(1) Background/Aim: People infected with SARS-CoV-2 may develop COVID-19 in a wide range of clinical severity. Pulmonary fibrosis is characterized by several grades of chronic inflammation and collagen deposition in the interalveolar space. SARS-CoV-2 infection has been demonstrated to cause lung fibrosis without a currently elucidated mechanism. Some studies emphasize the role of proinflammatory cytokines. This research studies the correlation of the released cytokines with mortality or lung injury in COVID-19 patients. (2) Methods: Electronic medical record data from 40 patients diagnosed with COVID-19 in the COVID-19 Department, Galilee Medical Center, Nahariya, Israel, were collected. Epidemiological, clinical, laboratory, and imaging variables were analyzed. The cytokine levels were measured upon admission and discharge. A correlation between cytokine levels and severity and mortality or lung involvement was undertaken. (3) Results: IFN-gamma and IL-10 are the most powerful risk factors for mortality in the COVID-19 patient groups in a multivariate analysis. However, in a univariate analysis, TGF-β, CXCL-10, IFN gamma, and IL-7 affected mortality in COVID-19 patients. MMP-7 was significantly correlated with a cytokine storm and a high 4-C (severity) score in COVID-19 patients. MMP-7, TGF-β, IL-10, IL-7, TNF-α, and IL-6 were correlated with high lung involvement in COVID-19 patients. Serum concentrations of IGF-1 were significantly increased upon discharge, but MMP-7 was decreased. (4) Conclusions: Proinflammatory cytokines predict clinical severity, lung fibrosis, and mortality in COVID-19 patients. High concentrations of TGF-β, CXCL-10, IL-10, IL-6, and TNF-α are correlated to severity and lung injury. However, certain cytokines have protective effects and higher levels of these cytokines increase survival levels and lower lung damage. High levels of INF-γ, IL-7, MMP-7, and IGF-1 have protection probabilities against lung injury and severity.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with a continuously growing prevalence. The pathophysiology of the disease is complex and includes several mechanisms, with metabolic syndrome and insulin resistance playing a major role. It is crucial to diagnose NAFLD before it advances to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis, presented by its complications which include ascites, portal hypertension, bleeding varices and encephalopathy. Another important complication of NAFLD and cirrhosis is hepatocellular carcinoma (HCC), a cancer with increasing incidence and poor prognosis. Even with the growing prevalence of NAFLD, diagnosis via liver biopsies is unrealistic, considering the costs and complications. Noninvasive tests, including serum biomarkers and elastography, are cost-effective and convenient, thereby replacing liver biopsies in diagnosing and excluding liver fibrosis. However, currently, these noninvasive tests have several limitations, such as variability, inadequate accuracy and risk factors for error. The limitations and variability of these tests comet the investigator to propose combining them in diagnostic algorithms to produce more accurate tools. Identifying patients with significant fibrosis is important for targeted therapies to prevent disease progression. Effective screening using noninvasive tests can be crucial for patient risk stratification and early diagnosis.

Sepsis is a life-threatening complication among patients with liver cirrhosis and is associated with high morbidity and mortality. Early diagnosis is challenging due to immune dysfunction, chronic systemic inflammation, and overlap between clinical and laboratory findings during infection and hepatic decompensation. Therefore, there is a need to identify routinely available predictors that may enable the stratifying of patients at risk of developing sepsis in this population and facilitate intensive monitoring, antibiotic treatment, and potentially reduce mortality. The aim of this study is to evaluate the association between routine laboratory parameters and the development of sepsis among cirrhotic patients. A total of 171 cirrhotic patients met the inclusion criteria and were followed at a tertiary liver clinic between February 2015 and February 2022. Sepsis was defined according to Sepsis-3 criteria. Univariate analyses were performed to compare sepsis patients versus non-sepsis patients. Multivariable logistic regression was conducted to identify independent predictors of sepsis. Among 171 patients, 41 (24%) developed sepsis and 130 (76%) did not. Baseline characteristics were similar between groups: patients with sepsis were slightly older (67.5 ± 10.9 vs. 64.5 ± 12.3 years, p = 0.172), with no significant differences in sex (53.7% vs. 56.2%, p = 0.78) or ethnicity (Arab ethnicity 56.1% vs. 39.1%, p = 0.055). Ascites was more frequent in the sepsis group (53.7% vs. 26.2%, p = 0.001), whereas esophageal varices were less common (12.2% vs. 35.4%, p = 0.006). Rates of hepatic encephalopathy and acute kidney injury did not differ significantly. Higher creatinine (1.35 (0.80–3.35) vs. 0.80 (0.70–1.49) mg/dL, p < 0.001), INR (1.50 (1.20–1.80) vs. 1.30 (1.10–1.50), p = 0.011), and total bilirubin (1.90 (0.61–2.85) vs. 0.90 (0.59–1.70) mg/dL, p = 0.049) was observed in the sepsis group. In the multivariable model including age, sex, ethnicity, ascites, esophageal varices, INR, creatinine, neutrophil-to-lymphocyte ratio, and CRP, baseline serum creatinine was the only independent predictor of sepsis (adjusted OR 1.58 per 1 mg/dL increase, 95% CI 1.08–2.33, p = 0.01). Receiver operating characteristic (ROC) analysis demonstrated that the multivariable model had acceptable discriminative ability for prediction of sepsis, with an area under the curve (AUC) of 0.741 (95% CI 0.647–0.835). Among ambulatory patients with liver cirrhosis, baseline serum creatinine was independently associated with the development of sepsis. These findings highlight the need for dedicated risk-stratification tools in the outpatient setting. Further external validation in independent cohorts is required.