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2005

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News 2004

2003 Research News and Articles

HCV News Archives 2001-2002

	Update From EASL 2005: HCV drugs in clinical development as well as some interesting data on Pegasys and PegIntron that will be discussed in this article
	Enhanced Response to Peginterferon Alfa-2a (Pegasys)-based Triple Therapy in Previously Non-responsive HCV Patients: Final Results of the PRETTY Study
	Sexual Transmission
	New HCV Therapies Show Promise: Etanercept and Lambda Interferon
	Diabetes & Lipids Associated with Liver Disease

Update From EASL 2005
Alan Franciscus, Editor-in-Chief

The European Association for the Study of the Liver (EASL) was recently held in Paris, France on April 13th through April 17th. There was limited amount of news on hepatitis C at the conference, but there was some exciting new data on various HCV drugs in clinical development as well as some interesting data on Pegasys and PegIntron that will be discussed in this article. In May 2005, the Digestive Disease Weekly (DDW) conference will take place in Chicago, IL and some of the studies presented at DDW will contain information from EASL that will be updated and covered on the HCV Advocate Web site and subsequent articles in the HCV Advocate newsletter.

HCV Investigational Therapies
Reports on a number of new drugs in development for treating hepatitis C were presented at EASL. Those which looked the most promising as future HCV medical treatments were viramidine, albuferon, and NM283.

Viramidine
Ribavirin induced hemolytic anemia is reported in about a quarter of HCV patients taking the combination therapy of pegylated interferon plus ribavirin. Preliminary data on the safety and tolerability of viramidine (in combination with pegylated interferon) was presented at the 2004 American Association for the Study of Liver Disease (AASLD). It was reported that the incidence of hemolytic anemia was dramatically lower in the viramidine arm of the study compared to the ribavirin arm (4% vs. 27% respectively).

The data on the sustained virological response (SVR-undetectable HCV during and 24 weeks post treatment) from the same clinical trial was presented at this year’s EASL conference.

One hundred seventy-one previously untreated patients received the full dose of 400 mg (47 patients), 600 mg (43 patients), and 800 mg (44 patients) twice a day (BID) of viramidine versus 1000/1200 mg/day ribavirin (37 patients) in combination with pegylated interferon. Treatment duration was 48 weeks for genotype 1, and 24 weeks for genotypes 2 and 3 with a follow-up period of 24 weeks. The patient characteristics were male (64%), Caucasian (76%), and genotype 1 (72%). The median HCV viral load was 6.5 log10 copies/mL. In the viramidine group, the highest SVR rate was in the patients that received 600 mg BID dose.

	SVR viramidine 600 mg/ BID	SVR ribavirin 1,000/1,200/daily
Overall
Genotype 1	27 %	35%
Genotypes 2, 3	62%	73%

It is difficult to draw any concrete conclusions about the SVR rates since the study included a limited number of patients. Phase III trials (with a much larger patient population) of viramidine vs. ribavirin are underway and the results from this study should give us a better understanding of the effectiveness of viramidine compared to ribavirin. However, since the response rates were similar between the different study arms, it does appear that viramidine may produce similar treatment response rates but with less of the ribavirin-induced hemolytic anemia.

Albuferon
Albuferon is a form of time-released interferon that is produced by fusing human serum albumin to interferon. In a previous phase I/II clinical trial of 119 adults (HCV positive non-responders to previous interferon therapy) who received albuferon, it was found that the drug was safe and well-tolerated with no discontinuations due to side effects. The side effects from the treatment were found to be transient (temporary) and mild to moderate in severity. The authors of this study found that the HCV RNA (viral load) decline was dose-dependent and concluded that albuferon has the potential to address an unmet need for HCV therapy with less frequent dosing (injections).

Data from a new phase II trial on 56 previously untreated genotype 1 patients also found that albuferon was safe and well-tolerated. Furthermore, it was reported that after 4 weeks of albuferon therapy there was a 99.9 percent decrease in viral load in the patients who received the two highest doses of albuferon. After 42 days, 23% of the same patients remained HCV negative. The authors concluded, based on this study, that albuferon could be dosed (injected) every 2-4 weeks and that it showed a strong antiviral activity after two doses. A larger 48-week combination study of albuferon plus ribavirin in previously untreated HCV patients is being planned.

Valopicitabine (NM283)
Valopicitabine is an oral nucleoside analog, a new class of drugs that block the hepatitis C virus from replicating (reproducing) by inhibiting the HCV RNA polymerase. HCV polymerase is the enzyme of the hepatitis C virus that is critical in the replication process of hepatitis C. The data presented at EASL on valopicitabine is noteworthy because this is the first time that 24 week data has been reported on an HCV drug with direct antiviral properties against the hepatitis C virus.

Preliminary data from a phase II study was presented at EASL on the genotype 1 patients (previously untreated) who completed 24 weeks of treatment of valopicitabine combined with pegylated interferon. So far 9 out of 30 patients have completed 24 weeks of therapy. It was found that the HCV RNA (viral load) reduction was more than 99.0% in the 9 patients. The HCV viral load declined in 8 out of 9 patients to below the level of detection of < 600 IU/mL (Amplicor PCR)—six of the patients had a reduction of HCV viral load to below the level of detection by a more sensitive viral load test with a lower limit of 10 IU/mL (TaqMan PCR). The authors reported that there were no serious adverse events (side effects) and no patient was required to discontinue therapy due to valopicitabine-related side effects. A larger trial of 171 HCV genotype 1 patients who failed a previous course of pegylated interferon plus ribavirin is currently underway. The patients will receive valopicitabine monotherapy, valopicitabine plus pegylated interferon or pegylated interferon plus ribavirin. Enrollment in the new trial is expected to be completed by June 2005.

PegIntron
The EPIC3 (Evaluation of PegIntron in Control of Hepatitis C Cirrhosis) is an on-going clinical trial that is evaluating PegIntron plus Rebetol (ribavirin) for previous interferon based treatment non-responders and relaspers. The study will evaluate the effectiveness of PegIntron combination therapy in this patient population. There is also a PegIntron long term maintenance phase in this study that will evaluate whether the use of low dose PegIntron monotherapy can delay or prevent cirrhosis.

Preliminary results from the EPIC study involving over 2,200 HCV patients worldwide were released at EASL. In this study on people who failed a previous course of interferon based therapy, patients were treated with weight based PegIntron (1.5 mcg/kg/week) plus Rebetol (ribavirin-800-1400 mg/day) for up to 48 weeks. Twenty-one percent of the 978 patients who had completed up to 48 weeks of therapy achieved an SVR. Breaking it down by genotype, patients with genotype 1 achieved a 14% SVR compared to a 56% SVR in patients with genotypes 2 or 3. As expected it was found that treatment relapsers achieved higher SVR rates (41% SVR compared to 14% SVR in the treatment non-responders group) and that people with mild to moderate fibrosis achieved a higher SVR compared to people with more advanced scarring (26% vs. 15%).

Pegasys
Generally, people with persistently normal ALT levels have a milder course of HCV disease progression. However, about 30% of people with persistently normal ALT levels will progress on to advanced fibrosis and/or cirrhosis. Clinical trials have found that people with normal ALT levels can be treated successfully and achieve similar treatment response rates as people with elevated ALT levels. Data from a previous study using Pegasys plus Copegus (ribavirin) combination therapy for treatment of HCV in patients with persistently normal ALT levels was analyzed to find out if there was a relationship between the age and baseline characteristics of patients and response to therapy.

In this retrospective study, information on 422 patients was analyzed. It was found that people under 40 years old were more likely to achieve an SVR—54% in the group under 40 years old compared to 34% in the group that was over 40 years old. The authors concluded that age appears to be an important factor in treatment response. It was also pointed out that other confounding factors such as male gender, African American race and high HCV RNA (viral load) play an important role in treatment response.

Adherence to HCV medicines is also an important factor in achieving an SVR and data from another clinical trial was examined. A retrospective analysis of 569 patients who received Pegasys plus Copegus (ribavirin) found that the dose of Copegus was an important factor in treatment response. It was found that 66% of the patients in this group who took greater than 97% of their ribavirin dose achieved an SVR compared to the SVR rate of 33% for patients who took less than 60% of their ribavirin dose. The authors concluded that patients in this trial were more likely to maintain the Pegasys dose compared to the ribavirin dose and that avoiding ribavirin dose reductions and dose discontinuations will likely improve the overall SVR rates.

Weight is also another poor prognostic factor for achieving a successful treatment response, but a study presented at EASL reported that it appears that body weight is not solely responsible for the lower treatment response rates. Studies from two multinational phase III studies of 2,404 patients were analyzed and it was reported that the heavier patients were more likely to be male, black, cirrhotic and infected through intravenous drug use, which are all factors associated with a lower treatment response rate. The authors concluded: “This clustering of poor prognostic characteristics may explain the lower SVR rates observed in heavier patients.”

http://www.hcvadvocate.org/news/newsLetter/2005/advocate0505.html#1

Enhanced Response to Peginterferon Alfa-2a (Pegasys)-based Triple Therapy in Previously Non-responsive HCV Patients: Final Results of the PRETTY Study

Patients with chronic hepatitis C who are non-responders to interferon+ribavirin combination therapy are difficult to manage and show progressive liver disease. In the current study, researchers aimed to assess the efficacy and safety of triple antiviral therapy in the re-treatment of hepatitis C.

178 consecutive adult patients (M/F: 119/59) with chronic active hepatitis C, HCV-RNA positive at the end of previous interferon alfa-2b + ribavirin therapy, were randomly assigned to receive peginterferon alfa-2a (Pegasys) 180 mcg weekly (Group A) or interferon alfa-2a (Roferon-A) 6 MU on every other day (Group B) for 48 weeks.

In addition, all patients received ribavirin 1000-1200 mg and amantadine 200 mg, daily. Response was assessed by ALT determination and by qualitative PCR for HCV-RNA (Amplicor v. 2.0).

Results

78% (Group A) and 86% (Group B) of patients had HCV genotype 1. During treatment, mean ALT values significantly decreased in both groups:

Group A from 115.02 to 45.21 IU/L (p< 0.001) in genotype 1, and from 140.77 to 34.8 IU/L (p< 0.001) in genotype non-1;

Group B from 115.22 to 47.71 IU/L (p< 0.001) in genotype 1, and from 167.9 to 47.44 IU/L (p= 0.008) in genotype non-1.

At the end of therapy, 65.7% of patients in Group A and 50% in Group B had normal ALT (p= 0.04);

HCV-RNA was negative in 49% and in 28.9% of patients, respectively (p= 0.008).

After therapy, for genotype 1, sustained virological response (SVR) was 18.7% in Group A and 10.6% in Group B (p= NS), and for genotype non-1 was 31.8% in Group A and 40% in Group B (p= NS).

Reductions in treatment doses were necessary in 43% and in 41% of patients, respectively, due to side effects.

Conclusions

Based on these results, the authors conclude, “In chronic hepatitis C patients, non-responder to interferon+ribavirin, triple antiviral therapy is able to significantly reduce ALT values and to induce ALT normalization in the majority of patients.”

“Pegasys-based regimen is superior and able to suppress HCV infection in about 50% of patients.”

“Virological relapse is common after therapy, but about 20% of genotype 1 and 40% of genotype non-1 infected subjects have SVR.

“Longer treatment deserves investigation to reduce relapse in this difficult-to-treat population.”

Italian Multicenter P.R.E.T.T.Y. Study Group, Italy.

05/02/05

Reference
A Mangia and others. ENHANCED RESPONSE TO PEGINTERFERON-ALFA-2A-BASED TRIPLE THERAPY IN PREVIOUSLY NON-RESPONSIVE CHRONIC HEPATITIS C: FINAL RESULTS OF PRETTY STUDY. Abstract 551. 40^th EASL. April 13-17, 2005. Paris, France.

http://hivandhepatitis.com/2005icr/easl/docs/050205_hcv_a.html

Sexual Transmission

Over the past year, clusters of HCV infections among gay men in London and Paris have led some experts to suggest that sexual transmission of HCV may be more common than previously believed. However, to date no similar outbreaks have been reported in North America. According to an article in the March American Journal of Public Health, a recent Canadian study found sexual transmission of HCV to be rare among HIV negative gay men. M. Alary and colleagues studied a cohort of more than 1,000 gay men in Montreal. During eight months of follow-up (2,653 person-years), only one new HCV infection was detected (in a man who reported sharing drug injection equipment), even though 63% of men said they had engaged in unprotected anal sex. After controlling for injection drug use, sexual behavior was not significantly linked to HCV infection. Notably, the suspected sexually transmitted HCV cases in Europe occurred among HIV/HCV coinfected men, who may be at higher risk for HCV transmission.

A related study by V. Tahan and colleagues reported in the April American Journal of Gastroenterology confirms that HCV sexual transmission is rare among monogamous heterosexual couples. The researchers studied 216 HIV negative heterosexual spouses of individuals with chronic hepatitis C; the spouses were tested each year for HCV antibodies. They found that none of the initially HCV negative spouses seroconverted during an average follow-up period of about three years, which included an average of 257 instances of sexual intercourse.

http://www.hcvadvocate.org/news/newsRev/2005/HJR-2.5.html#1

New HCV Therapies Show Promise: Etanercept and Lambda Interferon

Given that a considerable proportion of patients do not achieve sustained virological response after treatment with pegylated interferon-alpha plus ribavirin, researchers are continually searching for new and potentially more effective therapies.

In the March 2005 Journal of Hepatology, researchers looked at whether adding etanercept to a standard interferon/ribavirin regimen could improve response rates. Etanercept (Enbrel) is a medication that blocks tumor necrosis factor (an immune system chemical messenger) that is used to treat rheumatoid arthritis. In this Phase II trial, 50 subjects were randomly assigned to receive interferon/ribavirin plus etanercept or interferon/ribavirin plus placebo. After 24 weeks, 63% (12 out of 19) in the etanercept arm achieved undetectable HCV RNA, compared with 32% (8 out of 25) in the placebo arm. The authors concluded that adding etanercept “significantly improved virologic response…and was associated with decreased incidence of most adverse effects associated with interferon and ribavirin.” While these results appear promising, further study with longer follow-up is needed to see if response is sustained over time and if similar results are also seen using today’s standard of care, pegylated interferon plus ribavirin.

In the March Journal of Virology, M.D. Robek and colleagues reported on the use of a new type of interferon ¾ interferon-lambda ¾ in the treatment of hepatitis B and C. Interferons promote the body’s immune response and protect cells from infection. Interferon-alpha is standard therapy for chronic hepatitis C, while interferon-gamma and consensus interferon are under study for the treatment of HCV nonresponders and relapsers. Interferon-lambda is a newly discovered member of this family that appears to induce an intracellular antiviral response similar to that of interferon-alpha, but using a different cell receptor. In laboratory studies, the researchers found that interferon-lambda inhibited HBV replication in mouse liver cells and blocked HCV replication in human liver cells. While much more study is needed, the authors suggest that interferon-lambda may one day join the armamentarium of treatments for hepatitis B and C

http://www.hcvadvocate.org/news/newsRev/2005/HJR-2.5.html#1

Diabetes & Lipids Associated with Liver Disease

	Reported by Jules Levin These studies were reported at the 40th annual EASL liver meeting in Paris (April 2005). The studies support numerous previous studies that insulin resistance and diabetes can contribute to advancing liver disease, particularly in people with viral hepatitis C or B. As well, elevated lipids may contribute. Impact of Overweight & Diabetes on Liver-Related Death in Patients with Alcoholic & Viral Hepatitis C Cirrhosis G. N'Kontchou1, M. Tin Tin Htar1, J. Paries2, F. Kazemi1, V. Bourcier1, N. Ganne-Carrie1, P. Nahon1, V. Grando-Lemaire1, J.C. Trinchet1, M. Beaugrand1 1 Liver Unit, Jean Verdier Hospital, Bondy, France 2 Public Health Unit, Jean Verdier Hospital, Bondy, France Obesity and diabetes have been suggested to be risk factors of liver-related death in recent population-based cohort studies. This study was aimed to assess prospectively the impact of these factors on liver-related death (including liver transplantation). Overweight & diabetes type II are risk factors of cirrhosis in patients with alcoholic & viral HCV. They are also risk factors for liver cancer (hepatocellular carcinoma). Their influence on liver-related death in patients has not yet been evaluated. A large cohoht of 963 patients with compensated cirrhosis regularly followed for a screening program for HCC were included. All clinical and biological variables were collected at inclusion. Ultrasonography & alfa-feto protein were used for follow-up evaluation. Outcomes evaluated were: liver-related death, liver-related death including liver transplantation (HCC, liver failure, portal hypertension), & occurrence of HCC was also recorded. Predictive factors for overall and liver-related death were determined by log-rank test and Cox proportional hazards model. Survival to events was estimated by Kaplan-Meier method. BASELINE CHARACTERISTICS n=963: Age: 57 63% male Etiologies: (alcohol/HCV/mixed): 484/322/157 Diabetes: 298 (31%) BMI (kg/m2): 25/6 +/-4.7 Prothrombine time: 72+/-17 Platelet counts: 137 +/-64 Bilirubin: 28 mmol/l Albumin (g/l): 39+/-6 AST (N): 2 ALT (N): 2 AP (N): 1.4 y-GT (N): 3.9 Results -There were 484 alcoholic cirrhosis, 322 HCV, 157 HCV+alcohol. -Mean age was 57.2±11 yr and mean BMI was 25.6 kg/m2. -607 were male patients. -298 patients were diabetic. -After a mean follow-up of 66.7±45.2 months, 384 patients died, of which 279 were liver-related deaths (liver failure: 142; hepatocellular carcinoma: 117; portal hypertension: 20). In univariate analysis, factors associated with liver-related death were: --BMI ³27.5 [OR 1.9; 1.5-2.4; p < 0.0001] --age >57 yr [OR 1.6; 1.3-2.0; p < 0.0001] --male sex [1.7; 1.3-2.1; p < 0.0001] --platelet count <140,000/mm3 [OR 1.9; 1.5-2.5; <0.0001] --serum albumin <42 g/l [2.8; 2.0-3.9; p < 0.0001] --prothrombin activity <82% [2.3; 1.7-3.1; p < 0.0001] --alkaline phosphatase >1.4 ULN [OR 1.9; 1.5-2.4; p < 0.0001] --total bilirubin >17 mm/ml [OR 1.9; 1.5-2.4, p < 0.0001]. Diabetes was not significantly related. In multivariate analysis, independent risk factors for liver-related death were: --serum albumin <42 g/l [OR 2.00; 1.4-2.9; p = 0.0004] --BMI ³27.5: [OR 1.8; 1.4-2.4; p < 0.0001] --age >57 yr [OR 1.7; 1.3-2.3; p = 0.0002] --male sex [OR 1.5; 1.1-2.1; p = 0.01] --prothrombin activity <82% [OR 1.6; 1.1-2.2 p = 0.02] --alkaline phosphatase >1.4 ULN [OR 1.4; 1.0-1.9; p = 0.03]. These results were confirmed in different etiological subgroups. Conclusion: Overweight was an independent and important predictive factor of liver-related death in patients with compensated HCV and alcohol cirrhosis. Diabetes is Strongly Associated with Advanced Fibrosis; Elevated Lipids May Be Associated with Fibrosis --Patient Populations with High prevalence of Diabetes, like Hispanics, May Be Particularly At Risk for Advancing Liver Disease "ASSOCIATION BETWEEN DIABETES, OVERWEIGHT, OBESITY AND DYSLIPIDEMIA WITH FIBROSIS PROGRESSION IN CHRONIC HEPATITIS C PATIENTS" A. Loaeza-del Castillo, F. Vargas-Vorackova 1 Department of Gastroenterology, Instituto Nacional de Ciencias MŽdicas y Nutrici—n, Mexico 2 Department of Gastroenterology, Instituto Nacional de Ciencias MŽdicas y Nutrici—n, Mexico Fibrosis progression in chronic hepatitis C (CHC) patients is variable, factors associated with an accelerated progression have been identified, but they do not account for the heterogeneity seen between individuals. Aim: To determine the prevalence of diabetes, overweight, obesity and dyslipidemia in CHC patients and the association of these metabolic factors with liver fibrosis progression. Method: Patients with CHC seen in our institution between 1993 and 2003 were retrospectively studied (n = 1618). Patients with a known duration of infection acquired by transfusion with a liver biopsy performed before any antiviral treatment were included. Patients with overt hepatic insufficiency were excluded. The diagnoses of diabetes, overweight, obesity and dyslipidemia were investigated and liver fibrosis stage (METAVIR). Variables were tested for their association with significant fibrosis (F2, F3, F4). RESULTS --108 patients were included, 71 (66%) female and 37 (34%) male, --mean age was 48.7+12.2 years. --Age at infection was 24.7±13 years, acquired between 1944-2000. --78% were HCV-genotype 1. --Fibrosis stage was: F0 = 15 (14%), F1 = 38 (35%), F2 = 9 (8%), F3 = 8 (8%) and F4 = 38 (35%). --Mean fibrosis progression rate was 0.106±0.101 (0-0.44). --26 patients (24%) had diabetes, 10 (9%) glucose intolerance, 24 (22%) obesity [body mass index (BMI) ³30 kg/m2] and 49 (45%) overweight (25 £ BMI < 30 kg/m2). --Dyslipidemia was investigated in 75 patients and confirmed in 25 (33.3%). Association between these variables and fibrosis is depicted in the table. Conclusions: Diabetes is a factor strongly associated with advanced fibrosis and cirrhosis. In populations with a high prevalence of diabetes, such as Hispanics, this association must be taken into account. Lipid metabolism has a specific role in the pathogenesis of CHC and the possible protector role of dyslipidemia for significant liver fibrosis should be investigated in further studies. "INSULIN RESISTANCE PROMOTES FIBROSIS PROGRESSION AND PREDICTS NECRO-INFLAMMATORY ACTIVITY IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE" D. Sanchez-Munoz1, E. Suarez1, M.V. Galan1, L. Grande1, G. Munoz2, M. Romero-G—mez1 1 Hepatology Unit, Hospital Universitario de Valme, Sevilla, Spain 2 Pathology Unit, Hospital Universitario de Valme, Sevilla, Spain Aims: To assess the presence of metabolic syndrome X (MSx) and insulin resistance (IR), and its relationship with histologic damage, in patients with non-alcoholic fatty liver disease (NAFLD). Patients and Methods: Thirty-five patients, 25 male and 10 female, with an average age of 45.7±12.7 [24-76] years, diagnosed by NAFLD, were included. Liver biopsy was carried out after persistence for, at least, six months of altered liver enzymes with appropriate diet and physical activity therapies. Histological damage was assessed according to Brunt criteria (Semin Liver Dis 2001; 21: 3-16). Body mass index (BMI) was calculated. MSx was diagnosed according to ATP III criteria. IR was calculated using the HOMA-IR index = [Glucose(mmol/l) _ Insulin(UI/ml)]/22.5. RESULTS Only one patient (2.5%) showed normal weight; 17/35 (48.6%) patients showed overweight and 17/35 (48.6%) patients were obese. --MSx was present in 14/35 (42.5%) patients; --central obesity in 65.7%, --high triglyceride levels in 62.9%, --altered glucose metabolism in 28.6%, --hypertension in 31.4% and --low HDL-colesterol levels in 24%. --IR was present (HOMA-IR >2) in 23/33 (74.3%) patients. --The histologic diagnosis was simple hepatocyte steatosis (HS) in 8/35 (22.9%) patients and steatohepatitis (NASH) in 27/35 (77.1%) patients: Fibrosis degree was: absent in 13 patients, mild fibrosis (F1-F2) in 6 patients, bridging fibrosis (F3) in 7 patients and cirrhosis (F4) in 1 patient. Patients with HS showed lower triglyceride levels (99±43 vs 169±85 mg/dl; p = 0.034) and HOMA-IR (2.54±0.9 vs 4.5±2.5; p = 0.002) than patients with NASH. Triglycerides >180 mg/dl or HOMA IR >4.5 was associated with NASH (Specificity: 100% and Sensitivity: 54.3%. Fibrosis correlated with age (r = 0.37; p = 0.027), AST (r = 0.5; p = 0.002), and HOMA-IR (r = 0.45; p = 0.007). In multiple lineal regression, the only factor associated with fibrosis was the HOMA-IR (R = 0.60; p = 0.0001). All of the patients with advanced fibrosis (F3-F4) showed a HOMA-IR index >4.5, but only 8/26 (30%) patients with F0-F2; p < 0.001. Conclusions: Insulin resistance is present in the majority of the patients with non-alcoholic fatty liver disease. HOMA-IR index >4.5 or triglyceride levels >180 mg/dl are predictors of the presence of NASH. Insulin resistance may play a role in the pathogenesis of fibrosis progression in patients with NAFLD. Drugs able to decrease insulin resistance could be useful in the therapy of this disease. Total Calories May Contribute to Development of Fatty Liver "LIVER STEATOSIS (Fatty Liver) IN OPEN POPULATION: PREVALENCE AND RELATIONSHIP TO THE DIET. PRELIMINARY RESULTS OF THE "ARSITA-ONE" PROJECT" I. Petridis1, E. Lattanzi1, B. Marraccini1, I. Carderi1, E. Claar1, C. Liani1, S. Lobello1, O. Di Andrea2, M. Chiaramonte1 1 Hepato-Gastroenterology and Nutrition Unit - Dept. of Internal Medicine and Public Health - L'Aquila University, L'Aquila, Italy 2 Arsita Family Doctor, Italy Background and Aim: This study, part of a larger epidemiological study for liver and metabolic diseases carried out on Arsita (Abruzzo) (805 adult registered inhabitants), was designed: 1) to assess the prevalence of liver steatosis; 2) to evaluate the relationship with the diet. Materials and Methods: All subjects aged over 18 yr were invited to have liver ultrasound (US) and an alimentary questionnaire computer analyzed (Winfood 1.5). Liver steatosis was classified as none, mild, moderate and severe. Diet was classified as: diet 1, a traditional local diet, hypercaloric (3500-4500 kcal), hyperlipidic (55% of calories); diet 2, similar but with less calories (2500-3500 kcal); diet 3, classic Mediterranean (2000-2500 kcal). RESULTS --541 subjects (253 M and 288 F), completed the US and diet study. --Moderate/severe steatosis was found in 89/253 (35%) males and 75/288 (26%) females; in 41/164 (25%) subjects under 40 yr, in 63/119 (33%) subjects aged 40-59 yrs and in 92/196 (47%) subjects over 60 yr. --143/253 males (57.5%) and 86/288 females (30%) followed diet 1, which was related to obesity (BMI > 30) in 61% of males and 69% of females, while 14% of subjects having diet 2 were obese. --All subjects with mediterranean diet had normal BMI. --In diet 1 group, 71.5% of males and 64.5% of females had steatosis, while in diet 2 this was respectively 25.1% and 31.3%. --In subjects with steatosis, alcohol consumption was present in 82% of males and in 48% of females, while BMI > 30 was present in 61% of males and 78% of females. --Out of 164 subjects with steatosis 22 (13%) had altered AST and/or ALT (13 anti-HCV+). Conclusions: Prevalence of steatosis is increasing with age and is more frequent in males. In females severe steatosis is mainly correlated with overweight and in males with alcohol abuse. The amount of total calories instead of the proportion of fat seems to be related to liver steatosis. Elderly people had moderate/severe in 47%, however in most cases steatosis is indolent. Hepato cytolisis, without virus, seems to be very rare. Liver steatosis without "a second hit" seems to be a benign condition.
http://www.natap.org/

Reviewed May 06 2005