Surface characterizations of the specimens were carried out with X-ray photoelectron spectrometry, scanning electron microscopy, and energy dispersive X-ray spectroscopy. The results indicated that the bond strengths of all the Ti/porcelain groups were greater than the minimum requirement (25 MPa) as

prescribed by ISO 9693. The gold sputter coating increased the oxidation resistance (or decreased the oxide content) of the Ti surface during porcelain sintering, which positively affected the bond strength of Ti/porcelain (approximately 36 MPa) compared to the untreated Ti/porcelain specimen (approximately 29 MPa). The fracture morphologies of all the Ti/porcelain groups revealed an adhesive bond failure as the interfacial fracture mode between the Ti and IWR-1 in vitro the porcelain. A practical and simple sandblasting/gold sputter coating treatment of Ti surfaces prior to porcelain sintering significantly strengthens the bond between the milled, noncast Ti and the dental porcelain. “
“To compare prevalence of systemic health conditions (SHC) between African American and Caucasian edentulous patients presenting for complete dentures (CD) at an urban dental school. The study included patients presenting for CD 1/1-12/31/2010, ages 20 to 64 years, and either African American or Caucasian. Covariates included: age group, gender, employment status, Medicaid status, smoking history, and alcohol consumption.

learn more SHC included at least one of the following: arthritis, asthma, cancer, diabetes, emphysema, heart MCE公司 attack, heart murmur, heart surgery, hypertension, or stroke. The group (n = 88) was 44.3% African American, 65.9% ≥50, 45.5% male, 22.7% employed, and 67.0% with at least one SHC. African Americans were older (p = 0.001) and more likely to have one or more SHC (p = 0.011). Patients with at least one SHC were older (p = 0.018) and more likely female (p = 0.012). The total sample logistic regression

model assessing SHC yielded only gender as statistically significant (males < OR 0.32, 95% CI 0.11 to 0.92). Caucasian males were less likely to have SHC (OR 0.17, 95% CI 0.04 to 0.77), and Caucasians ≥50 were more likely (OR 5.36, 95% CI 1.19 to 24.08). African Americans yielded no significant associations. Among selected completely edentulous denture patients at an urban dental school, two out of three patients had at least one SHC. This exploratory study suggests there may be health status differences between African American and Caucasian patients in this setting, calling for further study. "
“Purpose: To test the hypothesis that the type of cement used for fixation of cast dowel-and-cores might influence fracture resistance, fracture mode, and stress distribution of single-rooted teeth restored with this class of metallic dowels. Materials and Methods: The coronal portion was removed from 40 bovine incisors, leaving a 15 mm root.

Additional Supporting Information may be found in the online version of this article. “
“Secondary stomach cancer in lesions of the remnant stomach occurs relatively soon after distal gastrectomy using the Billroth I reconstruction procedure. Prophylactic eradication of Helicobacter pylori after endoscopic resection of early gastric cancer should be

used to prevent the development of metachronous gastric carcinoma. However, the effect of H. pylori eradication on the gastric remnant has not been clearly determined. Eight patients who were H. pylori-positive after distal gastrectomy for primary gastric cancer underwent eradication therapy and were followed by endoscopy for 9 years. Upper gastroenteroscopy series were done before and at 1, 3, 5, 7 and 9 years after eradication, and biopsy specimens were taken from the lesser and greater curvatures, respectively. Histological changes, including chronic PLX-4720 molecular weight inflammation, activity, atrophy, and intestinal metaplasia, were evaluated using the updated Sydney system. Successful eradication was confirmed using the urea breath test in all eight patients. Chronic inflammation scores were improved after eradication at both the lesser

(mean scores ± SD: before eradication, 2.9 ± 0.5; 1 year after, 2.3 ± 0.4; 3 years, 1.8 ± 0.3; 5 years, 1.5 ± 0.3; 7 years, 1.3 ± 0.3; and 9 years, 1.0 ± 0.3) and greater curvatures (before, 2.9 ± 0.4; 1 year after, 1.9 ± 0.3; 3 years, 1.4 ± 0.4; 5 years, www.selleckchem.com/products/Adriamycin.html 1.3 ± 0.3; 7 years, 1.1 ± 0.2; and 9 years, 0.6 ± 0.3). Atrophy scores improved more quickly after eradication than MCE chronic

inflammation scores at both the lesser (before, 2.4 ± 0.5; 1 year after, 1.8 ± 0.4; 3 years, 0.8 ± 0.3; 5 years, 0.3 ± 0.1; 7 years, 0.0; and 9 years, 0.0) and greater curvatures (before, 2.2 ± 0.4; 1 year after, 1.3 ± 0.3; 3 years, 0.5 ± 0.3; 5 years, 0.0; 7 years, 0.0; and 9 years, 0.0). No secondary stomach cancers were found on endoscopy. Undergoing H. pylori eradication improved possible precancerous lesions of the gastric remnant among patients who had undergone distal gastrectomy. Prophylactic H. pylori eradication in the gastric remnant may be useful in preventing the development of metachronous gastric carcinoma. Since the first report by Marshall and Warren in 1984 identifying curved bacilli adjacent to the gastric epithelium of patients with chronic gastritis,[1] the link between Helicobacter pylori and chronic gastritis has grown stronger.[2] The bacteria colonize the stomach for years or decades, and causes continuous inflammation. Chronic gastritis caused by H. pylori infection does not produce symptoms in the majority of infected persons, but is a significant risk factor for the subsequent development of atrophic gastritis and gastric adenocarcinoma. Uemura et al.[3] prospectively studied 1526 Japanese patients, 1246 with H.

These results raise the question of what mechanism(s) STAT3 uses to exert its proviral effect. It is plausible that specific sets of STAT3-dependent target genes may be up-regulated in hepatocytes during HCV infection; this in turn would allow for the expression of host proteins that may assist in creating a cellular environment favorable for HCV replication. Alternatively, STAT3 dependent host cell factors, or STAT3 itself, may interact directly with viral proteins to enhance HCV

replication. One such example is that STAT3 is a known transcriptional activator of VEGF,[25] a protein capable of promoting HCV entry into hepatocytes in vivo.[26] Thus, it is conceivable that in the HCV-infected liver STAT3 activation may facilitate HCV entry into hepatocytes. Alternatively, RXDX-106 molecular weight STAT3 may impact the host antiviral response, as STAT3 has been recently described to act as a negative regulator of the type I interferon response, by way of direct suppression of the interferon-stimulated genes OAS, PKR, and IRF7.[27] We explored this possibility; however, we were unable to show in Huh-7 cells or primary human hepatocytes that inhibition of STAT3 activation in the presence of IFN-α resulted in increased expression of known anti-HCV ISGs (data not shown). We have demonstrated

in our study that STAT3 plays a role in HCV replication, as inhibition of STAT3 with the specific PF-02341066 supplier inhibitor STA-21 or siRNA-mediated knockdown of STAT3 markedly reduced HCV replication

in the genomic replicon system (50%) and in the infectious JFH-1 system 上海皓元医药股份有限公司 (70%). Moreover, we have shown that the converse set of experiments in which a constitutively active form of STAT3 is expressed both transiently and stably leads to increased HCV replication. Collectively, these results indicate that STAT3 is playing an important role in HCV RNA replication. However, as the effect of inhibition with STA-21 is greater in the context of the full life cycle of HCV, it is possible that STAT3 may also be acting at another stage of the HCV life cycle. We have shown that cell-to-cell spread of the virus is not affected by STA-21 inhibition of STAT3 and that STA-21 is still effective at inhibiting replication in an established infection. These findings suggest that STAT3 does not play a role in mediating HCV entry or spread in Huh-7.5 cells. However, in accordance with previous findings in the literature we have shown that STAT3 is likely to be involved in HCV RNA replication.[2] It is now becoming clear that STAT3 plays a direct and integral role in controlling the dynamics of the MT network. Activated STAT3 has been demonstrated to directly bind to, and attenuate the action of, STMN1, a known tubulin deploymerizer.[22, 23] As such, STAT3 positively regulates MT activity. The MT network and the process of MT polymerization is necessary for many viruses, including HCV, to establish a productive infection.

A life expectancy of 10 years is predicted for patients with a serum bilirubin level <2.0 mg/dL, 5 years for 2.0–3.0 mg/dL, and 1 year for >6.0 mg/dL. Recommendations: Total bilirubin, prothrombin (INR), albumin, and the serum creatinine level, which are essential to calculate the MELD score, should be measured when considering liver transplantation. (LE 2b (2a in part), GR A) Patients with PBC should be referred to transplant hepatologists when serum total bilirubin level is >5 mg/dL. To encourage the patients to prepare for liver transplantation, an earlier and appropriate explanation of liver transplantation is desirable. (LE 4,

GR B) Although there is no completely curative treatment for PBC, ursodeoxycholic acid (UDCA) is currently considered the first-line treatment for the disease. UDCA delays the progression of PBC, although it does learn more not have a significant benefit for PBC at the advanced stage. The GS-1101 solubility dmso clinical usefulness of UDCA is evaluated according to the following factors: (i) improvement of serum biochemical markers, such as ALP, GGT, AST, ALT and total bilirubin; (ii) histological improvement of cholangitis, liver inflammation and liver fibrosis; and (iii) delay in the disease progression until end-stage liver disease, death, or liver transplantation. The following Paris

and Barcelona criteria are useful for evaluating the clinical outcome of UDCA treatment. 上海皓元 (i) Paris criteria: total bilirubin ≤1.0 mg/dL, ALP ≤3 × the upper normal limit (UNL), and AST ≤ 2 × UNL at 1 year after introduction of UDCA. (ii) Barcelona criteria: decrease of ALP ≥40% at 1 year after introduction of UDCA. Liver transplantation is the only therapeutic approach for patients in the advanced stage when medical treatment shows little improvement. Prevention and treatment strategies for comorbid autoimmune

diseases, cholestasis, and cirrhosis-related symptoms and complications are required. Although the term cirrhosis is included in the name PBC, most patients (70–80%) with PBC have little clinical and histological evidence of liver cirrhosis. Patients should be informed accordingly to prevent misunderstanding of their prognoses. Currently, patients are likely to be diagnosed at earlier stages and disease progression is likely to be delayed by UDCA. Therefore, the prognosis of patients with aPBC, as long as they remain asymptomatic, is equivalent to that in the general population. No restrictions are necessary in daily life for patients with aPBC. By contrast, some restrictions in daily life and nutritional education are required for patients with sPBC, depending on symptoms, expected future complications, and disease severity. Extensive clinical trials including randomized clinical trials (RCT) and meta-analyses were carried out for UDCA after the first report by Poupon et al.

In this subset a decrease of eGFR to <60 mL/min at week 12 was observed in 33/398

(8.3%) patients Crizotinib manufacturer on TLV, 4/113 (3,5%) on BOC, and 1/80 PEG/RBV (1.3%) (P < 0.05). At week 24 eGFR <60 mL/min was observed in 5/398 (1.3%) in the TLV group, who were at this timepoint on dual therapy with PEG/RBV, as the approved treatment duration with TLV is limited to the first 12 weeks of therapy. An eGFR of <60 mL/min was observed at week 24 in 5/113 (4.4%) patients on BOC and 1/80 patients on PEG/RBV (1.3%) (P < 0.05). The time course of eGFR from week 12 to 24 in patients on TLV therapy for the first 12 weeks and with a reduction in eGFR <60 mL/min is shown in Fig. 1. In most patients the decrease in eGFR <60 mL/min occurred in the first 12 weeks and was reversed until week 24. Renal impairment has not been reported as a safety signal in clinical trials with TLV or BOC. This may be due to the selected patient population in clinical trials frequently excluding patients with comorbidities or specific comedications. In this large cohort a substantial proportion of patients had risk factors for renal impairment such as older age, arterial hypertension, or diabetes mellitus.

All these variables were associated with a marked decrease in eGFR to <60 mL/min at least selleck chemicals in univariate analysis. In addition, being treated with TLV or BOC was an additional risk factor in univariate and multivariate logistic regression analysis. About 5% of patients on triple HCV therapy with BOC or TLV showed at least temporary renal insufficiency stage 3. For TLV it could be demonstrated that this is a reversible effect in the vast majority of patients. The improvement of renal function after discontinuation of the HCV protease inhibitor argues strongly for a causal

relationship. However, the pathophysiologic mechanism remains unknown to date and should be subject to further research. The involvement of both TLV and BOC may 上海皓元医药股份有限公司 indicate a class effect, at least for the first generation of HCV protease inhibitors. In addition, a more pronounced anemia was observed in patients with decreased renal function. This is likely due to an accumulation of ribavirin due to an impaired renal elimination. As a consequence, substantial ribavirin dose reductions should be considered in these patients. A limitation of this study is the lack of data on urine, in particular proteinuria, which may have given additional information on the origin of the renal impairment, i.e., tubular, glomerular, or combined. “
“Abdominal pain is common in school-aged children and is rarely organic, but there is a diverse and extensive differential diagnosis. The Rome III criteria set out diagnostic features of the functional bowel disorders. Most cases require screening investigations, and “reg flags” identify those more likely to have underlying pathology. Management is often multi-disciplinary, especially important when chronic pain is debilitating and responds poorly to drug or dietary intervention.

Disclosures: Young-Suk Lim – Advisory Committees or Review Panels: Gilead Science, Bayer; Grant/Research Support: Gilead Science, Novartis, Bayer; Speaking and Teaching: BMS The following people have nothing to disclose: Gi-Ae Kim, Seungbong Han, Jihyun An Introduction: Therapy for chronic delta (HDV) hepatitis

infection is unsatisfactory with poor response rates to interferon. Prenylation inhibitors have Hydroxychloroquine in vivo demonstrated effectiveness against HDV in in vitro and in vivo models. As a proof-of-concept study, we evaluated the antiviral effect and safety of the prenylation inhibitor, lonafarnib in patients with chronic HDV. Methods: 14 HDV infected patients were enrolled into 2 groups in a phase 2a double-blinded, randomized, placebo-controlled study and received: Group 1 – lonafarnib 100 mg twice daily and Group 2 – lonafarnib 200 mg twice daily for 28 days followed by 6 months of off-therapy follow-up. Both groups enrolled 6 treatment and 2 placebo subjects, where Group 1 placebo Selleckchem Fulvestrant subjects were offered open-label lonafarnib as Group 2 participants. Patients underwent 72-hour viral kinetic and pharmacokinetic evaluations at the start of therapy. Serial measurements of safety parameters,

liver tests, pharmacokinetics, virologic (HDV RNA and HBV DNA) markers and symptom questionnaires were performed. Results: This ongoing study is completely enrolled and all patients have completed medchemexpress 28 days of therapy, and data is available on the first 15 of 16 patients. Patients enrolled were mostly males (71%) with a median age of 38 years and included Asian (50%), Caucasian (43%) and African (7%). Median baseline evaluations include: ALT (89 IU/mL), AST (61 IU/mL), Ishak fibrosis (3), HBV DNA (<21 IU/mL) and HDV RNA (1.01E+06 IU/mL). There were no differences in baseline parameters between therapeutic groups. After 28 days of therapy, the mean log HDV RNA change from baseline was -0.13 log IU/mL

in the placebo group (p=0.31), -0.74 log IU/mL in Group 1 (p=0.02) and -1.60 log IU/mL in Group 2 (p<0.0001), with half of patients in Group 2 achieving a decrease from baseline-to-nadir of greater than -2 log IU/mL. Lonafarnib serum concentrations correlated with HDV RNA change (R2=0.76, p<0.0001). Adverse events were mild to moderate and included nausea, vomiting, dyspepsia, anorexia, diarrhea, and weight loss. There were no treatment discontinuations for adverse events. Conclusions: This is the first demonstration that treatment of chronic HDV with the pre-nylation inhibitor lonafarnib significantly reduces virus levels in patients. The decline in virus levels significantly correlated with serum drug levels, providing further evidence for the efficacy of prenylation inhibition in chronic HDV.

Disease patterns vary in areas of differing endemicity and correlate with socioeconomic status and access to clean water and sanitation. In many parts of the world, economic development and improved sanitation and living standards have resulted in significant shifts in the acquisition of HAV infection from infancy and childhood to older ages.4 In developing countries, where infection is endemic, most persons are infected in early childhood when asymptomatic infection is likely. In developed

countries, where the incidence rate is lower, infection typically occurs at older ages when clinical symptoms become more apparent.5 Community-wide epidemics contribute significantly to the burden of disease in developed countries. In these settings, disease tends to occur Fostamatinib concentration in circumscribed groups, such as travelers to hepatitis A endemic areas, or as outbreaks among high-exposure groups such as intravenous drug users or men who have sex with men.5-7 Prior to the introduction of vaccines against HAV in the United States, hepatitis A occurred as large nationwide epidemics approximately every 10 years. The last epidemic occurred during the mid-1990s and affected particularly adolescents and young adults,8 causing substantial morbidity and economic losses estimated at $489 million annually.9 Since the introduction of an HAV vaccine in 1995, the incidence of hepatitis

A has decreased markedly for all age groups; 上海皓元 however, an estimated 25,000 new infections still occurred in 2007.10 Approximately 50% of all reported mTOR inhibitor hepatitis A cases have no specific risk factors identified.11 In cases where risk factors have been identified, the majority of adults

are international travelers, men who have sex with men, or intravenous drug users.6, 7 Host genetic factors have played an important role in determining the differential susceptibility to infectious diseases such as hepatitis B and C, malaria, HIV/AIDS, tuberculosis, and invasive pneumococcal disease.12 In outbreaks of hepatitis A, some people are infected while others remain uninfected after exposure, suggesting that people vary in their susceptibility to HAV infection.5, 6 However, to date, the number of studies of human genetic variation and HAV infection are few, except for two small candidate gene studies,13, 14 and twin studies showing that genetic factors accounted for ≈36% of the total variability in HAV-specific immune response to vaccination.15, 16 There are no reports investigating host genetic factors for hepatitis A in the United States population, though many public health researchers have focused on behavior, environment, and viral factors. Examining host factors may provide insight into pathogenesis and susceptibility to HAV infection and also help to identify and target high-risk populations for vaccination.

Disease patterns vary in areas of differing endemicity and correlate with socioeconomic status and access to clean water and sanitation. In many parts of the world, economic development and improved sanitation and living standards have resulted in significant shifts in the acquisition of HAV infection from infancy and childhood to older ages.4 In developing countries, where infection is endemic, most persons are infected in early childhood when asymptomatic infection is likely. In developed

countries, where the incidence rate is lower, infection typically occurs at older ages when clinical symptoms become more apparent.5 Community-wide epidemics contribute significantly to the burden of disease in developed countries. In these settings, disease tends to occur CX-4945 cell line in circumscribed groups, such as travelers to hepatitis A endemic areas, or as outbreaks among high-exposure groups such as intravenous drug users or men who have sex with men.5-7 Prior to the introduction of vaccines against HAV in the United States, hepatitis A occurred as large nationwide epidemics approximately every 10 years. The last epidemic occurred during the mid-1990s and affected particularly adolescents and young adults,8 causing substantial morbidity and economic losses estimated at $489 million annually.9 Since the introduction of an HAV vaccine in 1995, the incidence of hepatitis

A has decreased markedly for all age groups; medchemexpress however, an estimated 25,000 new infections still occurred in 2007.10 Approximately 50% of all reported PD98059 hepatitis A cases have no specific risk factors identified.11 In cases where risk factors have been identified, the majority of adults

are international travelers, men who have sex with men, or intravenous drug users.6, 7 Host genetic factors have played an important role in determining the differential susceptibility to infectious diseases such as hepatitis B and C, malaria, HIV/AIDS, tuberculosis, and invasive pneumococcal disease.12 In outbreaks of hepatitis A, some people are infected while others remain uninfected after exposure, suggesting that people vary in their susceptibility to HAV infection.5, 6 However, to date, the number of studies of human genetic variation and HAV infection are few, except for two small candidate gene studies,13, 14 and twin studies showing that genetic factors accounted for ≈36% of the total variability in HAV-specific immune response to vaccination.15, 16 There are no reports investigating host genetic factors for hepatitis A in the United States population, though many public health researchers have focused on behavior, environment, and viral factors. Examining host factors may provide insight into pathogenesis and susceptibility to HAV infection and also help to identify and target high-risk populations for vaccination.

Disease patterns vary in areas of differing endemicity and correlate with socioeconomic status and access to clean water and sanitation. In many parts of the world, economic development and improved sanitation and living standards have resulted in significant shifts in the acquisition of HAV infection from infancy and childhood to older ages.4 In developing countries, where infection is endemic, most persons are infected in early childhood when asymptomatic infection is likely. In developed

countries, where the incidence rate is lower, infection typically occurs at older ages when clinical symptoms become more apparent.5 Community-wide epidemics contribute significantly to the burden of disease in developed countries. In these settings, disease tends to occur Ibrutinib mw in circumscribed groups, such as travelers to hepatitis A endemic areas, or as outbreaks among high-exposure groups such as intravenous drug users or men who have sex with men.5-7 Prior to the introduction of vaccines against HAV in the United States, hepatitis A occurred as large nationwide epidemics approximately every 10 years. The last epidemic occurred during the mid-1990s and affected particularly adolescents and young adults,8 causing substantial morbidity and economic losses estimated at $489 million annually.9 Since the introduction of an HAV vaccine in 1995, the incidence of hepatitis

A has decreased markedly for all age groups; medchemexpress however, an estimated 25,000 new infections still occurred in 2007.10 Approximately 50% of all reported ICG-001 ic50 hepatitis A cases have no specific risk factors identified.11 In cases where risk factors have been identified, the majority of adults

are international travelers, men who have sex with men, or intravenous drug users.6, 7 Host genetic factors have played an important role in determining the differential susceptibility to infectious diseases such as hepatitis B and C, malaria, HIV/AIDS, tuberculosis, and invasive pneumococcal disease.12 In outbreaks of hepatitis A, some people are infected while others remain uninfected after exposure, suggesting that people vary in their susceptibility to HAV infection.5, 6 However, to date, the number of studies of human genetic variation and HAV infection are few, except for two small candidate gene studies,13, 14 and twin studies showing that genetic factors accounted for ≈36% of the total variability in HAV-specific immune response to vaccination.15, 16 There are no reports investigating host genetic factors for hepatitis A in the United States population, though many public health researchers have focused on behavior, environment, and viral factors. Examining host factors may provide insight into pathogenesis and susceptibility to HAV infection and also help to identify and target high-risk populations for vaccination.

Of the 47 patients who discontinued treatment prior to Year 5, 10 had HBV DNA ≥300 copies/mL at the last on-treatment measurement. Genotypic testing of isolates from these 10 patients found no evidence of entecavir resistance. The safety profile for this cohort during treatment with open-label entecavir (study ETV-901) is summarized in Table 2. During ETV-901, no patient in this cohort discontinued entecavir due to an adverse event (Table 2). Adverse events occurring in ≥10% of patients are shown in Table 3. The most common serious adverse events were increased

ALT and liver abscess, both occurring in two (1%) patients. One patient, who stopped study medication 172 weeks after initially starting on entecavir, experienced an ALT flare that was associated with a ≥2-log increase in HBV DNA. This patient

was subsequently lost http://www.selleckchem.com/products/bgj398-nvp-bgj398.html to follow-up at Week 176. The safety profile for the entecavir long-term cohort during study ETV-901 was consistent with the safety profile reported for all entecavir-treated patients through 2 years in study ETV-022.19 Within study ETV-901, there was no observed difference between the cumulative safety profile of the entecavir long-term cohort (n = 146) and that of the larger patient population treated in the rollover study (ETV-901). Through 5 years of entecavir treatment YAP-TEAD Inhibitor 1 research buy and posttreatment follow-up, one patient (of 146) in the entecavir long-term cohort developed HCC (described below). For the entecavir long-term cohort, five deaths were reported during study ETV-901, including off-treatment follow-up. No death was attributed to study medication. The investigator-assigned causes of death were liver failure (1), 上海皓元医药股份有限公司 motor vehicle accident (3), and unknown (1). The patient

who died from liver failure was diagnosed with HCC at Week 51 of study ETV-022, and completed 2 years of dosing in that study. The patient subsequently enrolled in study ETV-901, was treated for 40 weeks and died during Week 136 (total entecavir treatment time) of liver failure secondary to progression of HCC. This analysis provides data on long-term treatment with entecavir in nucleoside-naïve, HBeAg-positive patients with CHB, and demonstrates that long-term entecavir therapy in this population achieved and maintained HBV DNA suppression. At Year 5, 94% of patients in the entecavir long-term cohort had HBV DNA <300 copies/mL. The importance of maintaining prolonged HBV DNA suppression to avoid or minimize the long-term complications of CHB has been recognized in several long-term studies of disease progression and outcome.3, 4, 24 Patients with persistently elevated viral load are at the greatest risk of developing liver disease progression and adverse outcomes.3, 4 It has also been shown that even patients with low-level HBV DNA viremia (below 104 to 105 copies/mL) are at risk of fibrosis, cirrhosis, and HCC.