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.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

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.

A mathematical model to study the effect of hepatitis B virus vaccine and antivirus treatment among the Canadian Inuit population.

The prevalence of hepatitis B among the Canadian Inuit population is 4%. This study will use a mathematical model to compare the roles of vaccination and therapy to predict future prevalence and incidence among the Canadian Inuit population for the next 50 years. We applied a mathematical model developed by Medley et al. (Nat Med 7(5):619-624, 2001), combined with data on hepatitis B incidence, prevalence, and vaccination coverage, to predict trends of hepatitis B virus (HBV) among the Inuit population over the next 50 years. The current estimated prevalence of HBV is 6.04% and the incidence is 3.4/100,000 persons among Canadian Inuit. If HBV vaccination coverage levels of 47.2% remain unchanged, the prevalence of HBV will decrease to 1.91% and the incidence will decrease to 0.81/100,000 persons by 2058. If vaccination coverage levels are increased to 57.2%, the prevalence and incidence of HBV will decrease to 1.74% and 0.63/100,000 persons, respectively. If we increase both immunization and therapy by 10%, this will produce the greatest reduction in prevalence and incidence, to 1.56% and 0.54/100,000 persons, respectively. The combination of immunization and treatment programs seems to have the best result in decreasing the prevalence and incidence of HBV among the Inuit population.

An independent and prospective comparison of two commercial fibrosis marker panels (HCV FibroSURE and FIBROSpect II) during albinterferon alfa-2b combination therapy for chronic hepatitis C.

SUMMARY: Noninvasive markers that accurately follow changes in fibrosis may provide alternatives to liver biopsy for assessment of histological endpoints of antiviral therapy in chronic hepatitis C (CHC). This study compared two commercially available serum marker panels (HCV FibroSURE and FIBROSpect II) during interferon-based therapy. Ninety-five interferon-naïve patients with genotype 1 CHC were enrolled in a phase 2b, active-controlled study of albinterferon alfa-2b/ribavirin for 48 weeks. Proprietary and simple biochemical marker panels were independently evaluated in serum before and during the study. Baseline liver biopsies were evaluated for METAVIR fibrosis by a single pathologist. Index scores were obtained for HCV FibroSURE (n = 84) and FIBROSpect II (n = 95); mean biopsy length: 17.8 +/- 8.0 mm. For detecting fibrosis stages 2-4 (prevalence 23% [22/95] and 21% [18/84]), HCV FibroSURE and FIBROSpect II indicated high sensitivity (1.00 and 0.95, respectively), lower but comparable specificity (0.61 and 0.66, respectively), and a good area under the receiver operating characteristic curve (0.89 and 0.90, respectively). Simple indices had high indeterminate rates (31-40%) at baseline. Patients with a sustained virological response had lower baseline scores than nonresponders, and reduced median percent changes in index scores for HCV FibroSURE (-20.0%vs 2.9%; P = 0.14) and FIBROS Spect II (-6.8%vs 18.4%; P = 0.05). The panels demonstrated comparable performance characteristics for differentiating mild from moderate-severe stage disease in CHC. Lower index scores at baseline that continue to decline likely reflect reduced fibrogenesis activity in patients with successful antiviral responses to therapy.

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.

Hepatitis C infection and survivals of liver transplant patients in Canada, 1997-2003.

INTRODUCTION: Liver transplantation is an important health and health care issue for Canadians. Very few studies have estimated the survival results among liver transplant patients infected with hepatitis C virus (HCV) in Canada. METHODS: We carried out a retrospective cohort study to analyze 1- to 5-year survival rates among liver transplant patients, using Canadian Organ Replacement Registry data (1997-2003). Patients less than 19 years old were excluded from the study. The patients were categorized according to previous HCV infection status. The HCV-positive and HCV-negative groups were compared in the following characteristics: age group, gender, ethnicity, blood groups, donor type, pretransplantation medical status. Survival curves were plotted by Kaplan-Meier method. Stepwise regression model was applied to control the confounding impact related to gender, age, and HCV infection status. RESULTS: A total of 1842 liver transplant patients were included in the analysis. One-year survival rate for all patients was 85.4%. There were 319 HCV-positive recipients in the exposed group and 813 in the HCV-negative group. The HCV-positive and HCV-negative groups were comparable in age groups, ethnicity, ABO blood group, pretransplantation medical status, and donor organ type. The HCV-positive group had the higher male:female ratio (2.32:1) than the HCV-negative recipients (1.49:1) (Mantel Haenszel (MH) chi2 = 10.0311, P = .0015). There was no significant difference in 1-year survival rate between HCV-positive and HCV-negative groups, but the differences in the 2-year and 5-year survival rates were significant even after adjusting gender factor by stepwise regression analysis (MH chi2 = 4.4203, P = .0355). CONCLUSION: In Canada, the first-year survival rate is about 85.4%, which is comparable with other industrialized countries. The exaggerated survival disadvantage for HCV-positive recipients seems to be middle and long term, not short term.

Induction versus noninduction antiviral therapy for chronic hepatitis C virus in patients with congenital coagulation disorders: a Canadian multicentre trial.

BACKGROUND: Patients with congenital coagulation disorders and chronic hepatitis C virus (HCV) infection have multiple risk factors (ie, infection predominantly with genotype-1 HCV, long duration of the disease, HIV coinfection and male sex) for poor response to antiviral therapy. The present study compared induction therapy with interferon-alpha (IFN-alpha)-2b with standard IFN-alpha2b therapy. Pegylated IFN was not available at the time that the study was initiated. PATIENTS AND METHODS: A randomized study was performed comparing the efficacy of traditional IFN-alpha2b therapy (group A -- three million units, three times weekly for 24 to 48 weeks) and daily ribavirin (1.0 g to 1.2 g according to weight for 24 to 48 weeks), with induction IFN-alpha2b therapy (group B -- three million units, daily for eight weeks followed by the same dose administered three times a week for a further 16 to 40 weeks) and daily ribavirin (same dose as above) in IFN-naive patients with congenital coagulation disorders and chronic HCV infection. RESULTS: Between 2000 and 2003, 54 HIV-negative patients were recruited and randomly assigned to group A or B (n=27 each). Both groups were comparable in terms of age, sex, ethnicity, body mass index, baseline HCV RNA titre, viral genotype, liver fibrosis stage and type of coagulation disorder. Induction therapy did not significantly alter sustained virological response rates (group A 50%, group B 50%; P=1.0). Multiple logistic regression analysis indicated that induction therapy did not benefit individuals with difficult-to-treat infection (ie, those infected with genotypes 1 and 4, or those with high baseline viral loads). CONCLUSIONS: There was no benefit with induction antiviral therapy for HCV infection in individuals with congenital coagulation disorders.

Survival analysis of liver transplant patients in Canada 1997-2002.

UNLABELLED: Liver transplantation is an important health care issue for Canadians. Very few studies have assessed survival and determinants of survival in liver transplant patients in Canada. METHODS: We carried out an epidemiological analysis of 1 year survival and determinants of 1 year survival in liver transplant patients, using Canadian Organ Replacement Registry data (1997-2002). Survival curves were plotted by the Kaplan-Meier method. Cox proportional hazards analysis was applied to evaluate hazard ratios with different age groups, gender, ethnicity, blood groups, donor type, pretransplantation medical status, and HBV infection status. RESULTS: A total of 1164 liver transplant patients were included in the analysis. One-year survival rate was 84.7%. Male recipients had a 21% higher risk of developing organ failure than females. Recipients over 60 years of age had a 5% lower survival probability in comparison with recipients below 20 years of age. Pacific Islanders and Aboriginals had 32% and 9% lower survival probabilities, respectively, in comparison with Caucasians. Type B blood recipients had a 12% higher survival probability, whereas type AB blood recipients had a 7% lower survival probability compared with type O blood recipients. Twenty-six live organ recipients had 40% higher survival probabilities than 1138 cadaveric organ recipients. Patients with fulminant hepatitis (status 3F) had the highest survival, while patients with fulminant failure in ICU with intubation/ventilation (status 4F) had the lowest survival. One hundred sixty-seven recipients with positive HBsAg antigen showed 10% lower survival probability than 997 cases with negative HBsAg antigen. CONCLUSION: In Canada, the first year survival rate is about 85%, which is comparable with other industrialized countries. Type of donor organs and recipient gender, ethnicity, ABO blood group, pretransplantation medical status, and HBV infection status had significant affects on the recipient survival.

Peginterferon alfa-2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy.

BACKGROUND: The management of patients with chronic hepatitis C who have relapsed or failed to respond to interferon based therapies is an important issue facing hepatologists. AIMS: We evaluated the efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in this population by conducting a multicentre open label study. PATIENTS: Data from adults with detectable serum hepatitis C virus (HCV) RNA who had not responded or had relapsed after previous conventional interferon or conventional interferon/ribavirin combination therapy were analysed. METHODS: Patients were retreated with peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 800 mg/day for 24 or 48 weeks at the investigators' discretion. The study was conceived before the optimal dose of ribavirin (1000/1200 mg/day) for patients with genotype 1 was known. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA (<50 IU/ml) after 24 weeks of follow up. The analysis was conducted by intention to treat. RESULTS: A total of 312 patients (212 non-responders, 100 relapsers) were included. Of these, 28 patients were treated for 24 weeks and 284 for 48 weeks. Baseline characteristics between non-responders and relapsers were similar although more non-responders had genotype 1 infection (87% v 69%). Overall SVR rates were 23% (48/212) for non-responders and 41% (41/100) for relapsers. When data were analysed by genotype, SVR rates were 24% (61/253) in genotype 1 and 47% (28/59) in genotype 2/3. CONCLUSIONS: These results in a large patient cohort demonstrate that it is possible to cure a proportion of previous non-responders and relapsers by retreating with peginterferon alfa-2a (40KD) plus ribavirin.

Epidemiological study of hepatitis B virus infection in Manitoba, Canada, 1992-2003.

In comparison with other Canadian provinces and most Western countries, the province of Manitoba maintains a different vaccination policy for hepatitis B. This policy provides selective antenatal screening for hepatitis B in women and an inoculation program for hepatitis B vaccination for fourth-grade pupils. There has been increasing concern for this policy with regard to its influence on secular trends of acute hepatitis B incidence in Manitoba. This created a need to summarise the epidemiological characteristics of hepatitis B virus (HBV) infection in Manitoba and to allocate finances and human resources for future prevention programs. The Cadham Provincial Laboratory in Winnipeg, a Canadian Public Health Laboratory, is responsible for testing all specimens for diagnosis of various common infectious diseases in Manitoba. During the period from 1 January 1992 to 31 December 2003, a total of 285,946 clinical specimens were submitted to this laboratory, which confirmed 310 cases of acute HBV and 7,556 cases of chronic HBV infection. A total of 18,168 individuals were identified as having vaccine-induced immune status. The incidence rate of acute HBV infection has significantly decreased from 6.52/100,000 person-years in 1996 to 0.86/100,000 person-years in 2003. Annual prevalence rates of chronic HBV infection in Manitoba increased slightly from 42.96 cases/100,000 population in 1992 to 71.47 cases/100,000 population in 2003. Incidence rates were generally higher in men than in women at all age groups, with values of 2.65 and 1.65 per 100,000 population, respectively (chi-square=15.768, p value <0.001). The highest incidence rate for both males and females was observed in the age group 30-34 years. The North Eastman and Winnipeg Regional Health Authorities showed significantly higher incidence rates of acute hepatitis B compared with the other nine Regional Health Authorities. Selective hepatitis B vaccination programs for children in Manitoba had achieved the greatest success in the prevention of vertical and horizontal transmission. There is an urgent need to develop cost-effective harm-reduction strategies for hepatitis B prevention among adults (aged 30-34) and groups at risk in Manitoba.

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.

A multicentre study of the usefulness of liver biopsy in hepatitis C.

The role of liver biopsy in the assessment of chronic hepatitis C is generally accepted yet there is no prospective data available to quantify its contribution. A previous single centre pilot study suggested that the clinician could predict the amount of fibrosis and to a lesser extent, inflammation with moderate accuracy. The 2002 National Institute of Health Hepatitis C Consensus Conference recommended further study of the role of liver biopsy. Our objective was to compare a prediction of biopsy findings by expert clinicians using usually available clinical and laboratory data to actual biopsy results in order to determine whether biopsy is required routinely. This was a prospective observational study conducted at seven university centres in which the accuracy of clinician's predictions of the degree of inflammation and fibrosis were compared with the actual liver biopsy using an adaptation of a standard histological scoring system. We studied 81 adults with previously untreated chronic hepatitis C, raised serum transaminases and positive HCV-RNA in serum. Clinicians predicted the inflammatory grade in 44 of 80 cases (55%) and the fibrosis stage in 46 of 81 cases (57%). Nine of 17 cirrhotic cases were predicted (sensitivity 53%, specificity 56%). No unexpected additional diagnoses were made on the biopsies. Thus despite knowledge of the clinical and laboratory investigations of patients with hepatitis C, clinicians are unable to accurately predict the hepatic inflammatory grade and fibrotic stage. Liver biopsy is an essential investigation to accurately evaluate the grade and stage of liver disease patients with hepatitis C.

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.

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.

Viral hepatitis in a Canadian street-involved population.

BACKGROUND: Data on the prevalence and compliance with management of viral hepatitis in the street-involved population are limited. METHOD: Hepatitis A (HAV), B (HBV) and C (HCV) serology and compliance with HBV vaccination were documented in 533 street-involved individuals. RESULTS: The mean age of the study population was 25.7 years (range: 11-65) and 53% were female. Serologic evidence of HAV infection was present in 53%; HBV, 12% (3% ongoing infection); and HCV, 17%. HAV infections were associated with Aboriginal/Metis ethnicity and age over 25 years; HBV with injection drug use (IDU); and HCV with IDU, sex trade work and age over 25 years. Compliance with three-step HBV vaccination was 98%, 77% and 63%. CONCLUSIONS: HAV, HBV and HCV are common infections in urban street-involved persons. Successful HBV (and presumably HAV) vaccination can be achieved in the majority of this population, but concerns exist regarding compliance with more long-term, parenterally-based antiviral therapies.

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.

Outcomes following liver transplantation for patients with alcohol- versus nonalcohol-induced liver disease.

OBJECTIVE: To document and compare the outcomes of adult patients who received liver transplants for alcohol- and nonalcohol-induced liver diseases who attended a liver transplantation follow-up clinic in an urban, nontransplantation centre at a time when no formal alcohol abuse program for transplant candidates and/or recipients was offered. PATIENTS AND METHODS: The study population comprised 10 alcoholic patients and 48 nonalcoholic patients followed for an average of 41 months (range five to 79 months) and 46 months (range two to 116 months), respectively. Primary outcome variables included rates of recidivism, duration of abstinence after transplantation and compliance with post-transplant medical follow-up visits. Time to discharge after transplantation, episodes of graft rejection, liver and renal biochemical abnormalities, diabetes, hypertension, sepsis, strictures, complications unrelated to transplantation and changes in psychosocial status were secondary outcome variables. RESULTS: Significant differences were found with respect to a higher incidence of recidivism (50% for alcoholic patients compared with 2% for nonalcoholic patients, P<0.0001), a shorter period of abstinence after transplantation (14.7+/-17.2 months for alcoholic patients compared with 26.3+/-23.0 months for nonalcoholic patients, P<0.05) and more missed office visits (2.7+/-3.5 for alcoholic patients compared with 1.0+/-1.9 for nonalcoholic patients, P=0.05) in the alcoholic group. The alcoholic group also had a lower incidence of rejection episodes (10% for alcoholic patients compared with 44% for nonalcoholic patients, P<0.05) but higher rates of post-transplantation diabetes (40% for alcoholic patients compared with 2% for nonalcoholic patients, P<0.05), more nontransplantation-related complications (20% for alcoholic patients compared with 0% for nonalcoholic patients, P<0.05), and higher serum creatinine but lower bilirubin and cyclosporine A levels (P<0.05, respectively). Marital separations were also more common in the alcoholic group (20% for alcoholic patients compared with 0% for nonalcoholic patients, P<0.05). CONCLUSIONS: In the absence of formal alcohol abuse programs, the post-transplantation outcome in alcoholic patients generally does not compare well with that of patients who undergo transplantation for nonalcohol-related liver diseases.