SUMMARY. Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT). Liver biopsy (LB) is the current gold standard for assessing hepatic inflammation and fibrosis in patients with chronic HBV. However, associated risks have led to the development of noninvasive models. Their utility in patients with normal ALT is unknown. FIB-4 and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) were calculated for patients with chronic HBV infection undergoing biopsy. The performance of each model and AUROC for predicting significant fibrosis (Scheuer's score ! S2) were determined for the entire cohort and stratified by elevated ( ! 50 U/L) and normal ALT. Twohundred and thirty-one liver biopsies were included. The number of patient with normal ALT was 140, and 22.1% had significant fibrosis. The AUROC curve for patients with normal ALT was 0.81 for FIB-4 and 0.80 for APRI, compared with 0.71 for FIB-4 and 0.72 for APRI for those with mildly elevated ALT level. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FIB-4 were 0.63, 0.88, 0.61 and 0.93, for patients with normal ALT; the values for APRI were 0.40, 0.88, 0.33 and 0.93. Both FIB-4 and APRI are useful for identification of those without significant fibrosis. However, because they have poor PPV, LB will continue to be used for assessment of HBV-infected patients with normal ALT and mildly elevated ALT.

Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer's classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT, lower platelet count and HBV DNA < 7 log10copies/mL may have histologically significant changes associated with liver disease. Multivariate analysis showed that PLT and HBV DNA levels were significantly associated with liver disease in patients with normal ALT while gender and HBV DNA levels were significantly associated with liver disease in patients with mildly elevated ALT. Assessing liver damage via biopsy in patients with normal or mildly elevated ALT may help to identify those who would benefit from antiviral therapy.

Among patients presenting with low HBV DNA levels and normal ALT levels, about 38.2% had significant liver disease. Neither serum HBsAg nor HBV DNA levels correlate with liver histology. However, APRI≥0.24 might be considered an indicator of liver biopsy.

The proposed fibrosis scoring system predicted the probability of significant fibrosis in CHB patients with ALT levels 2-fold lower than the ULN with sufficient accuracy. It identified individuals with a very high risk for significant fibrosis in whom liver biopsy would most likely yield a diagnostic benefit. It also identified individuals with a low risk of moderate fibrosis in whom a liver biopsy can be delayed or avoided.

Background and aim: The outbreak of coronavirus disease 2019 (COVID-19) is quickly turning into a pandemic. We aimed to further clarify the clinical characteristics and the relationship between these features and disease severity. Methods: In this retrospective single-center study, demographic, clinical and laboratory data were collected and analyzed among moderate, severe and critically ill group patients. Results: 88 hospitalization patients confirmed COVID-19 were enrolled in this study. The average age of the patients was 57.11 years (SD, ±15.39). Of these 88 patients, the median body mass index (BMI) was 24.03 (IQR, 21.64-26.61; range 15.05-32.39), the median duration from disease onset to hospital admission were 11 days (IQR, 6.50-14.50). 46.59% patients had one or more comorbidities, with hypertension being the most common (26.14%), followed by diabetes mellitus (12.50%) and coronary atherosclerotic heart disease (CAD) (7.95%). Common symptoms at onset of disease were fever (71.59%), cough (59.09%), dyspnea (38.64%) and fatigue (29.55%). 88 patients were divided into moderate (47 [53.41%]), severe (32 [36.36%]) and critically ill (9 [10.23%]) groups. Compared with severe and moderate patients, lymphocytopenia occurred in 85.71% critically ill patients, and serum IL-2R, IL-6, IL-8, TNF-α, LDH, and cTnI were also increased in 71.42%, 83.33%, 57.14%, 71.43%, 100% and 42.86% in critically ill patients. Through our analysis, the age, comorbidities, lymphocyte count, eosinophil count, ferritin, CRP, LDH, PT and inflammatory cytokines were statistically significant along with the disease severity. Conclusion: We found some clinical characteristic and inflammatory cytokines could reveal the severity of COVID-19 during the outbreak phage. Our research could assist the clinicians recognize severe and critically ill patients timely and focus on the expectant treatment for each patient.

The present digital imaging analysis technique is reproducible and available worldwide, allowing its use in clinical practice, and can be considered as a complementary tool to traditional histological methods.

Purpose: Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury in reports worldwide. But no studies to date have described hypoxic hepatitis (HH) in patients with COVID-19. We aim to identify the prevalence of and possible mechanisms of HH in COVID-19 patients in the Intensive Care Unit (ICU).Methods: This retrospective study was conducted on 51 patients with confirmed SARS-CoV-2 infection in the ICU at Zhongnan Hospital of Wuhan University from December 21, 2019, to March 11, 2020. Information on clinical features of enrolled patients was collected for analysis.Results: HH was observed in 5.88% of the ICU patients with SARS-CoV-2 infection. All HH patients were progressing to respiratory failure and peak alanine aminotransferase (ALT) values were 1665, 1414, and 1140 U/L during hospitalization, respectively. All patients with HH died as a result of the deterioration of multiple organ failure (MOF). The dynamic changes of ALT, aspartate transaminase (AST), and total bilirubin (TBIL) levels were more dramatic in HH groups. Levels of TBIL, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6(IL-6) showed statistically significant elevation in HH cases compared with that in non-HH cases (P &lt; 0.001). Besides, the median survival time of the HH group was significantly shorter than the non-HH group (P &lt; 0.05).Conclusions: In ICU, HH was not a rare condition in patients with severe COVID-19 and has a high mortality. The main causes of HH are respiratory and cardiac failure and may be associated with the immune-mediated inflammatory response. Clinicians should search for any underlying hemodynamic or respiratory instability even in patients with normal ALT levels on admission.

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