Immunological Remission as a Basis for Dose Reduction of Immunosuppressors in Autoimmune Hepatitis: Results of Monocenter Surveillance Study

Aim of the study: evaluate the role of normalization of humoral immunity to address dose reduction or discontinuation of immunosuppressors in patients with autoimmune hepatitis (AIH).Patients and methods. The data of 47 patients with AIH who received immunosuppressive therapy from April 2001 to August 2023 were analyzed: 10 men (21 %), 37 women (79 %); the average age was 37 (17–66) years. The follow-up period was 10–180 months. Type 1 AIH was diagnosed in 37 patients, type 2 AIH — in 7 patients, seronegative AIH — in 3 patients. The diagnosis was established according to the IAIHG point system. To confirm the diagnosis, a liver biopsy was performed in 17 patients, a histological picture of AIH was detected in all of them. The most used combination was prednisolone and azathioprine — in 25 patients (53.2 %), as well as methylprednisolone and azathioprine — in 8 patients (17 %).Results. In some patients, when the immunosuppressive therapy decreased below the recommended dose, a relapse of the disease developed (Group 1), and in others, remission persisted (Group 2). The concentration of гамма-globulins in patients of Group 1 was 22.5 mg%, in Group 2 — 17.95 mg% (p = 0.00055). IgG level after achieving remission in Group 1 was 1709.7 mg/dL, in Group 2 — 1381.7 mg/dL (p = 0.000001). The terms of ALT normalization in Group 1 were 2.14 months, in Group 2 — 1.47 months (p = 0.037); AST normalization in Group 1 made 2.22 months, in Group 2 — 1.48 months (p = 0.026).Conclusions. Normalization of humoral immunity, as well as rapid normalization of ALT and AST can be considered as markers of maintaining AIH remission when immunosuppressor doses are reduced below standard doses, and in individual patients — the possibility of immunosuppressive therapy withdrawal. This will reduce the risk of adverse events and increase adherence to the therapy. We propose introducing the term “immunological remission” into the clinical lexicon, which, along with biochemical and histological remission, acts as a predictor of persistent remission of AIH

Cause-and-effect relationship between thyroid and liver diseases

Thyroid gland (TG) and the liver are in a complex relationship in both physiological and pathological conditions. Thyroid hormones accelerate metabolic processes, intensify the synthesis of proteins and vitamins, play an important role in the development and differentiation of all cells, including hepatocytes. In addition to the central role in the deiodination of thyroid hormones with the formation of their more active and inactivated forms, the liver also carries out their transport. Dysfunction of TG can lead to changes in liver function, and in liver diseases, abnormalities in the metabolism of thyroid hormones can occur. Most often, liver pathology in diseases of TG is manifested by an increase in the serum activity of enzymes of cytolysis and/or cholestasis. Changes in liver function tests are often observed in patients with thyrotoxicosis. They are based on oxidative stress or cholestasis. The increased activity of osteoblasts in hyperthyroidism leads to an increase in the bone fraction of alkaline phosphatase, which must be taken into account in the differential diagnosis. Hepatotoxicity of thyreostatic drugs is relatively common, ranging from minimal hepatocellular damage to fulminant liver failure. In the case of hypothyroidism, the pathophysiological mechanisms are mainly represented by lipid metabolism disorders leading to fatty degeneration. It should be remembered that severe hypothyroidism can be manifested by hyperammonemia and edematous-ascitic syndrome, requiring differential diagnosis with liver failure. Treatment of liver pathology in TG diseases includes normalization of thyroid status, and in cases of drug hepatitis – temporary withdrawal of a potentially hepatotoxic drug. The data on the association of hypothyroidism and non-alcoholic fatty liver disease in the aspect of developing new therapies are very interesting

Is Combined Bulevirtide and Pegylated Interferon Therapy for Chronic Hepatitis D Superior over Bulevirtide Monotherapy?

Bulevirtide is a novel antiviral agent approved for suppression of chronic hepatitis D but requiring further research into optimising the treatment scheme.Aim. Comparative assessment of bulevirtide monotherapy versus combined treatment with bulevirtide and pegylat-ed interferon (PEG-IFN) using published trial data.Key points. MYR201 and MYR203 trials expose a higher frequency of HBsAg and HDV RNA extinction, as well as more effective HDV suppression for combined bulevirtide/PEG-IFN therapy compared to bulevirtide monotherapy.Conclusion. Combined bulevirtide/PEG-IFN therapy has particular advantages over bulevirtide monotherapy in patients with chronic hepatitis D. Further research is required to optimise bulevirtide dosage and duration of therapy

Long-Term Results of the Etiotropic Therapy of Subcompensed Liver Cirrhosis in the Outcome of Chronic Hepatitis C

Aim. The evaluation of long-term results of antiviral therapy (AVT) with ombitasvir/paritaprevir/ritonavir and dasabuvir in patients with noncompensated liver cirrhosis (LC) in the outcome of chronic hepatitis C.Material and methods. A retrospective analysis included the data from patients with subcompensated liver cirrhosis (LC) of HCV etiology (genotype 1b) (7–9 points of the Child-Pugh score) having received interferon-free antiviral therapy (AVT) with ombitasvir/paritaprevir/ritonavir and dasabuvir during 12 weeks from September to December 2015. In total, 66 patients (27 men and 39 women) received such a therapy, the median age was 56.4 years.Results. 147 weeks (IQR 56–156) following AVT completion, the long-term results were evaluated. At that time, 27 patients were available for observation. The assessment of liver function compensation using the Child-Pugh score showed improvement in 25 (93 %) patients. The assessment of laboratory data revealed a decrease in the median of total bilirubin by 13.6 μmol/l, as well as an increase in the median of serum albumin by 9.7 g/L and the median of platelets by 41,700/μl. Two deaths were reported due to hepatocellular cancer (HCC) and bleeding from esophageal varices. HCC was detected in 8 patients. Two patients underwent liver transplantation.Conclusion. AVT in patients with LC of HCV etiology is associated with a high frequency of virologic response. Longterm follow-up results indicate a significant improvement of liver function, but also a continuing high risk of developing complications of underlying disease, primarily HCC

Diagnostic and Prognostic Value of Hyperammonemia in Patients with Liver Cirrhosis, Hepatic Encephalopathy, and Sarcopenia (Experts’ Agreement)

Introduction. In cirrhotic patients, hyperammonemia develops due to impaired ammonia detoxification and portosystemic blood shunting and is most commonly associated with hepatic encephalopathy and sarcopenia. Currently, there are questions regarding the diagnosis of hyperammonemia and the effect of ammonia-lowering therapy on disease outcomes.Materials and methods. The Russian Scientific Liver Society selected a panel of seven experts in liver cirrhosis research and management of patients with this disease to make reasoned statements and recommendations on the issue of diagnostic and prognostic value of hyperammonemia in patients with liver cirrhosis, hepatic encephalopathy and sarcopenia.Results. The Delphi panel identified the most relevant topics, in the form of PICO questions (patient or population, intervention, comparison, outcome). The Delphi panel made six questions relevant to clinical practice and gave reasoned answers, framed as ‘clinical practice recommendations and statements’ with evidence-based comments. The questions and statements were based on the search and critical analysis of medical literature by keywords in Englishand Russian-language databases. The formulated questions could be combined into four categories: hepatic encephalopathy, sarcopenia, hyperammonemia, and ammonia-lowering therapy.Conclusions. The results of the experts' work are directly relevant to the quality management of patients with liver cirrhosis, and their recommendations and statements can be used in clinical practice

Инфекция H. PYLORI У Больных острыми кишечными инфекциями

The objective: to assess clinical features of food-borne diseases in patients with H. pylori infection.Materials and methods: 98 patients with an acute intestinal infection were examined for the presence of helicobacter pylori infection. Clinical and laboratory parameters were estimated in 82 subjects. Patients were distributed to two groups: 41 H. pylori-infected patients (H. pylori IgG antibodies and DNA in feces) and41 H. pylori-noninfected patients.Results: in patients with Helicobacter pyloriinfection a higher range of leukocytosis were indicated: 10,7±2,5×109/l vs 8,6±2,6×109/l respectively, р<0,05, and ESR – 16,2±8,7 mm/h vs 11,2±7,8 mm/h respectively, p<0,05. In H. pyloriinfected patients number of bowel movementsand vomitswere indicated more often than those in the control group: (9,4±5,3 vs 6,7±3,6 times/day respectively, р<0,05; and 4,8±3,4 and 1,0±1,4 times/day, р<0,05). Normalization of bowel function was observedearlier in control group compare with H. pylori-infected patients (3,0±0,7 day of disease and 4,4±1,4 day of disease respectively, in р<0,05).Conclusions: H. pylori-infected patients had clinically and laboratory more severe presentation of acute intestinal infection. Clinical improvementin this patientsoccurredat a later date.Цель: оценить течение ОКИ у больных с сопутствующей геликобактерной инфекцией.Материалы и методы: обследованы 98 больных острыми кишечными инфекциями на наличие геликобактерной инфекции. Оценены клинико-лабораторные показатели у пациентов 2 групп: основной – 41 больной с подтвержденной инфицированностью H. pylori (выявлены специфические IgG в сыворотке крови и H. pylori в кале методом ПЦР) и контрольной – 41 пациент без лабораторных маркеров геликобактерной инфекции.Результаты: при поступлении у пациентов с сопутствующей геликобактерной инфекцией выявлены высокие значения лейкоцитоза – 10,7±2,5×109/л и 8,6±2,6×109/л соответственно, р<0,05, и СОЭ – 16,2±8,7 мм/ч, 11,2±7,8 мм/ч соответственно, p<0,05. У пациентов основной группы регистрировали большую частоту стула и рвоты, чем у больных контрольной группы (9,4±5,3 и 6,7±3,6 раз в день, р<0,05; 4,8±3,4 и 1,0±1,4 раз в день, р<0,05 соответственно). При анализе клинического течения ОКИ установлено, что у больных контрольной группы нормализацию стула фиксировали достоверно раньше,чем у больных основной группы (3,0±0,7 день заболевания и 4,4±1,4 день заболевания соответственно, при р<0,05).Заключение: у больных ОКИ с сопутствующим геликобактериозом отмечается более выраженные клинико-лабораторные проявления заболевания по сравнению с пациентами контрольной группы. Клиническое улучшение у них наступало в более поздние сроки

Important problems in the diagnosis and treatment of autoimmune hepatitis (based on the Russian consensus 2017)

The analysis of publications devoted to the Russian Consensus on the Diagnostic and Treatment of Autoimmune Hepatitis (AIH), which was considered at the 43rd annual Scientific Session of the CNIIG From Traditions to Innovation (March 4, 2017) is carried out. The presence of clear algorithms and recommendations for the diagnosis and treatment of AIH significantly help the doctor in real clinical practice, but do not exclude a personified approach to the patient