Coronavirus disease 19 (Covid-19): A comparative study of pattern of liver injury in adult patients in different waves of Covid-19 infection.

BACKGROUND AND STUDY AIMS: Liver dysfunction is a common manifestation of the COVID-19 infection. We aimed to study transaminase abnormalities through different waves of COVID-19 and their relations to disease severity or mortality. PATIENTS AND METHODS: A retrospective study included 521 Egyptian patients diagnosed with COVID-19. Data was retrieved from the medical records of patients who were admitted from April 2020 to October 2021 in Kasr Al-Ainy Hospitals, Cairo University, with categorization according to disease severity in correspondence to the four waves. RESULTS: The median age was lower in the first wave compared to other waves, with male predominance across all waves. The most commonly encountered comorbidity overall was hypertension, followed by diabetes mellitus. White blood cells, ferritin, and interleukin-6 showed the highest median values in the second wave, with significantly higher median C-reactive protein on day 1 in the first wave. Forty percent of the patients showed elevated hepatic transaminases on admission in four waves, with no statistically significant difference between waves. On day 5, around half of the patients had elevated transaminases, with no significant difference between waves. Most CT findings were of moderate severity. Clinical severity was higher in the second wave. It was observed that the higher the disease severity, the greater the proportion of patients with elevated hepatic transaminases. The mortality rate was markedly high in cases who had elevated ALT or AST on day 5. The association between elevated enzymes on admission and mortality was seen in the first wave only, with a fatality rate of 22.5% in cases with increased baseline ALT and AST versus 5% in those with normal baseline enzymes. CONCLUSION: There was no significant difference in transaminases between the four waves. Elevated transaminases were positively associated with increased mortality and severity, reflecting their prognostic value.

Multidrug resistance Gene-1 polymorphisms (C3435T and G2677T) and the risk of inflammatory bowel disease in Egyptian patients.

BACKGROUND AND STUDY AIMS: The multidrug resistance 1 (MDR1) gene is a gene involved in the pathogenesis of inflammatory bowel disease (IBD).The aim of the study is to investigate the association of MDR-1 gene polymorphisms (C2345T and G2677T) and IBD incidence in Egyptian patients, and its relation with disease severity. PATIENTS AND METHODS: This is a case-control study where genotyping of MDR-1 gene C3435T and G2677T single nucleotide polymorphisms (SNPs) were assayed. RESULTS: Forty naïve IBD patients, who were composed of 25 UC and 15CD, were compared to 60 healthy controls. They were young aged with significant female predominance, particularly in CD (P = 0.004). UC was mainly (48 %) presented in moderate severity while CD was mainly (53.3 %) presented with mild severity. MDR-1 gene C3435T SNP was not statistically related to IBD, whether in terms of genotypes or alleles, yet its T allele was significantly related to moderate cases of UC (P = 0.014). However, GG genotype of G2677T SNP was significantly low in IBD (P = 0.013), while TT genotype and T allele were significantly related to CD (P = 0.011, and 0.012 respectively). Moreover, G allele proved to be associated significantly with moderate cases of UC (P = 0.001) and mild cases of CD (P = 0.002). CONCLUSIONS: MDR-I gene G2677T SNP GG genotype proved to be protective against IBD, thus may be considered in diagnostic workup of IBD including its severity.

Schistosoma mansoni infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade.

Schistosoma mansoni infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187-2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.

Increased liver stiffness by transient elastography and acoustic radiation force impulse imaging in patients with extrahepatic cholestasis.

BACKGROUND: Transient elastography and acoustic radiation force impulse (ARFI) imaging are noninvasive tools for liver stiffness measurement (LSM), which may be influenced by cholestasis. AIM: The aim of the study was to evaluate the performance of transient elastography and ARFI in extrahepatic cholestasis and correlate changes in LSM with biochemical activity. MATERIALS AND METHODS: A total of 38 patients with extrahepatic cholestasis prospectively underwent transient elastography and ARFI. Changes in LSM by transient elastography/ARFI were evaluated after 1 week of ERCP and correlated with biochemical parameters. The optimal ARFI cutoffs according to stages of clinical interest were analyzed. RESULTS: Biliary obstruction was calcular in 21 (55.3%) and noncalcular in 17 (44.7%) (benign n = 15, malignant n = 2). After 1 week, adequate biliary drainage reduced total bilirubin from 7.7 to 2.2 mg/dL (P < 0.001) which significantly correlated with reduction of LSM by transient elastography from 12.38 ± 6.68 kPa to 8.08 ± 3.21 kPa (P < 0.001), and by ARFI from 1.73 ± 0.51 m/s to 1.56 ± 0.70 m/s (P = 0.014). The LSM percentage change showed a decrease (nonsignificant, P = 0.843) by 25.83% using transient elastography and a significant decrease (P < 0.001) by 18.42% using ARFI in the improved patients. At initial visit, transient elastography positively correlated with ARFI, bilirubin and platelets, also, transient elastography had a positive correlation with ARFI, bilirubin, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) in follow-up visit. LSM by ARFI (visit 1) negatively correlated with ALT, while in (visit 2), ARFI positively correlated with bilirubin, ALP, GGT and negatively correlated with albumin. CONCLUSION: The increased LSM in patients with extrahepatic cholestasis is reduced after adequate biliary drainage, implying that increased values are not solely due to liver fibrosis, but due to biliary congestion leading temporarily to increased elasticity.

Is urinary ß2-microglobulin a reliable marker for assessment of renal tubular dysfunction in chronic hepatitis B patients receiving tenofovir therapy?

BACKGROUND AND AIM: Urinary ß2-microglobulin (ß2-M) is a marker for renal tubular dysfunction. The current study aimed to assess urinary ß2-M as a reliable marker for early prediction of tenofovir disoproxil fumarate (TDF)-related nephrotoxicity among hepatitis B virus (HBV) patients. METHODS: Forty-two HBV patients who were a candidate for TDF therapy or have recently started it (for less than 6 months) were enrolled and subjected to demographic, clinical, laboratory assessment, abdominal ultrasound and transient elastography. The glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. Also, urinary ß2-M was measured by the ELISA method within 6 months after the introduction of TDF treatment and 6 months later. RESULTS: Mean age was 41.8 (9.55) years, 27 were males and 59.5% of patients have elevated urinary ß2-M after 6 months follow-up of TDF therapy. Urinary ß2-M was 0.07 ± 0.07 µg/ml at baseline and insignificantly increased up to 0.09 ± 0.08 µg/ml after 6 months follow-up. Despite the insignificant increase in serum creatinine from 0.85 ± 0.23 mg/dl at baseline to 0.9 ± 0.21 mg/dl after 6 months and the insignificant decrease in eGFR from 126.2 ± 39.72 ml/min at baseline and 117.64 ± 42.23 ml/min at 6 months follow-up. No correlation was found between the changes in urinary ß2-M and the changes in other renal function indices at baseline and 6 months follow-up. CONCLUSIONS: Short-term TDF therapy is associated with nonsignificant changes either in eGFR or urinary ß2-M; these changes are not clinically relevant that indicates disease progression. Therefore, the suitability of urinary ß2-M as a screening tool for tenofovir induced tubular dysfunction should be further.

Analysis of clinical and virologic features in Hepatitis B e Antigen (HbeAg)-negative and HbeAg-positive Egyptian chronic hepatitis B patients.

BACKGROUND: HBeAg-negative chronic hepatitis B infection has a divergent clinical course from that of HBeAg-positive infection. OBJECTIVES: To analyze the frequency and to compare the different features of HBeAg-negative and HBeAg-positive chronic hepatitis B patients. METHODS: One hundred and twenty one Egyptian patients with chronic hepatitis B (CHB), underwent laboratory investigations and transient elastography (TE). Comparisons according to HBeAg status were conducted regarding their demographic, liver biochemical and virologic characters. RESULT: 97 patients (80.2%) were HBeAg-negative while 24 patients (19.8%) were HBeAg-positive. HBeAg-negative patients were significantly older in age than CHBeAg-positive patients (p=0.001). ALT levels in HBeAg-negative patients were significantly lower than those in HBeAg-positive patients (p=0.02), whereas serum albumin was lower in the HBeAg-positive group (p=0.03). The percentage of HBV DNA higher than 20000 IU/mL in HBeAg-negative patients was lower than those in HBeAg-positive patients (p=0.24). Stages of fibrosis by TE showed that 30.9% of HBeAg-negative and 41.7% of HBeAg-positive had a fibrosis score >F2. Four patients (3.3%) were diagnosed with HCC; all of whom were HBeAg-negative. CONCLUSION: HBeAg-negative patients compared with HBeAg-positive patients had older age, lower ALT and serum HBVDNA levels, but more incidence of HCC.

Liver stiffness measurement by acoustic radiation forced impulse and transient elastography in patients with intrahepatic cholestasis.

BACKGROUND: Transient elastography (TE) and acoustic radiation force impulse (ARFI) imaging enable a noninvasive assessment of liver stiffness measurement (LSM) and liver fibrosis/cirrhosis staging. However, their use in cholestatic diseases is still scarce. AIM: The aim of this study was to evaluate the performance of TE and ARFI for the initial assessment of hepatic fibrosis in intrahepatic cholestatic (IHC) diseases and assess LSM changes after 3 months of specific therapy. PATIENTS AND METHODS: This prospective study was carried out on 50 IHC patients. Assessment at baseline and after 3 months of LSM by TE and ARFI was performed. RESULTS: Overall, 60% of the patients were women (36.5±9.2 years). IHC etiologies were 23 (46%) autoimmune hepatitis, eight (16%) primary sclerosing cholangitis, eight (16%) drug induced, and five (10%) primary biliary cirrhosis. TE could diagnose ≥F2, ≥F3, and F4 stages at cutoffs of at least 6.7, 9.4, and 14.0 kPa, sensitivity/specificity were 100/50% for ≥F2, 88.2/83% for ≥F3, and 90/100% for F4. Moreover, the sensitivity and specificity of ARFI were 93/50% for ≥F2 (cutoff: 1.53 m/s); 71/67% for ≥F3 (cutoff 1.77 m/s); and 90/100% for F4 (cutoff: 2.43 m/s).Follow-up showed a significant decrease in TE and ARFI values by 27 and 22.3% (P<0.001 and <0.001, respectively) and, accordingly, fibrosis stages decreased significantly by both TE and ARFI (P=0.002 and <0.001, respectively). CONCLUSION: TE and ARFI represent noninvasive methods with adequate diagnostic performance for the assessment of fibrosis, and monitoring disease progression and treatment response in intrahepatic cholestasis.

Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D.

Hepatitis delta virus (HDV) usually have an unfavorable clinical outcome in chronic hepatitis B virus (HBV) patients. In Egypt, data about epidemiology, the spectrum of disease, and impact of HDV on HBV infection are rare. To assess the prevalence, clinical and virological characteristics of HDV infection among Egyptian patients with chronic HBV. Adult patients with Hepatitis B surface antigen (HBsAg)-positive were evaluated for the presence of HDV using anti HDV-IgG and HDV RNA by RT-PCR. Routine laboratory investigations, genotypes and subtypes for both HBV and HDV, abdominal sonography, and transient elastography (TE) were done. Liver biopsy was performed only in whenever indicated. One hundred and twenty-one treatment-naïve chronic HBV patients were included. Wild HBV genotype-D2 was found in 98.2% and 81.9% were HBeAg negative. Prevalence of HDV was 8.3% by anti-HDV IgG and 9.9% by RT-PCR. Wild HDV genotype-IIb was reported in 83.3%. HDV infection was more common in males, 90.9% of delta patients were HBeAg negative. Compared to the mono-infected HBV, concomitant HBV/HDV infection was not associated with more derangment in ALT nor advanced stage of fibrosis. 66.7% of HDV patients had significantly lower HBV-DNA level compared to the non-delta patients (P < 0.001). HDV is not uncommon in Egypt. HBV genotype-D was associated with HDV genotype-IIb. Delta infection was associated with negative HBeAg status, reduction of HBV replication, but neither influenced the clinical course nor increased significant liver damage risk.