Review : Liver Transplantation

( Deok Bog Moon ),( Sung Gyu Lee ) The Editorial Office of Gut and Liver 2009 Gut and Liver Vol.3 No.3

Liver transplantation has become a lifesaving procedure for patients who have chronic end-stage liver disease and acute liver failure. The satisfactory outcome of liver transplantation has led to insufficient supplies of deceased donor organs, particularly in East Asia. Hence, East Asian surgeons are concentrating on developing and performing living-donor liver transplantation (LDLT). This review article describes an update on the present status of liver transplantation, mainly in adults, and highlights some recent developments on indications for transplantation, patient selection, donor and recipient operation between LDLT and deceased-donor liver transplantation (DDLT), immunosuppression, and long-term management of liver transplant recipients. Currently, the same indication criteria that exist for DDLT are applied to LDLT, with technical refinements for LDLT. In highly experienced centers, LDLT for high-scoring (>30 points) Model of End-Stage Liver Disease (MELD) patients and acuteon- chronic liver-failure patients yields comparably good outcomes to DDLT, because timely liver transplantation with good-quality grafting is possible. With increasing numbers of liver transplantations and longterm survivors, specialized attention should be paid to complications that develop in the long term, such as chronic renal failure, hypertension, diabetes mellitus, dyslipidemia, obesity, bone or neurological complications, and development of de novo tumors, which are highly related to the immunosuppressive treatment. (Gut and Liver 2009;3:145-165)

ORiginal Article : Disease Progression in Chronic Hepatitis B Patients under Long-Term Antiviral Therapy

( Jin Chang Moon ),( Seong Hun Kim ),( In Hee Kim ),( Chang Hun Lee ),( Sang Wook Kim ),( Seung Ok Lee ),( Soo Teik Lee ),( Dae Ghon Kim ) The Editorial Office of Gut and Liver 2015 Gut and Liver Vol.9 No.3

Background/Aims: We investigated factors associated with the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients during long-term oral nucleos(t)ide analog (NA) therapy. Methods: This retrospective study included 524 naive CHB patients who received oral NA therapy for more than 48 weeks between January 2003 and December 2007. The primary outcome was 5-year cumulative probability of disease progression and HCC development. Disease progression was defined as cirrhosis development, cirrhotic complications, HCC or liver-related mortality. Results: For the 524 patients, the cumulative probabilities of disease progression and HCC development at 1, 2, 3, 4 and 5 years were 1.1%, 6.3%, 9.0%, 11.6%, and 16.2% and 0.2%, 1.8%, 3.6%, 5.8%, and 9.3%, respectively. In multivariate analysis, age >50 years (hazard ratio [HR], 1.05) and cirrhosis (HR, 2.95) were significant factors for disease progression. Similarly, age >50 years (HR, 1.05), family history of HCC (HR, 5.48), and cirrhosis (HR, 17.16) were significant factors for HCC development. Importantly, longer duration (>12 months) of maintained virological response (<20 IU/mL) reduced the risks of disease progression (HR, 0.19) and HCC development (HR, 0.09). Conclusions: Longer duration of maintained virological response significantly reduces the risk of disease progression or HCC development in CHB patients undergoing long-term oral NA therapy. (Gut Liver 2015;9:395-404)

Review : Dietary Factors: Major Regulators of the Gut`s Microbiota

( Alexander R. Moschen ),( Verena Wieser ),( Herbert Tilg ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.4

Dietary factors and the associated lifestyle play a major role in the pathophysiology of many diseases. Several diets, es-pecially a Western lifestyle with a high consumption of meat and carbohydrates and a low consumption of vegetables, have been linked to common diseases, such as metabolic syndrome, atherosclerosis, inflammatory bowel diseases, and colon cancer. The gastrointestinal tract harbors a com-plex and yet mainly molecularly defined microbiota, which contains an enormous number of different species. Recent advances in sequencing technologies have allowed the characterization of the human microbiome and opened the possibility to study the effect of "environmental" factors on this microbiome. The most important environmental fac-tor is probably "what we eat," and the initial studies have revealed fascinating results on the interaction of nutrients with our microbiota. Whereas short-term changes in dietary patterns may not have major influences, long-term diets can affect the microbiota in a substantial manner. This issue may potentially have major relevance for human gastrointestinal health and disease because our microbiota has features to regulate many immune and metabolic functions. Increas-ing our knowledge on the interaction between nutrients and microbiota may have tremendous consequences and result in a better understanding of diseases, even beyond the gas-trointestinal tract, and finally lead to better preventive and therapeutic strategies. (Gut Liver 2012;6:411-416)

ORiginal Article : What Is the Most Effective Drug Delivery System for Cisplatin during the Treatment of Hepatic Tumors with Single-Session Transcatheter Chemotherapy? A Pilot Study

( Yusuke Kawamura ),( Kenji Ikeda ),( Taito Fukushima ),( Yuya Seko ),( Tasuku Hara ),( Hitomi Sezaki ),( Tetsuya Hosaka ),( Norio Akuta ),( Masahiro Kobayashi ),( Satoshi Saitoh ),( Fumitaka Suzuki ) The Editorial Office of Gut and Liver 2013 Gut and Liver Vol.7 No.5

Background/Aims: The aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion thera-py for hepatocellular carcinoma (HCC). Methods: We divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gela-tin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes. Results: The mean free cisplatin concentrations were as fol-lows. For group A, the mean was 48.58 μg/mL at 0 minute, 7.31 mL at 5 minutes, 5.70 mL at 10 minutes, and 7.15 mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 μg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C. Conclusions: These results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver. (Gut Liver 2013;7:576-584)

Case Report : Spontaneous Rupture of a Gastric Stromal Tumor Causing Hemoperitoneum

( Gun Wha Lee ),( Young Seok Kim ),( Sang Gyune Kim ),( Bong Min Ko ),( Moon Sung Lee ),( Kyu Seok Cho ),( Seong Jin Park ),( Hee Kyung Kim ) The Editorial Office of Gut and Liver 2010 Gut and Liver Vol.4 No.2

We describe a 39-year-old man with spontaneous rupture of a gastric stromal tumor causing hemoperitoneum. Ultrasonography showed a large mass broadly abutting the stomach and liver. Computed tomography demonstrated a heterogeneous enhanced mass arising from the stomach and focal perforation of the tumor with hemoperitoneum; endoscopic ultrasonography showed an exophytic heterogeneous mass originating from the gastric muscle layer. Angiography revealed that the right gastric artery was the main artery supplying the tumor. A gastric stromal tumor with bloody fluid in the peritoneal cavity was seen at the laparotomy. The tumor was excised completely, and subsequent histological and immunohistochemical studies indicated that it was a gastric stromal tumor. We report a relatively rare case of gastric stromal tumor causing hemoperitoneum due to spontaneous rupture of the tumor. (Gut Liver 2010;4:278-282)

Case Report : Obstructive Jaundice after Bilioenteric Anastomosis: Transhepatic and Direct Percutaneous Enteral Stent Insertion for Afferent Loop Occlusion

( Hans Ulrich Laasch ) The Editorial Office of Gut and Liver 2010 Gut and Liver Vol.4 No.s1

Recurrent tumour after radical pancreaticoduodenectomy may cause obstruction of the small bowel loop draining the liver. Roux-loop obstruction presents a particular therapeutic challenge, since the postsurgical anatomy usually prevents endoscopic access. Careful multidisciplinary discussion and multimodality preprocedure imaging are essential to accurately demonstrate the cause and anatomical location of the obstruction. Transhepatic or direct percutaneous stent placement should be possible in most cases, thereby avoiding long-term external biliary drainage. Gastropexy T-fasteners will secure the percutaneous access and reduce the risk of bile leakage. The static bile is invariably contaminated by gut bacteria, and systemic sepsis is to be expected. Enteral stents are preferable to biliary stents, and compound covered stents in a sandwich construction are likely to give the best long-term results. Transhepatic and direct percutaneous enteral stent insertion after jejunopexy is illustrated and the literature reviewed. (Gut Liver 2010; 4(Suppl. 1):S89-95)

Review : Molecular Pathogenesis of Hepatitis-B-virus-associated Hepatocellular Carcinoma

( Neung Hwa Park ),( Il Han Song ),( Young Hwa Chung ) The Editorial Office of Gut and Liver 2007 Gut and Liver Vol.1 No.2

Hepatocellular carcinoma (HCC) is one of the most frequent and malignant diseases worldwide. Epidemiological studies have clearly demonstrated that chronic hepatitis B virus (HBV) infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes associated with malignant transformation have been identified. The predominant carcinogenic mechanisms of HBV-associated HCC are chronic inflammation and the effects of cytokines in the development of fibrosis and liver cell proliferation. An important role is also played by the integration of HBV DNA into host cellular DNA, which disrupts or promotes the expression of cellular genes that are important in cell growth and differentiation. Especially, HBx protein is a transactivating protein that promotes cell growth, survival, and the development of HCC. Continued investigation of the mechanisms underlying hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformation in the liver. Prevention of HBV infections and effective treatments for chronic hepatitis B are still needed for the global control of HBV-associated HCC. This review summarizes the current knowledge on the mechanisms involved in HBV-associated hepatocarcinogenesis. (Gut and Liver 2007;1:101-117)

Predicting Liver-Related Events Using Transient Elastography in Chronic Hepatitis C Patients with Sustained Virological Response

Lee, Hye Won,Chon, Young Eun,Kim, Seung Up,Kim, Beom Kyung,Park, Jun Yong,Kim, Do Young,Ahn, Sang Hoon,Jung, Kyu Sik,Park, Young Nyun,Han, Kwang-Hyub Editorial Office of Gut and Liver 2016 Gut and Liver Vol.10 No.3

<P><B>Background/Aims</B></P><P>Few studies have investigated prognostic factors for the development of liver-related events (LREs) in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR).</P><P><B>Methods</B></P><P>We analyzed 190 patients with CHC who achieved SVR after treatment with pegylated interferon (peg-IFN) plus ribavirin. LREs were defined as any complications related to cirrhosis, hepatocellular carcinoma (HCC), or liver-related mortality.</P><P><B>Results</B></P><P>The mean age was 54.1 years, and 84 of the patients (44.2%) were male. The mean liver stiffness (LS) value at SVR was 7.1±5.4 kPa. During the follow-up period (median, 43.0 months), LREs occurred in 10 patients (5.3%; HCC in eight patients, ascites in one patient, and liver-related mortality in one patient). By multivariate Cox regression analysis, age, α-fetoprotein level, and LS value were independent predictors for LRE development (all p<0.05). Patients with LS values ≥7.0 kPa had a greater risk (hazard ratio, 9.472; 95% confidence interval, 1.018 to 88.126; p=0.048) for LRE development compared to those with LS values <7.0 kPa.</P><P><B>Conclusions</B></P><P>The LS value at SVR is useful for predicting LRE development in CHC patients who achieve SVR after treatment with peg-IFN plus ribavirin. Thus, LRE surveillance strategies might be optimized according to the LS values at SVR, even with complete viral eradication.</P>

Original Article : Clinical Features, Image Findings, and Prognosis of Inflammatory Pseudotumor of the Liver: A Multicenter Experience of 45 Cases

( Jun Young Park ),( Moon Seok Choi ),( Young Suk Lim ),( Jang Won Park ),( Seung Up Kim ),( Yang Won Min ),( Geum Youn Gwak ),( Yong Han Paik ),( Joon Hyoek Lee ),( Kwang Cheol Koh ),( Seung Woon Pai The Editorial Office of Gut and Liver 2014 Gut and Liver Vol.8 No.1

Background/Aims: Inflammatory pseudotumor (IPT) of the liver is a rare disease characterized by chronic infiltration of inflammatory cells. However, the clinical characteristics and outcomes of IPT remain uncertain. Methods: Clinical features, image findings, and outcomes of 55 patients with histologically proven IPT were evaluated. Results: They consisted of 26 men and 19 women with median age of 65 years. Serum carcinoembryonal antigen and carbohydrate antigen 19-9 levels were normal in 42 patients (93.3%). Enhanced CT scans indicated poorly defined peripheral enhancement (82.5%) at the arterial phase and poorly defined hyperattenuating lesions with internal hypoattenuating areas at the equilibrium phase (77.0%). Gadolinium-enhancement MRI revealed poorly defined peripheral rim-like enhancement (77.8%). Ten patients underwent surgical resection and 35 were treated conservatively with or without antibiotics. No recurrence was noted after surgical resection during follow-up (1 to 48 months). In all patients who received conservative treatment, complete resolution or size reduction was noted during follow-up (1 to 192 months). Conclusions: CT and MRI provide clues to the diagnosis of IPT in patients with liver masses and normal tumor markers. However, due to the lack of pathognomonic findings, the clinician`s suspicion and histological diagnosis are necessary to make an accurate diagnosis of IPT. (Gut Liver 2014,8:58-63)

Review : NASH is an Infl ammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications

( Geoffrey C. Farrell ),( Derrick Van Rooyen ),( Lay Gan ),( Shivrakumar Chitturi ) The Editorial Office of Gut and Liver 2012 Gut and Liver Vol.6 No.2

While non-alcoholic fatty liver disease (NAFLD) is highly prevalent (15% to 45%) in modern societies, only 10% to 25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma. Apart from pre-existing fibrosis, the strongest predictor of fibrotic progression in NAFLD is steatohepatitis or non-alcoholic steatohepatitis (NASH). The critical features other than steatosis are hepatocellular degeneration (ballooning, Mallory hyaline) and mixed infl ammatory cell infi ltration. While much is understood about the relationship of steatosis to metabolic factors (over-nutrition, insulin resistance, hyperglycemia, metabolic syndrome, hypoadiponectinemia), less is known about infl ammatory recruitment, despite its importance for the perpetuation of liver injury and fi brogenesis. In this review, we present evidence that liver infl ammation has prognostic signifi cance in NAFLD. We then consider the origins and components of liver infl ammation in NASH. Hepatocytes injured by toxic lipid molecules (lipotoxicity) play a central role in the recruitment of innate immunity involving Toll-like receptors (TLRs), Kupffer cells (KCs), lymphocytes and neutrophils and possibly infl ammasome. The key pro-infl ammatory signaling pathways in NASH are nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK). The downstream effectors include adhesion molecules, chemokines, cytokines and the activation of cell death pathways leading to apoptosis. The upstream activators of NF-κB and JNK are more contentious and may depend on the experimental model used. TLRs are strong contenders. It remains possible that infl ammation in NASH originates outside the liver and in the gut microbiota that prime KC/TLR responses, infl amed adipose tissue and circulating infl ammatory cells. We briefl y review these mechanistic considerations and project their implications for the effective treatment of NASH. (Gut Liver 2012;6:149-171)