الفهرس 
Hepatitis B VirusOnly 14 pages are availabe for public view
Abstract
Hepatitis B virus infection is a major public health problem worldwide; roughly 30% of the world’s population show serological evidence of current or past infection (Christian et al., 2014). HBV is hyperendemic in Africa as more than 8% of the general population are chronic carriers with Hepatitis B surface antigen (HBsAg) in some sub-Saharan countries as Nigeria. While the north African countries as Egypt, Tunisia and Morocco show less affection and low endemicity level (< 2%) (Rosa et al., 2015)
Hepatitis B virus (HBV) is considered one of the most significant public health challenges due to its chronicity and complications that happen after several years of infection. approximately 15-40% of infected patients suffer from HBV complications as cirrhosis, liver cell failure, hepatocellular carcinoma (HCC) and death in almost one million people every year (Nicolini et al., 2019)
The main event in HBV effect is its recognition as a foreign antigen which activates the immunity to target and destroy infected cells, hence HBV is not a cytotoxic virus. This destruction happens intermittently through the course of chronic infection leading to inflammation and necrosis of the liver tissue. The repetition of these periods of liver injury yields liver fibrosis and hepatocellular carcinoma (Tang et al., 2018).
HBV DNA integration plays a role in escaping the immune response via modulation of HBV transcription. Integrated forms are known to express both wild-type and mutant versions of the HBsAg. it could be a mechanism for persistence by maintaining liver expression of HBsAg, while not producing HBeAg that is targeted by the anti-viral immune response as the anti-HBe antiviral response intensifies, clonal expansion of hepatocytes would increase the number of cells containing integrated HBV that express immunosuppressive HBsAg proteins, thereby creating a new equilibrium where HBV is still persistent within the liver (Tu et al., 2017).
Chronic HBV infection can lead to liver fibrosis and cirrhosis due to episodes of highgrade liver inflammation and activation of the fibrogenic processes. If untreated, these can be complicated by decompensated liver disease and/or development of hepatocellular carcinoma due to the additional oncogenic potential of HBV after integration into the host genome. Nearly 25% of untreated individuals with chronic HBV infection will die of cirrhosis complications and/or HCC (Yeun et al., 2018).
A lot of complications can be caused by HBV infection which can be intrahepatic as acute hepatitis, chronic hepatitis, fulminant liver Failure, liver cirrhosis and Hepatocellular carcinoma. While extrahepatic manifestations can complicate acute or chronic Hepatitis. The pathophysiology of these associated complications is mainly based on immune complex reactions that occur in the skin, joints, muscles, and kidneys (Kappus and Sterling., 2013)
Chronic hepatitis B is diagnosed by the persistence of HBsAg for more than six months. The initial evaluation of individuals with chronic hepatitis B includes a complete history and examination focused on signs and symptoms of cirrhosis, evaluation of alcohol intake and metabolic risk factors, family history of HCC, and hepatitis A and B vaccination status. Laboratory measurements include a complete blood count with platelets, AST, ALT, total bilirubin, alkaline phosphatase, albumin, and INR. Serology testing includes HBeAg, antiHBe, HBV DNA quantitation or viral load, HBV genotype, and anti–hepatitis A virus to determine the need for vaccination. Testing for coinfection with hepatitis C virus and HIV is recommended (Wilkins et al., 2019). Assessment of the fibrosis and cirrhosis status in patients with chronic HBV infection is also important for disease prognostication, treatment indication and management. An accurate but invasive test of liver disease is liver biopsy, whereas noninvasive tests include transient elastography (to measure liver stiffness) or various serum biomarker (Yeun et al., 2018).
The goals of treatment are to decrease mortality due to liver disease, improve survival by preventing the progression of liver fibrosis to cirrhosis and preventing HCC. The aims of anti-HBV treatment include ALT normalization, undetectable serum HBV DNA, serum HBeAg loss or seroconversion, and serum HBsAg loss or seroconversion Specifically, serum HBsAg loss or seroconversion is proposed as an ideal endpoint for CHB treatment (Yim et al., 2020)
All patients considered for treatment with a NA with high barrier to resistance (ETV, TDF, TAF) should undergo periodical monitoring. At baseline, full blood count, liver, and kidney (eGFR and serum phosphate levels) function tests, serum HBV DNA levels assessed by a sensitive PCR assay should be performed. During treatment, liver function tests should be performed every 3–4 months during the first year and every six months thereafter. Serum HBV DNA should be determined every 3– 4 months during the first year and every 6–12 months thereafter. HBsAg should be checked at 12-month intervals if HBV DNA remains undetectable, while patients who clear HBsAg should be tested for anti-HBs (EASL 2017).
Hepatic fibrosis is an intermediate stage in the progression of chronic hepatic disease from mild hepatitis to decompensated cirrhosis. Therefore, timely and accurate assessment of hepatic fibrosis stage is helpful to determine the optimal treatment plan to minimize and delay the progression of liver injury. Although liver biopsy is the gold standard for evaluating the stage of liver fibrosis, it is invasive, expensive, and accompanied by potential complications and sampling errors. Transient elastography (FibroScan) is a new non-invasive test that can replace biopsy, and it has been widely recommended by the guidelines on HBV management for assessing the stage of hepatic fibrosis. the optimal diagnostic LSM values of FibroScan for significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 7.3 kPa, 9.7 kPa , and 11.3 kPa respectively (Huang et al., 2021).
A full blood count is a routine, automated, inexpensive, easy test that provides information about red and white cells as well as platelets. The platelet-lymphocyte ratio (PLR) is calculated as the ratio of the platelet to lymphocyte count. The plateletlymphocyte ratio (PLR) is a novel inflammatory marker, which may be used in many diseases for predicting inflammation and mortality. The PLR can be easily calculated and is widely available, but it may be affected by several inflammatory conditions (Balta and Ozturk, 2014)
Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have attracted attention as inflammatory biomarkers. It can be used also as a novel noninvasive marker to predict advanced disease in non-alcoholic steatohepatitis. However, there are few studies conducted to assess APRI or NLR for predicting the fibrosis stage of patients with HBV-related fibrosis and inflammation. marker for systemic inflammation. Lymphomononuclear cells play a fundamental role in inflammatory pathways during the development of cirrhosis. It was noted that the lymphocyte count was markedly higher in patients with significant fibrosis compared with patients with no/minimal fibrosis. It can reflect the mononuclear inflammation occurring at the tissue level. Thus, it was found NLR of the significant fibrosis were lower (Altun et al., 2017)
We aim to correlate hepatitis B viral replication, liver function tests and liver fibrosis to platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) and follow up treatment response of HBV with PLR and NLR
This prospective study was conducted on 60 patients with HBV eligible for antiviral treatment with Nucleot(s)ide agents, agreeable to regular follow up, recruited from Ain Shams University virology center in Cairo during the period from January 2022 to January 2023, after informed consents were taken from the patients and agreement for follow up
Our study demonstrates that PLR and NLR are lower in cirrhotic patients in the 2 studied periods than normal liver patients and the correlation between PLR and Liver texture in the two studies periods show statistical significant difference with p value <0.001. while NLR does not show any statistical significant difference. These were confirmed with the correlation between PLR and NLR with fibroscan as it shows inverse correlation between fibrosis stages in fibroscan with PLR and NLR in patients before treatment and 6 months after treatment initiation. Only the correlation between PLR and Fibroscan show statistical significant difference with p value < 0.001 before and after treatment. (Ding et al., 2021) Found that as liver fibrosis histological scores increased, PLR and NLR decreased with Spearman’s correlation analysis presented that PLR (r = −0.372) and NLR (r = −0.194),
That concludes to the presence of statistically significantly reverse correlations between the PLR values and liver fibrosis However performances of NLR to predict liver fibrosis showed lower statistical significance.
We did not find any statistical significance in the correlation between PLR and NLR with HBV DNA PCR or liver function tests in patients before treatment and 6 months after treatment intitiation.
Conclusions
Our study concluded that PLR partially correlated with HBV DNA but strongly correlated with fibrosis stage in fibroscan with an inverse correlation and can be used as a marker of fibrosis. While NLR neither correlates with HBV DNA nor fibrosis stage in fibroscan and cannot be used as a marker of fibrosis
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Recommendations
• Prolong the duration of follow up of patients during treatment
• Increase the sample size.
• Investigate HDV infection.