Appropriateness of Liver Biopsy for Nonalcoholic Fatty Liver Disease in Obese Patients during Laparoscopic Cholecystectomy for Gallstone Disease

( Sang-hyub Han ),( Ji Hae Nahm ),( Do Young Kim ),( Seung Woo Park ),( Young Nyun Park ),( Kyung Sik Kim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Obesity is well known as a risk factor for gallstone disease and is also a risk factor for fatty liver. Before laparoscopic cholecystectomy, it is not easy to detect fatty liver, except for the cases of severe fatty liver by blood chemistry and imaging diagnostic tools. However liver biopsy is particularly useful in patients without definite clinical manifestations. Liver biopsy is invasive and is not recommended except in special cases, but hepatic biopsy is not a relatively risky procedure during laparoscopic cholecystectomy. Therefore, we investigated the clinical characteristics in biopsy proven non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in obese patients during laparoscopic cholecystectomy for gallstone disease. Methods: We retrospectively reviewed medical records in obese patients with gallstone disease who underwent laparoscopic cholecystectomy with liver biopsy. The definition of obesity was based on the Asian obesity criteria. (overweight :23~24.9, obese class I :>25, & obese class II >30). Total 74 patients were included, and 30 patients were diagnosed as fatty liver(A) and compared with patients without fatty liver disease(B) using various parameters. Results: There were 9 male and 21 female in fatty liver group and 18 male and 26 female without fatty liver. In the fatty liver group, 6 overweight, 19 obese class I, & 5 obese class II, but in the group without fatty liver, 21 overweight, 19 obese class I, & 4 obese class II. The degree of obesity in the fatty liver group was more severe(P=.022). Except level of aminotransferase, all biochemical parameters were not different between two groups. Conclusions: The liver biopsy could be recommended in obese I & II patients with abnormal levels of aminotransferase.

Effect of Korea red ginseng on nonalcoholic fatty liver disease: an association of gut microbiota with liver function

Ji Taek Hong,Min-Jung Lee,Sang Jun Yoon,Seok Pyo Shin,Chang Seok Bang,Gwang Ho Baik,Dong Joon Kim,Gi Soo Youn,Min Jea Shin,Young Lim Ham,Ki Tae Suk,Bong-Soo Kim 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.2

Background: Korea Red Ginseng (KRG) has been used as remedies with hepato-protective effects in liver-related condition. Microbiota related gut-liver axis plays key roles in the pathogenesis of chronic liver disease. We evaluated the effect of KRG on gut-liver axis in patients with nonalcoholic statohepatitis by the modulation of gut-microbiota. Methods: A total of 94 patients (KRG: 45 and placebo: 49) were prospectively randomized to receive KRG (2,000 ㎎/day, ginsenoside Rg1þRb1þRg3 4.5㎎/g) or placebo during 30 days. Liver function test, cytokeraton 18, and fatigue score were measured. Gut microbiota was analyzed by MiSeq systems based on 16S rRNA genes. Results: In KRG group, the mean levels (before vs. after) of aspartate aminotransferase (53 ± 19 vs. 45 ± 23 IU/L), alanine aminotransferase (75 ± 40 vs. 64 ± 39 IU/L) and fatigue score (33 ± 13 vs. 26 ± 13) were improved (p < 0.05). In placebo group, only fatigue score (34 ± 13 vs. 31 ± 15) was ameliorated (p < 0.05). The changes of phyla were not statistically significant on both groups. In KRG group, increased abundance of Lactobacillus was related with improved alanine aminotransferase level and increased abundance of Clostridium and Intestinibacter was associated with no improvement after KRG supplementation. In placebo group, increased abundance of Lachnospiraceae could be related with aggravation of liver enzyme (p < 0.05). Conclusion: KRG effectively improved liver enzymes and fatigue score by modulating gut-microbiota in patients with fatty liver disease. Further studies are needed to understand the mechanism of improvement of nonalcoholic steatohepatitis.

Updates in the quantitative assessment of liver fibrosis for nonalcoholic fatty liver disease: Histological perspective

( Gwyneth Soon ),( Aileen Wee ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.1

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a major cause of liver fibrosis and cirrhosis. Accurate assessment of liver fibrosis is important for predicting disease outcomes and assessing therapeutic response in clinical practice and clinical trials. Although noninvasive tests such as transient elastography and magnetic resonance elastography are preferred where possible, histological assessment of liver fibrosis via semiquantitative scoring systems remains the current gold standard. Collagen proportionate area provides more granularity by measuring the percentage of fibrosis on a continuous scale, but is limited by the absence of architectural input. Although not yet used in routine clinical practice, advances in second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy imaging show great promise in characterising architectural features of fibrosis at the individual collagen fiber level. Quantification and calculation of different detailed variables of collagen fibers can be used to establish algorithm-based quantitative fibrosis scores (e.g., qFibrosis, q-FPs), which have been validated against fibrosis stage in NAFLD. Artificial intelligence is being explored to further refine and develop quantitative fibrosis scoring methods. SHG-microscopy shows promise as the new gold standard for the quantitative measurement of liver fibrosis. This has reaffirmed the pivotal role of the liver biopsy in fibrosis assessment in NAFLD, at least for the near-future. The ability of SHG-derived algorithms to intuitively detect subtle nuances in liver fibrosis changes over a continuous scale should be employed to redress the efficacy endpoint for fibrosis in NASH clinical trials; this approach may improve the outcomes of the trials evaluating therapeutic response to antifibrotic drugs. (Clin Mol Hepatol 2021;27:44-57)

Nonalcoholic fatty liver disease versus metabolic-associated fatty liver disease: Prevalence, outcomes and implications of a change in name

Cheng Han Ng,Daniel Q. Huang,Mindie H. Nguyen 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.4

Nonalcoholic fatty liver disease (NAFLD) affects about a third of the world’s adult population and is a major public health concern. NAFLD is defined by the presence of hepatic steatosis and the absence of other causes of liver disease. As NAFLD is closely associated with the presence of the metabolic syndrome, several experts have called for a change in nomenclature from NAFLD to metabolic-associated fatty liver disease (MAFLD) to better reflect the underlying pathophysiology of NAFLD as a metabolically driven disease and shift to a “positive” diagnostic criteria rather than one of exclusion. Recent studies have suggested that the global prevalence of MAFLD is higher than that of NAFLD, and patients with MAFLD have more metabolic comorbidities compared to those with NAFLD. Emerging data also suggest that all-cause and cardiovascular mortality may be higher in MAFLD compared with NAFLD. In this synopsis, we discuss differences in clinical features, prevalence and clinical outcomes between NAFLD and MAFLD. In addition, we highlight the advantages and disadvantages of a name change from NAFLD to MAFLD from the perspective of the scientific community, care providers and patients.

비알코올성지방간의 유관 인자 임상 연구: 종양표지자, 심박변이도, 사상체질

곽시라,신뢰,박수정,권영미,주종천 사상체질의학회 2019 사상체질의학회지 Vol.31 No.2

Objectives The aim of this study is to investigate the related factors of nonalcoholic fatty liver disease (NAFLD). Methods The subjects were 187 persons diagnosed as fatty liver by abdominal ultrasonography. They were divided into three groups according to the severity of fatty liver: control, mild, moderate or severe. The three groups' general characteristics, laboratory results, liver function indexes, metabolic syndrome indexes, tumor markers, heart rate variability values and Sasang constitution distribution were compared and analyzed. Results Male ratio, height, weight, body mass index, red blood cell count, hemoglobin level and creatinine level were higher in NAFLD groups than in control group. The levels of sodium and amylase were higher in control than in NAFLD. In liver function, the levels of aspartate transaminase, alanine transaminase and gamma-glutamyl transpepsidase of NAFLD were higher. In metabolic syndrome index, systolic blood pressure, diastolic blood pressure, waist circumference, total cholesterol, triglyceride and low density lipoprotein cholesterol levels were higher in NAFLD, while high density lipoprotein cholesterol level was higher in control. The alpha-feto protein level was higher in NAFLD, and the heart rate variability was not different between NAFLD and control groups. In Sasang constitution, Taeeumin ratio of NAFLD was higher than of control. Conclusions The results suggest that nonalcoholic fatty liver is clinically related to liver dysfunction, metabolic syndrome, tumor markers, and Sasang constitution. Further studies are needed to control nonalcoholic fatty liver disease and prevent severe disease such as cirrhosis and cancer caused by fatty liver.

비알코올성 지방간 질환

이창우,이재욱 東國大學校醫學硏究所 2005 東國醫學 Vol.12 No.1

비알코올성 지방간질환(Nonalcoholic fatty liver disease, NAFLD)란 음주 경력이 없는 환자에서 알코올성 간질환(alcoholic liver disease, ALD)과 유사한 지방축적(특히 중성지방), 염증, 간세포의 풍선양변성(balloning degeneration), Mallory소체(Mallory bodies) 및 간섬유화등의 다양한 조직학적 소견을 보이는 질환이다. 과거에는 여러 가지 이름, 즉 pseudoalcoholic liver disease, alcoholic-like hepatitis, nonalcoholic steatohepatitis (NASH) 등으로 불리어졌으나 최근에는 비알코올성 지방간질환(NAFLD)라는 용어를 많이 사용하고 있다. 최근 알코올과 연관성이 없이 당뇨병, 과체중과 비만인구의 증가로 인한 비알코올성 지방간질환의 발생이 증가하는 추세에 있고, 또 비알코올성 지방간질환은 대부분 정상으로 회복되는 것으로 알려져 있으나 치료를 하지 않으면 일부에서 간경변증으로 진행이 가능하고, 또한 간암까지 합병될 수 있다는 개념이 정립되면서 이에 관심이 많아진 상태이다. The NAFLD has state that accumulation of fat (especially triglyceride) in hepatocyte above 5% of its weight. This is a clinically common disease but incidentally found, because it is asymptomatic. Nonalcoholic fatty liver disease has a similar histologic pattern with alcoholic fatty liver disease, such as inflammation, balloon degeneration, mallory bodies and fibrosis of hepatocyte. Recently, alcohol, type Ⅱ DM, and overweight population with no correlation with alcohol is increasing, and mostly NAFLD is known to recover. However, it is a concern that untreated NAFLD may develope to liver cirrhosis, and eventually hepatocellular carcinoma. NAFLD is a broad word from simple steatosis to NASH associated with hepatic fibrosis and liver cirrhosis. The term of nonalcoholic steatohepatitis (NASH) was first used by Ludwig (1980) that has no relation to alcohol and it has a similar pattern to pathologic features by alcohol in the liver. At present, NAFLD has clinical importance, presumption of the fact that adult population is affected with a disease by high prevalence rate, no alternative diagnostic procedure, no known nature history, no effective therapeutic agents, although insuin resistance is thought as common cause. These subjects must be solved and additional therapeutic procedure are expected by constructive and various approach.

심혈관계 위험인자로서 비알콜성 지방간질환: 프래밍햄 위험 점수 및 경동맥 경화로 평가

금신호,이근미,정승필 대한임상건강증진학회 2012 Korean Journal of Health Promotion Vol.12 No.4

Background: Nonalcoholic fatty liver disease (NAFLD) is known to be associated with obesity, type 2 diabetes,and dyslipidemia and highly related to metabolic syndrome. The purpose of this study was to examine NAFLD as a risk factor for cardiovascular disease using the Framingham risk score and carotid intima media thickness. Methods: We examined 189 Korean adults older than 20 years who participated in a health screening test and had both carotid and abdominal ultrasounds. Patients with viral hepatitis and history of cardiovascular disease and alcohol consumption (>20 g/day) were excluded. We compared clinical characteristics, the Framingham risk scores, and carotid intima media thickness according to the presence of nonalcoholic fatty liver disease. Results: Framingham risk scores and the estimated 10-year risk for coronary heart disease were higher in subjects with NAFLD (11.5±4.7 vs 10.2±4.3 P=0.04, 8.7±7.3% vs 4.9±5.0% P<0.001). Carotid intima media thickness was higher in subjects with NAFLD (0.72±0.18 mm) compared to the controls (0.63±0.15 mm) (P<0.001). This result persisted significantly after adjusting for age, sex, and the 5 components of metabolic syndrome. Multiple logistic regression analysis showed that the presence of NAFLD (odds ratio [OR], 2.95; 95% confidence interval [CI], 1.495-5.812) and triglyceride level (OR, 2.06; 95% CI, 1.041-4.066) were independently related with carotid atherosclerosis. Conclusions: These results suggest that NAFLD is a risk factor for cardiovascular disease. Physicians should be mindful of this association when seeing patients with NAFLD. 연구배경: 비알콜성 지방간질환(nonalcoholic fatty liver disease, NAFLD)은 비만, 제2형 당뇨, 고지혈증과 흔히 동반되어 나타나며 대사증후군과 밀접한 관련성이 있는 것으로 알려져 있다. 이에 본 연구는 상복부초음파검사를 통해진단된 NAFLD가 프래밍햄 위험 점수와 경동맥 내중막 두께로 평가한 심혈관계 위험인자인지를 알아보고자 한다. 방법: 일개 대학병원 건강증진센터에 내원한 수진자중심혈관계 질환이나 간질환의 과거력이 없고 하루 20 g 이상 알코올 복용력이 없으며 상복부초음파와 경동맥초음파를 동시에 시행한 20세 이상 성인남녀 238명을 대상으로신체계측, 생화학적 검사와 프래밍햄 위험 점수를 산출하였고 경동맥초음파검사로 경동맥 내중막 두께를 구하여비알콜성 지방간질환군과 대조군에서 차이를 분석하였다. 결과: NAFLD군에서 체질량지수와 수축기혈압 및 요산이 유의하게 높았으며 고밀도 지단백 콜레스테롤은 낮았다. 프래밍햄 위험 점수 총점은 NAFLD군에서 유의하게높았으며(11.5±4.7 vs. 10.2±4.3, P=0.040), 관상 동맥 질환의 10년 위험도 또한 NAFLD군에서 유의하게 높았다(8.7±7.3% vs. 4.9±5.0% P<0.001). 양측 경동맥 내중막 두께의 평균도 NAFLD군(0.72±0.18 mm)에서 대조군(0.63±0.15 mm)보다 두꺼워져 있었으며(P<0.001), 교란변수를 보정한 후에도 통계적으로 유의한 차이를 보였다(P<0.001). 다중 로지스틱 회귀분석을 시행한 결과, 교차비는 NAFLD의 존재가 2.95 (95% confidence interval [CI],1.495-5.812), 대사증후군의 항목 중 중성지방이 2.06 (95%CI, 1.041-4.066)으로 나타났다. 결론: 대사증후군과 밀접한 관련이 있는 NAFLD는 단순히 간질환적 측면뿐만 아니라, 심혈관계 질환의 위험인자로서 고려하여야 한다.

Nonalcoholic fatty liver disease and non-liver comorbidities

Richie Manikat,Mindie H. Nguyen 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.-

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.

Potential Roles of Hedgehog and Estrogen in Regulating the Progression of Fatty Liver Disease

Jeongeun Hyun(현정은),Youngmi Jung(정영미) 한국생명과학회 2011 생명과학회지 Vol.21 No.12

현대인의 고지방 식습관과 당뇨와 비만인구 증가로 인한 비 알코올성 지방간(nonalcoholic fatty liver)의 유병률(prevalence rate)은 나날이 증가하고 있는 추세이며, 특히 남성과 폐경기 여성에게서 두드러진다. 이런 성 특이적(sex-specific) 간질환의 차이는 여성 호르몬인 에스트로겐(estrogen)의 보호 역할 때문일 것으로 추정되고 있으나, 에스트로겐의 보호 기작을 포함한 지방간의 만성 간질환으로의 진행 메커니즘이 규명되어 있지 않기 때문에 간질환의 효과적인 예방 및 치료책이 없는 실정이다. 그런데 최근에 간 섬유화(fibrosis)를 포함한 만성 간질환의 진행에서 헤지호그(hedgehog) 신호전달계가 주요한 역할을 함이 보고되면서 손상된 간의 회복과 간질환 진행 메커니즘 조절을 위한 연구대상으로서 주목 받고 있다. 헤지호그는 발생 및 분화를 조절하는 모포젠(morphogen)으로 성인의 건강한 간에서는 발현되지 않으나, 손상된 간에서 손상 정도에 비례하게 재 발현되며, 섬유화 유발세포인 근섬유아세포(myofibroblasts) 및 간 줄기세포(hepatic progenitor cells)의 활성 및 증식인자로 작용하여 지나친 간 섬유화를 일으킨다. 이에 반해, 에스트로겐은 간 성상세포(hepatic stellate cells)가 근섬유아세포로 활성화되는 것을 억제함으로써 간 섬유화를 막는 것으로 보고되고 있다. 간 섬유화에 대한 헤지호그와 에스트로겐의 상반된 역할 사이의 관련성은 아직 밝혀지지 않고 있으나, 간 섬유화 유발 물질인 오스테오폰틴(osteopontin) 발현에 대한 에스트로겐의 억제효과와 헤지호그에 의한 오스테오폰틴 발현 유도는 오스테오폰틴에 의해 매개되는 에스트로겐과 헤지호그 신호전달계 사이의 연관성을 시사한다. 따라서, 에스트로겐에 의한 헤지호그 신호전달계 조절 메커니즘을 규명하는 것은 간질환 환자에서의 간 섬유화 및 만성 질환으로의 진행을 억제할 수 있는 치료제 개발에 대한 기초 지식을 제공할 수 있다. 이를 위해 간 섬유화에 대한 헤지호그와 에스트로겐의 역할을 확실하게 이해하고, 상호 관련성 및 조절 기작을 밝히는 연구가 선행되어야 할 것이다. Non-alcoholic fatty liver disease accompanies the rise in the prevalence of obesity, diabetes and the tendency toward high-fat dietary habits. Specifically, the higher prevalence of non-alcoholic fatty liver disease in men and postmenopausal women seems to be caused by the protective effects of estrogen against liver fibrosis, or lack thereof. There are no effective preventive therapies for liver diseases because the mechanisms underlying the progression of fatty liver diseases to chronic liver diseases and the protective effects of estrogen against fibrogenesis remain unclear. Recently, it has been reported that the hedgehog signaling pathway plays an important role in the progression of chronic liver diseases. Hedgehog, a morphogen regulating embryonic liver development, is expressed in injured livers but not in adult healthy livers. The level of hedgehog expression parallels the stages of liver diseases. Hedgehog induces myofibroblast activation and hepatic progenitor cell proliferation and leads to excessive liver fibrosis, whereas estrogen inhibits the activation of hepatic stellate cells to myofibroblasts and prevents liver fibrosis. Although the mechanism underlying the opposing actions of hedgehog and estrogen on liver fibrosis remain unclear, the suppressive effects of estrogen on the expression of osteopontin, a profibrogenic extracellular matrix protein and cytokine, and the inductive effects of hedgehog on osteopontin transcription suggest that estrogen and hedgehog are associated with liver fibrosis regulation. Therefore, further research on the estrogen-mediated regulatory mechanisms underlying the hedgehog-signaling pathway can identify the mechanism underlying liver fibrogenesis and contribute to developing therapies for preventing the progression of fibrosis to chronic liver diseases.

비알코올 지방간 질환의 역학

정고은 ( Goh Eun Chung ),김동희 ( Dong Hee Kim ) 대한내과학회 2014 대한내과학회지 Vol.86 No.4

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common liver disease with an estimated prevalence of 20-30% in the Western world and 16-33% in Korea. NAFLD encompasses a broad spectrum of hepatic dysfunction ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The increasing prevalence of NAFLD is particularly worrying because patients appear to have higher non-liver-related and liver-related death, as compared to the general population. Given its well-known association with metabolic comorbidities, NAFLD is commonly asso ?ciated with obesity, type II diabetes, dyslipidemia, and metabolic syndrome. The natural history of NAFLD remains unclear due to its indolent clinical course and the lack of well-designed prospective studies. The prognosis of NAFLD depends on the histological subtype, while NASH may be associated with liver fibrosis and cirrhosis and may progress to hepatocellular carcinoma. The overall and liver-related mortality are increased in patients with NASH, as compared to NAFL and the general population. NAFLD is strongly associated with cardiovascular disease and type 2 diabetes, so it should also be considered a metabolic liver disease. Further long-term studies of the natural course of NAFLD are warranted. (Korean J Med 2014;86:399-404)