clinical spectrum of non-alcoholic steatohepatitis (nash) in non-diabetic population of pakistan

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showed that the DF is relatively poor at predicting outcome. Although the value of 32 maximizes sensitivity and specificity of the DF in predicting mortality, there is a high mortality in patients with AH and a DF greater than 32. Alternative effective agents should be considered in patients with milder AH. 244 SURPRISING LACK OF ASSOCIATION OF PRIOR ALCOHOL CONSUMPTION ON HEPATITIS C INFECTION AND HEPATIC HISTOLOGY Alan W. Chang, M.D., Manjushree Gautam, M.D., Swati Patel, Pharm. D., Brenda Horwitz, M.D., Martin Black, M.D., Frank Friedenberg, M.D.*. Temple University Hospital, Philadelphia, PA. Background: Chronic alcoholism is common in patients with chronic hepatitis C (CHC) infection. Alcohol can exacerbate liver damage in hepatitis C infection by causing oxidative stress. Heavy alcohol consump- tion has been associated with higher levels of viremia and more advanced fibrosis. Studies have also suggested that chronic alcoholism causes more rapid progression to cirrhosis and hepatocellular carcinoma in patients with CHC, however alcohol intake has been poorly quantified in these studies. Purpose: To compare the effect of prior alcohol consumption on degree of hepatitis C viremia and degree of hepatic fibrosis. Methods: Patients about to undergo treatment for CHC (no prior CHC treatment, HIV negative, other forms of liver disease ruled out) were evaluated for lifetime cumulative alcohol consumption and duration of abstinence prior to treatment (all had minimum of 6 months). Each inter- view was performed by a physician or R.N. with emphasis on lifetime alcohol use. Reliability was confirmed by repeated questioning. Results: We interviewed 57 consecutive eligible patients, 63% male and 46% African American, 33% Caucasian, 19% Hispanic. Age 46.9 8.6 (range 21 to 69). Most common risk factor for CHC was intravenous drug abuse (57%). Prevalence of HCV genotype 1 was 77%. Mean fibrosis score 2.511.3 (0 to 6 scale), mean activity grade 7.613.1 (1 to 18 scale). The group’s median daily alcohol consumption was 56 g per day and 344 kg cumulative. Initial viral load, activity grade, and fibrosis score were not associated with alcohol consumption nor duration of abstinence (median 2 years) prior to treatment. Conclusions: In a carefully interviewed group of treatment naı ¨ve CHC patients, quantity of alcohol consumption had minimal impact on hepatic histology or viral load. Our results differ considerably from previous studies. Patients will now be followed to determine whether alcohol con- sumption affects treatment response. 245 HEPATOCELLULAR CARCINOMA IN HOUSTON, TEXAS: RISING INCIDENCE OVER THE LAST TEN YEARS Ketan Kulkarni, M.D., Eric Barcak, Hashem El-Serag, M.D., Richard Goodgame, M.D.*. Baylor College of Medicine, Houston, TX. Purpose: Several published series have suggested an increasing incidence of hepatocellular carcinoma (HCC) in the United States. The cause of an increased incidence may be multifactorial including immigration, viral hepatitis, or aging population. This study was carried out in order to clarify the incidence and cause of HCC in Houston, Texas. Methods: We performed a 10-year retrospective analysis at Ben Taub General Hospital, the largest public hospital in Houston, Texas. 269,162 admissions and 1,364,955 clinic records from 1992-2001 were searched for suspected HCC on the basis of discharge diagnosis, radiology findings, pathology reports, or laboratory abnormalities. HCC was definite if asso- ciated with diagnostic histopathology or the presence of a suggestive imaging study with an AFP greater than 400 ng/mL. Confirmed cases were thoroughly assessed for possible causative factors associated with HCC, ethnicity, and place of birth. Yearly incidence of HCC was calculated using the number of hospital admissions and outpatient clinic visits. Age-adjusted incidence was determined by calculating age-specific incidence according to 5 year age groups using the population of each age group in Harris County from 1992– 01. Then age-specific incidence was adjusted to the standard national population of year 2000. Results: 111 definite cases of HCC were identified. Comparing the time periods 1992–1996 and 1997–2001, the incidence of HCC increased from 4.13 per 100,000 hospital admissions and clinic visits to 8.05 (P0.001).From 1992–1996 to 1997–2001 the proportion of HCC patients of non-US nationality decreased (P0.021). The age-adjusted incidence from 1997– 01 was statistically greater than that of 1992–96. Comparing the time periods 1992–1996 and 1997–2001, the percentage of HCC cases associated with HCV increased from 52% to 74%, and the proportion of cases with a history of alcohol abuse rose from 42.5% to 58% (P0.083 and 0.18, respectively). Conclusions: The incidence of HCC in Houston, Texas, has increased during the past decade, and this increase cannot be explained by cases imported from other countries or by the rising elderly population. The rising incidence of HCC is likely due to chronic hepatitis C infection and alcohol use. The increasing incidence of HCC underscores the need for more effective screening tests to detect HCC earlier and new treatment and preventative strategies for high-risk individuals. 246 CLINICAL SPECTRUM OF NON-ALCOHOLIC STEATOHEPATITIS (NASH) IN NON-DIABETIC POPULATION OF PAKISTAN Mohammad Umar, F.C.P.S., Hamama Tul Bushra, F.C.P.S.*, Amir Chohan, M.B.B.S., Mohammad Zahid, F.C.P.S., Zahid Latif, F.C.P.S., Rizwan, M.B.B.S. Rawalpindi Medical College, Rawalpindi, Punjab, Pakistan. Purpose: Twenty-one patients of liver biopsy proven NASH between the ages of 21 to 50 years with no history of alcohol consumption, non-diabetic and without any known hepatic disease were studied for clinical presen- tation, risk factors and morphology characteristics. Fifteen were mails and six were females. Mean age was 31.5 7.15 years. Average weight 91.5 33.6 kg and mean BMI 32.6 9.6. Mean Serum ALT was 88.4 38.3 u/L. Data of lipid profile showed mean cholesterol of 219.9 40.9 mg/dl and mean triglyceride 170.3 42.2 mg/dl. Ultrasound abdomen was normal in 3 patients (14%) while fatty changes in liver were seen in 17 (81%) patients. Ultrasound abdomen of one patient showed course parenchyma of the liver. In 81% of the patients, the major presenting complaint was the pain in right hypochondrium followed by dyspeptic symptoms. 19% of the patients were asymptomatic. Liver biopsy revealed that 9 patients (42.9%) had grade 1 (mild) changes of steatohepatitis while 11 patients had grade 2 (moderate) changes. Only 1 (4.8%) had grade 3 (severe) steatohepatitis. It is concluded that majority of the patients with NASH have complaints of pain in the right hypochondrium. They have distributed ALT level. Obesity and dyslipidemia are the risk factors in development of NASH in absence of diabetes. Most patients with NASH have fatty changes seen on ultra- sound and biopsy. Methods: An observational cohort study done in tertiary care teaching hospital of Rawalpindi Medical College, Rawalpindi, Pakistan. Results: Already given in Abstracts Conclusions: In conclusion, although NASH is more prevelant in Diabetic patients but it is also common in Non-Diabetic population as a cause of S84 Abstracts AJG – Vol. 98, No. 9, Suppl., 2003

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showed that the DF is relatively poor at predicting outcome. Although thevalue of 32 maximizes sensitivity and specificity of the DF in predictingmortality, there is a high mortality in patients with AH and a DF greater than32. Alternative effective agents should be considered in patients with milder AH.

244

SURPRISING LACK OF ASSOCIATION OF PRIOR ALCOHOLCONSUMPTION ON HEPATITIS C INFECTION AND HEPATICHISTOLOGYAlan W. Chang, M.D., Manjushree Gautam, M.D.,Swati Patel, Pharm. D., Brenda Horwitz, M.D., Martin Black, M.D.,Frank Friedenberg, M.D.*. Temple University Hospital, Philadelphia, PA.

Background: Chronic alcoholism is common in patients with chronichepatitis C (CHC) infection. Alcohol can exacerbate liver damage inhepatitis C infection by causing oxidative stress. Heavy alcohol consump-tion has been associated with higher levels of viremia and more advancedfibrosis. Studies have also suggested that chronic alcoholism causes morerapid progression to cirrhosis and hepatocellular carcinoma in patients withCHC, however alcohol intake has been poorly quantified in these studies.Purpose: To compare the effect of prior alcohol consumption on degree ofhepatitis C viremia and degree of hepatic fibrosis.Methods: Patients about to undergo treatment for CHC (no prior CHCtreatment, HIV negative, other forms of liver disease ruled out) wereevaluated for lifetime cumulative alcohol consumption and duration ofabstinence prior to treatment (all had minimum of 6 months). Each inter-view was performed by a physician or R.N. with emphasis on lifetimealcohol use. Reliability was confirmed by repeated questioning.Results: We interviewed 57 consecutive eligible patients, 63% male and46% African American, 33% Caucasian, 19% Hispanic. Age 46.9 � 8.6(range 21 to 69). Most common risk factor for CHC was intravenous drugabuse (57%). Prevalence of HCV genotype 1 was 77%. Mean fibrosis score2.51�1.3 (0 to 6 scale), mean activity grade 7.61�3.1 (1 to 18 scale). Thegroup’s median daily alcohol consumption was 56 g per day and 344 kgcumulative. Initial viral load, activity grade, and fibrosis score were notassociated with alcohol consumption nor duration of abstinence (median 2years) prior to treatment.Conclusions: In a carefully interviewed group of treatment naı̈ve CHCpatients, quantity of alcohol consumption had minimal impact on hepatichistology or viral load. Our results differ considerably from previousstudies. Patients will now be followed to determine whether alcohol con-sumption affects treatment response.

245

HEPATOCELLULAR CARCINOMA IN HOUSTON, TEXAS:RISING INCIDENCE OVER THE LAST TEN YEARSKetan Kulkarni, M.D., Eric Barcak, Hashem El-Serag, M.D.,Richard Goodgame, M.D.*. Baylor College of Medicine, Houston, TX.

Purpose: Several published series have suggested an increasing incidenceof hepatocellular carcinoma (HCC) in the United States. The cause of anincreased incidence may be multifactorial including immigration, viralhepatitis, or aging population. This study was carried out in order to clarifythe incidence and cause of HCC in Houston, Texas.Methods: We performed a 10-year retrospective analysis at Ben TaubGeneral Hospital, the largest public hospital in Houston, Texas. 269,162admissions and 1,364,955 clinic records from 1992-2001 were searched forsuspected HCC on the basis of discharge diagnosis, radiology findings,pathology reports, or laboratory abnormalities. HCC was definite if asso-ciated with diagnostic histopathology or the presence of a suggestiveimaging study with an AFP greater than 400 ng/mL. Confirmed cases werethoroughly assessed for possible causative factors associated with HCC,ethnicity, and place of birth. Yearly incidence of HCC was calculated usingthe number of hospital admissions and outpatient clinic visits. Age-adjustedincidence was determined by calculating age-specific incidence accordingto 5 year age groups using the population of each age group in HarrisCounty from 1992–01. Then age-specific incidence was adjusted to thestandard national population of year 2000.

Results: 111 definite cases of HCC were identified. Comparing the timeperiods 1992–1996 and 1997–2001, the incidence of HCC increased from4.13 per 100,000 hospital admissions and clinic visits to 8.05(P�0.001).From 1992–1996 to 1997–2001 the proportion of HCC patientsof non-US nationality decreased (P�0.021). The age-adjusted incidencefrom 1997–01 was statistically greater than that of 1992–96. Comparingthe time periods 1992–1996 and 1997–2001, the percentage of HCC casesassociated with HCV increased from 52% to 74%, and the proportion ofcases with a history of alcohol abuse rose from 42.5% to 58% (P�0.083and 0.18, respectively).Conclusions: The incidence of HCC in Houston, Texas, has increasedduring the past decade, and this increase cannot be explained by casesimported from other countries or by the rising elderly population. Therising incidence of HCC is likely due to chronic hepatitis C infection andalcohol use. The increasing incidence of HCC underscores the need formore effective screening tests to detect HCC earlier and new treatment andpreventative strategies for high-risk individuals.

246

CLINICAL SPECTRUM OF NON-ALCOHOLICSTEATOHEPATITIS (NASH) IN NON-DIABETIC POPULATIONOF PAKISTANMohammad Umar, F.C.P.S., Hamama Tul Bushra, F.C.P.S.*,Amir Chohan, M.B.B.S., Mohammad Zahid, F.C.P.S.,Zahid Latif, F.C.P.S., Rizwan, M.B.B.S. Rawalpindi Medical College,Rawalpindi, Punjab, Pakistan.

Purpose: Twenty-one patients of liver biopsy proven NASH between theages of 21 to 50 years with no history of alcohol consumption, non-diabeticand without any known hepatic disease were studied for clinical presen-tation, risk factors and morphology characteristics. Fifteen were mails andsix were females. Mean age was 31.5 � 7.15 years. Average weight 91.5 �33.6 kg and mean BMI 32.6 � 9.6. Mean Serum ALT was 88.4 � 38.3 u/L.Data of lipid profile showed mean cholesterol of 219.9 � 40.9 mg/dl andmean triglyceride 170.3 � 42.2 mg/dl. Ultrasound abdomen was normal in3 patients (14%) while fatty changes in liver were seen in 17 (81%)patients. Ultrasound abdomen of one patient showed course parenchyma ofthe liver. In 81% of the patients, the major presenting complaint was thepain in right hypochondrium followed by dyspeptic symptoms. 19% of thepatients were asymptomatic. Liver biopsy revealed that 9 patients (42.9%)had grade 1 (mild) changes of steatohepatitis while 11 patients had grade2 (moderate) changes. Only 1 (4.8%) had grade 3 (severe) steatohepatitis.It is concluded that majority of the patients with NASH have complaints ofpain in the right hypochondrium. They have distributed ALT level. Obesityand dyslipidemia are the risk factors in development of NASH in absenceof diabetes. Most patients with NASH have fatty changes seen on ultra-sound and biopsy.Methods: An observational cohort study done in tertiary care teachinghospital of Rawalpindi Medical College, Rawalpindi, Pakistan.Results: Already given in Abstracts

Conclusions: In conclusion, although NASH is more prevelant in Diabeticpatients but it is also common in Non-Diabetic population as a cause of

S84 Abstracts AJG – Vol. 98, No. 9, Suppl., 2003

high ALT. All of our patients were young. ALT was high 100%. Ultra-sound showing fatty changes in 81%. Clinical symptomtolgy was non-specific. Obesity and hyperlipidaemia were important risk factors in ab-sence of Diabetes. Biopsy was diagnostic showing moderate to severesteatohepatitis in 50% of the cases.

247

USEFULNESS THERAPY FOR HEPATOCELLULARCARCINOMA LOCATED AT HEPATIC DOME: VALUE OFARTIFICIAL PLEURAL EFFUSIONNaoki Hotta, Yoshitaka Fukuzawa, Akihiko Okumura, Tetsuya Ishikawa,Shinichi Kakumu*. Ngakute, Japan.

Purpose: The diaphragm right under in the abdomen echo becomes a blindspot, and becomes a difficult description. An artificial pleural effusion tosuch a case in, and describing in most cases become possible.Methods: Between April 2000 and May 2003,Twenty-two patients of 25HCC nodules infected with hepatitis C virus (HCV) were studied. Theywere diagnosed as having HCC with helical dynamic CT and/or celiacangiography. All patients showed hypervascular enhancement of HCC ondynamic CT. The diameters of tumors were 1.1–2.0 cm in 9 nodules,2.1–3.0 cm in 14, and 3.1–5.0 cm in 2, respectively. A total of 1500–2000ml of was saline infused into the pleural cavity by puncture of specialneedle. In a total of 24 HCCs nodules located at the subphrenic regiontreated radiofrequency ablation(RFA) therapy,and one HCC treated bypercutaneous etanol injection(PEIT).Results: All tumors were treated with sonograhy guided RFA and PEITafter saline infused into the pleural cavity. In 25 0f 25HCC cases, sub-phrenic HCCs were well visualized. Treatment session of RFA required forcomplete ablation was one in 22 nodules and two in 2 nodule. Treatmentsession of PEIT complete was two in 1 nodule.No complication wereobserved in any patients during artificial plural effusion. Major complica-tion of RFA procedure was noted in only one case associated with liverabscess, but it was cured by medical treatment. No other severe compli-cations such as deterioration of ascites, jaudice or renal function wereobserved during and after RFA.Conclusions: RFA and PEIT under artificial pleural effusion combinedwith is an useful method therapy for HCCs located at the subphrenic region.The procedure is safe and can be peformed .

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IMMUNOHISTOCHEMICAL ANALYSIS OF p53, CYCLIND1,RB,C-FOS AND N-RAS GENES EXPRESSION INHEPATOCELLULAR CARCINOMA IN IRANMohammad Reza Zali, M.D., FACG*,Seyed Javad Mirhassani Moghaddam, M.D., Saeed Samie, M.D.,Negin Shahid, M.D., Alireza Keramati, Medical Student,Ehsan Nobakht Haghighi, Medical Student,Mohammad Ali Daneshmand, M.D. Research Center forGastroenterology and Liver Disease, Shaheed Beheshti University ofMedical Sciences, Tehran, Islamic Republic of Iran.

Purpose: Though several studies have demonstrated the role of some genesin development of hepatocellular carcinoma, there is still a shade ofcontroversy around the issue. This study was performed to analyze simul-taneous status of p53, cyclin D1, Rb, C-fos and N-ras genes in Iranianpatients.Methods: The paraffin-embedded tissue samples of 25 patients (18 maleand 7 female) with documented hepatocellular carcinoma were collectedfrom 22 pathology centers in Tehran in one year (2001). Using immuno-histochemistry method (Avidin-Biotin-Peroxidase), they were stained fordetection of p53, cyclin D1, Rb, C-fos and N-ras proteins accumulation.Results: All of the 25 tumors were in grade I (well differentiated). Six(24%), 5(20%), 13(52%) and 2(8%) of the samples were positive for p53,cyclin D1, C-fos and N-ras, respectively. Besides, 22(88%) cases showedcomplete loss of Rb gene expression. Compared with the p53 negative

ones, p53 positive cases showed a 9 times higher rate of being positive forRb gene. This rate was 2.66, 2.75 and 3.6 for cyclin D1, C-fos and N-ras,respectively. Rb loss of expression in association with p53 over-expressionwas observed in 4(16%) of the samples. This figure was 5(20%) for Rb andcyclinD1, 2(8%) for Rb and N-ras and 11(44%) for Rb and C-fos. Com-paring cyclin D1 positive cases with the negative ones, the former groupshowed a higher (2.85 and 4.75 times respectively) rate of being positivefor C-fos and N-ras genes.Conclusions: As shown in previous studies, the development of mutationin some of these genes especially C-fos, Rb and p53 appears to have a keyrole in the carcinopathogenesis of hepatocellular carcinoma in Iran. Also,it is likely that there is a significant association between simultaneousmutations of some of these genes during development of hepatocellularcarcinoma.

249

HIGH INCIDENCE OF DEPRESSION AND SLEEPDISTURBANCES ASSOCIATED WITHPEGIFN-ALPHA-2b/RIBIVIRIN THERAPY FOR HEPATITIS CIN ROUTINE CLINICAL PRACTICEDavid Finkelman, M.D.*. Digestive Care Associates, Atlanta, GA.

Purpose: Current treatments for hepatitis C virus (HCV) include interfer-on-alpha (IFN-alpha) or pegylated IFN-alpha (PegIFN-alpha) alone or incombination with ribavirin. PegIFN-alpha-2b/ribavirin is a well- estab-lished HCV therapy that is also associated with psychiatric adverse effects.In the PegIFN-alpha-2b/ribavirin pivotal phase III clinical trial, 77% ofpatients experienced one or more psychiatric adverse effects includingdepression (40%) and sleep disturbances (41%). The objective of this studywas to determine incidence of psychiatric adverse effects prior to and whileon therapy with PegIFN-alpha-2b/ribavirin therapy for HCV in routineclinical practice.Methods: A retrospective review was performed of 50 randomly selectedpatient charts from 3 private practice gastroenterology offices in Atlanta,GA. Record retrieval began on 7/1/02. The study included patients ontreatment at the time of record abstraction (n�37) and those who haddiscontinued therapy between 3/30/02 and 9/30/02, the last date of studyinclusion (n � 13). To be eligible, patients must have received PegIFN-alpha-2b/ribavirin for at least 1 month. PegIFN-alpha-2b/ribavirin wasadministered by body weight according to manufacturer’s instructions.Diagnosis of depression was based on the treating physician’s clinicalassessment as documented in the medical record.Results: Of the 50 patients, 29 were men, 38 were white, and the averageage was 44.3 (24–63) years. Forty-four patients had no history of depres-sion prior to therapy. The average length of therapy was 5.8 (1–10) months.Of the 44 patients without pre-existing depression, therapy-related depres-sion was documented in 20 patients (45%). All but 4 of these patientsreceived anti-depressants. The average time to onset of depression wasapproximately 2 (0–5) months. The incidence of depression increased withthe starting dose of PegIFN-alpha-2b/ribavirin: 3 (15%) at 80 or 100 mcg;5 (25%) at 120 mcg and 12 (60%) at �150 mcg. Sleep disturbances werereported for 19 patients (38%), of whom 14 received anti-insomnia med-ications.Conclusions: These data from clinical practice support observations inclinical trials that depression and insomnia are common adverse effectsassociated with PegIFN-alpha-2b/ribavirin. Practitioners should be aware

S85AJG – September, Suppl., 2003 Abstracts