Nonalcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury that is closely associated with insulin resistance and genetic susceptibility. The continuum of liver injury in NAFLD can range from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and even lead to cirrhosis and liver cancer. The pathogenesis of NAFLD is complicated. Pro-inflammatory cytokines, lipotoxicity, and gut bacterial metabolites play a key role in activating liver-resident macrophages (Kupffer cells, KCs) and recruiting circulating monocyte-derived macrophages (MoDMacs) to deposit fat in the liver. With the application of single-cell RNA-sequencing, significant heterogeneity in hepatic macrophages has been revealed, suggesting that KCs and MoDMacs located in the liver exert distinct functions in regulating liver inflammation and NASH progression. This study focuses on the role of macrophage heterogeneity in the development and occurrence of NAFLD and NASH, in view of the fact that innate immunity plays a key role in the development of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/pathology* ; Liver/pathology* ; Macrophages/metabolism* ; Liver Cirrhosis/complications* ; Disease Progression

BACKGROUND/AIMS: To determine the treatment modalities and the prognosis of a patient with liver cirrhosis, quantitative estimation of liver function is important. We assessed the Child-Pugh score (CPS), the common method as a severity index for the cirrhosis, the Promthombin, gamma GT, and Apolipoprotein A1 (PGA) index and model for end-stage liver disease (MELD) score. The purpose of this study was to evaluate the correlation between these indices in the patients with cirrhosis only and hepatocellular carcinoma (PHC), according to underlying causes (HBV and alcohol). METHODS: We reviewed medical records of 339 cirrhotic patients with/without hepatocellular carcinoma and divided patient groups by disease and underlying cause: cirrhosis caused by alcohol; LC-Al, cirrhosis caused by HBV; LC-B, hepatocellular carcinoma with cirrhosis caused by alcohol; HCC-Al, hepatocellular carcinoma with cirrhosis caused by HBV; HCC-B. We assessed the CPS, PGA index and MELD score and calculated the correlation coefficient between these scores. RESULTS: Among the total of 339 patients, 201 patients were diagnosed on the liver cirrhosis only, and 138 patients on the hepatocellular carcinoma with cirrhosis. In each groups, mean score values were not significantly different in CPS, PGA index and MELD score. The correlation of CPS, PGA index and MELD score in all groups, except for the correlation of PGA index and MELD score in HCC-Al group, was significantly positive (p<0.05). Compared to correlation coefficients between three indices, the patients with cirrhosis only had higher tendencies than the patients with hepatocellular carcinoma. The patients by HBV had higher tendencies than by alcohol. CONCLUSIONS: The correlations between CPS, PGA index and MELD score showed significantly positive correlations in the patients with liver cirrhosis only and hepatocellular carcinoma with cirrhosis (except in HCC-Al group). The patients with cirrhosis only had higher correlation coefficients than the patients with PHC and the patients by HBV had higher than by alcohol.
Adult ; Aged ; Carcinoma, Hepatocellular/*complications ; Female ; Hepatitis B/*complications ; Humans ; Liver Cirrhosis/*complications ; Liver Cirrhosis, Alcoholic/complications ; Liver Neoplasms/*complications ; Male ; Middle Aged ; Prognosis ; *Severity of Illness Index

The study of the epidemiology of toxic liver injury has been limited in Korea. The number of hospitalizations for toxic liver injury has been estimated to be 2,400 persons per year. About 30~40% of fulminant hepatitis was attributed to toxic hepatitis. The frequent causative agents of toxic hepatitis in Korea are herbal medicines (34~40%), folk remedies (23~34%), and prescribed medicines (24~55%). However, the most common agents causing severe liver injury including fulminant hepatitis are herbal medicine and folk remedies. Antituberculosis drugs and acetaminophen are two common causes of fulminant hepatitis among prescribed drugs. Alcohol is one of the leading causes of chronic liver disease in Korea. No nationwide study on the epidemiology of alcoholic liver disease (ALD) has been carried out, but 7~31% of cirrhosis has been reported to be alcoholic in a few single-center studies. Alcohol could be a risk factor for the development of hepatocellular carcinoma (HCC) in chronic viral hepatitis. Several studies have shown that alcohol increased the risk of HCC in liver cirrhosis with HBsAg or anti-HCV. Furthermore, alcoholic cirrhosis with occult hepatitis B virus infection increased the risk of HCC.
Drug-Induced Liver Injury/diagnosis/*epidemiology/etiology ; Humans ; Korea/epidemiology ; Liver Cirrhosis, Alcoholic/complications/epidemiology ; Liver Diseases, Alcoholic/complications/*epidemiology ; Liver Neoplasms/etiology ; Risk Factors

Nonalcoholic and alcoholic rabbit models of fatty liver were established by feeding on high-fat diet and alcohol, respectively, and fatty liver stiffness at different pathological stages was assessed with real-time shear-wave elastography (SWE), so as to investigate the fibrosis process during the development of fatty liver. The fatty liver stiffness of rabbit in nonalcoholic and alcoholic groups was higher than that in the control group, and that in alcohol group was higher than that in the nonalcoholic group (P<0.01). The elasticity modulus of liver in fatty liver rabbits of nonalcoholic and alcoholic groups showed a positive correlation with progression of liver fibrosis (P<0.01). Real-time SWE, as a noninvasive diagnostic method, can objectively reflect the liver stiffness change and progression of liver fibrosis during the development of fatty liver.
Animals ; Elasticity ; Elasticity Imaging Techniques ; methods ; Fatty Liver, Alcoholic ; complications ; diagnostic imaging ; Liver Cirrhosis ; diagnostic imaging ; etiology ; Male ; Non-alcoholic Fatty Liver Disease ; complications ; diagnostic imaging ; Rabbits

Hematoma, Epidural, Spinal ; etiology ; Humans ; Liver Cirrhosis, Alcoholic ; complications ; Male ; Middle Aged

BACKGROUND/AIMS: Rhabdomyolysis is a serious and lethal condition that can be induced not only by traumatic causes but also by a variety of nontraumatic causes. However, there are few reports about rhabdomyolysis developed in patients with liver cirrhosis. We carried out this study to elucidate the clinical characteristics and courses of rhabdomyolysis in patients with liver cirrhosis. METHODS: We analyzed 19 cases of nontraumatic rhabdomyolysis in patients with liver cirrhosis who had admitted at Korea University Ansan Hospital between October 2001 and September 2004. RESULTS: Alcohol (50%) was the main etiology of rhabdomyolysis in alcoholic liver cirrhosis patients, and the precipitating factors were not apparent (69.2%) in majority of nonalcoholic liver cirrhosis patients with rhabdomyolysis. Nonalcoholic liver cirrhosis patients had complaints of pain referable to the musculoskeletal system, but alcoholic liver cirrhosis patients had no typical complaints. Mortality of rhabdomyolysis in liver cirrhosis patients was high (42.1%), especially in decompensated liver cirrhosis patients (p=0.04). In nonalcoholic liver cirrhosis patients, the development of oliguria (p=0.007) and acute renal failure (p=0.049) in the course of rhabdomyolysis increased the mortality significantly. CONCLUSIONS: In cirrhosis patients, rhabdomyolysis showed a poor prognosis, especially in nonalcoholic liver cirrhosis with oliguria, acute renal failure, or decompensated liver cirrhosis. It is believed that a high clinical suspicion for the occurrence of rhabdomyolysis in liver cirrhosis patients can lead to quicker recognition and better patient care.
Adult ; Aged ; Female ; Humans ; Kidney Failure, Acute/complications ; Liver Cirrhosis/*complications ; Liver Cirrhosis, Alcoholic/complications ; Male ; Middle Aged ; Rhabdomyolysis/*diagnosis/etiology/mortality ; Survival Rate

Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and also have organ failure(s) are at high risk of short-term death. These patients have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now considered as a new syndrome that it is distinct from "mere" AD not only because of the presence of organ failure(s) and high short-term mortality but also because of younger age, higher prevalence of alcoholic etiology of cirrhosis, higher prevalence of some precipitants (such as bacterial infections, active alcoholism), and more intense systemic inflammatory response. ACLF is a new syndrome also because severe sepsis or severe alcoholic hepatitis do not account for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown" origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of "unknown origin" are subcategories of the syndrome.
Acute-On-Chronic Liver Failure/complications/mortality/*pathology ; Age Factors ; Cytokines/metabolism ; Hepatitis, Alcoholic/complications ; Humans ; Liver Cirrhosis/*complications/diagnosis ; Sepsis/complications ; Severity of Illness Index ; Survival Rate

BACKGROUNDThe etiological spectrum of cirrhosis has changed over the years, but our knowledge of it is limited. The present study aimed to investigate the etiological features of cirrhosis inpatients and their variation in the past 18 years in Beijing.

METHODSA retrospective analysis was performed on all patients with cirrhosis diagnosed for the first time in Peking University People's Hospital from January 1, 1993, to October 25, 2010. Data were analyzed using SPSS 20.0.

RESULTSA total of 2119 cirrhosis inpatients were included in this study: 1412 (66.6%) male and 707 (33.4%) female. Chronic hepatitis B accounted for 58.7%; chronic hepatitis C for 7.6%; chronic hepatitis B and hepatitis C virus co-infection for 0.8% (16 cases); alcoholic liver disease for 9.4% (200 cases); and autoimmune diseases for 9.4% (199 cases). In the past 18 years, the percentage of chronic hepatitis B has decreased from 75.2% to 48.7%; alcoholic liver disease has increased from 5.1% to 10.6%; and autoimmune disease has increased from 2.2% to 12.9%. The percentages of chronic hepatitis B and alcoholic liver disease were higher among men, whereas the percentages of chronic hepatitis C, autoimmune diseases and cryptogenic cirrhosis were higher among women.

CONCLUSIONSChronic hepatitis B was still the most common etiology of cirrhosis in China, but the percentage has been decreasing. The percentages of alcoholic liver disease and autoimmune diseases have been increasing. The etiological spectrum of cirrhosis inpatients differed significantly according to sex.

Adult ; Aged ; Female ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Liver Cirrhosis ; etiology ; Liver Diseases, Alcoholic ; complications ; Male ; Middle Aged ; Retrospective Studies ; Sex Characteristics

In view of the high prevalence of diabetes mellitus in patients with liver cirrhosis and the increasing trend of non-alcoholic fatty liver disease-associated cirrhosis, the diagnosis and treatment of diabetes mellitus in patients with liver cirrhosis are becoming widespread concerns. Therefore, the Chronic Disease Management Branch, China Pharmaceutical Biotechnology Association, organized multidisciplinary experts from gastroenterology, infective disease, endocrinology, etc, to draw up expert consensus on the management of diabetes mellitus in patients with liver cirrhosis, with focusing on the classification and management of hyperglycemia in cirrhotic patients. The consensus summarizes the prevalence, pathogenesis, clinical setting and prognosis of the concomitant diabetes mellitus in patients with liver cirrhosis, and definitely puts forward a proposal regarding "hepatogenous diabetes" as one of the four subtypes of diabetes mellitus in cirrhotic patients, and further recommends the basic principles for diagnosing and monitoring diabetes mellitus and the selection of antidiabetic drugs based on liver functions in patients with liver cirrhosis.
Consensus ; Diabetes Mellitus/therapy* ; Diabetes Mellitus, Type 2/complications* ; Humans ; Hypoglycemic Agents/therapeutic use* ; Liver Cirrhosis/therapy* ; Non-alcoholic Fatty Liver Disease/complications*

Most hypervascular nodules in a cirrhotic liver are hepatocellular carcinomas (HCCs); however, some are benign hypervascular hyperplastic nodules. We report a case of benign hypervascular hyperplastic nodules in a 41-year-old male patient without hepatitis B or C virus infection, with a history of alcohol abuse, and diagnosed with an aortic aneurysm. The dynamic computerized tomography of the liver demonstrated multiple nodular lesions on both liver lobes with arterial enhancement and delayed washout. The hepatic angiography showed multiple faint nodular staining of both lobes in the early arterial phase. Magnetic resonance imaging revealed numerous nodules showing high signals on T1 weighted images, with some nodules showing a low central signal portion. The clinical impression was HCC. The ultrasonography-guided liver biopsy, which was performed on the largest nodule (2.5 cm in size), revealed hepatocellular nodules with slightly increased cellularity, unpaired arteries, increased sinusoidal capillarization, and focal iron deposition. However, both cellular and cytological atypia were unremarkable. Although the clinical impression was HCC, the pathological diagnosis was hypervascular hyperplastic nodules in alcoholic cirrhosis. Differential diagnosis of hypervascular nodules in cirrhosis and HCC is difficult with imaging studies; thus, histological confirmation is mandatory.
Tomography, X-Ray Computed ; Male ; Liver Neoplasms/diagnosis ; Liver Cirrhosis, Alcoholic/*complications ; Liver/*pathology/radiography/ultrastructure ; Hyperplasia ; Humans ; Diagnosis, Differential ; Carcinoma, Hepatocellular/diagnosis ; Biopsy ; Adult