Diagnostic Value of Serum Procalcitonin Level in HCV Cirrhotic Patients with Spontaneous Bacterial Peritonitis

INTRODUCTION

Hepatitis is an inflammatory condition of the liver that may be caused by a virus (viral hepatitis). When persisting for years, it may progress to lethal conditions, such as cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C is also a systemic disease affecting the whole body causing a multitude of extrahepatic manifestations. Viral hepatitis is the seventh most frequent cause of death in the world, surpassing HIV.¹Among the five viral agents capable of causing hepatitis, hepatitis C virus (HCV) is one of the deadliest, causing some 400,000 deaths annually.²Globally, there are an estimated 71 million people actively infected with HCV, and 11-14 million of them reside in Europe.³

Bacterial infections account for significant morbidity and mortality in end-stage liver disease (ESLD) patients. Spontaneous bacterial peritonitis (SBP) is the most frequent and life-threatening infection in these patients.⁴ Cirrhotic patients with SBP frequently develop a rapidly progressive impairment in systemic hemodynamics, leading to severe renal and hepatic failure, aggravation of portal hypertension, encephalopathy, and death.⁵ When first described, its mortality exceeded 90%, but it has been reduced to  20% with early diagnosis and treatment.⁶

Early diagnosis of SBP is essential in hospitalized patients with liver disease; however, this presents a challenge for clinicians because of the frequent lack of symptoms in the early stages of SBP.⁷ At present, most guidelines recommend that a diagnostic paracentesis should be performed in all patients with ascites admitted to hospital regardless of whether or not there is clinical suspicion. Diagnosis is established by an ascites polymorphonuclear cells (PMN) count >250 cells/mm.⁸

Although paracentesis is usually a safe procedure, complications may occur from time to time. It has been reported that abdominal wall hematomas in 1% of patients, and even more severe complications such as hemoperitoneum or bowel penetration by the needle occurred in 1 case per 1000 paracenteses.⁹ In rare cases, pathogenic bacteria such as staphylococci can be introduced along with the needle to the ascites. It is therefore clear that using blood for routine examinations is more convenient and safer than ascitic fluid, and the measurement of serum biomarkers has consequently received much attention recently for the early diagnosis of SBP.¹⁰

Procalcitonin (PCT) is a precursor of calcitonin, normally secreted by C cells of the thyroid in healthy individuals. In the absence of infection, the extra-thyroidal expression of the PCT gene in the liver, lung, kidney, adrenal tissue, monocytes, granulocytes, testis, prostate gland, and small intestine is suppressed.¹¹ Procalcitonin in the blood of healthy individuals is below the limit of detection of clinical assays, but microbial infection, especially of bacterial origin, induces a ubiquitous increase in PCT gene expression, resulting in the constitutive release of PCT from parenchymal tissues throughout the body. In bacterial infections, serum PCT levels start to rise 4 h after the onset of systemic infection and peak between 8 and 24 h.16 The half-life of PCT in serum is 20 to 24 h, which makes it suitable for early detection and daily monitoring.¹¹

PATIENT AND METHODS

A prospective case control study was conducted on 60 post-HCV cirrhotic patients and 20 normal individuals (54 M and 26 F), at internal medicine department, Zagazig General Hospital. All subjects signed an informed written consent after explanation of the aim of the study and the study details. They were divided into four main groups: Group I:Included 20 post-HCV cirrhotic ascitic patients with Spontaneous bacterial peritonitis. Group II:Included 20 post-HCV cirrhotic ascitic patients without Spontaneous bacterial peritonitis. Group III:(negative control)Included 20 post-HCV cirrhotic patients without ascites. Group IV:(negative control)Included 20 normal individuals.The study was approved by the ethical committee of Al Azhar Faculty of Medicine and an informed consent obtained from all subjects before the study was commenced.

The subjects included in this study were selected according to inclusion and exclusion criteria. Inclusion criteria: Post-HCV cirrhotic patients. All patients and participants have normal kidney functions (serum urea and creatinine levels).Exclusion criteria: Patients who were co-infected with HBV, Patients with thrombosis of the portal or supra hepatic veins or IVC, Patients who have Other co- morbidity that might affect portal pressure, Patients with DM, HTN, CKD, thyroid diseases, and malignancy, Patients who had undergone surgery for the correction of portal hypertension, gastrectomy's, and/or vagotomies, Patients with any ongoing infection other than SBP, Patients with ongoing ingestion of alcohol, patients with gastrointestinal malignancy, or hepatocellular carcinoma, patients who refuse to participate in the study and dropped out patients.

Method of Sampling: Sample size was calculated using computer sample block randomization type. Samples were obtained during routine investigations. 5 CC sample of venous blood drained by sterile syringes, put in a tube containing dipotassium EDTA reagent, the sample were shaken gently and analyzed by (Medonic 20, Sweden).All patients included in the study were subjected to:Complete history taking: which included past history of encephalopathy, SBP, hematemesis, hematochezia, melena, endoscopic or surgical intervention of varices, cardiac and chest symptoms. Full Clinical Examination: which included cardiac, chest, manifestations of chronic liver disease (such as jaundice, flapping tremors, lower limb edema, organomegaly or ascites).

Diagnostic paracentesis for ascites fluid analysis. (count of PMN), and culture (groups 1, 2). Urine analysis, Chest x ray.

Investigations: HCV IgG antibodies (HCV Ab). Hepatitis B surface antigen (HBsAg).

Serum procalcitonin level. Complete blood picture (CBC): including hemoglobin concentration (Hb %), red blood cells (RBCs), white blood cells (WBCs), platelet count using Sysmex KX-21 automatized hematology analyzer (Sysmex corporation, Japan).Liver profile: alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, total bilirubin and direct bilirubin, prothrombin time and INR. measured using a bio chromatic (405- 510 nm) rate technique. Renal function tests: including blood urea and serum creatinine using the open system autoanalyzer synchron CX5 (Beckman USA). Tumor markers: AFP.CRP and ESR. All patients were submitted to abdominal ultra-sonographic examination for the liver (size, surface, echogenicity, focal lesions and biliary tree), Portal and splenic vein diameters and patency, Splenic size, ascites, and abdominal masses.

Statistical Analysis: Results were tabulated and statistically analyzed by using a personal computer using MICROSOFT EXCEL 2016 and SPSS v. 21 (SPSS Inc., Chicago, IL, USA. Statistical analysis was done using: Descriptive: e.g. percentage (%), mean and standard deviation. Analytical: that includes: ANOVA F test. A value of P less than 0.05 was considered statistically significant.

RESULTS

The average age was 58.2±6.1 years for group 1, 60.3±4.4 years for group 2, 53.9±4.8 years for group 3, and 50.2 ±7.0 years for group 4. The majority of patients were males that represent 60 % for group 1, 70 % for group 2, 65 % for group 3 and 75 % for group 4, with no statistically significant difference (p-value > 0.05) between all groups as regard age and gender, (Figure 1). Also, no definitive source of infection was found other than SBP for group 1. While, ascetic fluid analysis and culture for patients in groups 1 and 2 revealed that all patients in group 1 have SBP (PMN count >250 c/mm, and all patients in group 2 have sterile ascites (PMN count

Tables

Fig. 1: Description of age and gender of studied patients and participants

Table 1: Description of U/S findings of studied patients and participants

Data presenting in table 1 shows that, Highly statistically significant difference (p-value < 0.001) between groups 1, 2, 3 and group 4 according to liver cirrhosis, and between groups 1,2 and groups 3, 4 according to ascites. The U/S findings of studied patients and participants. As regard liver, all patients of group 1, 2 and 3 are cirrhotic, and all participants of group 4 are normal. As regard ascites, 15 patients of group 1 have tense ascites and 5 have moderate ascites, 10 patients of group 2 have tense ascites and 10 have moderate ascites, and all patients and participants of group 3 and 4 are not ascitic.

Fig. 2: Description of ALB of the studied patients and participants.

Fig. 3: Description of total of the studied patients and participants.

Fig. 4: Description of ALT of the studied patients and participants.

Fig. 5: Description of AST of the studied patients and participants.

Fig. 6: Description of INR of the studied patients and participants.

Table 2: Description of (PCT) results of the studied patients and participants.

Table 2 shows that Highly statistically significant difference (p-value < 0.001) between all groups according to PCT. PCT is positive in 95% of patients of group 1, and negative in 95% of patients of group 2,3 and participants of group 4.

Fig. 7: Description of PCT results of the studied patients and participants.