肝癌经肝动脉化疗术后上消化道出血的原因与预防

本文分析４０８例肝癌行肝动脉化疗术后二周内上消化道出血的发病情况。甲组７５例，肝动脉化疗后未使用甲氰脒胍；乙组３３３例，肝动脉化疗后常规使用甲氰脒胍。甲、乙两组肝功能无显著性差异。肝动脉化疗方式有三种：（１）单纯肝动脉化疗，甲与乙组均无上消化道出血。（２）碘油化疗药物混悬剂栓塞化疗，甲与乙组出血各为１９％与２．５％。（３）ＬＰ－ＴＡＥ＋明胶海绵栓塞，甲与乙组出血各为１７Ｔ及３．２％。肝功能Ａ级、Ｂ     

肝动脉化疗,栓塞损害肝功能的临床研究

肝动脉化疗，栓塞对肝功能损害的系统分析，国内外文献报道甚少。笔者对收治的５２例肝癌肝动脉化疗，栓塞后的肝功能变化进行了前瞻性研究。结果显示：（１）全部患者治后肝功能均有不同程度的损害，某些肝功能指标高达治前水平的３－４倍，为正常的５－１０倍；（２）大部分肝功能有１月内恢复至汉前水平或正常，３例肝功能持续性恶化，直至肝功能衰竭而死亡；（３）栓塞组的肝功能损害较化疗组严重。     

糖尿病酮症酸中毒并肝损害临床分析

目的探讨导致糖尿病酮症（ＤＫ）及酮症酸中毒（ＤＫＡ）患者肝损害的相关因素．方法ＤＫ或ＤＫＡ患者９９例,其中ＡＬＴ及ＡＳＴ均异常升高１１例（Ａ组）,单项ＡＬＴ异常升高１３例（Ｂ组）,肝功能正常７５例（Ｃ组）,对以上各组患者的血二氧化碳结合力（ＣＯ２ＣＰ）、尿素氮（ＢＵＮ）、血糖（ＢＧ）和血浆渗透压（ＯＳＭ）进行了统计分析．结果Ａ,Ｂ两组患者的ＣＯ２ＣＰ明显低于Ｃ组（Ｐ＜００１,ｔ＝６３３和ｔ＝６４３）,而ＢＵＮ则明显升高（Ｐ＜００１,ｔ＝３６１,ＡｖｓＣ;Ｐ＜００１,ｔ＝４３５,ＢｖｓＣ）,Ａ组的ＢＧ（Ｐ＜００５,ｔ＝２８４）和血浆ＯＳＭ（Ｐ＜００５,ｔ＝３１０）水平也显著高于Ｃ组,而Ｂ组患者的ＢＧ及血浆ＯＳＭ与Ｃ组比较无差异;与Ｂ组相比,Ａ组患者的ＣＯ２ＣＰ明显降低（Ｐ＜００２,ｔ＝２７１）,ＢＧ（Ｐ＜００５,ｔ＝２８９）和血浆ＯＳＭ（Ｐ＜００５,ｔ＝２３６）明显升高．此外,Ⅰ型糖尿病患者血清转氨酶异常升高的发生率明显高于Ⅱ型糖尿病患者（Ｐ＜００５,χ２＝４３８）．结论酸中毒和脱水是导致糖尿病酮症及酮症酸中毒患者肝损害的重要因素,酸中毒及脱水程度与肝损害程度相关．     

软肝冲剂抗肝纤维化的临床研究

选择中度以上慢性肝炎和早期肝硬化患者１２０例，分为治疗组和对照组各６０例。治疗组采用软肝冲剂治疗，对照组以干扰素治疗，疗程均为３个月有乙昨观察血清质酸（ＨＡ）、Ⅲ型血清南酸（ＨＡ）、Ⅲ型前胶原肽（ＰⅢＰ）Ⅳ型胶原（Ｃ－Ⅳ）、板层素（ＬＮ）等肝纤维化指标，以及肝功能和病毒复制指标。结果治疗组ＨＡ、Ｃ－Ⅳ、ＬＮ、ＡＬＴ 和γ－Ｇｌｂ明显下降，与对照组比较有显著性差异。ＨＢｅＡｇ和ＨＢＶＤＮＡＢ有转率略     

拉米夫定、治肝灵冲剂联合治疗慢性乙型肝炎近期疗效研究

研究单用拉米夫定（３－ＴＣ）及联合应用中药治肝灵冲剂对慢性乙型肝炎（ＣＨＢ）的治疗作用，探讨两者联合治疗的近期疗效和安全性。５０例ＣＨＢ患者随机分为Ａ，Ｂ两组，Ａ组采用３－ＴＣ和治肝灵冲剂联合治疗；Ｂ组单用３—ＴＣ，疗程均为６个月，治疗前、治疗２周、４周、８周、１２周、１６周，２０周、２６周分别检测ＨＢＶ标志、肝功能，血清学指标，肾功能，并记录治疗期间临床和实验室检查发生的一切不良事件。治疗２６周后Ａ组血清ＨＢｅＡｇ转阴率６４．０％（１６／２５）．明显高于Ｂ组１６．０％（４／２５）Ｐ＜０．０１． Ａ组与Ｂ组分别有４例（１６．０％），２例（８．０％）实现ＨＢｅＡｇ血清转换。Ｐ＞０．０５。转阴患者未发现ＨＢＶ前Ｃ区变异株。Ａ组和Ｂ组ＨＢＶＤＮＡ转阴例数分别为２４（９６．０％）和２３（９２．０％）Ｐ＞０．０５。治疗结束时Ａ组和Ｂ组ＡＬＴ的复常率分别为８８．０％（２２／２５）、６４．０％（１６／２５），Ｐ＜０．０５。采用３－ＴＣ与治肝灵冲剂联合治疗ＣＨＢ，短期疗效明显优于单一用药组，且副作用少，是安全、有效的治疗ＣＨＢ的方案。     

肝动脉化疗栓塞治疗原发性肝癌的疗效及影响因素

目的观察肝动脉化疗栓塞治疗对原发性肝癌的疗效及影响因素．方法单纯化疗（Ａ组）；化疗加碘油栓塞（Ｂ组）；化疗加碘油加明胶海绵栓塞（Ｃ组）．结果５年内肝动脉化疗栓塞治疗中、晚期肝癌４２８例，３８６例经２个月～５０个月随访．肿瘤缩小率：Ａ组１４％，Ｂ组５５％，Ｃ组７９％（三组间Ｐ＜００１）．肿瘤基本消失：Ｃ组５％，Ａ，Ｂ两组无１例消失．生存时间：１年生存率Ａ组０％，Ｂ组１０％，Ｃ组４５％，其中１２例患者获Ⅱ期手术切除，切除标本病理检查见肿瘤区癌细胞全部或部分凝固坏死，瘤旁癌细胞稀疏．结论影响疗效因素与肿瘤的病理类型及血供情况，门静脉主干瘘和癌栓、肝动脉插管治疗方式有关．     

原发性肝癌肝切除术（附97例报告）

报告原发性肝癌切除术９７例（１０２例次）其中３例术后复发再次肝切除１，２，５年生存率分别为６６．１％，５２．１％，２３．０％，作者认为，手术切除是肝癌治疗的有效方法，术后应定期复查Ｂ超和甲胎蛋白（ＡＦＰ）并进行综合治疗，对不能切除的大肝癌，可经区域血管栓塞和化疗缩小后行二期手术切除。     

B7-1在乙型肝炎肝组织的表达及其与病变的关系

目的阐明Ｂ７－１在乙型肝炎肝组织中的表达及其与病变发生、发展的关系。方法用免疫组织化学方法检测连续切片的乙型肝炎肝组织Ｂ７－１及表面抗原表达。结果正常对照２例均为阴性；１７例慢性迁延性肝炎（ＣＰＨ）中，胞浆Ｂ７－１阳性的有１６例，轻度阳性８例，中度５例，重度３例；１４例慢性活动性肝炎（ＣＡＨ）全部阳性，其中轻度阳性２例，中度３例，重度９例，经等级秩和检验，两者差异显著（Ｐ＜００１）。急性黄疸性肝炎、亚急性重型肝炎轻度阳性。在３４例乙型肝炎肝组织中，３３例ＨＢｓＡｇ阳性，轻度阳性３例，其余为中到重度阳性，且ＣＰＨ与ＣＡＨ两组之间无统计学差异。结论（１）乙型肝炎病毒感染可诱导Ｂ７－１在肝组织表达，且表达强弱与肝炎病变程度正相关；（２）乙型肝炎表面抗原在组织中表达强弱与Ｂ７－１表达无关。（３）Ｂ７－１在肝组织中的表达可能是肝细胞活化积极参与免疫反应的佐证。     

动脉血酮体比对肝性脑病时肝脏能量储备功能的评价

对３９例肝性脑病患者连续测定动脉血酮体比率（ＡＫＢＲ），以快速评价肝脏能量储备功能及其预后情况。结果显示上述病人在未昏迷时ＡＫＢＲ值均明显低于健康者（Ｐ＜０．００５），肝昏迷出现时ＡＫＢＲ均在０．６５以下。病人按昏迷后ＡＫＢＲ变化可分为Ａ组：ＡＫＢＲ逐渐上升并超过０．７以上；Ｂ组：０．４≤ＡＫＢＲ＜０．７及Ｃ组：ＡＫＢＲ＜０．４，３组病人死亡率分别为０、３３．３％（５／１５）及１００％（１４／１４），经比较差异有显著性（Ｐ＜０．００１），而一般肝功能指标谷。丙转氨酶、血清总胆红素、凝血酶原时间及血清白蛋白相比较差异无显著性。我们认为ＡＫＢＲ能准确评价肝细胞能量储备，当其值小于０．７，尤其是０．４以下时，病情重、预后差。     

激活素和卵泡抑素mRNA在肝纤维化形成过程中的作用

目的 观察四氯化碳（ＣＣｌ４）诱导实验性肝纤维化模型大鼠肝纤维化形成过程中激活素（ＡＣＴ）βＡ、βＣ、βＥ及卵泡抑素（ＦＳ）ｍＲＮＡ的表达。方法 ４０％ＣＣｌ４皮下注射制备大鼠实验性肝纤维化模型，注射 ＣＣｌ４后１、２、３、４、５、６、７周分批处死动物，每次 ６～１２只，采用半定量 ＲＴ—ＰＣＲ检测 ＡＣＴ βＡ、βＣ、βＥ亚基及 ＦＳｍＲＮＡ的表达。结果 正常肝脏可检测到ＡＣＴ βＡ、βＣ、βＥ及ＦＳ亚基ｍＲＮＡ，往射ＣＣｌ４２～３周后，βＡ水平下降至检测不到的水平，４周以后，又逐渐升高，注射 ６～７周时其表达水平明显高于正常对照组（Ｐ＜０．０１）；注射ＣＣｌ４１～４周可检测到βＣ亚基ｍＲＮＡ，５～７周后其表达水平明显高于正常对照组（Ｐ＜０．０５）。βＥ亚基ｍＲＮＡ在 ＣＣｌ４注射１～５周后水平下降至检测下到的水平，注射 ６～７周后其表达水平则明显高于正常对照组（Ｐ＜０．０５）。ＣＣｌ４注射后的各个时期均未检测到ＦＳ ｍＲＮＡ表达。结论 肝纤维化形成过程中ＡＣＴ、ＦＳ表达发生了不同的变化，ＡＣＴ—ＦＳ系统失衡可能参与了肝纤维化的形成。     

Retinyl palmitate reduces hepatic fibrosis in rats induced by dimethylnitrosamine or pig serum

Background/Aims: Lipid peroxidation has been found to be associated with Ito cell activation. Ito cells are the principal collagen-producing cells and the main storage sites of retinoids. However, the relationship between retinoids and hepatic fibrosis is complex. The aim of this study was to elucidate the role of retinoids as a fibrosuppressant: the effects of retinoids on hepatic fibrosis induced in rats by dimethylnitrosamine or pig serum, as well as on rat Ito cells in primary culture, were examined in order to assess the antioxidant activity of retinoids.Methods: Male Wistar rats were given a single injection of 40 mg/kg dimethylnitrosamine or 0.5 ml PS twice weekly for 10 weeks. In each model, rats were treated with retinyl palmitate for 2 weeks before hepatotoxin treatments or for the last 2 weeks of the treatments. The cumulative amount of retinyl palmitate administered in each experiment was 2, 10, or 20×10⁴ IU/rat.Results: Retinyl palmitate treatment before or after administration of dimethylnitrosamine or pig serum suppressed the induction of hepatic fibrosis, restored hepatic retinyl palmitate levels, prevented increases in hepatic levels of collagen and malondialdehyde, a product of lipid peroxidation, and prevented increases in deposition of type III collagen and the number of α-smooth muscle actin (α-SMA) positive-Ito cells in the liver. Retinyl palmitate supplementation resulted in a dose-dependent reduction of α-SMA expression and an oxidative burst in cultured Ito cells. In addition, retinyl palmitate inhibited Fe²⁺/adenosine 5′-diphosphate-induced lipid peroxidation in rat liver mitochondria and showed radical scavenging activity.Conclusions: These findings suggest that retinyl palmitate may suppress the induction of hepatic fibrosis, at least in part, by the inhibition of Ito cell activation through its antioxidant activity.     

Reduced incidence of hepatic metastases by perioperative treatment with recombinant human interleukin-2

Abdominal operations induce immunosuppression during the time when tumors are manipulated and tumor cells are released into the circulation. The authors tested the hypothesis that the combined effect of these factors may promote the development of metastatic tumor implants and that perioperative treatment with Human Recombinant Interleukin-2 (RIL-2), a known immunostimulant of t, natural killer (NK), and lymphokine activated killer (LAK) cells may reduce the incidence of liver metastases from transplantable rat colon cancers. Hepatic metastases were induced in male Fischer 344 (F344) rats by injecting 10(7) rat colon tumor cells into the portal venous system during laparotomy. Control rats developed tumors by four weeks and were dead by ten weeks. Eleven groups of rats underwent celiotomy with portal vein injection of tumor on day three. Rats received either no RIL-2, RIL-2, or excipient buffer at varying doses on days 1 through 5 or 3 through 7 of these experiments. Animals were assessed for the presence of tumor and the incidence of liver metastases at autopsy (sacrifice and autopsy performed at seven weeks). Eighty-five percent of the rats in the untreated group developed tumor. This compared with only 50 percent of animals receiving 10(3) u/dose (P less than .025) and 42 percent of animals receiving 10(4) u/dose (P less than .01) of Interleukin-2 on days 1 through 5. Animals receiving very high doses of RIL-2 (10(5) or 4 X 10(5) units per dose) had a greater chance of developing tumors than did control rats, or rats receiving lower doses of RIL-2 (P less than .05). It is concluded that the perioperative period may be critical for the implantation and growth of metastatic disease and that perioperative immunostimulation with RIL-2 can decrease the incidence of tumors in these animals. This model may have relevance to the treatment of human colon cancer.     

The effects of amiodarone on serum thyroid hormones and hepatic thyroxine 5'-monodeiodination in rats

Amiodarone (2-n-butyl-3,4'-diethylaminoethoxy-3', 5'-diiodobenzoyl-benzofurane) is an antiarrhythmic drug which increases serum T4 and rT3 levels in patients and lowers serum T3 levels. To investigate its effects on T4 metabolism and its cardiac action, we fed amiodarone to male Fisher rats at doses of 5, 15, and 45 mg/kg BW X day; controls received potassium iodide for 4-7 weeks, and another group received sodium ipodate. At 4 weeks, amiodarone caused a dose-dependent increase in the serum T4 concentration and a slight reduction of serum TSH without a change in the serum T3 concentration. These changes were not present at 7 weeks. Sodium ipodate raised serum T4 concentrations at both times. Rats treated with T4 (150 micrograms/kg BW X day) to suppress thyroidal secretion of hormone and with amiodarone (15 mg/kg) had marked reduction of serum T3 concentrations compared with controls receiving T4 without amiodarone. Liver homogenates from rats treated with amiodarone showed marked reduction on T4 5'-monodeiodinase activity in a dose-related manner. Amiodarone added to liver homogenates in vitro at concentrations of 0.001-1 mM did not inhibit T3 production from T4, whereas ipodate added in vitro (0.01-1 mM) did inhibit T3 production. Rats treated with amiodarone showed a lowering of the resting heart rate and a reduction of the increment in heart rate after iv isoproterenol administration. The cardiac Ca++ myosin ATPase activity was reduced in rats receiving amiodarone (45 mg/kg) compared with that in controls. The data indicate that rats treated with amiodarone have reduced peripheral conversion of T4 to T3 owing to impaired hepatic T4 5'-monodeiodinase activity. In addition, these rats have slowing of heart rate and reduction of cardiac Ca++ myosin ATPase activity. These findings are consistent with the hypothesis that amiodarone blocks some effects of thyroid hormone on the heart, but additional studies are needed to test this hypothesis.     

A randomized controlled trial of acarbose in hepatic encephalopathy.

BACKGROUND & AIMS: Hepatic encephalopathy in cirrhosis is contributed to by toxic products deriving from the proteolytic bacterial flora-related degradation of dietary nitrogen substances. Acarbose is a novel hypoglycemic agent acting through the inhibition of glucose absorption in the gut and the promotion of intestinal saccharolytic bacterial flora at the expense of proteolytic flora. We assessed whether acarbose exerts a beneficial effect on hepatic encephalopathy and on postprandial hyperglycemia in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus. METHODS: One hundred seven cirrhotic patients with grade 1-2 hepatic encephalopathy and type 2 diabetes mellitus were randomized to acarbose 100 mg 3 times daily or placebo for 8 weeks; after a 2-week washout period, treatments were switched, and patients were followed for 8 more weeks. Ammonia blood levels, Reitan's number connection test, intellectual function, fasting and postprandial glucose levels, glycated hemoglobin values, and C peptide values were determined 2 weeks before and 4, 8, 11, 14, and 18 weeks after treatment. RESULTS: (1) Acarbose significantly decreased ammonia blood levels and improved Reitan's test score and intellectual function score compared with placebo (P < .01). (2) Acarbose caused a 33% decrease in fasting glucose level and an approximately 50% decrease in postprandial glucose level compared with placebo (P < .01). (3) Acarbose significantly lowered glycated hemoglobin values and postprandial C peptide compared with baseline values, whereas placebo did not. (4) No change in biochemical parameters of liver function was observed after acarbose treatment. CONCLUSIONS: Acarbose is a safe and effective drug in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus.     

Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) levels in experimental biliary fibrosis

BACKGROUND/AIMS: Angiotensin-converting enzyme 2 (ACE2), its product, angiotensin-(1-7) and its receptor, Mas, may moderate the adverse effects of angiotensin II in liver disease. We examined the expression of these novel components of the renin angiotensin system (RAS) and the production and vasoactive effects of angiotensin-(1-7) in the bile duct ligated (BDL) rat. METHODS: BDL or sham-operated rats were sacrificed at 1, 2, 3 and 4 weeks. Tissue and blood were collected for gene expression, enzyme activity and peptide measurements. In situ perfused livers were used to assess angiotensin peptide production and their effects on portal resistance. RESULTS: Hepatic ACE2 gene and activity (P<0.0005), plasma angiotensin-(1-7) (P<0.0005) and Mas receptor expression (P<0.01) were increased following BDL compared to shams. Perfusion experiments confirmed that BDL livers produced increased angiotensin-(1-7) (P<0.05) from angiotensin II and this was augmented (P<0.01) by ACE inhibition. Whilst angiotensin II increased vasoconstriction in cirrhotic livers, angiotensin-(1-7) had no effect on portal resistance. CONCLUSIONS: RAS activation in chronic liver injury is associated with upregulation of ACE2, Mas and hepatic conversion of angiotensin II to angiotensin-(1-7) leading to increased circulating angiotensin-(1-7). These results support the presence of an ACE2-angiotensin-(1-7)-Mas axis in liver injury which may counteract the effects of angiotensin II.     

Intensive liver care and management of acute hepatic failure

In describing acute liver failure, the term fulminant hepatic failure (FHF) is used to denote patients with the most rapid progression, normally defined as the onset of encephalopathy within eight weeks of the onset of symptoms. For patients with a slower onset of encephalopathy, ranging from eight weeks to six months after the onset of symptoms, late-onset hepatic failure is the term used to reflect the overlap in clinical features with some patients with FHF. The importance of accurately determining the type of acute liver failure results from increasing evidence of an inverse relationship between the tempo of disease progression and the chances of recovery. Prognosis is also dependent on the underlying etiology. Principles of management are as follows: (1) an accurate recognition of the tempo of the hepatic failure—fulminant, late onset, acute on chronic—and the establishment of a likely etiology; (2) early detection and treatment of complications, particularly metabolic acidosis (early), renal failure, cerebral edema, and infection (late); (3) optimization of conditions for regeneration by maintenance of a near normal metabolic milieu (with removal of toxins by various methods of artificial liver support if necessary); and (4) early consideration of an orthotopic liver transplant for those patients in the poor prognosis group. Variations in the natural history and clinical features of acute liver failure (ALF) have led to a number of different classifications and subgroupings. Knowledge of these is important in relation to the assessment of prognosis and is even more important now that transplantation is a therapeutic option. Fulminant hepatic failure (FHF) is the term used to denote the subgroup where the tempo is greatest and is variously defined as the onset of encephalopathy within four weeks (1), six weeks (EASL, 1979) and eight weeks [as described by Trey and Davidson (2)] of the onset of symptoms, or within two weeks of the onset of jaundice (3). The patients with a more protracted course are designated by the terms subacute or late-onset hepatic failure (LOHF) (4) or subfulminant hepatic failure (3). The etiology of the hepatic failure also has a major influence on the likely prognosis.Presented at the Proceedings of International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.     

Comparison of two chemical models to induce hepatic preneoplasia in male Wistar rats

Background. One established model to induce hepatic preneoplasia (HP) (DEN 150) uses diethylnitrosamine (DEN) as initiator agent and 2-acetylaminofluorene (2-AAF) as a promoter drug. In addition, both chemicals cause liver cholestasis and fibrosis. Aim. We compared DEN 150 model with another adapted by us, DEN 200 to simplify the first one and to evaluate the effectiveness of both treatments to induce HP in rats.Material and methods. Male Wistar rats were divided in 3 groups: controls; DEN 150 (rats received 2 doses of DEN, 150 mg/kg body weight, 2 weeks apart, and then 2-AAF, 20 mg/kg body weight, 4 doses per week during 3 weeks); and DEN 200 (rats received a single dose of DEN 200 mg/kg body weight, and 2 weeks apart 2-AAF, 20 mg/kg body weight, 2 doses per week during 3 weeks). Four hepatic enzymes, prothrombin time percentage, the number of bile ductules, total collagen amount, the number of altered hepatic foci (AHF) per liver and the percentage of liver occupied by foci were analyzed.Results. There were no differences in the number of AHF per liver between treated groups. Rats from DEN 200 group showed a significant diminution in the volume of liver occupied by foci. DEN 200 group had no fibrosis and better hemostatic conditions than DEN 150 group. Both groups developed cholestasis. Conclusion. In conclusion, both protocols are good alternatives to induce HP in rats and the new protocol proposed is an effective and a simple methodology to provide subclinic states of liver cancer.     

A very low carbohydrate ketogenic diet prevents the progression of hepatic steatosis caused by hyperglycemia in a juvenile obese mouse model

Objective:

To investigate whether the improvement in hyperglycemia by dietary control influences hyperglycemia-induced pathologies in tissues of juvenile obese (ob/ob) mice.

Design:

Five-week-old ob/ob mice were fed a very low carbohydrate ketogenic diet (KD) for 7 weeks. The blood glucose levels and body weight were monitored during this period. Biochemical parameters in the serum and tissue pathologies of the mice were analyzed at the end of the 7-week period.

Results:

The hyperglycemic phenotype of the ob/ob mice was improved by KD feeding for 7 weeks. Surprisingly, we found that KD feeding also drastically reduced the hepatic steatosis phenotype in ob/ob mice, while their obesity phenotype was unaltered. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that several proteins found in the liver of ob/ob mice fed a regular chow diet were undetectable after being fed KD. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) MASCOT search and western blot analysis revealed that the proteins absent from the mice fed KD included fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1), which are key enzymes for lipogenesis in the liver. Fatty acid analysis supported the results because the ratio of C18:1, which is a major product of lipogenesis, was reduced by KD feeding. However, C18:2, which cannot be synthesized in mammalian cells but is present in the KD, was found to be a major component in the liver of KD-fed ob/ob mice.

Conclusion:

Hyperglycemia promotes hepatic steatosis via the lipogenic pathway in the liver of juvenile ob/ob mice. However, the development of steatosis is prevented by feeding KD owing to an improvement in hyperglycemia. We found that the progression of steatosis is reflected by the composition of fatty acids in the total lipids of the liver and serum.