Vol 51, No 4 (2023)
ARTICLES
Causes for the absence of thrombocytopenia in patients with liver cirrhosis and portal vein thrombosis: A case-control study
Abstract
Background: Complications of liver cirrhosis (LC), such as thrombocytopenia and portal vein thrombosis (PVT), have similar pathophysiology. However, the association between PVT and platelet count in LC patients is contradictory.
Aim: To assess factors affecting the platelet count in patients with LC and PVT.
Materials and methods: This was a retrospective case-control study. The cases were 114 patients with LC of various etiologies and newly diagnosed PVT unrelated to invasive hepatocellular carcinoma. From the database of LC patients without PVT, 228 controls were randomly selected with stratification by gender, age and etiology of cirrhosis. The patients from both groups were divided into subgroups with thrombocytopenia (< 150 × 109/L) and without thrombocytopenia (≥ 150 × 109/L). We analyzed the LC etiology, portal hypertension severity (ascites, hepatic encephalopathy, gastroesophageal varices and associated bleedings, the spleen length, and portal vein diameter), laboratory parameters (white blood cell counts, neutrophils, lymphocytes, hemoglobin levels, total protein, albumin, total bilirubin, fibrinogen, neutrophil-to-lymphocyte ratio, and prothrombin); also, the rates of newly diagnosed malignant tumors was assessed. The statistical analysis included calculation of odds ratios (OR) and 95% confidence intervals (CI), logistic regression models with assessment of the model accuracy, and the area under the ROC curve (AUC).
Results: There were no differences in the severity of thrombocytopenia between the case and control groups: thrombocytopenia was severe in 15.8% (18 patients) vs 13.6% (31 patients, p = 0.586); moderate, in 41.2% (47 patients) vs 46.1% (105 patients, p = 0.398) and mild, in 31.6% (36 patients) vs 24.5% (56 patients, p = 0.168). The proportion of the patients without thrombocytopenia was 11.4% (13 patients) in the case group and 15.8% (36 patients) in the control group, with the between-group difference being non-significant (p = 0.276). In the subgroups of patients without thrombocytopenia (both in the cases and in the controls), the proportion alcoholic etiology of LC, white blood cells counts, neutrophils, lymphocytes, and fibrinogen concentrations were significantly higher (p < 0.05) than in those with thrombocytopenia. The model based on the outcome "absence of thrombocytopenia" included white blood cells counts, hemoglobin and albumin levels, the presence of newly diagnosed malignant tumors in the case group (model accuracy 90.4%, AUC 0.873), and neutrophil counts and spleen length in the control group (model accuracy 86.4%, AUC 0.855). In the patients with PVT and platelet counts of ≥ 150 × 109/L, the OR for all newly diagnosed malignant tumors was 26.3 (95% CI 7.37–93.97, р < 0.0001), for newly diagnosed hepatocellular carcinoma without portal vein invasion 17.42 (95% CI 4.84–62.65, р < 0.0001).
Conclusion: In LC patients, the prevalence and severity of thrombocytopenia are not different depending on the PVT presence or absence. The absence of thrombocytopenia in PVT patients is associated with a higher risk of malignant tumors identification, primarily that of hepatocellular carcinoma.
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Postpartum progression of chronic kidney disease in patients with chronic glomerulonephritis
Abstract
Background: In the recent years, pregnancy outcomes in women with primary chronic glomerulonephritis (CGN) have been encouraging despite increased incidence of complications and preterm birth. However, the impact of pregnancy on CKD progression in glomerulonephritis remains understudied.
Aim: To evaluate the effect of pregnancy on CKD progression in the postpartum period in patients with primary CGN.
Materials and methods: This was an observational longitudinal study. The study group included 40 patients with CGN and CKD G1–G3b, who had 40 deliveries from January 2009 to November 2022. The control group included 35 patients with CGN who had no pregnancies after CKD was diagnosed. Serum creatinine and estimated glomerular filtration rate (GFR) were assessed during the follow up, recording the development of CKD G5.
Results: The annual rate of GFR decline in the study group was -4.6 [-8.0; -2.5] ml/min/1.73 m2, and in the control group -1.8 [-5.8; +1.5] ml/min/1.73 m2 (p = 0.056). After complicated pregnancy (preeclampsia, placental insufficiency, increase in proteinuria, worsening of arterial hypertension, acute kidney injury), the annual rate of GFR decline was -6.4 [-13.4; -3.5] ml/min/1.73 m2, which was higher than in the controls (p = 0.042). There were no significant differences in survival without GFR decrease by 30%, 50% and without CKD G5 between the study and the control groups. However, CKD G5-free survival in the patients with complicated pregnancy was lower than that in the controls (p = 0.022) and in those with uncomplicated pregnancies (p = 0.009).
Eleven (11) of 40 patients in the main group and 3/35 in the control group reached CKD G5. The time from delivery to CKD G5 was 4.83 [2.08; 7.07] years. Among women who reached end-stage renal failure after childbirth, there were significantly more patients with CKD G3, proteinuria ≥ 1 g/day during pregnancy, arterial hypertension at baseline and during pregnancy, preeclampsia, acute kidney injury, delivery at less than 37 weeks of gestation, with neonates requiring treatment at intensive care unit, and unfavorable pregnancy outcomes.
Conclusion: Renal survival in the women with primary CGN who had been pregnant was not significantly different from that in the women who did not have pregnancies; however, complicated pregnancy increased the rate of kidney function decline.
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Pegylated interferon in the treatment of chronic delta hepatitis: the experience from real-world clinical practice
Abstract
Rationale: The high prevalence of hepatitis D virus (HDV) infection in the Republic of Dagestan, significantly exceeding that in the European part of the Russian Federation, as well as the limited choice of therapeutic options, have led to the need to analyze the accumulated experience of interferon therapy in the real clinical practice to further select possible treatment regimens.
Aim: To evaluate the efficacy of pegylated interferon alpha (Peg-IFN-α) in patients with chronic hepatitis D (CHD) in real world clinical practice.
Materials and methods: In a retrospective study, the efficacy, safety and tolerability of Peg-IFN-α were analyzed in 34 patients with CHD living in the Republic of Dagestan. Main virological parameters (anti-HDV antibodies (anti-HDV), HDV RNA and HBV DNA), alanine aminotransferase levels, changes over time in liver density by elastometry, and clinical parameters (hematology and urine tests, clinical chemistry, thyroid function tests) were assessed at 24 and 48 weeks of therapy, as well as at 48 weeks after its completion.
Results: The treatment with Peg-IFN-α for 48 weeks resulted in a virological response, defined as a HDV RNA decrease by more than 2 lg copies/mL, in 32% (11/34) of the patients. A sustained virological response, defined as undetectable HDV RNA at 48 weeks after the end of therapy, was not observed in any case. Treatment with interferon was associated with a decrease in liver density by average 4.1 kPa by week 48 on therapy. Normalization of alanine aminotransferase levels after 48 weeks of treatment was observed in 59% (20/34) of the patients; however, sustained biochemical response was achieved in none of them. Serious adverse events of high or moderate severity that resulted in the discontinuation of therapy were observed in 12% (4/34) of the cases.
Conclusion: The results obtained indicate low efficacy of Peg-IFN-α in the treatment of CHD in the Dagestan patients. Further research is needed to refine optimal interferon therapy regimens, to search for predictors of treatment response, and to evaluate the impact of interferon treatment regimens on the risk of hepatic complications, clinical outcomes, and patient survival. However, the most obvious solution to the problem of CHD therapy is the development and implementation of interferon-free treatment regimens.
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The results of real-world practice with glecaprevir/pibrentasvir for the treatment of chronic hepatitis C virus infection genotypes 1 and 3 in adolescents aged 12 to 17 years in the Moscow region
Abstract
Rationale: The first direct anti-viral agents (DAVA) for the treatment of adolescents with chronic hepatitis C virus (HCV) infection have been approved quite recently, i. e. in 2017 worldwide and in 2019 in Russia. Currently, only few adolescents are treated worldwide, their proportion in the Russian Federation not exceeding 9 to 15%. The results of real-world practice with various DAVA regiments in adolescents aged 12 to 17 years could be useful to choose the strategies for local healthcare bodies.
Aim: To evaluate the efficacy and safety of the fixed combination of glecaprevir and pibrentasvir (GLE/PIB) in adolescents aged 12 to 17 years with HCV infection genotypes (GT) 1 and 3 in the Moscow region.
Materials and methods: We retrospectively analyzed the results of treatment of 32 adolescents (gender ratio 1:1) who were treated for HCV infection (GT1, 49.9% of the cases, GT3, 53.1%; F1 fibrosis according to the METAVIR scale, 37.5% of the patients, F2, 9.4%) with GLE/PIB during 2019 to 2022 within the Program of State-guaranteed free medical care to the citizens of the Moscow region. The treatment course lasted for 8 weeks in 31 treatment-naïve patients and 16 weeks in one patient who had failed on interferon treatment. The information was extracted from medical files of the patients treated on the outpatient basis and from discharge letters from the day care unit. Concomitant diseases were diagnosed in 75% of the adolescents.
Results: At week 4 of GLE/PIB treatment, HCV RNA was undetectable in 90.6% (95% confidence interval (CI) 75.0–98.0) of the patients, and alanine aminotransferase activity reached the reference interval in all patients (100%). The rate of sustained viral response at 12 week of therapy was 96.9% (95% CI 83.8–99.9), including 100% (95% CI 78.2–100) in the GT1 patients and 94.1% (95% CI 71.3–99.9) in the GT3 patients. At week 24 after the GLE/PIB treatment had been finished, the rate of liver fibrosis according to METAVIR decreased from 46.9% to 12.5% (p < 0.001). The lack of response to GLE/PIB in one patient with GT1 HCV appeared to be due to missed doses of the drug. GLE/PIB-related adverse events (headache, fatigue, nausea, and diarrhea) were rare and were recorded in 9.4% (95% CI 1.9–25.0) of the patients, whereas unrelated adverse events (acute respiratory infection symptoms) in 15.6% (95% CI 5.3–32.8) of the patients. All adverse events were mild, occurred at 2–3 weeks of the treatment and did not require additional pharmacological intervention.
Conclusion: The results obtained indicate a high efficacy and safety profile of GLE/PIB for the treatment of chronic HCV infection in adolescents aged 12 to 17 years. They can be used by local healthcare authorities to choose the treatment regimens effective for all genotypes and most suitable for children.
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CLINICAL CASES
The diagnosis of retroperitoneal tumors from a radiologist perspective: a case report of a giant intramuscular hemangioma in a 23-year old patient
Abstract
Primary retroperitoneal tumors are a heterogeneous group of neoplasms with a prevalence of 0.02 to 1%. The results of diagnostic visualization of such tumors are usually ambiguous due to their diversity and similar radiological semiotics of malignant and benign tumor types. The paper describes a rare case of the diagnosis and management of a patient with one of retroperitoneal tumor, i. e. a giant intramuscular hemangioma.
A 23-year old male patient was referred with complaints of episodic pains in the right inguinal area for 7–8 years. The multiaxial computed tomography showed a mass of 145 × 125 × 125 mm located in the trunk and pelvis, and spreading to the right thigh. The tumor structure was markedly heterogeneous and contained calcinates, adipose tissue, soft tissue and vascular components. The mass showed a heterogeneous contrast accumulation, with predominant delayed-phase enhancement. The tumor was surgically resected, with the histological investigation characteristic of intramuscular hemangioma.
Rare retroperitoneal tumors are always challenging in the interpretation of the results of diagnostic visualization. Since their various types have similar radiological semiotics, the differential diagnosis is often impossible. Therefore, the main diagnostic issue should be the exact localization of the neoplasm, identification of the feeding vessels, and the assessment of the adjacent tissue abnormalities.
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A clinical case of pyoderma gangrenosum as a severe extraintestinal manifestation of Crohn’s disease
Abstract
Pyoderma gangrenosum is a rare neutrophilic dermatosis associated with a number of immune-mediated disorders, most frequently with inflammatory bowel disease and rheumatoid arthritis. Despite significant success in the treatment in inflammatory bowel disease, the problem of multidisciplinary management of patients with extraintestinal manifestations in routine medical practice remains unsolved. The paper presents a clinical case of a 32-year old female patient with a life-threatening extraintestinal manifestation of Crohn's disease, i. e. pyoderma gangrenosum. Late diagnosis of Crohn's disease, underestimation of the inflammation activity in the gut and respective lack of disease-modifying treatment were the reasons for the occurrence of pyoderma gangrenosum and its uncontrolled course. The untimely diagnosis of the skin purulent wound as an extraintestinal manifestation of Crohn's disease has led to delay in the immunosuppressive therapy required. The patient needed an intensive course of systemic glucocorticosteroids, prompt addition of a tumor necrosis factor-alpha inhibitor and surgery as a circulatory autodermoplasty.
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