natural course of hepatitis B and hepatitis C virus infection

Chronic hepatitis B and hepatitis C virus infections maintain a significant risk for the development of liver cirrhosis and hepatocellular carcinoma and cause a considerable morbidity in the population. Among patients with chronic HBV infection and histologically confirmed hepatitis the annual incidence of liver cirrhosis is 2%. The risk for hepatocellular carcinoma in chronic HBsAg carriers is elevated about 40-230 fold. 20-30% of patients with chronic HCV infection will develop cirrhosis over 20-30 years. Hepatocellular carcinoma evolves yearly in about 3% of patients with chronic HCV infection and cirrhosis, whereas HCV-carriers without cirrhosis usually do not develop hepatocellular carcinoma. The high incidence of serious sequelae warrants a regular surveillance of chronic virus carriers.     

Vertical transmission of hepatitis C virus infection

BACKGROUND: Cavernous carotid aneurysms are generally benign entities. Certain indications exist for their treatment, however, including transient ischemic events, subarachnoid hemorrhage or risk of subarachnoid hemorrhage, epistaxis or its risk, ophthalmoplegia, pain, and progressive visual loss. We feel certain angiographic features may indicate a greater likelihood that cavernous carotid aneurysms extend into the subarachnoid space, thus making their rupture a life-threatening event. METHODS: A case report of an intracavernous carotid aneurysm, which at surgery extended into the subarachnoid space, is described. RESULTS: In this particular case, deformation of the aneurysm (waisting) as seen at angiography was in retrospect an indication that the cavernous carotid aneurysm extended into the subarachnoid space, either through the dural ring or through the eroded dural roof of the cavernous sinus. This finding was verified at surgery when the lesion was explored and trapped. CONCLUSION: Angiographic waisting of a cavernous carotid aneurysm may indicate that the aneurysm extends into the subarachnoid space. Such extension means that rupture would be a life-threatening event. While deformation of the aneurysm may be secondary to compression against the optic nerve or anterior clinoid process with an intact layer of dura overlying the aneurysm, the neurosurgeon confronted with such findings should analyze such lesions carefully and consider surgical exploration.     

Interferon alpha in the treatment of prolonged hepatitis A virus infection

Hepatitis A viral infection usually lasts up to 12 weeks, but in 3-16% of patients relapses may occur and the course of the disease is protracted. The outcome of hepatitis A is always good, so that antiviral therapy is not necessary. However, from the aspect of patients with protracted course of the disease up to a year, it might be important to restore clinical recovery in a shorter period of time. Knowing about antiviral and immunomodulatory effects of endogenous interferon (virally activated) in treatment of protracted hepatitis A, we introduced interferon-alpha in the 12th week of the disease and followed-up its effects on the further course of the disease. The study comprised 80 patients with established diagnosis of acute protracted hepatitis A, excluding hepatitis B, Epstein-Barr, cytomegalovirus, adenovirus or toxic liver lesion. In 40 patients treated with interferon we followed up the activity of aminotransferases and persistence of IgM-anti-HAV in correlation with the same parameters in 40 patients treated symptomatically. The registered persistence of aminotransferases' pathological activity was 20:30 weeks (interferon: symptomatic therapy). In greater doses interferon affected the length of persistence IgM-anti-HAV, 20:34 weeks (interferon: symptomatic therapy).     

The elimination of hepatitis B virus infection: changing seroepidemiology of hepatitis A and B virus infection in Okinawa, Japan over a 26-year period

Serial changes in hepatitis A virus (HAV) and B virus (HBV) markers were determined from 1970 to 1996 in healthy Japanese residents of a rural area of Okinawa, Japan. All 190 serum samples taken in 1970, 791 in 1980, 708 in 1988, and 523 in 1996 from residents 0 to more than 60 years of age were tested for antibody to HAV (anti-HAV), antibody to hepatitis B core antigen (anti-HBc), and hepatitis B surface antigen (HBsAg). The age-adjusted prevalences of anti-HAV and anti-HBc decreased significantly from 83.9% and 74.9%, respectively, in 1970 to 39.7% and 36.6%, respectively, in 1996. In residents < or = 29 years of age, the prevalences of anti-HAV and anti-HBc decreased significantly from 65.3% and 83.8%, respectively, in 1970 to 0.7% and 8.2%, respectively, in 1996. The age-adjusted HBsAg prevalence decreased significantly from 8.2% in 1980 to 4.1% in 1988. These results indicate that exposure to HAV and HBV infections among Okinawa residents less than 29 years of age is decreasing, probably because of improvements in socioeconomic conditions since 1970. Infection with HBV may be eliminated there in the near future.     

Hepatitis GB virus C infection in Japanese hemophiliacs with persistent hepatitis C virus infection

We investigated the prevalence of infection of GBV-C, which has been cloned recently and is considered a parenterally transmissible virus. Ninety-one Japanese hemophiliacs who were persistently infected with HCV were evaluated. The presence of GBV-C RNA was measured by nested RT-PCR. We analyzed the prevalence and the association with subtypes of coinfected HCV. 20.9% of hemophiliacs were infected with GBV-C. The distribution of HCV subtypes of patients who are coinfected with GBV-C was similar to that of patients who are coinfected with HIV, and the prevalence of GBV-C infection of patients with HCV subtype la was significantly higher than that of patients without HCV subtype la. High prevalence of GBV-C infection was observed in Japanese hemophiliacs, and most were thought to be imported isolates from foreign origins, as well as HIV infection in these patients.     

Limited humoral immunity in hepatitis C virus infection

BACKGROUND & AIMS: The extremely high rate of chronicity to hepatitis C virus (HVC) infection suggests an inefficient immune response. The humoral immune response to HCV was evaluated in 60 patients with chronic HCV infection and in 12 patients acutely infected with HCV. METHODS: A number of recombinant HCV antigens including the core, envelope 2 (E2), nonstructural (NS) 3, NS4, and NS5 proteins, and NS4a and E2-HVR-1 peptides were used in enzyme-linked immunoassays. RESULTS: Immunoglobulin (Ig) G antibody responses to these viral antigens, except for the HCV core, were highly restricted to the IgG1 isotype. The prevalence of antibodies of the IgG1 isotype specific for the HCV core, E2, E2-HVR1, NS3 (helicase domain), NS4, and NS5 antigens was 97%, 98%, 28%, 88%, 33%, and 68%, respectively. Antibodies of the IgG3 isotype specific for E2, E2-HVR-1, NS3, NS4, and NS5 were detected in a minority of serum samples. The IgG2 and IgG4 isotypes were rarely if ever detected. Furthermore, antibody responses to HCV viral antigens were of relatively low titer and, with the exception of anti-HCV core, were delayed in appearance until the chronic phase of infection. CONCLUSIONS: The IgG1 restriction, low titer, and delayed appearance of antibody responses elicited during HCV infection suggest that the immunogenicity of HCV proteins is limited in the context of natural infection. Inasmuch as recombinant HCV viral antigens perform as relatively normal immunogens in small animals, we suggest that the defective humoral immune responses during HCV infection may be attributable to an "immune avoidance" strategy.     

Chronic hepatitis B virus infection in south Auckland

AIM: Previous studies have identified high prevalence rates of hepatitis B infection in New Zealand Maori, Pacific Island and Asian populations within New Zealand. However, the true impact of chronic hepatitis B virus (HBV) infection on health resources has not been evaluated. This study was designed to determine the incidence of serious sequelae of chronic HBV infection in a high prevalence community. METHODS: All patients treated for HBV-related conditions at Middlemore Hospital from January 1995 to January 1997 were identified through discharge coding and laboratory records. Demographic characteristics and laboratory results, including liver function tests, hepatitis serology and liver histology were recorded. Number of admissions, average length of stay and survival were calculated from Casemix data. RESULTS: During the study period, 215 patients were referred for management of hepatitis B infection, of whom 179 had persistently elevated aminotransferases. Forty six percent of patients were hepatitis B 'e' antigen (HBeAg) negative, and 21% of these had delta co-infection (all Samoan). Liver biopsy was performed in 87 patients with raised aminotransferases. No features of chronic hepatitis were found in 5%, mild chronic hepatitis in 30%, moderate to severe chronic hepatitis in 44% and cirrhosis in 22%. Fifty five patients were admitted to hospital during the two year period with an HBV-related diagnosis, with an average length of stay of 12.2 days compared to 4.9 days for all other medical and surgical admissions during this period (p < 0.001). Twenty eight of the 55 subsequently died, 20 from hepatocellular carcinoma. CONCLUSIONS: Chronic hepatitis B infection is associated with significant morbidity and mortality in Maori, Pacific Islanders and Asians living in South Auckland. Screening of these high risk populations with vaccination of noninfected individuals should reduce the incidence of these serious sequelae and eventually lead to eradication of HBV.