Julia Uhanova

Occult hepatitis B virus infection in a North American adult hemodialysis patient population

Hepatitis B virus (HBV) infections continue to occur in adult hemodialysis units. A possible contributing factor is the presence of occult HBV (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive). Two hundred forty‐one adult hemodialysis patients were screened for occult HBV. HBV DNA testing was performed by real‐time polymerase chain reaction (PCR) with 2 independent primer sets (core promoter and surface). Two (0.8%) of the 241 patients were HBsAg positive. Of the remaining 239 HBsAg‐negative patients, 9 (3.8%) were HBV DNA positive. Viral loads in these individuals were low (102‐104 viral copies/mL). Seven of the 9 (78%) were nt 587 mutation (sG145R mutant) positive. Demographic, biochemical, and HBV serological testing did not help to identify those with occult HBV. In conclusion, the prevalence of occult HBV in adult hemodialysis patients in this North American urban center is approximately 4 to 5 times higher than standard HBsAg testing would suggest. The majority of these infections are associated with low viral loads and a high prevalence of the sG145R mutant. Finally, the demographic, biochemical, and/or serological features of HBV DNA–positive subjects do not distinguish these individuals from the remainder of the dialysis patient population. (HEPATOLOGY 2004; 40:1072–1077.)

Symptoms of obstructive sleep apnea in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a term often used to describe two related conditions: a relatively benign, nonalcoholic fatty liver (NAFL) and potentially aggressive, nonalcoholic steatohepatitis (NASH). Both conditions (NAFL and NASH) occur in the setting of peripheral insulin resistance. Recently, obstructive sleep apnea (OSA) has been proposed as an independent risk factor for insulin resistance. To date, few studies have documented the prevalence of OSA or symptoms of OSA (SOSA) in NAFLD patients. The objectives of this study were (1) to document the prevalence of SOSA in patients with NAFLD and (2) to determine whether prevalence rates for SOSA differ in NAFL versus NASH patients. One hundred ninety biochemically defined NAFLD patients (116 NAFL and 74 NASH), of whom 50 (18 NAFL and 32 NASH) had undergone liver biopsy, completed a Modified Berlin Sleep Apnea Questionnaire for SOSA. Risk factors for NAFLD were also documented in NAFL and NASH patients. Eighty-seven of the 190 (46%) NAFLD patients met questionnaire criteria for SOSA. The prevalence of SOSA was similar in both biochemically (45% versus 49%, respectively; P= 0.66) and histologically (39% versus 63%, respectively; P= 0.11) defined NAFL and NASH patients. Other risk factors for NAFLD such as body mass index, plasma cholesterol and triglyceride levels, and prevalence of diabetes were also similar in the two groups. Approximately one-half of NAFLD patients, whether NAFL or NASH, have SOSA. Further studies are required to determine whether a causal link exists between NAFLD and OSA.

Hepatorenal syndrome: diagnostic accuracy, clinical features, and outcome in a tertiary care center

Hepatorenal syndrome: diagnostic accuracy, clinical features, and outcome in a tertiary care center

Viral Hepatitis in the Canadian Inuit and First Nations Populations

OBJECTIVE To review published prevalence data regarding hepatitis A (HAV), B (HBV) and C (HCV) in Canadian Inuit and First Nations populations. METHODS PubMed database search and review of all papers describing data derived from seroepidemiological surveys. RESULTS The prevalence of anti-HAV positivity in Canadian Inuit and First Nations populations reported to date is high (range 75% to 95%) and approximately three times that of non-Aboriginal Canadians residing in the same communities. Among the Canadian Inuit, the prevalence of HBV infection is approximately 5%, or 20 times that of non-Aboriginal Canadians, while the risk of exposure to HBV is 25%, or five times higher. Regarding the First Nations population, preliminary data suggest the prevalences of HBV infection (0.3% to 3%) and exposure (10% to 22%) are similar to rates in non-Aboriginals residing in the same regions and participating in similar high risk activities. Serological evidence of HCV infection (anti-HCV) is more common in the Canadian Inuit and First Nations (1% to 18%) than the remainder of the Canadian population (0.5% to 2%); however, viremia (HCV-RNA positivity) is less common (less than 5% versus 75% of anti-HCV positive individuals, respectively). CONCLUSIONS Viral hepatitis is common in the Canadian Inuit and First Nations populations. In the absence of coexisting human immunodeficiency virus infection and alcohol abuse, the outcomes of HBV and HCV appear to be more benign than in non-Aboriginal Canadians.

Serum immunoglobulins predict the extent of hepatic fibrosis in patients with chronic hepatitis C virus infection

Summary.  Recently, we documented that immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. The aim of the present study was to determine whether there is any association between serum immunoglobulin levels and hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection. Charts from 116 patients with biochemical, serologic, virologic and histologic evidence of chronic hepatitis C infection and serum immunoglobulin levels (IgA, IgG, IgM and total) were reviewed. The mean (±SD) age of the study population was 46 ± 11 years and 67 (58%) were male. There were significant correlations between serum IgA (r = 0.39, P = 0.00001), IgG (r = 0.49, P = 0.000002) and total (r = 0.51, P = 0.000003) immunoglobulin levels and the stage of hepatic fibrosis. When serum immunoglobulin levels were included into logistic regression analysis with variables known to be associated with advanced disease (male gender, age >40 years at onset of infection, duration of infection beyond 20 years and concurrent alcohol abuse) only IgA, IgG and total immunoglobulin levels (P < 0.05, <0.05 and <0.005, respectively) emerged as independent predictors of hepatic fibrosis. Our data indicate a strong association between serum immunoglobulin levels (IgA, IgG and total) and hepatic fibrosis in patients with HCV infection. This finding supports the need to further investigate whether immunoglobulins independently promote disease progression in patients with chronic HCV infection.

Autoimmune Hepatitis in a North American Aboriginal/First Nations Population

North American Aboriginal populations are at increased risk for developing immune-mediated disorders, including autoimmune hepatitis. In the present study, the demographic, clinical, biochemical, serological, radiological and histological features of autoimmune hepatitis were compared in 33 First Nations (FN) and 150 predominantly Caucasian, non-FN patients referred to an urban tertiary care centre. FN patients were more often female (91% versus 71%; P=0.04), and more likely to have low serum albumin (69% versus 36%; P=0.0006) and elevated bilirubin (57% versus 35%; P=0.01) levels on presentation compared with non-FN patients. They also had lower hemoglobin, and complement levels, more cholestasis and higher serum immunoglobulin A levels than non-FN patients (P=0.05 respectively). Higher histological grades of inflammation and stages of fibrosis, and more clinical and radiological evidence of advanced liver disease were observed in FN patients, but the differences failed to reach statistical significance. The results of the present study suggest that in addition to being more common, autoimmune hepatitis may be more severe in FN populations, compared with predominantly Caucasian, non-FN populations.

A population-based study of the epidemiology of hepatitis C in a North American population

BACKGROUND & AIMS Chronic hepatitis C virus (HCV) infection is a major public health problem with approximately 3% of the worlds population thought to be chronically infected. However, population-based data regarding HCV incidence rates, prevalence, residence, age, and gender distributions within North America are limited. We aimed at providing a detailed descriptive epidemiology of HCV infection in a North American population with a focus on time trends in incidence rates and prevalence of newly diagnosed HCV infection since 1991, the time when laboratory testing for HCV infections became first available. METHODS A Research Database was developed linking records from multiple administrative sources. HCV positive residents of the Canadian province of Manitoba were identified during a twelve-year period (1991-2002). The cumulative and annual incidence rates and the prevalence of newly diagnosed HCV infection in Manitoba were examined and compared between different demographic groups and urban vs. rural residents. RESULTS A total of 5018 HCV positive cases were identified over a 12-year period. The annual number of newly diagnosed HCV infections peaked in 1998 (59.2/100,000). On the other hand, the known prevalence of HCV continued to increase (4.6-fold during the 12-year study period) among both men and women reflecting the chronic nature of the disease. Males were 1.7 times more often infected than females. HCV infections were more common in urban centers. CONCLUSIONS Between 1995 and 2002, there was a fairly constant trend for newly diagnosed HCV infection, ranging from approximately 500 to 600 new cases annually. Hence, with a stable population size, and a low case fatality rate, the prevalence of HCV infected persons in our population has been steadily rising. There is no evidence to suggest that the incidence of HCV infection will raise, however, the burden of chronic HCV infection will continue to increase, particularly amongst older males and those residing in urban centers.

Hepatic 31P MRS in rat models of chronic liver disease: assessing the extent and progression of disease.

Background: Hepatic adenosine triphosphate (ATP) levels are an accurate reflection of functioning hepatic mass following surgical resections and acute liver injury. Objective: To determine whether hepatic ATP levels can serve as a non-invasive means of documenting progression of chronic liver disease to cirrhosis. Methods: In vivo phosphorus-31 magnetic resonance spectroscopy (31P MRS) was performed in three animal models of chronic liver disease. Sixty six adult Sprague- Dawley rats were subjected to either thioacetamide, carbon tetrachloride (CCl4), or common bile duct ligation (CBDL) to induce liver disease (n=35, 21, and 10, respectively). Serial MRS examinations, blood samples, and liver biopsies (when appropriate) were obtained throughout and/or on completion of the study. Results: Over the course of the chronic liver disease, a progressive decrease in hepatic ATP levels was consistently observed in each model. The findings were most striking when end stage liver disease (cirrhosis) was established. The reduction in hepatic ATP levels correlated with significant changes in serum albumin concentrations (CCl4 and CBDL models) and the extent of hepatocyte loss seen histologically (all models). Conclusion: The results of this study indicate that during progression of chronic liver disease to cirrhosis, there is a progressive reduction in hepatic ATP levels. In addition, changes in hepatic ATP levels correlate with changes in liver function and histology. Thus hepatic 31P MRS provides a non-invasive means of documenting the severity and progression of parenchymal and cholestatic models of chronic liver disease in rats.

Insights into SEN Virus Prevalence, Transmission, and Treatment in Community- Based Persons and Patients with Liver Disease Referred to a Liver Disease Unit

To document the prevalence and routes of transmission of SEN virus (SEN-V) in community-based individuals and patients referred to a liver disease unit, stored serum samples obtained from 160 Canadian Inuit and 140 patients with liver disease were tested for SEN-V DNA by polymerase chain reaction. In the community-based population, SEN-V was present in 57 (36%) of 160 persons. SEN-V-positive individuals tended to be younger and were more often male. Liver enzyme levels and serologic markers for hepatitis A and B viruses were similar in SEN-V-positive and SEN-V-negative individuals. SEN-V was present in 30 (21%) of the 140 patients with liver disease. Age, sex, risk factors for viral acquisition, prevalence of symptoms, and liver biochemical and histological findings were similar in SEN-V-positive and SEN-V-negative patients. These results indicate that SEN-V infection is a common viral infection in both healthy individuals and patients with chronic liver disease, that transmission likely occurs via nonparenteral routes, and that SEN-V infection is not associated with higher rates of or more-severe liver disease in persons with preexisting liver disease.

Serological Evidence of Hepatitis E Virus Infection in an Indigenous North American Population

BACKGROUND Hepatitis E virus (HEV) infections are thought to be uncommon in North America. Recently, HEV transmission has been reported following the consumption of deer meat. Because deer are closely related to caribou and caribou meat is a staple of the Canadian Inuit and the American Eskimo diet, the present study explored the seroprevalence of HEV infection in an isolated Canadian Inuit community. METHODS Stored sera were thawed and tested for immunoglobulin (Ig) G and IgM anti-HEV by ELISA, and tested for HEV-RNA by reverse transcriptase polymerase chain reaction. RESULTS The study consisted of 393 sera (representing approximately 50% of the communitys inhabitants). Eleven samples (3%) were IgG anti-HEV-positive. Their mean age was 29+/-8 years and three were male. Two of 11 (18%) were also IgM anti-HEV-positive. All IgG anti-HEV-positive individuals were HEV-RNA-negative. Liver biochemistry was normal in all. Seven of 11 (64%) were also positive for anti-hepatitis A virus, five (46%) were hepatitis B virus seropositive and none (0%) were positive for anti-hepatitis C virus. There were no associations between infections with HEV and other hepatropic viruses. Serological testing was negative for HEV infection in 25 caribou from an adjacent region. CONCLUSION The results of the present study showed that serological evidence of HEV infection was present in 3% of the observed Canadian Inuit population; the presence of IgM anti-HEV suggested recent infection and HEV did not appear to coinfect with other common hepatotropic viruses. The source of HEV infection in the population remains unclear. These findings are interesting but preliminary. Additional data are required to determine whether HEV infections are responsible for otherwise unexplained acute hepatitis in the Canadian Inuit population and visitors returning from northern North American communities.