Hamid, Saeed

Ismail, Faisal Wasim

English

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eCommons@AKUDepartment of Medicine Department of MedicineMarch 2004Hepatic steatosis and hepatitis C.Faisal Wasim IsmailAga Khan University, faisal.ismail@aku.eduSaeed Hamidsaeed.hamid@aku.eduFollow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_med_medPart of the Gastroenterology CommonsRecommended CitationIsmail, F., Hamid, S. (2004). Hepatic steatosis and hepatitis C.. JPMA. The Journal of the Pakistan Medical Association, 54(3), 108-109.Available at: http://ecommons.aku.edu/pakistan_fhs_mc_med_med/542Hepatic steatosis is increasingly being recognized asa condition that may progress to end-stage liver disease. Theclinical implications of fatty liver disease are derivedmostly from its common occurrence in the generalpopulation and its potential of causing a wide spectrum ofliver damage, ranging from simple steatosis tosteatohepatitis, advanced fibrosis and cirrhosis.1Hepatic steatosis can occur with the use of alcohol(alcohol-related fatty liver) or in the absence of alcohol(nonalcoholic fatty liver disease).2 Fatty liver associatedwith the use of alcohol may occur with as little as 10 oz ofalcohol ingested per week. If steatohepatitis is present but ahistory of alcohol use is not, the condition is termednonalcoholic steatohepatitis (NASH). Fatty change in theliver results from excessive accumulation of lipids withinhepatocytes. It is recognized on liver biopsy specimens andthus is a morphological rather than a clinical diagnosis.1,2Nonalcoholic fatty liver disease (NAFLD) affects10-25% of the general population in various countries. Thisprevalence increases to 57-75% in obese individuals. Theprevalence of NASH is 2-3%. NASH has been detected in1.2-8% of patients undergoing routine liver biopsy, althoughstudies have reported rates as high as 7-9%.2,3Fatty liver occurs in all age groups, with a femalepredominance. It is caused by the accumulation oftriglycerides and other lipids in liver cells. In some cases,this may be accompanied by hepatic inflammation and livercell death, when it is known as steatohepatitis. Potentialpathophysiological mechanisms include decreasedmitochondrial fatty acid beta-oxidation, increasedendogenous fatty acid synthesis or enhanced delivery offatty acids to the liver and deficient incorporation or exportof triglycerides as very-low density lipoprotein from theliver.2Obesity, type 2 diabetes mellitus, andhyperlipidemia are coexisting conditions most commonlyassociated with (NAFLD), but choline deficiency, obesity,protein-calorie malnutrition, starvation, rapid weight lossand total parenteral nutrition are important metaboliccauses. Frequently overlooked causes of NAFLD aremedications. Drugs associated with fatty liver includeamiodarone, bleomycin, warfarin, estrogens, glucocorticoids,methotrexate and tetracycline.3The diagnosis should be considered in all patientswith unexplained elevations in serum aminotransferases.Noninvasive studies such as ultrasound usually identify thepresence of a fatty liver. However, imaging techniquescannot distinguish between benign steatosis andsteatohepatitis. Benign steatosis may be focal or diffuse,whereas steatohepatitis usually is diffuse. No laboratorystudies can help definitively establish a diagnosis of fattyliver or NASH. The only abnormality may be an elevatedaspartate aminotransferase (AST) or alanineaminotransferase (ALT) level. These may be elevated asmuch as 10-fold. However, the AST and ALT may benormal in some patients with fatty liver or NASH.2Before the diagnosis of NASH can be made, viralmarkers should be tested and viral infection excluded. Aliver biopsy and histopathological examination are requiredto establish the diagnosis. Specific histologic features onbiopsy include (1) steatosis, which usually ismacrovesicular but may be microvesicular or mixed; (2)inflammation that is mixed neutrophilic and mononuclearcell and (3) Mallory bodies and glycogen nuclei. Fibrosis orcirrhosis may be present in advanced cases.4One of the most important and potentially reversiblecauses of NAFLD is Hepatitis C infection.4 The mechanismby which the hepatitis C virus (HCV) causes chronic,progressive liver damage is multifactorial, but factors otherthan the virus itself have been implicated. Nonalcoholicfatty liver disease (NAFLD) and hepatitis C virus (HCV)related liver disease are common in the general population,but their concurrence is 2 to 3 times higher than would beexplainable by chance alone.5 In patients with chronic HCVinfection, steatosis is attributable to a variable combinationof the mechanisms considered to play a role in thepathogenesis of NAFLD-insulin resistance, and a directeffect of HCV on hepatic lipid metabolism that leads totriglyceride accumulation through inhibition of exportproteins that are required for very low density lipoprotein(VLDL) assembly and secretion.4,5Hepatic steatosis is a common histological findingoccurring in more than 50% of patients with chronichepatitis C.6 Studies from Pakistan have indicated equallyhigh prevalence rates, of upto 65.7%.7 In this issue of thejournal, Khokhar8 et al report another series of 109 chronicHCV patients who underwent a liver biopsy and the largemajority (62%) were found to have some degree ofsteatosis, although they could not determine if there was aclear association with inflammation or fibrosis.  Both host and viral factors have been demonstratedto play an important role in the development of steatosis. InEditorialHepatic Steatosis and Hepatitis CF. W. Ismail, S. S. HamidDepartment of Medicine, The Aga Khan University, Karachi.Vol. 54, No. 3, March 2004 108those patients infected with genotype 1, steatosis appears tobe due to the co-existence of NASH with HCV andassociated with an increased body mass index (BMI).4Another possibility is of a direct effect of specific viralsequences on the pathogenesis of lipid accumulation. This isespecially true in the case of genotype 3.9 Furthermore,hepatic steatosis attributed to genotype 3 correlates directlywith serum and intra hepatic titters of HCV RNA. Theresolution of steatosis after successful antiviral therapy aswell as steatosis being a sign of recurrent HCV infection inpatients with genotype 3 add convincing evidence thatsteatosis is viral related. The pathogenic mechanisminduced by genotype 3 is speculative, but the correlationbetween steatosis, intra hepatic HCV RNA and core proteinexpression suggest a direct effect.9It seems likely that in patients infected withgenotype 1, BMI has a role in the pathogenesis of steatosiswhile in those infected with genotype 3, steatosis may bedue to a virus-specific cytopathic effect.5 Regardless ofetiology, it is clear that the presence of steatosis contributesto fibrosis in patients with hepatitis C.10 The degree offibrosis has been found to correspond to HCV RNA levels.11Even more alarming is the finding that hepatic steatosis maybe a risk factor for the development of hepatocellularcarcinoma in these patients.12Based on these findings, it is essential that steatosisbe diagnosed early, and be treated appropriately.Unfortunately, treatment modalities are few and not highlyeffective.1 Hepatitis C should be treated appropriately.Abstinence from alcohol is essential. In patients withdiabetes mellitus or hyperlipidemia, good metabolic controlis recommended. No medications have been proved todirectly reduce or reverse liver damage independently ofweight loss. Only small pilot studies lasting one year or lesshave been reported to date. Gemfibrozil, vitamin E, andmetformin have been shown to improve liver-test results.Ursodiol, betaine, vitamin E, and the thiazolidinediones ledto improvement in liver-test results as well as histologicfindings. These medications deserve further evaluation incarefully controlled clinical trials that have sufficientstatistical power. 13It is clear that there are many facets of hepaticsteatosis that need to be explored. Particular attentionshould be paid towards preventive strategies, and futuretherapy should be aimed at exploiting the interactions ofHCV with host insulin and lipid metabolism. References1. Angulo P. Non-alcoholic fatty liver disease. N Engl J Med 2002;346:1221-1231.2. Patel T. Fatty Liver. Medicine J [serial online] August 2001 [cited 2004 Feb14]; 3(4). Available from URL: http://www.emedicine.com/gastroenterology/fatty liver.3. Hamama K, Umar M, Khurram M. Non-alcoholic steatohepatitis (NASH). JRawal Med Coll 2001;5:96-100.4. Lonardo A, Adinolfi LE, Loria P, et al. Steatosis and hepatitis C virus:mechanisms and significance for hepatic and extrahepatic disease.Gastroenterology 2004;126:586-97.5. Ramalho F. Hepatitis C virus infection and liver steatosis. Antiviral Res2003;60:125-7.6. Hwang SJ, Luo JC, Chu CW, et al. Hepatic steatosis in chronic hepatitis Cvirus infection: prevalence and clinical correlation. J Gastroenterol Hepatol2001;16:190-5.7. Latif Z, Khaar HB, Umar M, et al. Liver steatosis and fibrosis in chronichepatitis C: A study of 76 Cases. J Rawal Med Coll 2003;19:18-20.8. Khokhar N, Mushtaq M, Mukhtar AS, et al. Steatosis and Chronic Hepatitis CVirus Infection. J Pak Med Assoc 2004;54:110-12.9. Rubbia-Brandt L, Quadri R, Abid K, et al. Hepatocyte steatosis is a cytopathiceffect of hepatitis C virus genotype 3. J Hepatol 2000;33:106-15.10. Ratziu V, Trabut JB, Poynard T. Fat, diabetes and liver injury in chronichepatitis C. Curr Gastroenterol Rep 2004;6:22-29.11. Adinolfi LE, Utili R, Andreana A, et al. Serum HCV RNA levels correlatewith histological liver damage and concur with steatosis in progression ofchronic hepatitis C. Dig Dis Sci 2001;46:1677-83.12. Ohata K, Hamasaki K, Toriyama K, et al. Hepatic steatosis is a risk factor forhepatocellular carcinoma in patients with chronic hepatitis C virus infection.Cancer 2003;97:3036-43.13. Liangpunsakul S, Chalasani N. Treatment of nonalcoholic fatty liver disease.Curr Treat Options Gastroenterol 2003;6:455-63.          J Pak Med Assoc109

Hepatic steatosis and hepatitis C.

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Hepatic steatosis and hepatitis C.

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