Does SEN-V and other non-A-E hepatotropic viruses contribute to the development and progression of non-alcoholic fatty liver disease?

Approximately 10-20% of patients with non-alcoholic fatty liver disease (NAFLD) are at risk of progressing to cirrhosis. The cause of such progression is unclear. SEN-V is a hepatotropic virus that has been associated with more severe and advanced liver disease in patients with chronic hepatitis C virus infections. In this study we tested 32 NAFLD patients for evidence of SEN-V infection and correlated the results with histologic findings. The results of the study revealed similar disease severity and stage of progression in SEN-V positive and negative patients. Although not supportive of our hypothesis, the possibility that SEN-V and/or other non-A-E hepatotropic viruses contribute to the development and course of NAFLD is discussed.

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.

Effects of low-density lipoprotein docosahexaenoic acid nanoparticles on cancer stem cells isolated from human hepatoma cell lines.

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid with anti-cancer properties. Recently, DHA packaged within low-density lipoprotein (LDL) nanoparticles (LDL-DHA) was demonstrated to be effective in a murine model of hepatocellular carcinoma (HCC). Cancer stem cells (CSCs) are a subpopulation of tumor cells that are resistant to most cancer therapies and thereby, contribute to tumor recurrences. To determine whether LDL-DHA is effective against CSCs derived from human HCC cell lines and tumor bearing rats. Epithelial cellular adhesion molecule positive and CD133 negative (EpCAM+CD133-) CSCs were isolated from HuH-7 and HepG2 human HCC lines and exposed to varying concentrations (1-60 µM) of LDL-DHA nanoparticles for 0-72 h. HCC tumor bearing rats were treated with 2 mg/kg LDL-DHA nanoparticles for 3 days. Regardless of the cell line employed, LDL-DHA nanoparticles achieved 70-100% killing of EpCAM+CD133- CSCs at a concentration of 40 µM after 48 h of exposure while DHA and LDL alone had minimal or no cytotoxic effects. Similar results were obtained with LDL-DHA nanoparticle treatment of EpCAM-CD133- adult cancer cells (ACCs). In keeping with these findings were similar levels of low density lipoprotein receptor expression and LDL-DHA nanoparticle induced lipid peroxidation activity and reactive oxygen species in the CSC and ACC populations. However, differences in sensitivity to LDL-DHA treatment were observed in vivo experiments where LDL-DHA nanoparticle treated tumors had a higher percent of surviving CSCs relative to ACCs. Further research on LDL-DHA nanoparticle therapy for human HCC is warranted.

Hepatitis B viral infection of hepatic progenitor cells. Resolving unresolved questions?

Accumulated data to date do not entirely explain the; propensity of the hepatitis B virus (HBV) to cause chronic infections in newborns; failure of antiviral agents to resolve infections or precise mechanism whereby HBV causes hepatocellular carcinoma (HCC). Based on the increased numbers of hepatic stem/progenitor cells (HPCs) present within the neonatal liver, the refractoriness of these cells to the effects of interferons and xenobiotics and their ability to undergo malignant transformation, we hypothesize that HBV infection of HPCs could explain these and perhaps other clinical features of chronic HBV.

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.

Genetic diversity of hepatitis B virus genotypes B6, D and F among circumpolar indigenous individuals.

Hepatitis B virus (HBV) infection is highly prevalent in circumpolar indigenous peoples. However, the clinical outcome is extremely variable, such that while hepatocellular carcinoma (HCC) is uncommon in Canadian Inuit, the incidence of HCC is slightly higher in Greenlanders than in Danes, and it is especially high in Alaskan Native people infected with HBV genotypes F (HBV/F) and C (HBV/C). These differences may be associated with the genomic variability of the predominant HBV genotype in each group. The purpose of this study was to determine the rate, nature and regional susceptibility of HBV genomic mutations among circumpolar indigenous individuals. Paired serum samples, separated by 5-6 years, were analysed from Canadian and Greenlandic Inuit infected with HBV genotype B6 (HBV/B6) and HBV/D, respectively, and from Alaskan Native people infected with HBV/F, each having subsequently developed HCC. Phylogenetic and mutational analyses were performed on full-genome sequences, and the dynamic evolution within the quasispecies population of each patient group was determined by clonal analysis of the non-overlapping core coding region. Mutations associated with severe outcomes predominated in HBV/F, mostly within the precore/core and PreS1 region. HBV/B6 genomes exhibited higher diversity compared to HBV/D and HBV/F, particularly within the core coding region. Thus, differing mutational profiles and genetic variability were observed among different HBV genotypes predominating in circumpolar indigenous patients. The unusual observation of persistently high genetic variability with HBV/B6 despite clinical inactivity could be due to the evolution of a host-pathogen balance, but other possible factors also need to be explored.

The prevalence and long term outcome of occult hepatitis B virus infections in community based populations.

Features of occult hepatitis B infection in community-based populations have yet to be described. In this study we documented: (1) the prevalence and demographics, (2) associated serology and viral loads, and (3) clinical outcomes of occult hepatitis B infection in community-based populations. Hepatitis B surface antigen (HBsAg)-negative sera collected from three Northern Canadian communities (HBsAg prevalences: 11-12%) in 1983-1985 were tested for HBV-DNA by nested stage polymerase chain reaction. Of 706 HBsAg negative sera, 9 (1.3%) were HBV-DNA positive. The median age of occult hepatitis B infected patients at the time of sampling was 9.8 years (range 3.1-50.4 years) and six (67%) were female. Two (22%) individuals were anti-HBs positive (in the absence of prior vaccination). Viral loads were undetectable in all but two samples (2.40 and 2.86 log10 IU/ml). Only one of the five (20%) patients who were assessed clinically, remained HBV-DNA positive at 25-30 year follow-up. There was no clinical, biochemical or radiologic evidence of chronic hepatitis, cirrhosis or hepatocellular carcinoma in these individuals or on review of the charts from the remaining four infected patients. The results of this study suggest that in community-based populations: (1) occult hepatitis B infection is not as common as HBsAg positive infection, (2) the majority of infected subjects are young females, (3) a minority are anti-HBs positive, (4) viral loads are either undetectable or low, and (5) in the absence of concurrent liver disease, occult hepatitis B infection does not appear to be associated with long term adverse clinical outcomes.

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.

The influence of North American Aboriginal ethnicity on pro-inflammatory and anti-inflammatory cytokine responses to IFN-alpha.

North American Aboriginals have an enhanced propensity to clear HCV infection. Interferon (IFN)-alpha is a critical agent in the clearance of hepatitis C virus (HCV) and other viruses; therefore the influence of Aboriginal ethnicity on IFN-alpha responses was investigated in healthy Caucasian population control and Aboriginal cohorts. Cohort peripheral blood mononuclear cells produced similar levels of IFN-alpha upon culture with reovirus, an innocuous virus capable of triggering IFN-alpha synthesis. In addition, similar IFN-gamma synthesis was observed in the presence IFN-alpha or reovirus. In contrast, Caucasian supernatants exhibited greater IL-10 levels (P<0.005), contributing to the overall cytokine balance as assessed by IFN-gamma/IL-10 ratios being consistently elevated in the Aboriginal cohort. The potential of HCV proteins to alter IFN-alpha cytokine induction was also investigated. Although there was some indication that HCV proteins might increase IFN-alpha induced IL-10 synthesis in Caucasians and conversely, IFN-gamma synthesis in Aboriginals, the addition of HCV proteins did not influence IFN-gamma/IL-10 ratios. Finally, signal transducer and activator of transcription (STAT) 3 nuclear translocation was examined by western blot because it is a required intermediate in IFN-alpha induced IL-10 synthesis. Supporting the differential IL-10 production, IFN-alpha and core synergistically enhanced STAT3 nuclear translocation in Caucasian (P<0.05); whereas, nuclear translocation of STAT3 remained unchanged in Aboriginal cells. Taken together, these findings suggest that ethnicity may influence certain responses to IFN-alpha, possibly even in the presence of viral agents. These differences could impact early immune events allowing for enhanced viral clearance in Aboriginal populations.

Cyanobacterial toxins and liver disease.

Blue-green algae, also known as cyanobacteria, produce a variety of toxins, some of which have been implicated in the pathogenesis of severe and potentially life-threatening diseases in humans. As the growth of cyanobacteria within freshwater lakes increases worldwide, it is important to review our present understanding of their toxicity and potential carcinogenicity to gain insight into how these organisms impact human health. This review addresses each of these topics, with special emphasis given to cyanobacterial hepatotoxins within freshwater environments.

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.

Histological benefits of virological response to peginterferon alfa-2a monotherapy in patients with hepatitis C and advanced fibrosis or compensated cirrhosis.

BACKGROUND: Patients with chronic hepatitis C virus and advanced fibrosis or cirrhosis are at risk for disease progression and hepatic decompensation. AIM: To determine the effects on hepatic histology of treatment with peginterferon alfa-2a (90 or 180 mug/week) or interferon alfa-2a (3 million units three times weekly) for 48 weeks in patients with paired biopsies. METHODS: Liver biopsies were obtained at baseline and 6 months after end of treatment. Histological and virological responses were compared. RESULTS: Patients attaining sustained virological response (n = 40) demonstrated the greatest improvements in fibrosis (-1.0, P < 0.0001) and inflammation (-0.65, P < 0.0001). Patients who cleared hepatitis C virus during treatment, but later relapsed (n = 59), experienced less improvement in fibrosis (-0.04, P < 0.0001) and inflammation (-0.14, P = 0.0768). Nonresponders (n = 85) showed no significant improvement in inflammation or fibrosis. Multiple regression analysis showed that the only factors contributing to improvement in fibrosis were sustained virological response (vs. nonresponder, P = 0.0005; vs. relapse, P = 0.7525) and body mass index < or =30 kg/m2 (P = 0.0995). CONCLUSIONS: These findings indicate that virological response to peginterferon alfa-2a improves inflammation and fibrosis in hepatitis C virus patients with advanced fibrosis or cirrhosis. Improving virological response and maintaining ideal body weight are critical for achieving optimal histological outcomes in hepatitis C virus patients.

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.

Lack of susceptibility to ischemic necrosis of the remnant liver following partial hepatectomy in the rat.

BACKGROUND/AIMS: The increase in liver lobule dimensions that occurs following partial hepatectomy could predispose living related donors to ischemic hepatic injury were shock-like states to occur in the future. METHODOLOGY: In the present study, rats that had undergone 70% partial hepatectomies or sham surgery six weeks earlier were progressively bled to a maximum of 40% total circulating blood volume. RESULTS: Despite significant increases in liver lobule dimensions (1.5x controls), hepatectomized rats did not manifest biochemical or histologic evidence of early or more extensive hepatic injury when compared to sham-operated controls. CONCLUSIONS: The results of this study suggest that despite theoretical concerns, living related donors are not predisposed to develop ischemic hepatic injury were shock-like states to develop in the future.

An assessment of endoscopic and concomitant management of acute variceal bleeding at a tertiary care centre.

BACKGROUND: Several therapies have been demonstrated to be beneficial in the management of acute variceal bleeding (AVB). The aim of the present study was to characterize the use of these therapies at a Canadian tertiary care centre. PATIENTS AND METHODS: A comprehensive chart review was performed to assess the management of all adult cirrhotic patients with AVB who were admitted to a university-affiliated, tertiary care centre between April 2001 and March 2004. RESULTS: A total of 81 AVB patients were identified with a mean age of 53.7+/-13.2 years and a median model for end-stage liver disease score of 14. Endoscopy was performed within 8.2+/-7.6 h of admission. Variceal banding was performed for 87% of patients with esophageal varices, which were the most common source of bleeding (80%). Octreotide was used in 82% of patients for a mean duration of 74.3+/-35.4 h; prophylactic antibiotics were used in 25% of patients and beta-blockers were used in 24% of patients without any contraindications. Follow-up endoscopy was arranged for 46 of 71 (65%) survivors. Prophylactic antibiotic use was associated with the presence of ascites, while beta-blockers were used more often in the last year of the study. CONCLUSIONS: There is a disconnection between the use of evidence-based recommendations and routine clinical practices in the management of AVB. Deficiencies identified include the lack of use of prophylactic antibiotics and beta-blockers, variable use of octreotide and inadequate follow-up recommendations. There is a need to identify measures to improve the process of care for patients with AVB which would ensure optimal management of these patients.

The effects of colectomy on immediate-early proto-oncogene expression and hepatic regeneration in the rat.

The intact liver exists in a state of replicative quiescence. The factor(s) responsible for maintaining this state and their tissue sources have yet to be identified. Because the colon synthesizes and/or absorbs numerous agents that inhibit hepatocyte proliferation, the principle purpose of this study was to determine whether total colectomy would result in the conversion of quiescent livers to a state of replicative competence. Thus, adult, male Sprague-Dawley rats (250-300 g) were randomized to undergo either total colectomy with ileostomy or sham surgery. Thereafter, rats were sacrificed (N=3-6/group) at times 15 and 30 min and 1, 2, 6, and 24 hr and the livers analyzed by Northern blot analyses for mRNA of the following immediate-early proto-oncogenes (IEP genes): c-fos, c-jun, and c-myc. Rats sacrificed at 24 hr also had hepatic regenerative activity documented by [3H]thymidine incorporation into hepatic DNA. The results of the study revealed that within 15 min, c-fos and c-jun mRNA expression increased in colectomized rats, with peak expression occurring at 30 and 60 min, respectively. c-myc mRNA expression was more delayed, with peak expression occurring at 6 hr post-colectomy. IEP gene expression also increased somewhat in sham-colectomy controls but the increases were not as prompt and, in general, were of lower magnitude than those in the colectomy group. Despite the differences in IEP gene expression between the two groups, [3H]thymidine incorporation at 24 hr was similar (mean+/-SE: colectomy group, 17.2+/-2.6 dpm/microg DNA; sham-colectomy controls, 14.8+/-1.4 dpm/microg DNA). To determine whether the increases in IEP gene expression expedite or augment the hepatic regenerative response to partial hepatectomy (PHx), rats that had undergone colectomy or sham colectomy 1 hr earlier and rats with no previous abdominal surgery then underwent a 70% PHx and were sacrificed at 8, 16, and 24 hr thereafter. At each time interval, [3H]thymidine incorporation was documented and found to be similar in the three groups. In conclusion, the results of this study indicate that total colectomy, and to a lesser extent abdominal surgery, induces the conversion of an intact, quiescent liver to a state of replicative competence. The results also suggest that, in addition to colectomy, the presence of mitogens and/or co-mitogens is required for further progression of hepatocytes through the cell cycle. Finally, a "primed" liver does not respond more promptly or vigorously to a regenerative stimulus than a "resting" liver.

Patient concerns regarding chronic hepatitis C infections.

Counselling of patients with chronic hepatitis C infections is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counselling strategies and content. Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them. The most common volunteered concerns of newly diagnosed patients in decreasing order were: disease progression (27%), premature death (19%), infecting family members (13%), side-effects of treatment (11%) and miscellaneous others. In decreasing order, prioritized concerns included: infecting family members, development of liver cancer, infecting others, development of cirrhosis, social stigma of having liver disease, need for liver transplant and loss of employment. The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, modes of viral acquisition and in the case of follow-up patients, duration of follow-up. These results indicate that health care providers who focus counselling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection.

Viral hepatitis and the surgeon.

BACKGROUND: Viral hepatitis is an infection of the liver caused by one or more of six known (HAV-HGV) hepatotropic viruses. It is a common problem among health care workers and their patients. Surgeons are at particular risk of both acquiring and transmitting some of these viruses from and to their patients. Unfortunately, specific immunoprophylaxis for viral hepatitis is presently limited to protecting against the spread of hepatitis A and B viral infections, leaving a high degree of vigilance and careful surgical technique as the only means available to prevent the transmission of other viruses relative to the surgeon. The purpose of this paper is to review the various forms of viral hepatitis including the nature of the virus, serologic testing, clinical features, epidemiology (with specific reference to those issues that arise in surgical practice), treatment and prevention.