Immunosenescence, Inflammaging and Resilience: An Evolutionary Perspective of Adaptation in the Light of COVID-19 Pandemic.

The evolution of immunology enabled the study of role of innate and adaptive immunity in systems biology network of immunosenescence and inflammaging. Due to global reduction in birth rates and reduced mortality, in year 2025 there will be about 1.2 billion of people over age of sixty, worldwide. The notion that the real age is not chronological, but the biological one led to the concept of "bioage", defining the biologic reactivity and resilience, including the immune competence of an individual. A competent immune network, systemic and mucosal is intrinsic to resilience and homeostasis of the human holobiont as the unit of evolution. In elderly, the immunosenescence could be associated with higher levels of proinflammatory mediators (such as IL-6), frialty and mortality. Proi-inflammatory state in elderly is denoted as inflammaging, characterized with low-grade (sterile) inflammation, as a physiologic response to life-long antigenic stimuli. When under control, inflammaging could be regarded as an efficient defense mechanism, oposed and regulated by anti-inflammatory pathways and molecules. Immunosensecence. The emerging concepts of "individual immunobiography" and "trained immunity" speak in favour that the immunological experience during the life would shape the ability of each individual to respond to various stimuli, strongly influencing the elements of innate and adaptive immunity, including macrophages and innate lymphoid cells. Older age is one of the main risk factors for the severe clinical picture and adverse outcome of COVID-19 infection, due to immunosenscence and chronic low-grade inflammation (inflammaging), both characterizing the immune reactioin in elderly. The senescent immune system, along with the advanced process of inflammaging is prone to react with uncontrolled activation of innate immune response that leads to cytokine release syndrome, tissue damage and adverse outcome of infection. Further research is aimed to nutritional and pharmacologic (immunomodulatory) interventions to influence the process of bioaging and immunosenscence, and to modulate the reaction of elderly to infection, including the COVID-19.

MODERN APPROACH TO DYSPEPSIA.

Dyspepsia is a disorder characterized by dyspeptic symptoms which are located in the epigastrium and related to digestion of food in the initial part of the digestive system. In functional dyspepsia, unlike organic dyspepsia, there is no underlying organic disease that would cause dyspeptic symptoms. Immune and mucosal function changes, gastric dysmotility, different composition of the gastrointestinal microbiota, and altered central nervous system processing are considered responsible for the onset of the disorder. The diagnosis is based on history, clinical presentation, and exclusion of other organic diseases of the gastrointestinal tract manifested by dyspeptic symptoms. Therapy includes eradication of Helicobacter pylori infection, proton pump inhibitors, prokinetics, neuromodulators, and herbal preparations. Unfortunately, in some patients, this therapy leads to little or no improvement. The prevalence of functional dyspepsia is increasing. It has become one of the more common gastroenterological diagnoses. In order to reduce the costs associated with the diagnosis and treatment of the disorder itself, its mechanisms need to be fully elucidated and thus enable finding appropriate therapy for all patient subgroups.

Comparison of Cytokine and Efflux Transporter Expression in Pediatric Versus Adult-onset Ulcerative Colitis.

OBJECTIVES: Ulcerative colitis (UC), a chronic inflammation of the colon, is often more severe in children than adults. Identification of altered expression of efflux transporters, cytokines, and suppressor of cytokine signaling (SOCS) molecules in pediatric versus adult patients could provide insight into the differential molecular patterns related to the age and disease pathology. METHODS: Mucosal samples from terminal ileum and colon in pediatric (9 UC-New, 4 UC-Remission) and adult (9 UC-New, 8 UC-Remission) patients were compared with healthy subjects (15 children and 10 adults) for mRNA expressions of several efflux transporters, cytokines, and SOCS molecules. RESULTS: The inflamed colon interleukin (IL)-6, IL-17A, and interferon-γ levels were elevated in UC-New subgroups but close to control values in UC-Remission. IL-1ß expression was increased only in UC-New children. Interestingly, uninflamed ileum also showed increased IL-6 and IL-1ß levels in UC-New subgroups. SOCS1/SOCS3 expression pattern followed a trend observed for inflammatory cytokines only in children. Both children and adults had decreased multidrug resistance protein 1 expression in colon, which inversely correlated with disease score, IL-6 and interferon-γ levels in UC-New children. IL-2 expression was upregulated in UC-Remission, compared with controls. CONCLUSIONS: Efflux transporter expression varies between UC children and adults except for decreased multidrug resistance protein 1. UC is characterized by a dysregulated TH1 and TH17 cytokine response irrespective of age at disease onset, with higher cytokine levels detected in children. Increased IL-2 levels in remission imply a protective role for regulatory T cells (Tregs).

Extragastric manifestations of Helicobacter pylori infection.

In the last year, different diseases possibly linked to Helicobacter pylori infection but localized outside of the stomach have been investigated. There are, in fact, several studies concerning cardiovascular diseases, hematologic disorders, neurologic diseases, metabolic, hepatobiliary diseases, and other conditions. Some of those studies, such as those on sideropenic anemia and idiopathic thrombocytopenic purpura, are quite large and well conducted, while in other cases there are just small or isolated studies or even case reports. Nonetheless, there is much interest among researchers all over the world for such a topic as demonstrated by the large number of studies published in the last year.

Quantitative analysis of troponin I serum values in patients with acute cholecystitis.

The diagnosis and staging of acute cholecystitis, upon a lot of diagnostic methods and some scoring systems, is still a great clinical problem. The aim of the study was to investigate if serum Troponin I is elevated in patients with acute cholecystitis. Following informed consent, 65 patients with clinical and laboratory signs of acute cholecystitis were enrolled. All patients had measured serum Troponin I level and an abdominal ultrasound was done before definitive treatment was performed. Increased serum Troponin I level was found in most patients with severe form of acute cholecystitis (p < 0.00001). It reached sensitivity of 94.5% and specificity of 57.1% of this test. In multiple regression analysis Troponin I significantly correlated (p < 0.05) with the serum aspartate aminotransferase (r = 0.27), gamma-glutamyl transferase (r = 0.25) and gallbladder wall (> 6 mm) thickness (r = 0.58). Our study confirms that in most patients with severe and acute cholecystitis, serum Troponin I is increased. Troponin I level is in a lower range than it would be in patients with cardiac muscle damage or necrosis. Measuring serum Troponin I is a fast, reliable and widely performed test that could, with other routinely measured parameters, help in early diagnosis of the severe form of acute cholecystitis.

Isolated splenic metastasis from colorectal carcinoma in a high risk patient: a case report.

Isolated splenic metastasis arising from a colorectal carcinoma is a rare finding. We report a case of 74-year-old man with a medical history of diabetes type II and paroxysmal atrial fibrillation, who underwent a right hemicolectomy for an adenocarcinoma of caecum in August 2004. In June 2007 the patient was diagnosed with high grade aortic valve stenosis as well as long segment stenosis of the first obtuse marginal branch of left coronary artery. He was suggested aortic valve replacement with coronary artery bypass grafting but he refused the surgery. In October 2007 the patient underwent alpha 18FDG - PET scanning, due to increasing values of CEA serum level, which showed a 5 cm big isolated hypermetabolic lesion in the spleen. Due to operative risk, splenectomy was refused by surgeons. The patient underwent a chemotherapy with capecitabine in total of 8 cycles before his CEA level began to rise and MSCT showed a progression in size of splenic metastasis. The patients condition was reevaluated by a team of experts and splenectomy was performed in September 2008. In May 2009 during the postoperative follow up, MSCT scanning revealed enlarged lymph nodes in celiac region and hepatic lesion suspicious of metastasis and the patient was admitted for further chemotherapy treatment. There is still no standardized treatment for this condition due to small number of cases reported in literature. Splenectomy followed by chemotherapy seems to be an optimal treatment but still no final conclusions can be made.

Biliary brush cytology for the diagnosis of malignancy: a single center experience.

Differentiation between benign and malignant biliary strictures is critical to the provision of adequate treatment. Brush cytology during the endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly used method for obtaining tissue confirmation of the nature of biliary strictures. It's specificity is remarkably high but reported sensitivities for the diagnosis of malignancy are low. Aim of our study was to assess sensitivity and specificity of biliary brush cytology in our institution, to find out main causes of false negative diagnoses and to confirm impression that the team approach has impact on sensitivity. Gold standard for diagnosis was definitive surgical histology or adequate clinical follow up for minimum of six month. Direct smears made by cytotechnician at the endoscopy room, and stained according to Papanicolaou and May-Grünwald Giemsa (MGG) were examined for well-recognized features of malignancy on conventional smears as a part of diagnostic routine. Cytologic diagnoses were benign, atypical/reactive, suspicious for malignancy and malignant. Of 143 brushings with available definitive diagnosis 36 (25%) had malignant cytologic diagnosis and 91(63.6%) were classified as benign, 3 were atypical/reactive and 13 suspicious for malignancy with 20 "false-negative" cases. When specimens with atypical and suspicious cytology were excluded from data analysis sensitivity was 64% and specificity was 100% and when suspicious findings were taken into account as true positives sensitivity rose to 71%. We find that biliary brush cytology, although mainly depending on the skill of endoscopist, as well as the experience of the cytologist, is a valuable method for obtaining accurate tissue diagnosis of biliary strictures, thus solving eternal diagnostic dilemma: benign or malignant.

The importance of P-glycoprotein multidrug transporter activity measurement in patients with Helicobacter pylori infection.

P-glycoprotein is important in local antibiotic resistance. Aim was to evaluate the role of P-glycoprotein in local antibiotic resistance in patients with antral gastritis during antibiotic therapy to Helicobacter pylori infection. In the group of 53 patients with pathohistologically verified gastritis and microbiologically confirmed H. pylori infection (no signs of antimicrobial resistance) we have determined P-glycoprotein activity in gastric mucosa biopsy specimens, and compared them with the P-glycoprotein activity in 12 control subjects with normal endoscopic findings. The H. pylori positive patients were treated according to Maastricht protocol with short-term 7-day therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor P-glycoprotein activity was determined in rhodamine dye efflux test and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. H. pylori was successfully eradicated in the first cycle in 20 patients, whereas therapy was continued in 33 patients. The mean pre-treatment RMF values were higher in patients with H. pylori infection then in control subjects (p < 0.0046). RMF was also higher in patients with multiple therapeutic failure than in those with successful H. pylori eradication (p < 0.0001). RMF increased significantly during the antibiotic therapy (p < 0.05). P-glycoprotein might be one of the causes of therapy failure in patients with H. pylori. Our study confirms the importance of quantitative evaluation of P-glycoprotein expression during antibiotic treatment response.

[Video capsule endoscopy--preliminary experience in university hospital setting]. / Endoskopska kapsula za tanko crijevo--pocetna iskustva u klinickoj bolnici.

INTRODUCTION: The use of video capsule endoscopy (VCE) started in late 2001 when it was approved by the Food and Drug Administration (FDA). Since then, we are able to visualize small bowel mucosa with a minimally invasive technique, very comfortable for patients, with very few complications and without the need of hospitalization. At Dubrava University Hospital, we have been using VCE since October 2006, and by February 2008 we examined 30 patients. AIM: The aim of the study was to present our preliminary results in the use of VCE during a period of one year and five months. We also report indications and contraindications for VCE, and patient preparation. METHODS: In this retrospective study we reviewed records on 30 patients that had undergone VCE at Dubrava University Hospital, Zagreb, Croatia, between October 2006 and February 2008. The indications for VCE were restricted to the investigation of obscure gastrointestinal bleeding (OGIB) (n = 10), iron deficiency anemia (n = 2), suspected Crohn's disease (n = 1), assessment of known small bowel Crohn's disease (n = 5), unexplained diarrhea (n = 6), chronic abdominal pain (n = 3), suspected ganglioneurinoma (n = 1) and suspected polyposis syndrome (n = 2). To be eligible for VCE, patients had to have previously undergone usual diagnostic methods of upper endoscopy, colonoscopy and small bowel follow-through, without discovering the cause of their symptoms. Before swallowing the capsule, patients were instructed not to eat anything the day before VCE and to drink 4 L of liquids, and additional 2 L magnesium sulfate. In all patients we used Olympus EndoCapsule Software (Tokyo, Japan). Results were interpreted by one specialist, gastroenterologist. RESULTS: Definitive diagnosis was made in 15 patients. Suspect findings were noted in 2 patients, whereas no diagnosis could be established in 13 patients. According to our experience, VCE is a promising new method that has a high diagnostic yield in patients with OGIB and known Crohn's disease. Use of VCE enabled definitive diagnosis to be made in 6 of 10 patients with OGIB after all previously used diagnostic methods had failed to reveal any pathological finding. In the group of OGIB patients, angiodysplasia was the most common findings (4 of 10 patients). In the group of patients with Crohn's disease, progression of the disease to neotherminal ileum was recorded in 3 of 5 patients. Our experience also confirmed the VCE to be a very safe method; capsule retention was recorded in only one patient. DISCUSSION: Although VCE enabled us to visualize the small bowel mucosa and therefore helped us establish the diagnosis in cases where other diagnostic methods had failed, it still has some important limitations, the major one being the impossibility to take biopsies and to perform any therapeutic procedures. However, it has a high diagnostic yield in cases of OGIB and Crohn's disease, is very comfortable for patients, and has a low incidence of complications (capsule retention). When making definitive diagnosis, one should always consider patient's history and physical examination findings as well as other possible causes of small bowel mucosal impairment. CONCLUSION: VCE is a promising new technique that has a high diagnostic yield in patients with OGIB and Crohn's disease. However, more studies need to be done to establish definitive indications, cost-effectiveness and the best way of patient preparation for VCE.

Informed consent for gastrointestinal endoscopy: a view of endoscopists in Croatia.

BACKGROUND/AIM: There are many differences and deficiencies in the process of informed consent. The aim of this study was to get the view of gastrointestinal endoscopists in Croatia on obtaining patients' consent before endoscopic procedures. METHODS: During the 2004 annual meeting of the Croatian Society of Gastroenterology, endoscopists were asked to answer a questionnaire according to common clinical practice in affiliated institutions. It included questions on endoscopists' experience and education in medical ethics, as well as on the nature and quality of information given to patients and their opinion on proposed measures for improvement of the informed consent process. RESULTS: The questionnaire was distributed to 96 endoscopists attending the meeting and the response rate was 54% (52/96). In only 50% of institutions was the obtained consent written and potential complications of endoscopic procedures are occasionally given to the patient. In the minority of cases the patient is provided with information about alternative diagnostic tests and/or treatment options, and the information about mortality rate was almost never discussed. CONCLUSIONS: In Croatia, the process of informed consent for endoscopy needs improvement and should be regarded against the background of education in medical ethics, regional burden in endoscopic practice and appropriateness of by-laws and local guidelines.

Ultrasound Grade of Liver Steatosis Is Independently Associated with the Risk of Metabolic Syndrome.

The aim of the study was to explore (a) prevalence and grade of nonalcoholic fatty liver (NAFL) among outpatients referred for abdominal ultrasound (US) examination and (b) relationship between the presence and severity of liver steatosis and metabolic syndrome (MS). This was a retrospective analysis of patients without history of liver disease examined by abdominal US in the University hospital setting. US was used to detect and semiquantitatively grade (0-3) liver steatosis. Data on patients' age, gender, body mass index (BMI), impaired glucose metabolism (IGM), atherogenic dyslipidaemia (AD), raised blood pressure (RBP), transaminases, and platelet counts were obtained from medical records. MS was defined as having at least 3 of the following components: obesity, IGM, AD, and RBP. Of the 631 patients (median age 60 years, median BMI 27.4 kg/m2, and 57.4% females) 71.5% were overweight and 48.5% had NAFL. In the subgroup of 159 patients with available data on the components of MS, patients with higher US grade of steatosis had significantly higher BMI and increased prevalence of obesity, IGM, AD, RBP, and accordingly more frequently had MS, whereas they did not differ in terms of age and gender. NAFL was independently associated with the risk of having MS in a multivariate model adjusted for age, gender, BMI, and IGM. The grade of liver steatosis did not correlate with the presence of liver fibrosis. We demonstrated worrisome prevalence of obesity and NAFL in the outpatient population from our geographic region. NAFL is independently associated with the risk of having MS implying worse prognosis.

[Is there any connection between angiotensin converting enzyme activity and liver cirrhosis of alcoholic genesis?]. / Postoji li povezanost izmedu serumske aktivnosti angiotenzin konvertirajuceg enzima i jetrene ciroze alkoholne geneze?

UNLABELLED: The objective of this study was to assess the serum angiotensin converting enzyme (ACE) activity in patients with liver cirrhosis caused by chronic alcohol consumption, in order to get better insight into the function of the renin-angiotensin system. PATIENTS AND METHODS: Serum level of ACE activity was measured by Neels spectrophotometry in 35 alcoholic liver cirrhosis patients classified according to Child-Pugh-Turcotte criteria and 35 dyspeptic patients with any liver disease excluded (control group). RESULTS: Serum values of ACE were statistically significantly higher (p < 0.00001) in the group of liver cirrhosis patients (x = 250.16 +/- 85.5 nmol) than in the control group (x = 115.88 +/- 58.19 nmol). The highest levels of ACE were measured in class B group of liver cirrhosis patients vs. class A and class B groups (p < 0.013). CONCLUSION: It is concluded that liver cirrhosis patients have elevated ACE levels, which coud be useful in the diagnosis and follow up of these patients.

Bleeding Peptic Ulcer - Tertiary Center Experience: Epidemiology, Treatment and Prognosis.

The aim of this study was to demonstrate epidemiological, clinical and endoscopic characteristics of acute upper gastrointestinal bleeding (UGIB) with special reference to peptic ulcer bleeding (PUB). The study included 2198 consecutive patients referred to our emergency department due to acute UGIB from January 2008 to December 2012. All patients underwent urgent upper GI endoscopy within 24 hours of admission, and 842 patients diagnosed with PUB were enrolled and prospectively followed-up. The cumulative incidence of UGIB was 126/100,000 in the 5-year period. Two out of five patients had a bleeding peptic ulcer; in total, 440 (52.3%) had bleeding gastric ulcer, 356 (42.3%) had bleeding duodenal ulcer, 17 (2%) had both bleeding gastric and duodenal ulcers, and 29 (3.5%) patients had bleeding ulcers on gastroenteric anastomoses. PUB was more common in men. The mean patient age was 65.9 years. The majority of patients (57%) with PUB were taking agents that attenuate the cytoprotective function of gastric and duodenal mucosa. Rebleeding occurred in 77 (9.7%) patients and 47 (5.9%) patients required surgical intervention. The 30-day morality was 5.2% and 10% of patients died from uncontrolled bleeding and concomitant diseases. In conclusion, PUB is the main cause of UGIB, characterized by a significant rebleeding rate and mortality.

Influence of various proton pump inhibitors on intestinal metaplasia in noneradicated Helicobacter pylori patients.

AIM: Intestinal metaplasia (IM) is more often found in patients with Helicobacter pylori (H pylori) infection, while eradication of H pylori results in significant reduction in the severity and activity of chronic gastritis. We aimed to determine in patients with unsuccessful eradication of H pylori the role of various proton pump inhibitors (PPIs) having different mechanisms in the resolution of IM. METHODS: We confirmed endoscopically and pathohistologically (Sydney classification) the IM in 335 patients with gastritis before and after medication for eradication of H pylori (Maastricht Protocol 2002). H pylori infection was determined by using histology, urease test and culture. Control endoscopy and histology were done after 30 d and thereafter (within 1 year). Unsuccessful eradication was considered if only one of the three tests (histology, urease and culture) was negative after therapy protocol. We used omeprazole, pantoprazole, lansoprazole in therapy protocols (in combination with two antibiotics). RESULTS: We found no significant difference in resolution of IM by using different PPI between the groups of eradicated and noneradicated patients (P<0.4821 and P<0.4388, respectively). CONCLUSION: There is no significant difference in resolution of intestinal metaplasia by different proton pump inhibitors.

Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection.

AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug out-pumping during Helicobacter pylori (H pylori) infection treatment with classic antibiotic therapy. METHODS: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. The H pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF). RESULTS: Upon the first cycle, H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P<0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P<0.0001) in patients with multiple therapeutic failure than in those with successful H pylori eradication and control subjects. CONCLUSION: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.

Elevated serum values of procollagen III peptide (PIIIP) in patients with ulcerative colitis who will develop pseudopolyps.

AIM: To assess the impact of procollagen III peptide as a marker of collagenesis in the development of pseudopolyps in patients with ulcerative colitis. METHODS: Development of pseudopolyps was monitored in 25 patients with ulcerative colitis classified according to Powell-Tuck index as mild (n=12) or moderate (n=13) form of disease. Patients with a mild form of disease were treated with oral mesalazine medication (2-4 g/day) and local mesalazine preparation (suppository). Patients with a moderate form of disease received oral mesalazine medication (2-4 g/day), local mesalazine preparation (suppository) and local methylprednisolone at an initial dose of 60 mg/day, followed by dose tapering. How many significant variables (previously determined by analysis of variance) were elevated in the groups with and without pseudopolyp developement was observed. ROC analysis for calculation of new index was made. RESULTS: Serum values of procollagen III peptide (PIIIP), C-reactive protein (CRP) and C4 complement component (C4) were statistically significantly lower in the group of patients free from pseudopolyp development than those who developed one or more pseudopolyps (0.45+/-0.12 vs 1.42+/-0.70, P<0.0027; 7.6+/-4.7 vs 17.8+/-9.17, P<0.035; and 0.46+/-0.11 vs 0.34+/-0.16, P<0.068, respectively) at endoscopic conrtrols with patohistologically samples during 13 months. There were no statistically significant differences in the values of C3, ceruloplasmin and IgM between the two groups (P>0.05). Discrimination function analysis yielded highest standardized cannon coefficients for PIIIP (0.876), CRP (0.104), C3 (-0.534) and C4 (0.184) (P<0.036). The elevation in two of three laboratory variables (PIIIP, CRP and C4) reached sensitivity of 93 % and specificity of 90 % in the development of pseudopolyps. CONCLUSION: It is proposed that an increase in two of the three laboratory parameters (PIIIP, CRP and C4) could improve the accuracy of prediction of the development of pseudopolyps. When using PIIIP, CRP and C4 on decision making, the positive predictive value and accuracy were 90 % and 92 %, respectively.

Predictive role of serum procollagen III peptide and Knodell's index in survival prognosis of patients with hepatitis B virus liver cirrhosis.

OBJECTIVE: The objective of the study was to improve the accuracy of survival prognosis in patients with liver cirrhosis using procollagen III peptide (PIIIP), as a marker of inflammation and fibrogenesis, and Knodell's histologic activity index (KI) in addition to previously used prognostic factors. PATIENTS AND METHODS: Five-year survival was followed in a group of 75 patients with hepatitis B virus (HBV) liver cirrhosis (patients testing anti-HBe positive and HBV-DNA negative). There were 31 patients with compensated cirrhosis and 44 with decompensated cirrhosis. The diagnostic procedure included clinical, laboratory, ultrasound and pathohistologic examination. We combined PIIIP and KI with other significant variables to achieve the highest possible sensitivity, specificity and accuracy for survival prognosis in HBV liver cirrhosis. The models were compared using ROC analysis. RESULTS: At the end of the five-year period of survival follow-up, there were 39 survivors and 36 patients had died (only three died from an extrahepatic cause). In the quantitative model, the discriminant canonical function (DCF) identified PIIIP, bilirubin, prothrombin time, ascites and KI as statistically significant parameters in the prognosis of five-year survival. Calculation of the score based on DCF yielded an accuracy of 89.3%. In the semiquantitative model, the analysis of variance identified PIIIP, bilirubin, albumin, pro-thrombin time, alkaline phosphatase, ascites and KI as significant variables. When PIIIP was added to the clinicohistologic diagnosis, Child-Pugh score and KI, the level of accuracy improved by 12% (from 78% to 90%), 11% (from 79% to 90%) and 10.6% (from 80% to 90.6%), respectively. When calculated with the three biochemical parameters (alkaline phosphatase, PIIIP and bilirubin) and KI identified by DCF, the accuracy was 90.6%. CONCLUSION: Combining PIIIP and KI with other prognostic parameters is useful in achieving a better precision of survival prognosis in patients with HBV liver cirrhosis.