[Treatment of toxic hepatitis in COVID-19 patients].

BACKGROUND: The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented. AIM: The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19. MATERIALS AND METHODS: On the basis of the newly created infection centers of the Central Clinical Hospital "RZhD-Medicine" and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy. RESULTS: On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower - 122 (55.2%) and 134 (58.8%); p<0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients. CONCLUSION: The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.

Recovery from post-COVID-19 vaccination biliary ductopenia and multiorgan inflammation: A case with insight from angiotensin II type 1 receptor antibody- mediated injury (preprint)

Background The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality. Spike messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 may contribute to immune-mediated injuries. Here we present a case of marked cholangiopathy with multiorgan injury and investigate the potential mechanisms associated with mRNA-based vaccines. Case summary and investigation A previously healthy 47-year-old man developed progressive jaundice 2 weeks after receiving his 3rd COVID-19 vaccination (1st mRNA-based vaccine). Apart from elevated serum total bilirubin levels (peaked at >70 mg/dL), deteriorating renal (blood urea nitrogen: peak, 108.5 mg/dL; creatinine: peak, 6 mg/dL) and exocrine pancreas (amylase: peak, 1717 U/L; lipase: peak, 5784 U/L) profiles were also seen. Vanishing bile duct syndrome characterized by ductopenia and cholangiocyte vacuolation, positive C4d deposition, and high titer of anti-angiotensin II type 1 receptor antibody consistently explain the overall antibody-mediated pathogenesis resembling antibody-mediated “rejection” in the solid organ transplant setting. Corticosteroids and plasmapheresis were administered, leading to gradual resolution of the symptoms, and the jaundice completely resolved 2 months later. Conclusion Here we reported a case of antibody-mediated multiorgan injury after an mRNA COVID-19 vaccine characterized by severe cholangiopathy. The patient recovered with corticosteroids and plasmapheresis, and long-term follow-up is needed.

Clinical outcomes associated with complementary and alternative medicine-related "immunity-boosting" practices in patients with cirrhosis during the COVID-19 pandemic - an observational study.

During the coronavirus disease 2019 pandemic, Ayurvedic herbal supplements and homeopathic immune boosters (IBs) were promoted as disease-preventive agents. The present study examined the clinical outcomes among patients with chronic liver disease who presented with complications of portal hypertension or liver dysfunction temporally associated with the use of IBs in the absence of other competing causes. This single-center retrospective observational cohort study included patients with chronic liver disease admitted for the evaluation and management of jaundice, ascites, or hepatic encephalopathy temporally associated with the consumption of IBs and followed up for 180 days. Chemical analysis was performed on the retrieved IBs. From April 2020 to May 2021, 1022 patients with cirrhosis were screened, and 178 (19.8%) were found to have consumed complementary and alternative medicines. Nineteen patients with cirrhosis (10.7%), jaundice, ascites, hepatic encephalopathy, or their combination related to IBs use were included. The patients were predominantly male (89.5%). At admission, 14 (73.75%) patients had jaundice, 9 (47.4%) had ascites, 2 (10.5%) presented with acute kidney injury, and 1 (5.3%) had overt encephalopathy. Eight patients (42.1%) died at the end of the follow up period. Hepatic necrosis and portal-based neutrophilic inflammation were the predominant features of liver biopsies. IB analysis revealed detectable levels of (heavy metals) As (40%), Pb (60%), Hg (60%), and various hepatotoxic phytochemicals. Ayurvedic and Homeopathic supplements sold as IBs potentially cause the worsening of preexisting liver disease. Responsible dissemination of scientifically validated, evidence-based medical health information from regulatory bodies and media may help ameliorate this modifiable liver health burden.

Severe acute hepatitis of unknown origin.

At the beginning of 2022, in the United Kingdom, and later in several European countries, a group of pediatric patients who developed acute hepatitis of so far unknown origin was reported. Clinical data include nausea, vomiting, jaundice, and liver failure; some patients require liver transplantation. The affected population is younger than 10 years of age. The probable etiological agent is adenovirus genotype F41, and toxic factors have been ruled out, as well as a relationship with COVID-19. There are several theories to explain this phenomenon, which are being investigated.

A inicios de 2022, en Reino Unido, y posteriormente en varios países europeos, se informó sobre un grupo de pacientes pediátricos que desarrollaron hepatitis aguda de origen desconocido hasta ahora. Los datos clínicos consisten en náusea, vómito, ictericia y falla hepática; algunos pacientes necesitan trasplante hepático. La población afectada es menor a los 10 años. El agente etiológico probable es el adenovirus genotipo F41 y se han descartado factores tóxicos, así como la relación con COVID-19. Existen varias teorías para explicar este fenómeno, las cuales se están investigando.

Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: a cohort study using OpenSAFELY-TPP (preprint)

Background Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We investigated the effect of the COVID-19 pandemic on the quantity of healthcare services delivered to people with pancreatic cancer. Methods With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models (GLM) and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to September 2022. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. Results The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 24,500 people diagnosed with pancreatic cancer from January 2015 to September 2022. The mean age at diagnosis was 72 (SD 11), 48% of people were female, 95% were of White ethnicity and 39% were diagnosed with diabetes. We found a reduction in surgical resections by nearly 25% during the pandemic. In addition, 20%, 10% and 5% fewer people received BMI, HbA1c and liver function tests respectively before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1 to 2 per person amongst those who made contact. Abdominal scans decreased by 7% and reporting of jaundice decreased by 20%, but recovered within six months into the pandemic. Emergency department visits, hospital admissions and deaths were not affected. Conclusions The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from services that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.

Quantitative G6PD point-of-care test can be used reliably on cord blood to identify male and female newborns at increased risk of neonatal hyperbilirubinaemia: a mixed method study (preprint)

ABSTRACT Introduction New point-of-care (POC) quantitative G6PD testing devices developed to provide safe radical cure for P. vivax malaria may be used to diagnose G6PD deficiency in newborns at risk of severe neonatal hyperbilirubinaemia, improving clinical care, and preventing related morbidity and mortality. Methods: We conducted a mixed-methods study analyzing technical performance and usability of the “STANDARD G6PD” Biosensor when used by trained midwives on cord blood samples at two rural clinics on the Thailand-Myanmar border. Results In 307 cord blood samples, the Biosensor had a sensitivity of 1.000 (95%CI 0.859-1.000) and a specificity of 0.993 (95% CI 0.971-0.999) as compared to gold standard spectrophotometry to diagnose G6PD deficient newborns using a receiving operator characteristic (ROC) analysis-derived threshold of ≤4.8IU/gHb. The Biosensor had a sensitivity of 0.727 (95%CI: 0.498-0.893) and specificity of 0.933 (95%CI: 0.876-0.969) for 30-70% activity range in females using ROC analysis-derived range of 4.9 to 9.9IU/gHb. These thresholds allowed identification of all G6PD deficient neonates and 80% of female neonates with intermediate phenotypes. Need of phototherapy treatment for neonatal hyperbilirubinaemia was higher in neonates with deficient and intermediate phenotypes as diagnosed by either reference spectrophotometry or Biosensor. Focus group discussions found high levels of learnability, willingness, satisfaction, and suitability for the Biosensor in this setting. The staff valued the capacity of the Biosensor to identify newborns with G6PD deficiency early (“We can know that early, we can counsel the parents about the chances of their children getting jaundice”) and at the POC, including in more rural settings (“Because we can know the right result of the G6PD deficiency in a short time. Especially for the clinic which does not have a lab”). Conclusions: The Biosensor is a suitable tool in this resource-constrained setting to identify newborns with abnormal G6PD phenotypes at increased risk of neonatal hyperbilirubinaemia.

Hemolysis and blood gas analysis: it's time for a change!

Modern blood gas analyzers are not able to identify hemolysis, lipemia and icterus; therefore, the aim of this study was to assess the influence of hemolysis on blood gas samples. Blood gas analysis represents an essential part in the diagnosis and treatment of critically ill patients, including those affected by the pandemic coronavirus disease 2019 (COVID-19). Hemolysis, lipemia, and icterus, are causes of clinical misinterpretation of laboratory tests. A total of 1244 blood gas specimens were collected over a one-week period from different clinical wards, including the Emergency Department, and were assessed for serum indices on Cobas C6000 CE (Roche Diagnostics, Mannheim, Germany). The prevalence of hemolysis, lipemia, and icterus were 5%, 12%, and 14%, respectively. Sample storage at room temperature, delivery to central laboratory using pneumatic tube system, as well as small sample size, strongly affected blood gas parameters (p < .01). Hemolysis led to an increase in analytical bias for pH, pO2, and potassium, and a significant decrease for pCO2, HCO3-, sodium, and Ca2+ (p <.01). Currently, hemolysis detection systems are not yet widespread, and a rapid centrifugation of samples after blood gas analysis along with the assessment of serum indices represent the only prompt approach to identify unsuitable results, avoiding pitfalls in clinical decision-making, although it cannot be applied to the Emergency Department routine. Blood gas analyzers manufacturers and suppliers should implement automated built-in serum indices detection systems.

Autoimmune hepatitis after COVID-19 vaccine - more than a coincidence.

The COVID-19 pandemic is still raging across the world and vaccination is expected to lead us out of this pandemic. Although the efficacy of the vaccines is beyond doubt, safety still remains a concern. We report a case of a 65-year-old woman who experienced acute severe autoimmune hepatitis two weeks after receiving the first dose of Moderna-COVID-19 vaccine. Serum immunoglobulin G was elevated and antinuclear antibody was positive (1:100, speckled pattern). Liver histology showed a marked expansion of the portal tracts, severe interface hepatitis and multiple confluent foci of lobular necrosis. She started treatment with prednisolone, with a favorable clinical and analytical evolution. Some recent reports have been suggested that COVID-19 vaccination can lead to the development of autoimmune diseases. It is speculated that the vaccine can disturb self-tolerance and trigger autoimmune responses through cross-reactivity with host cells. Therefore, healthcare providers must remain vigilant during mass COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) as a Potential Trigger for Benign Recurrent Intrahepatic Cholestasis (preprint)

Benign recurrent intrahepatic cholestasis (BRIC) is a rare disease characterized by recurrent severe itching and jaundice. Coronavirus disease 2019 (COVID-19) is a multisystemic acute viral disease and the liver is frequently affected. Here, we wanted to present a BRIC case triggered by COVID-19 infection, discussing it together with current information.

Acute Hepatitis B Associated Neuromyopathy (preprint)

A 67 year old man presented with abdominal discomfort and jaundice for 1 month with difficulty in walking with severe pain in both thighs of 3 days duration. He was a diabetic and hypertensive on medications. There was no history of HMG CoA reductase inhibitor use. On examination he had icterus and grade 2 power in the proximal upper and lower limbs. Deep tendon reflexes were inelicitable. On day 1, CRP was 37mg/L and liver function tests were deranged [ Total Bilirubin 16 mg%, direct 14.3mg%, SGOT [920 U/L], SGPT [590 U/L], Alkaline Phosphatase 276.5 U/L. Serum CPK levels [9768 U/L], LDH [979 U/L] and Ferritin [7264 ng/ml] were elevated on day 2. ANA profile was negative. Leptospiral antibody, dengue serology and SARS-CoV2 RT-PCR were negative. Hepatitis B serology was compatible with an acute infection. On day 3, nerve conduction studies showed an axonal sensory-motor polyneuropathy predominantly involving the lower limbs. F waves were absent. Fibrillations and positive waves were picked up from the Tibialis anterior muscles bilaterally. He was started on IVIG 2gm/kg x 5 days. On day 4, his CPK levels increased to >42,000 U/L and he was shifted to the ICU and started on forced alkaline diuresis. Urine myoglobin was positive.. On day 6, MRI whole body muscle STIR imaging showed patchy ill-defined STIR hyperintensities involving the muscles of the gluteal, pelvic girdle muscles, both thighs and leg muscles with fascial edema. The muscles of the upper limbs and shoulder girdles also showed patchy STIR hyperintensities. Diffuse subcutaneous oedema was noted in the soft tissue of the thighs, legs and abdominal wall. Over the next few days, the weakness in the upper limbs worsened and he developed a weak cough. He did not consent to a lumbar puncture or muscle biopsy. Over the next 9 days, his liver function tests and CPK levels gradually normalised. He was also started on Entacavir. By day 10, his upper limb and distal lower limb had improved to grade 4/5 power and he was able to stand with support and he was discharged.

Auto-immune hepatitis following COVID vaccination.

Unprecedented loss of life due to the COVID pandemic has necessitated the development of several vaccines in record time. Most of these vaccines have received approval without being extensively whetted for their adverse effect and efficacy profiles. Most adverse effects have been mild, nonetheless, more serious thromboembolic events have also been reported. Autoimmune hepatitis (AIH) can occur in predisposed individuals where an immune mediated reaction against hepatocytes is triggered by environmental factors. Vaccines are a very rare cause of AIH. We report two such cases of AIH triggered by COVID (Covishield) vaccination. While one patient made an uneventful recovery, another succumbed to the liver disease. Ours is the first report of Covishield vaccination related AIH and second ever after any form of COVID vaccination. We hope that our report does not deter COVID vaccination drives. However, we also hope to raise awareness of its potential side effects and the increased role of pharmacovigilance in guiding treatment.

Acute icteric hepatitis as the first isolated symptom of COVID-19.

Patients with COVID-19 may be asymptomatic or present with extrarespiratory symptoms, such as liver injury. It has been reported that 22.5%-46.2% of patients have moderate elevation of liver enzymes. To our knowledge, acute hepatitis has never been described as an isolated symptom of COVID-19 in a previously healthy patient. We report the case of a 53-year-old patient with COVID-19 whose first clinical presentation was acute icteric hepatitis, several days before the development of others symptoms. During the pandemic, we suggest that patients with acute hepatitis be considered as COVID-19 suspects, tested and isolated.

Secondary sclerosing cholangitis as cause of persistent jaundice in patients with severe COVID-19.

BACKGROUND & AIMS: Little is known about cholestasis, including its most severe variant secondary sclerosing cholangitis (SSC), in critically ill patients with coronavirus disease 19 (COVID-19). In this study, we analysed the occurrence of cholestatic liver injury and SSC, including clinical, serological, radiological and histopathological findings. METHODS: We conducted a retrospective single-centre analysis of all consecutive patients admitted to the intensive care unit (ICU) as a result of severe COVID-19 at the University Hospital Zurich to describe cholestatic injury in these patients. The findings were compared to a retrospective cohort of patients with severe influenza A. RESULTS: A total of 34 patients with severe COVID-19 admitted to the ICU were included. Of these, 14 patients (41%) had no cholestasis (group 0), 11 patients (32%, group 1) developed mild and 9 patients (27%, group 2) severe cholestasis. Patients in group 2 had a more complicated disease course indicated by significantly longer ICU stay (median 51 days, IQR 25-86.5) than the other groups (group 0: median 9.5 days, IQR 3.8-18.3, P = .001; and group 1: median 16 days, IQR 8-30, P < .05 respectively). Four patients in group 2 developed SSC compared to none in the influenza A cohort. The available histopathological findings suggest an ischaemic damage to the perihilar bile ducts. CONCLUSIONS: The development of SSC represents an important complication of critically ill COVID-19 patients and needs to be considered in the diagnostic work up in prolonged cholestasis. The occurrence of SSC is of interest in the ongoing pandemic since it is associated with considerable morbidity and mortality.