Liver enzymes and fibrosis markers in patients with non-alcoholic fatty liver disease and concomitant chronic viral hepatitis.

The impact of non-alcoholic fatty liver disease (NAFLD) on patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has yet to be determined. In this retrospective, cross-sectional analysis, untreated chronic HBV, hepatitis B e-antigen (HBeAg)-positive patients with NAFLD had similar liver biochemistry and FIB-4 values as age-, gender-, and viral-load-matched HBeAg-positive patients without NAFLD. Among HBeAg-negative patients with NAFLD, although liver biochemistry findings were similar, mean FIB-4 values were significantly lower (0.98, SD 1.46, versus 1.51, SD 4.04, respectively; p < 0.05) and the percentage of patients with FIB-4 values in keeping with advanced fibrosis or cirrhosis was less (0.3% versus 3.9%, p < 0.015) than that of matched HBeAg-negative patients without NAFLD. Chronic HCV-infected patients with NAFLD had higher mean serum aminotransferase values than those without NAFLD (123 U/L, SD 247, versus 90 U/L, SD 128, respectively; p < 0.05). These results suggest that NAFLD adversely affects chronic HCV infections but not HBV infections.

Pocket-Sized Versus Conventional Ultrasound for Detecting Fatty Infiltration of the Liver.

BACKGROUND AND AIMS: The high prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population warrants determining whether pocket-sized ultrasound devices (PoCUS) might serve as point-of-care screening for NAFLD in busy office practices. METHODS: One hundred adult subjects undergoing conventional abdominal ultrasound (US) examinations for various indications were screened by PoCUS immediately prior to the conventional US procedure. The PoCUS examination only assessed the presence or absence of excess fat. Assessment of other liver pathology was not performed. Investigators (conventional US: an experienced radiologist and PoCUS: a general internist recently trained in the use of PoCUS) were blinded to the results of the alternative imaging. RESULTS: Forty patients (40%) had fatty infiltration of the liver on both conventional US and PoCUS, and 49 (49%) were negative by both modalities. A consensus was reached in two of the 11 remaining subjects with initially discrepant results. The overall sensitivity and specificity of PoCUS relative to conventional US were 91% and 88%, respectively. CONCLUSIONS: These findings support the use of PoCUS by a trained physician for point-of-care screening of patients at risk for NAFLD.

A paucity of liver disease in Canadian Inuit with chronic hepatitis B virus, subgenotype B6 infection.

Clinical observations suggest that chronic hepatitis B virus (HBV) infections in the Canadian Inuit are less often associated with serious adverse outcomes than has been described in other HBV-infected patient populations. The aim of this study was to document the clinical and biochemical features, liver-related morbidity and all-cause mortality in Canadian Inuit with chronic HBV infections. Administrative databases were reviewed for individuals identified as hepatitis B surface antigen (HBsAg) positive during a 1983-85 seroepidemiological survey of viral hepatitis in Baffin Island, Canada. An equal number of age- and gender-matched HBsAg-negative individuals from the same communities served as controls. Baseline HBV viral loads, genotypes and specific mutations were compared in HBsAg-positive survivors and nonsurvivors. A subset of surviving HBsAg-positive carriers were reassessed 25-30 years following their initial diagnosis for evidence of advanced liver disease and changes to their serological/virological findings. One hundred and forty four HBsAg-positive individuals were identified. All were Canadian Inuit. The mean age at diagnosis was 38 ± 17 years and 69 (61%) were male. Median follow-up was 23 years (range: 2-28 years). Viral quantitation from stored sera could be performed in 70 infected individuals. The median viral load was 4.3 log 10 IU/ml (range: 2.3-8.8 log 10 IU/ml), and all were genotype B, subgenotype B6. Liver biochemistry, morbidity and all-cause mortality rates were similar in HBsAg-positive carriers and controls. Following multivariate analyses, only age at diagnosis predicted mortality in HBsAg carriers. In a subset of 30 HBsAg-positive survivors who underwent follow-up assessments, clinical, biochemical and radiological examinations of the liver were essentially normal. 23/30 (77%) remained HBsAg positive and 17/19 (90%) HBV-DNA positive. The genotype and prevalence of genomic mutations in this cohort remained largely unchanged, but quantifiable viral loads were significantly lower (P < 0.003). The results of this study suggest that chronic HBV infections in the Canadian Inuit are infrequently associated with serious adverse outcomes. Whether this finding reflects unique features of the host, presence or absence of external factors that influence the course of HBV and/or intrinsic properties of the HBV B6 subgenotype remains to be determined.

Liver transplant outcomes in a Canadian First Nations population.

BACKGROUND: A higher incidence of autoimmune disorders may predispose First Nations (FN) individuals to higher rates and more severe episodes of rejection, graft loss and mortality following liver transplantation for advanced liver disease. METHODS: A retrospective review of patient outcomes in a single centre providing long-term follow-up care for FN and non-FN patients transplanted for advanced liver disease was conducted. RESULTS: A total of 20 FN and 129 non-FN charts were available for review. FN subjects were younger at transplantation (mean [± SD] age 32.4±4.1 years versus 46.3±1.4 years; P=0.00005), less often male (35% versus 58%; P=0.05), more commonly transplanted for autoimmune hepatitis (30% versus 4.7%; P=0.006), less often from urban residences (25% versus 74%; P=0.0001) and less compliant with medical care (20% versus 80%; P=0.007). After a mean follow-up period of 11.0±1.5 years and 8.4±0.5 years in FN and non-FN subjects, respectively, the incidence and severity of rejection, graft and patient survival were similar between cohorts. CONCLUSION: Although demographic profiles, nature of the underlying disease and compliance differed, the rates and severity of rejection, graft and patient survival were similar in FN and non-FN patients who underwent liver transplantation for advanced liver disease.

Daily ciprofloxacin treatment for patients with advanced liver disease awaiting liver transplantation reduces hospitalizations.

BACKGROUND: Progressive deterioration in liver function is a common cause of hepatic decompensation and indication for liver transplantation in patients with advanced liver disease. Previous studies in animal models of acute and chronic liver disease revealed that daily ciprofloxacin improves biochemical parameters of hepatic function. AIMS: The primary objective of this study was to determine whether hepatic function improves in patients with advanced liver disease after 1 month of daily ciprofloxacin therapy. A secondary objective was to determine whether ciprofloxacin treatment for 1 or 3 months results in fewer hospitalizations for decompensated liver disease. METHODS: Forty-four patients with advanced liver disease awaiting liver transplantation received oral ciprofloxacin (250 or 500 mg twice daily) or placebo for 1 (n=22/group) or 3 (n=10 ciprofloxacin, 14 placebo) months. RESULTS: Compared to placebo recipients, ciprofloxacin-treated patients had mild improvements in serum albumin levels (+1.5 versus -3.4%, p=0.026) while bilirubin and international normalized ratios (INR) of prothrombin times remained unchanged. Overall, fewer hospitalizations occurred in ciprofloxacin-treated patients (1/22, 5% versus 7/22, 32%, respectively, p=0.02) during the study period. Treatment was well tolerated and no resistant infections occurred in either cohort. CONCLUSIONS: The results of this study suggest that daily ciprofloxacin may result in fewer hospitalizations for patients with advanced liver diseases awaiting liver transplantation but not by enhancing hepatic function.

Bone mineral densities in individuals with Gilbert's syndrome: a cross-sectional, case-control pilot study.

BACKGROUND: Unconjugated bilirubin inhibits osteoblastic proliferative activity in vitro, raising the possibility that Gilbert's syndrome (GS) patients are at increased risk of osteoporosis. OBJECTIVES: To compare bone mineral density (BMD), serum parathyroid hormone (PTH), C-telopeptide (CTX) and osteocalcin levels in GS subjects versus matched controls in a cross-sectional, case-control study. METHODS: BMD determinations were obtained with central dual energy x-ray absorptiometry. Serum PTH, CTX and osteocalcin levels were measured by enzyme immunoassay. RESULTS: A total of 17 GS and 30 control subjects were studied. Overall, there were no significant differences in BMD, PTH, CTX or osteocalcin levels between the two groups. However, when older (older than 40 years of age) and younger (40 years of age and younger) cohorts were considered separately, the older GS cohort had significantly decreased total hip BMD, T scores and Z scores, and femoral neck BMD, T scores and Z scores (P<0.005 for each parameter, respectively) compared with older control subjects. Serum osteocalcin levels were lower in the older versus younger GS cohort (P=0.006). An inverse correlation existed between all subjects' serum unconjugated bilirubin levels and total body BMD determinations (r=-0.42; P=0.04). On univariate analysis, the association between serum unconjugated bilirubin and total body BMD was not significant (P=0.066), nor was serum unconjugated bilirubin identified as a risk factor for low BMD when entered into multivariate analyses. CONCLUSIONS: The results of the present pilot study warrant further research involving larger numbers of subjects and longitudinal measurements to determine whether GS is associated with decreased BMD, particularly in older GS subjects.

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.

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 community's 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.

Rebound hepatitis following withdrawal of immunosuppressive therapy in patients with chronic Hepatitis B viral infections.

Background: Rebound hepatitis is a potentially life-threatening complication of withdrawal from immunosuppressive therapy in patients with chronic Hepatitis B viral (HBV) infections. Objectives: To document the incidence of rebound hepatitis and determine whether the hepatitis is associated with serologic evidence of immunological rebound or the appearance of specific mutations in the HBV genome. Methods: Serum cytokines (IL-6, IL-10, TNF-alpha and INF-gamma) were documented by enzyme linked immunoassays and previously described HBV mutants (surface, core, pre-core and basal core promoter) by signal probe hybridization analysis in chronic HBV carriers treated with either 6 weeks of prednisone followed by 6 weeks of acyclovir (PR/AC, n = 20) or placebo/placebo (PL/PL, n = 20). Results: Rebound hepatitis (serum ALT > 2X baseline) occurred in 6/20 (30%) PR/AC patients versus 2/20 (10%) PL/PL recipients (P = 0.24). Serum cytokine levels were similar in those who developed rebound hepatitis compared to those who did not. HBV mutants were absent prior to and during treatment but developed in the follow-up period in three patients. All three patients were PR/AC recipients and in each case, the HBV mutation was in the basal core promoter gene. In two of the three patients, the mutant appeared just prior to the onset of rebound hepatitis while in the third, rebound hepatitis did not occur. Conclusions: The results of this study indicate an association exists between some cases of rebound hepatitis and the development of HBV mutants.

Hepatitis B vaccination for patients with chronic renal failure.

BACKGROUND: Chronic renal failure patients are at particular risk of hepatitis B virus infection. Early studies have demonstrated that renal failure patients benefit from vaccination; however, not all studies have consistently shown benefit. OBJECTIVES: To determine the beneficial and harmful effects of hepatitis B vaccine and of a reinforced vaccination series in chronic renal failure patients. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Renal Group Controlled Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library (Issue 1, 2002),PubMed/MEDLINE (1966 to July 2003), EMBASE (1985 to November 2003), Current Clinical Practice Guidelines (Canadian Immunization Guide and Vaccine Preventable Diseases Surveillance Manual), and Science Citation Index as well as journals, published abstracts, and reference lists of articles. SELECTION CRITERIA: Randomised clinical trials comparing plasma vaccine with placebo, recombinant vaccine with placebo, recombinant vaccine with plasma vaccine, and a reinforced vaccination series (ie, more than three inoculations) with three inoculations of vaccine in chronic renal failure patients. DATA COLLECTION AND ANALYSIS: Primary outcome measures included incidence of patients developing hepatitis B virus antibodies and infections while secondary outcomes included adverse events, liver-related morbidity, and mortality. Random effects models were used and reported relative risks and 95% confidence intervals (RR and 95% CI). MAIN RESULTS: We included seven randomised clinical trials. None of them had high quality. Plasma vaccine was significantly more effective than placebo in achieving hepatitis B antibodies (RR 23.0, 95% CI 14.39 to 36.76, 3 trials). We found no statistically significant difference between plasma vaccine or placebo regarding hepatitis B virus infections (RR 0.50, 95% CI 0.20 to 1.24). We found no statistically significant differences between recombinant vaccine and plasma vaccine in achieving hepatitis B antibodies (RR 0.65, 95% CI 0.28 to 1.53, 2 trials). Heterogeneity was significant and appeared to be attributable to the dose of vaccine. Two trials examined a reinforced recombinant vaccine strategy, which was not statistically more effective than three inoculations of recombinant vaccine regarding development of hepatitis B antibodies (RR 1.36, 95% CI 0.85 to 2.16). REVIEWERS' CONCLUSIONS: Plasma derived vaccines are more effective than placebo in achieving hepatitis B antibodies, while no statistically significant difference was found between recombinant and plasma vaccines. No statistically significant difference of effectiveness was observed between a reinforced vaccination series versus routine vaccinations of three inoculations of recombinant vaccine.

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

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.

Transforming growth factor-beta (TGF-beta) protein levels are not elevated in the blood or bile of patients with primary sclerosing cholangitis: a pilot study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder of unknown etiology characterized by progressive fibrosis and stricturing of the biliary tract. Transforming growth factor-beta (TGF-beta) is a family of cytokines produced by biliary tract epithelial cells that promote fibrinogenesis. Our objective was to determine whether TGF-beta levels are increased in the blood and/or bile of PSC patients compared to patients with other causes of obstructed biliary tracts (controls). Serum and bile TGF-beta levels were documented by enzyme-linked immunoassay in 10 adult PSC and 10 control patients obtained at the time of endoscopic retrograde cholangiography. Serum and bile TGF-beta levels were similar in the two groups (PSC versus control sera, 33.4 +/- 4.3 versus 27.5 +/- 7.7 ng/ml, and bile, 367 +/- 275 versus 457 +/- 247 ng/mg, respectively). Serum and bile TGF-beta levels are not increased in patients with PSC. Hence, the results of this pilot study do not support the hypotheses that PSC is caused by dysregulated TGF-beta expression.

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.

Viral hepatitis in a Canadian First Nations community.

Serological markers for hepatitis A (HAV), B (HBV) and C (HCV) were documented in 315 inhabitants (27%) of a central Manitoba First Nations community. Serologic evidence of HAV infection (anti-HAV positive) was almost universal (92%) by the age of 20 years. HBV infection (antibody to hepatitis B core antigen positive) had occurred in only 2.3% of the study population and no chronic carriers were identified. Serological evidence of HCV infection (anti-HCV positive) was documented in 2.2% of the population but ongoing viremia (HCV-RNA positive by polymerase chain reaction) was absent. The results of this study highlight the importance of universal HAV vaccination; likely reflect the efficacy of existing prenatal screening and immunoprophylaxis programs for HBV; and raise the possibility that First Nations peoples have an enhanced ability to spontaneously clear HCV.

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 ((31)P MRS) was performed in three animal models of chronic liver disease. Sixty six adult Sprague- Dawley rats were subjected to either thioacetamide, carbon tetrachloride (CCl(4)), 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 (CCl(4) 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 (31)P MRS provides a non-invasive means of documenting the severity and progression of parenchymal and cholestatic models of chronic liver disease in rats.

Use of fluoroquinolones in patients with chronic hepatitis C virus-induced liver failure.

Fluroquinolone antibiotics have been reported to have antiviral properties against RNA viruses, including hepatitis C virus (HCV). In the present study, five patients with advanced liver disease secondary to chronic HCV received 500 mg daily of oral ciprofloxacin for 30 days. Serum HCV-RNA levels and liver enzyme abnormalities remained largely unchanged. Thus, the role of fluoroquinolones as antiviral agents for chronic HCV in patients with advanced liver disease appears to be limited.

The impact of medical informatics on the confidence of rural physicians caring for patients with chronic hepatitis C viral infections.

OBJECTIVE: The purpose of the present study was to determine whether CD-based medical informatics enhances rural physicians' confidence in the management of patients with chronic hepatitis C viral infections. METHODS: A total of 385 Canadian rural physicians were mailed a CD-based medical software programme that outlines all aspects of HCV care including diagnosis, counselling, treatment and follow-up. Accompanying the CD was a brief questionnaire that addressed physicians' confidence in the following areas: (i) identifying HCV patients in their practice; (ii) laboratory use and interpretation; (iii) patient counselling; (iv) selection of candidates for treatment; (v) sharing treatment delivery; and (vi) providing follow-up. Three months thereafter, the same questionnaire was repeated. RESULTS: Of the 385 mailings, 59 (15%) physicians returned the initial questionnaire and 57 (15%) the follow-up questionnaire. Twenty-five (44%) respondents indicated they had used the CD. Baseline physician confidence was low in three of the six areas addressed. At follow-up, in addition to now being confident in all areas, CD users were significantly more confident than those who had not used the CD. Increases in physician confidence for CD users were approximately 150-300% in the six areas addressed. The value assigned the CD programme was 8/10. CONCLUSION: The results of this study indicate that: (i) rural physicians are uncomfortable in dealing with many aspects of HCV management; (ii) CD-ROM-based medical informatics can significantly enhance rural physicians' confidence in these areas; (iii) approximately 50% of physicians will employ CD-ROM-based medical informatics in their offices; and (iv) physician level of satisfaction with such programmes is high.

Chronic hepatitis B infection in Canada.

Recent developments in the treatment and prevention of hepatitis B virus (HBV) infections warrant revisiting important epidemiological questions, such as how prevalent is chronic HBV infection in Canada, in which Canadian subpopulations are HBV prevalence rates the highest, in what percentage of infected individuals is the virus actively replicating, and how many infected Canadians are candidates for antiviral therapy? Currently available data suggest the overall prevalence of HBV-infected individuals in the general population is approximately 2%, with 5% to 10% having serological evidence of previous HBV infection. In high risk groups, such as street-connected individuals, Aboriginals and immigrants from endemic areas, these rates of viral prevalence and serological evidence of previous HBV infection are approximately two to 10 and five to 10 times higher, respectively, than in the general population. Candidates for antiviral therapy range from less than 1% of infected Aboriginals to 15% to 30% of Asians with chronic HBV. From these data, it is clear that chronic HBV remains an important public health problem in this country. Hence, resources must be identified to enhance Canadians' awareness of HBV infection, maintain, if not expand, efforts to identify and implement safe and effective antiviral therapy for HBV-infected individuals, and continue programs for universal vaccination to prevent new HBV infections.

Light ethanol consumption enhances liver regeneration after partial hepatectomy in rats.

BACKGROUND & AIMS: The effects of "social drinking" on the liver have yet to be fully documented. The aim of this study was to document the effects of daily light, moderate, and heavy ethanol exposure on hepatic regenerative activity in the rat. METHODS: Adult male Sprague-Dawley rats underwent daily gavages with 1.0 (light), 2. 0 (moderate), or 4.0 (heavy) g/kg of ethanol or tap water (controls) for 30 days before 70% partial hepatectomy (PHx). Hepatic regenerative activity was then documented on days 1, 3, 5, and 7 after PHx. RESULTS: Compared with controls, restitution of liver mass, [(3)H]thymidine incorporation, and proliferating cell nuclear antigen expression were decreased in the heavy (-10%, -60%, and -36%, respectively), unchanged in the moderate (-4%, -8%, and -16%, respectively), and increased in the light (+6%, +38%, and +29%, respectively) ethanol groups. Messenger RNA differential display of resected livers at PHx identified a band present only in the light ethanol group that encodes a unique 47-kilodalton protein with growth-promoting features designated light ethanol-induced stimulatory protein. CONCLUSIONS: The results indicate that light ethanol consumption enhances hepatic regenerative activity after PHx in rats. Further studies are required to determine the mechanism involved and whether social drinking has beneficial or adverse effects on the natural history of acute or chronic liver disease in humans.

The prevalence of intrinsic host risk factors associated with progressive disease in patients with chronic hepatitis C viral infections.

The prevalences of three risk factors that have been identified as important predictors of more progressive forms of chronic hepatitis C viral (HCV) infections (male gender, transfusion recipients and age greater than 50 years at the onset of infection) were documented by a retrospective chart review of 337 HCV-infected patients attending an urban, hospital-based, viral hepatitis clinic. One hundred and ninety-five patients (58%) were male. One hundred and eighteen (35%) had received blood or blood product transfusions in the past, 33% of whom also gave a history of intravenous drug use. Approximately 5% of patients were over the age of 50 years at the estimated time of infection. Twenty percent of patients had two and 4% had all three risk factors. In conclusion, intrinsic host risk factors associated with progressive HCV infection were common in this patient population. If confirmed in other centres, these results suggest that the medical and financial demand on the health care system is likely to be appreciable unless effective and safe therapies for HCV are identified and implemented in the near future.