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Sarcopenia (loss of muscle mass and/or strength) frequently complicates liver cirrhosis and adversely affects the quality of life; cirrhosis related liver decompensation and significantly decreases wait-list and post-liver transplantation survival. The main therapeutic strategies to improve or reverse sarcopenia include dietary interventions (supplemental calorie and protein intake), increased physical activity (supervised resistance and endurance exercises), hormonal therapy (testosterone), and ammonia lowering agents (L-ornithine L-aspartate, branch chain amino acids) as well as mechanistic approaches that target underlying molecular and metabolic abnormalities. Besides other factors, hyperammonemia has recently gained attention and increase sarcopenia by various mechanisms including increased expression of myostatin, increased phosphorylation of eukaryotic initiation factor 2a, cataplerosis of α ketoglutarate, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis. Sarcopenia contributes to frailty and increases the risk of minimal and overt hepatic encephalopathy.
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Acute liver failure (ALF) is a rare condition in which rapid deterioration of liver function results in altered mentation and coagulopathy in individuals without previously recognized liver disease. The outcomes of patients with ALF vary greatly according to etiology, and the etiology of ALF varies markedly by geographical region. In Korea, about 90% of ALF are associated with etiologies that usually result in poor outcomes, including hepatitis B virus (HBV) infection and herbal remedies. The main causes of death in patients with ALF are increased intracranial pressure, systemic infection, and multi-organ failure. Recent advances in the intensive care of patients with ALF have contributed to a marked improvement in their overall survival. Emergency adult to adult living-donor liver transplantation (LDLT) can be performed expeditiously and safely for patients with ALF, and greatly improves survival rate as well as deceased-donor transplantation. As the window during which transplantation is possible is limited, emergency adult LDLT should be considered to be one of the first-line treatment options in patients with ALF, especially in regions in which ALFs are caused by etiologies associated with poor outcome and the supply of organs is very limited. (Korean J Hepatol 2010;16:5-18)
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Korean J Hepatol 2010;16(1):19-28. Published online March 26, 2010
Background/Aims According to recent prevalence of hepatitis A virus (HAV) infection, acute liver failure ALF) due to HAV infection is observed frequently in parallel. The aim of this study was to elucidate the clinical, laboratory, and pathologic features of patients who have undergone emergency liver transplantation (LT) due to fulminant HAV infection. Methods: Clinical, laboratory, and pathologic data of 11 transplant recipients with anti-HAV IgM-positive ALF between December 2007 and May 2009 were analyzed, and compared with data of 10 recipients who underwent LT for the management of ALF due to other causes. Results: The median age of the patients with HAV-related ALF was 34 years (range: 15-43 years). The levels of hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were higher and the level of bilirubin was lower in the HAV-related ALF group than in the other group (P=0.005, 0.001, 0.001, 0.010, and 0.003, respectively). The time from the onset of initial symptoms to the development of encephalopathy was shorter in the HAV-related ALF group than in the other group (median 5 days, range: 4-13 days; P<0.001). In patients with HAV-related ALF, laboratory findings and clinical prognostic parameters including the Acute Liver Failure Study Group prognostic index, King`s College criteria, and model for endstage liver disease (MELD) and Child-Pugh scores were not associated with the grade of hepatic encephalopathy or time of progression to encephalopathy. Conclusions: The results of this study indicate that the clinical condition of patients with HAV-related ALF requiring emergency LT aggravates rapidly. Prognostic parameters are not sufficient for discriminating transplant candidates in patients with fulminant hepatitis A. (Korean J Hepatol 2010;16:19-28)
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Genotypic shift of the hepatitis A virus and its clinical impact on acute hepatitis A in Korea: a nationwide multicenter study Ji Hoon Kim, Jong Eun Yeon, Soon Koo Baik, Young Seok Kim, Hong Soo Kim, Sang Hoon Park, Myung-Seok Lee, Joo Hyun Sohn, Jin-Woo Lee, Sung Kyu Choi, So Young Kwon, Jong Young Choi, Ju Hyun Kim, Soon Young Kang, Hyonggin An, Yeon Seok Seo, Hyung Joon Yim, J Scandinavian Journal of Infectious Diseases.2013; 45(11): 811. CrossRef
Comparative analysis of disease severity between genotypes IA and IIIA of hepatitis A virus Young Kyung Yoon, Jong Eun Yeon, Ji Hoon Kim, Hee Sun Sim, Jeong Yeon Kim, Dae Won Park, Jang Wook Sohn, Byung Chul Chun, Min Ja Kim Journal of Medical Virology.2011; 83(8): 1308. CrossRef
Backgrounds/Aims The occurrence of acute hepatitis A is increasing and its progression to fulminant hepatic failure (FHF) is frequent. We investigated the frequency and clinical outcomes of fulminant hepatitis A and also analyzed the predictive factors of spontaneous survival. Methods: A total of 568 patients presented with acute hepatitis A from January 2003 to June 2008, of which the 35 (6.2%) patients with FHF were divided into two groups: spontaneous survival and transplant/death. These two groups were compared according to various clinical features including the MELD score and King`s College Hospital (KCH) criteria. Results: The rate of FHF development increased over time among patients with acute hepatitis A: 0% in 2003, 3.4% in 2004, 3.2% in 2005, 6.0% in 2006, 7.7% in 2007, and 13.0% in 2008. Twenty patients (57.1%) showed spontaneous survival, 13 (37.1%) received liver transplantation, and 5 (14.3%) died during hospitalization. The two groups of spontaneous survival (N=20) and transplant/death (N=15) showed significant differences in prothrombin time at admission and at its worst value, albumin at its worst value, and hepatic encephalopathy grade at admission and at its worst value. The MELD score was lower in the spontaneous-survival group than in the transplant/death group (27.0±7.8 vs. 37.0±7.1, mean±SD; P=0.001). However, KCH criteria did not differ significantly between the two groups. On multivariate analysis, HEP grade was the only significant predictive factor, being negatively correlated with spontaneous survival (OR=0.068, P=0.025). Conclusions: FHF due to hepatitis A has increased in recent years, and in our cohort the HEP grade was closely associated with spontaneous survival. (Korean J Hepatol 2008;14:474-482)
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Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A Hyun Woong Lee, Dong-Yeop Chang, Hong Ju Moon, Hye Young Chang, Eui-Cheol Shin, June Sung Lee, Kyung-Ah Kim, Hyung Joon Kim, Golo Ahlenstiel PLOS ONE.2015; 10(6): e0130728. CrossRef
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Il Hyun Baek, M.D., Byung-Ho Kim, M.D., Dong Kuen Lee, M.D., Yo Seb Han, M.D., Dae Il Jang, M.D.*,
Woo Suk Choi, M.D.†, Kyung Jin Kim, M.D., Seok Ho Dong, M.D., Hyo Jong Kim, M.D., Young Woon
Chang, M.D., Joung Il Lee, M.D., Rin Chang, M.D.
Backgroud/Aims : Increasing evidence suggests that manganese deposition in globus pallidus is responsible for MRI signal hyperintensity and for extrapyramidal symptoms in cirrhotics. However, the relationships between blood manganese, the severity of liver dysfunction, the pallidal signal intensity, and neurological signs have not been well established. Methods: Blood manganese concentrations were measured together with brain MRI and neurological evaluation in six controls, six patients with Parkinson's disease with normal liver function, and fourteen cirrhotic patients with hepatic encephalopathy including six cirrhotics with extrapyramidal symptoms. The neurological state was evaluated using the Columbia scale and the pallidal index (PI). The ratio of globus pallidus to frontal subcortical white-matter signal intensity was measured-multiplied by 100. Results : Pallidal signal hyperintensity was observed in 85.7% of cirrhotics, and the PI was higher in cirrhotics with extrapyramidal signs or high grade varices than those without them, but there was no increase in the Parkinson's disease patients. No correlations were demonstrated between the blood manganese level and PI as well as the Child-Pugh score. The blood manganese level was not significantly different between cirrhotics and other groups. However, there was an overt increase only in two cirrhotic patients with extrapyramidal signs. The Columbia scale did not reveal any correlations with the blood manganese level and the Child-Pugh score. Conclusions: Cirrhotics with extrapyramidal signs showed a significant increase in PI, but there was no increase in the patients with Parkinson's disease. The PI was not significantly correlated with the blood manganese level. These findings suggest that extrapyramidal signs in cirrhotics might be caused by a different mechanism than those in Parkinson's disease, which could possibly be related with manganese. (Korean J Hepatol 2000;6:24-32)
Myoung Hwan Kim, M.D., Kwang Hyub Han, M.D., Kwan Sik Lee, M.D.,
Yong Han Paik, M.D., Kun Hoon Song, M.D., Ho Kyun Na, M.D.,
Byung Soo Moon, M.D., Suk Hwa Yoon, R.N1 ., Chae Yoon Chon, M.D.,
Young Myoung Moon, M.D. In Suh Park, M.D.
Background/Aims A prospective, randomized study was performed to evaluate the efficacy and safety of the short-term administration of rifaximin in the treatment of hepatic encephalopathy. Methods: Of the 64 patients diagnosed as having decompensated liver cirrhosis with hepatic encephalopathy, 39 patients were randomized to receive rifaximin and 25 patients to receive lactulose for seven days. Before and after the treatment we assessed changes in the level of serum ammonia, flapping tremor, patient's mental status, number connection test (NCT), and hepatic encephalopathy indices. Results: In rifaximin-treated group, the mean grade of serum ammonia (1.8→0.9), mental status (1.3→0.3), NCT (3.0→2.0), and flapping tremor (1.7→0.4) were improved after treatment. In the lactulose-treated group, the mean grade of serum ammonia (1.9→1.0), mental status (1.5→0.5), NCT (3.3→2.1), and flapping tremor (1.4→0.3) were improved after treatment. Side effects of abdominal pain (rifaximin group) and excessive diarrhea (lactulose group) were noted in 2 cases. The efficacy of treatment was not significantly different between rifaximin and lactulose-treated groups (84.3% vs. 95.3%). Conclusion: Rifaximin was as efficient and safe in the treatment of hepatic encephalopathy as lactulose in terms of efficacy. Rifaximin may be useful drug for the short-term treatment of hepatic encephalopathy.(Korean J Hepatol 2001;7:55-60)
Background/Aims Data from previous studies on gastric acid secretion and the prevalence of H. pylori in liver cirrhosis patients remain poorly defined. H. pylori is a potential source of NH3, but the possible role of H. pylori in hepatic encephalopathy is not clear. The purpose of this study was to com pare gastric acid
secretion, the impact of H. pylori infection, and the production of NH3 between cirrhotic patients and healthy, matched controls. Methods: Twenty-nine patients with liver cirrhosis (HBV , n=12; Alcohol, n=12; HCV , n=5)
were matched with 33 healthy persons for age and sex. N one of the patients or controls were being treated with antacids, H2-receptor blockers or proton pump inhibitors. The pH and NH3 concentration was measured in gastric juice obtained by endoscopy. H. pylori infection was diagnosed using the rapid urease test. The level of NH3 in venous blood was also measured. Results: The average gastric pH was significantly higher in cirrhosis patients compared to controls (3.91 vs. 2.99, P < 0.05). In addition, the prevalence of hypochlorhydria (defined as pH > 4) was significantly greater in cirrhosis patients (45 vs. 21% , P < 0.05). In contrast, the
prevalence of H .pylori infection (62% vs.58% ) and gastric NH3 concentrations (3.4 vs.3.3 mM/L ) were similar between both groups. However, venous NH3 levels were significantly higher in cirrhotics than in controls (63.1 vs.25.2 μM/L ,P < 0.05).T he patients with H .pylori infection had significantly higher gastric NH3 concentration (3.8 vs. 1.6 mM/L) and gastric pH (3.87 vs. 2.76, P < 0.05) than those without infection, but no significant difference in venous NH3 levels were detected (39.6 vs. 48.1 μM/L ). In patients with cirrhosis, the presence of
H. pylori infection was not correlated with either gastric or blood NH3 levels. Conclusions: T he gastric pH of liver cirrhosis patients is higher than that of controls and a larger proportion of cirrhotic patients have hypochlorhydria. The prevalence of H. pylori in liver cirrhosis patients was similar to that in controls and no correlation was found between gastric and blood NH3 levels. Thus, H. pylori infection does not seem to play a major role in generation of elevated NH3 associated with hepatic encephalopathy. (Korean J Hepatol
2004;10:216-222)
Sung Jae Shin , Sang Hoon Ahn , Hee Man Kim , Ja Kyung Kim , Byung Chang Kim , Jae Hyun Lee , Yong Han Paik , Kwan Sik Lee , Kwang Hyub Han , Chae Yoon Chon , Young Myou
Background/Aims There have been scant reports on the prognostic factors of fulminant hepatic failure for selecting the patients who need liver transplantation. We investigated the clinical features and prognostic factors throughout the clinical course of
Background/Aims Minimal hepatic encephalopthy in patients with clinically asymptomatic chronic progressive liver disease may have adverse effects on daily activity. We evaluated the differences in the cognitive function of patients with chronic hepatitis and liver cirrhosis group according to the Child-Pugh classification. Methods: We enrolled 61 consecutive chronic liver disease patients. We used the following study instruments: visual continuous performance test, a spatial memory test, the Wisconsin card-sorting test chosen from Neuroscan and STIM system (Study of the Usefulness of Computerized Neuropsychological Test, Neurosoft company, New York, NY, USA), a global-local processing test and an electroencephalogram (EEG). Results: A significant correlation was found between neurologic abnormalities and the degree of liver disease. The result of the neuropsychological test and the EEG showed that cognitive function decreased according to the severity of chronic liver disease, especially in liver cirrhosis. Cirrhotic patients, especially in Child-Pugh C group, exhibited selective deficits in complex attention and fine motor skills as well as visual spatial perception, with preservation of memory. Conclusions: The STIM and EEG are simple, subjective and reproducible methods and may be used as early detection methods of minimal hepatic encephalopthy. (Korean J Hepatol 2005;11:329-338)
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