g certain SNPs), altering the function of key proteins involved

g. certain SNPs), altering the function of key proteins involved in the pathogenesis of INH-induced DILI. Furthermore, chemical

factors (e.g. comedication) may also greatly influence the extent of INH-induced DILI. Other risk factors, including underlying diseases or inflammatory episodes, will not be discussed, as they are outside the scope of this review. Traditionally, the acetylator phenotype (determined by NAT2 polymorphisms) has selleck screening library been implicated as a determinant of susceptibility to INH-induced DILI. This makes sense because NAT2 is involved in INH biotransformation. However, acetylation leads to both bioactivation (acetylhydrazine formation) and detoxication (diacetylhydrazine formation) (Fig. 2). Therefore, it is not surprising that some studies identified Dinaciclib research buy the fast acetylator phenotype as

a determinant of susceptibility,[70, 71] while others, more recently, linked the poor acetylator phenotype with an increased risk.[72, 73] Thus, the causal role of the NAT2 haplotype has remained controversial; furthermore, the current concept no longer implicates NAT2 polymorphisms as a major risk factor, particularly because these polymorphisms (e.g. coding for a slow acetylator phenotype) are extremely frequent in populations. Similarly, the role of CYP2E1 variants has remained controversial.[73] Since a direct role of CYP2E1 in the hepatic toxicity of INH has been questioned,[29] and because a number of INH metabolites can even be generated independently of CYPs,[28] the focus has somewhat shifted away from CYP2E1 being a major determinant of susceptibility. However, apart from the enzyme’s role in drug bioactivation/inactivation, two points are important: First, CYP2E1 is also expressed in mitochondria,[74] selleck and second, CYP2E1 is one of the CYP forms that has been shown to generate relatively high levels of ROS;[75] therefore, it is possible that

the role of CYP2E1 could simply be in enhancing the extent of oxidant stress. Another genetic variant that has been analyzed for its role as a potential determinant of susceptibility is the glutathione S-transferase (GST) family. A recent meta-analysis examining the association between selective GST variants and the risk for INH-associated DILI found that individuals with a null-genotype in GSTM1 may have an increased risk, while patients with a null-genotype in GSTM1 did not.[76] The exact role of these polymorphisms are unclear; however, it can be surmised that functional GST dependence reflects the trapping of a reactive intermediate. Furthermore, in Japanese patients, an association has been found between certain gene mutations in one of the anti-oxidant pathways and INH-induced DILI.[77] These positive correlations include mutations in NOS2A (encoding for inducible nitric oxide synthase, iNOS) resulting in gain of function, which leads to increases in NO production.

We therefore created a retroviral transduction system to stably o

We therefore created a retroviral transduction system to stably overexpress AQP-1 in vitro (pMMP-AQP1). IF (Fig. 3A) and western blotting (Fig. 3B) demonstrated robust overexpression of AQP-1 after treatment with pMMP-AQP1 compared with pMMP-LacZ controls, providing a mechanistic

in vitro model in which to study the biological effects of AQP-1. Based on our a priori hypothesis that AQP-1 promotes angiogenesis, we speculated that AQP-1 up-regulation would increase LEC motility. We therefore tested the effects of AQP-1 overexpression on LEC chemotaxis using modified Boyden chamber chemotaxis assays. However, contrary to our initial hypothesis, we found that after AQP-1 overexpression with pMMP-AQP1, traditional chemotaxis in LEC was actually reduced compared with LacZ controls, Ganetespib both in the basal state and in response to FGF (Fig. 4A). Similar results were BI-6727 observed using human hepatic sinusoidal endothelial cells, various chemotactic

agents, and both adenoviral and retroviral overexpression (Supporting Fig. 2A). Using AQP-1-specific siRNA or scrambled siRNA, we found, again, that AQP-1 expression was inversely correlated with HSEC chemotaxis in primary cells (Supporting Fig. 2B). Attempts to modulate AQP-1 function with chemical inhibitors, such as mercuric chloride, resulted in endothelial cell toxicity selleck products and therefore were not pursued in greater depth (Supporting Fig. 3). Recent studies have revealed that, in the context of desmoplasia, cells frequently modify their migration pattern from a traditional, actin-based, mesenchymal mechanism, to a membrane deformation mechanism that has been referred to as ameboid motility.36 This invasive form of motility, although slower, is nonetheless, more adaptable in circumstances requiring cell shape deformation and dynamic membrane blebbing events to squeeze through confined areas. We hypothesized that the dense fibrotic ECM of the cirrhotic microenvironment requires invasion

and that LECs undergo mode-switching to a more primitive form of amoeboid motility in this setting. We therefore tested the effects of AQP-1 overexpression on FGF-induced endothelial cell invasion capacity using three-dimensional collagen invasion assays. In striking contrast to our chemotaxis results, we observed that AQP-1 overexpression in TSEC significantly increased both basal and FGF-induced invasion (Fig. 4B), suggesting that bleb-based amoeboid motility occurs in this setting. Because dynamic membrane blebbing is the hallmark of amoeboid motility,15 we used phase-contrast, time-lapse video microscopy to examine blebbing behavior in TSEC. We hypothesized that altered blebbing dynamics may contribute to amoeboid motility and explain the increased invasion capacity conferred by AQP-1. Phase contrast and SEM (Fig.

We therefore created a retroviral transduction system to stably o

We therefore created a retroviral transduction system to stably overexpress AQP-1 in vitro (pMMP-AQP1). IF (Fig. 3A) and western blotting (Fig. 3B) demonstrated robust overexpression of AQP-1 after treatment with pMMP-AQP1 compared with pMMP-LacZ controls, providing a mechanistic

in vitro model in which to study the biological effects of AQP-1. Based on our a priori hypothesis that AQP-1 promotes angiogenesis, we speculated that AQP-1 up-regulation would increase LEC motility. We therefore tested the effects of AQP-1 overexpression on LEC chemotaxis using modified Boyden chamber chemotaxis assays. However, contrary to our initial hypothesis, we found that after AQP-1 overexpression with pMMP-AQP1, traditional chemotaxis in LEC was actually reduced compared with LacZ controls, Etoposide order both in the basal state and in response to FGF (Fig. 4A). Similar results were Selleck Selumetinib observed using human hepatic sinusoidal endothelial cells, various chemotactic

agents, and both adenoviral and retroviral overexpression (Supporting Fig. 2A). Using AQP-1-specific siRNA or scrambled siRNA, we found, again, that AQP-1 expression was inversely correlated with HSEC chemotaxis in primary cells (Supporting Fig. 2B). Attempts to modulate AQP-1 function with chemical inhibitors, such as mercuric chloride, resulted in endothelial cell toxicity selleck chemicals llc and therefore were not pursued in greater depth (Supporting Fig. 3). Recent studies have revealed that, in the context of desmoplasia, cells frequently modify their migration pattern from a traditional, actin-based, mesenchymal mechanism, to a membrane deformation mechanism that has been referred to as ameboid motility.36 This invasive form of motility, although slower, is nonetheless, more adaptable in circumstances requiring cell shape deformation and dynamic membrane blebbing events to squeeze through confined areas. We hypothesized that the dense fibrotic ECM of the cirrhotic microenvironment requires invasion

and that LECs undergo mode-switching to a more primitive form of amoeboid motility in this setting. We therefore tested the effects of AQP-1 overexpression on FGF-induced endothelial cell invasion capacity using three-dimensional collagen invasion assays. In striking contrast to our chemotaxis results, we observed that AQP-1 overexpression in TSEC significantly increased both basal and FGF-induced invasion (Fig. 4B), suggesting that bleb-based amoeboid motility occurs in this setting. Because dynamic membrane blebbing is the hallmark of amoeboid motility,15 we used phase-contrast, time-lapse video microscopy to examine blebbing behavior in TSEC. We hypothesized that altered blebbing dynamics may contribute to amoeboid motility and explain the increased invasion capacity conferred by AQP-1. Phase contrast and SEM (Fig.

151 Higher doses of UDCA were then studied on the grounds that la

151 Higher doses of UDCA were then studied on the grounds that larger doses might be necessary to provide sufficient enrichment of the bile acid pool in the context of cholestasis, and that these doses might also enhance a potential immunomodulatory effect of the drug. The Scandinavian UDCA trial in a group of 219 patients with PSC using a dose of 17–23 mg/kg/day for 5 years demonstrated a trend toward increased survival in the UDCA treated group when compared with placebo,152 but despite the relatively large number of patients

recruited, the study was still insufficiently powered to produce a statistically significant result. Recently, a multicenter study using high doses of 28–30 mg/kg/day of UDCA in 150 patients with PSC over 5 years has been aborted because of an enhanced risk in the UDCA treatment group for death or liver transplantation and serious selleck chemicals llc adverse events particularly in advanced disease whereas biochemical features improved in the whole UDCA group.153 Thus, the role for UDCA in slowing the progression of PSC-related liver disease is as yet unclear and indeed, high dose UDCA may be harmful.102 Treatment with corticosteroids and other immunosuppressant agents have not demonstrated any improvement in disease activity or in the outcome of PSC. Small randomized, placebo-controlled or pilot

trials have investigated the role of agents with immunosuppressive potency like prednisolone, budesonide, azathioprine, cyclosporin, methotrexate, mycophenolate, and selleck kinase inhibitor tacrolimus, agents with TNFα antagonizing effects like pentoxifyllin, etanercept and anti-TNF monocolonal antibodies and antifibrotic check details agents like colchicine, penicillamine, or pirfenidone.154 There is no evidence that any of these drugs are efficacious and, therefore, none can be recommended

for classic PSC. However, these drugs may well have a role in the context of a PSC/AIH overlap syndrome, because pediatric patients and those with evidence of a PSC/AIH overlap syndrome are more likely to respond to immunosuppressive treatment.36, 39, 155 A retrospective study in adults also suggested a beneficial role of corticosteroids in a subgroup with AIH overlap features.156 Corticosteroids may also be indicated as a therapeutic trial following thorough evaluation of suspected immunoglobulin G4-associated cholangitis (IAC)/autoimmune pancreatitis (AIP).44, 157 Recommendations: 28 In adult patients with PSC, we recommend against the use of UDCA as medical therapy (1A). Liver transplant indications for patients with PSC do not differ substantially from those with other forms of chronic liver disease and relate primarily to complications of portal hypertension, impaired quality of life, and chronic liver failure. Indeed, in the United States of America, organ allocation by the Model for End-Stage Liver Disease score is etiology independent.

This compilation includes 32 sightings of 54 whales from our reco

This compilation includes 32 sightings of 54 whales from our records or those previously reported (Clarke 1965; Aguayo-Lobo 1974; Aguayo and Torres 1986; Goodall and Galeazzi 1986; Canto et al. 1991; Aguayo et al. 1992; Van Waerebeek et al. 1992, 1998, 2009; Santillán

et al. 2004), plus a subset of the records in Aguayo et al. (2008). Aguayo et al. (2008) compiled 124 sightings of 232 southern right whales from 1964 to 2008 from Chilean waters off the west coast of Chile, selleckchem the Magellan Straits and Beagle Channel and the west Antarctic Peninsula (in the sector claimed by Chile). These were obtained from published reports and recent unpublished data from sightings networks. However, Aguayo et al. (2008) did not include two published sightings from the west coast of Chile (Aguayo

et al. 1992, Brito 1996) and we believe their sightings from the Magellan Straits and Beagle Channel are likely individuals from the Southwest Atlantic population based on the location of the sightings (Goodall and Galeazzi 1986, Gibbons et al. 2006, Belgrano et al. 2008). Also, based on geographical considerations Aguayo et al. (1992) proposed that southern right whales off Chile may feed off the Antarctic Peninsula, but no direct photographic link to that area has been made yet. Therefore, 30 records are not included that were from either the Antarctic or the Magellan Straits and Beagle Channel selleck compound (Aguayo et al. 1992, Akt inhibitor 2008). At present, we believe that only sightings off the Pacific coasts of Chile and Peru can be considered to represent the population in the eastern South Pacific. Also, we excluded seven more of the Aguayo et al. (2008) sightings: two that were attributed to our sighting network but do not exist in our records, three from a sighting network with unconfirmed species identification, and two sightings taken from Aguayo et al. (1992) that are probably not southern right whales. The first misidentification was seven adult whales sighted 20 miles

offshore of Pisagua (19º35′S) on 1 December 1985, apparently feeding on South American pilchard, Sardinops sagax. The second was a group of five adults and three calves sighted 22 miles off Constitución (35º36′S) observed by toothfish (Dissostichus eleginoides) fishermen on 10 September 1986. These are the only two sightings that report groups larger than four individuals and also the only two reports of right whales offshore. Furthermore, as southern right whales are not known to consume fish, the reports of pilchard or toothfish interaction are inconsistent with right whale foraging ecology, and therefore we did not accept these observations. Finally, Aguayo et al. (2008) included four sightings that should be considered resightings because of close proximity in space and time.

We did not estimate calf:cow ratios with sample sizes <20 groups,

We did not estimate calf:cow ratios with sample sizes <20 groups, as optimization was problematic when there were few groups and observers typically classify >20 groups. Calf:cow ratios in all simulations

were estimated with function dbetabinom within package bbmle in Program R using the Nelder-Mead algorithm for optimization. Selecting an appropriate level of precision is difficult, as the desired level of precision will depend upon how the data are used. Clearly, we would like to be able to identify years in which reproduction fails and a relative precision of 20% should be sufficient to delineate years of high vs. low calf production. For example, attaining 20% relative precision for a calf:cow ratios would allow differentiation of ratios that differ by more than 1 calf per 100 cows for small ratios, such as 0.05

find more (i.e., 0.05 × 0.2 = 0.01), or 3 calves per 100 cows for larger selleck chemicals ratios, such as 0.15 (i.e., 0.15 × 0.2 = 0.03). However, if calf:cow ratios are used as measures of fecundity in population models, more precision may be necessary. We chose to present relative precisions as functions of sample size, so users can decide what sample sizes are necessary. Nine surveys classified walrus groups along the ice edge between 1982 and 1999 (Fig. 3; Table 2). Two surveys occurred in 1981 and 1982, single surveys occurred in 1983, 1984, and 1998, and two surveys occurred in 1999. Walruses would sometimes enter the water before all individuals were counted and classified to

sex and age. A total of 1,200 groups of walruses were encountered; of these, 1,107 (92%) were completely this website counted and 886 were completely classified to sex and age. A total of 773 groups were completely classified and contained at least one cow. Pooling within sample years, the number of groups with cows that were classified ranged from 59 in 1983 and 1998 to 218 in 1982 (Table 2). The average size of groups with cows was 7.03 (SD = 10.35) and ranged from 5.52 (SD = 4.92) in 1982 to 9.48 (SD = 16.47) in 1981. The maximum observed sizes of groups with cows were 133 in 1981, 109 in 1982, 22 in 1983, 62 in 1984, 32 in 1998, and 30 in 1999. The entire sea ice front, from Alaska to Russia, was surveyed in 1982, 1998, and 1999 (Fig. 3). In 1981, during the Polar Star survey, time of day was not recorded for 30 cow groups (115 individual cows) and these data were not used for covariate modeling. The data were more appropriately modeled with a beta-binomial distribution (Δ AIC = 0; 2 parameters) than a zero-inflated beta-binomial distribution (Δ AIC = 2.1; 3 parameters), a zero-inflated binomial distribution (Δ AIC = 78.6; 2 parameters), or a binomial distribution (Δ AIC = 127.1; 2 parameters). Hence, a beta-binomial distribution was assumed for subsequent analyses.

Conclusion: ER stress-mediated mitochondrial apoptotic pathway pl

Conclusion: ER stress-mediated mitochondrial apoptotic pathway plays an Epigenetic Reader Domain inhibitor important role in the pathogenesis of CCl4-induced acute liver injury in mice. Key Word(s): 1. liver injury; 2. endoplasmic reticulum

stress; 3. apoptosis; 4. carbon tetrachloride Presenting Author: CHUN-JEN LIU Additional Authors: Na Corresponding Author: CHUN-JEN LIU Affiliations: National Taiwan University College of Medicine and Hospital Objective: Spontaneous seroclearance of hepatitis B surface antigen (HBsAg) is usually associated with favorable clinical outcomes in hepatitis B withy hepatitis B virus (HBV) monoinfection. However, in patients with dual HBV and hepatitis C virus mTOR inhibitor (HCV) infection, the annual rate and outcomes of HBsAg seroclearance were not clarified. Factors associated

with this event were also largely unknown. Methods: We addressed these issues by retrospectively collecting a cohort of 157 untreated HBsAg-positive and anti-HCV-positive patients (M:F = 94 : 63; median age: 47.6 years) who received regular follow-up for a median period of 10 years. selleck compound Results: At enrollment, 31 (19.8%) patients had active HBV infection (serum HBV DNA >2000 IU/mL) and inactive HCV infection (serum HCV RNA negative), 41 (26.1%) had active HCV and inactive HBV infection, 10 (6.4%) had active HBV and active HCV infection, and 75 (47.8%) had inactive HBV and

inactive HCV infection. After 1,278 patient-years of follow-up, annual incidence of HBsAg seroclearance was 2.0 per 100 patient-year; the 10-year cumulative incidence was 18.9 per 100 patient-years. The incidence was highest in patients with active HCV and inactive HBV infection. Multivariate analysis revealed that serum ALT >80 U/L (p = 0.003), baseline HBsAg <100 IU/mL (p < 0.001), and rs3077 GG genotype (p = 0.034) were associated with HBsAg seroclearance. None developed HCC after HBsAg seroclearance. Conclusion: Spontaneous seroclearance of HBsAg is not common in HBV and HCV dually infected patients, but the outcomes are generally good. Key Word(s): 1. hepatitis B; 2. hepatitis C; 3. dual infection; 4.

TNF-α induced a relocalization of tight junction protein occludin

TNF-α induced a relocalization of tight junction protein occludin and increased

the lateral diffusion speed of HCV receptor tetraspanin CD81 in polarized HepG2 cells, providing a mechanism for their increased permissivity to support HCV entry. High concentrations of HCV particles could stimulate macrophages to express TNF-α, providing a direct mechanism for the virus to promote infection. Conclusion: This study shows a new role for TNF-α to increase virus entry and highlights the potential for HCV to exploit existing innate immune responses in the liver to promote de novo infection events. (Hepatology 2014;59:1320-1330) “
“Background and Aim:  The widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN < 40 U/L) was recently challenged by several reports. Both ALT and aspartate aminotransferase PF-02341066 in vitro (AST) are commonly used as surrogate markers of liver disease, but almost all studies of aminotransferase activity were conducted on ALT. We investigated not only ULN of ALT but EPZ015666 clinical trial also AST activity and to identify factors modulating them in healthy Korean. Methods:  A cross-sectional study of 411 240 registered blood donors in all nationwide blood banks belonging to the Korean Red Cross were conducted. ULN of ALT and AST was evaluated adjusting their age according to the national population census database.

“Decision tree model” was used to identify the affecting factors of ALT and AST and optimal cut-off points of affecting factors. Results:  “ULN of ALT” was 34 U/L in men and 24 U/L in women and “ULN of AST” was 32 U/L in men and 26 U/L in women in the blood donor database. Decision tree analysis showed that ALT levels

were mostly influenced by body mass index level and its critical two cut-off points were 23.5 kg/m2 and 25.8 kg/m2, respectively. The most affecting factor of AST was gender. Conclusion:  Upper limits of normal of ALT and AST in Koreans were lower than conventional accepted values (< 40 U/L) but higher than recently suggested values (male < 30 U/L and female < 19 U/L). Body mass index was the most determining factor for ALT and gender was the most influencing factor for AST activity. "
“Nonsteroidal anti-inflammatory drugs (NSAIDs), including low-dose aspirin, see more are very frequently prescribed in older patients in order to palliate or prevent age-related degenerative joint diseases or cardiovascular events. From the perspective of the gastrointestinal system, their most frequent serious adverse effect is hemorrhage from gastric or duodenal ulcers, occurring overall in about 0.5–2.0% per patient year of continuous use. Much more common are gastric erosions – at least a few will be found in most patients if an endoscopy is performed – but these usually heal uneventfully and are normally asymptomatic. Dyspepsia is a common side-effect but there is little correlation with the macroscopic injury and the pathogenetic mechanisms are less well understood.

8 The direct measurement of the portal pressure is a very invasiv

8 The direct measurement of the portal pressure is a very invasive technique that is no longer performed in patients with cirrhosis; the indirect, less invasive technique of measuring the hepatic venous pressure gradient (HVPG) is used. This indirect method can be performed in 10 minutes but can last more than 30 minutes when hepatic vein catheterization is difficult. It is also a very safe technique; in our experience with more than 13,000 procedures, only minor complications (mainly transient cardiac arrhythmias) have occurred (<1% of patients), and no deaths have been observed. Most of these HVPG measurements have been performed in association with transjugular liver biopsy. The results provide information

FK506 supplier about the type and severity of portal hypertension and may also help us to diagnose cirrhosis, particularly when the HVPG is greater than 20 mm Hg.7 The HVPG is the difference between the wedged or occluded hepatic venous pressure and the free hepatic venous pressure.7 Portal hypertension is considered moderate

when the HVPG ranges from 5 to 10 mm Hg and severe when the HVPG is greater than 10 mm Hg. In patients with cirrhosis, although the HVPG is elevated, it differs greatly from one patient to another and ranges from 7 to 35 mm Hg.7 The HVPG is a good reflection of portal pressure in patients with alcoholic or viral cirrhosis but is not in patients with LY294002 noncirrhotic portal hypertension.9-12 After the acute administration of a drug acting on the splanchnic circulation, the HVPG measurement does not necessarily provide a reliable estimation selleck compound of the magnitude of the changes in the portal pressure.10 In fact, changes in the HVPG depend not only on wedged and free hepatic venous pressure changes but also on variations in other factors such as the portal pressure, portal and hepatic artery blood flows, and intrahepatic vascular resistance. Patients with cirrhosis are at risk of developing complications from portal hypertension when the HVPG reaches 10 to 12 mm Hg.13, 14 Below these values, moderate portal hypertension may be present, but the risk of complications

is low. Above these values, severe portal hypertension is known to be present, and although there is no correlation between the degree of the HVPG and the risk of complications,13 an HVPG greater than 20 mm Hg has been associated with a higher mortality rate.15 Over the last 30 years, significant progress has been made in understanding the pathophysiology of portal hypertension. At the same time, the natural history of portal hypertension and its complications still remains unclear; for example, the exact mechanism of the development of severe portal hypertension in patients with cirrhosis and moderate portal hypertension needs to be elucidated. Thus, the evaluation of moderate or severe portal hypertension must be studied in patients with cirrhosis.

8 The direct measurement of the portal pressure is a very invasiv

8 The direct measurement of the portal pressure is a very invasive technique that is no longer performed in patients with cirrhosis; the indirect, less invasive technique of measuring the hepatic venous pressure gradient (HVPG) is used. This indirect method can be performed in 10 minutes but can last more than 30 minutes when hepatic vein catheterization is difficult. It is also a very safe technique; in our experience with more than 13,000 procedures, only minor complications (mainly transient cardiac arrhythmias) have occurred (<1% of patients), and no deaths have been observed. Most of these HVPG measurements have been performed in association with transjugular liver biopsy. The results provide information

Fulvestrant chemical structure about the type and severity of portal hypertension and may also help us to diagnose cirrhosis, particularly when the HVPG is greater than 20 mm Hg.7 The HVPG is the difference between the wedged or occluded hepatic venous pressure and the free hepatic venous pressure.7 Portal hypertension is considered moderate

when the HVPG ranges from 5 to 10 mm Hg and severe when the HVPG is greater than 10 mm Hg. In patients with cirrhosis, although the HVPG is elevated, it differs greatly from one patient to another and ranges from 7 to 35 mm Hg.7 The HVPG is a good reflection of portal pressure in patients with alcoholic or viral cirrhosis but is not in patients with EPZ-6438 clinical trial noncirrhotic portal hypertension.9-12 After the acute administration of a drug acting on the splanchnic circulation, the HVPG measurement does not necessarily provide a reliable estimation selleck kinase inhibitor of the magnitude of the changes in the portal pressure.10 In fact, changes in the HVPG depend not only on wedged and free hepatic venous pressure changes but also on variations in other factors such as the portal pressure, portal and hepatic artery blood flows, and intrahepatic vascular resistance. Patients with cirrhosis are at risk of developing complications from portal hypertension when the HVPG reaches 10 to 12 mm Hg.13, 14 Below these values, moderate portal hypertension may be present, but the risk of complications

is low. Above these values, severe portal hypertension is known to be present, and although there is no correlation between the degree of the HVPG and the risk of complications,13 an HVPG greater than 20 mm Hg has been associated with a higher mortality rate.15 Over the last 30 years, significant progress has been made in understanding the pathophysiology of portal hypertension. At the same time, the natural history of portal hypertension and its complications still remains unclear; for example, the exact mechanism of the development of severe portal hypertension in patients with cirrhosis and moderate portal hypertension needs to be elucidated. Thus, the evaluation of moderate or severe portal hypertension must be studied in patients with cirrhosis.