RU2695021C1 - Diagnostic technique for drug-induced liver injury in patients with non-alcoholic fatty liver disease - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to functional diagnostics, and can be used for diagnosing drug-induced liver injury in patients with non-alcoholic fatty liver disease. Data of medical history and clinical picture are taken into account. Additionally, AlT/AsT ratio is determined, RUCAM scale score is evaluated, microscopic examination of biopsy materials is performed. In the presence of hepatocyte necrosis, intralobular and portal infiltration and extralobular cholestasis, AlT/AsT ratio of 5 and more, RUCAM 6 and more, the drug-induced liver involvement is diagnosed in the patients with non-alcoholic fatty liver disease.

EFFECT: method provides higher diagnostic accuracy of drug-induced liver injury in patients with non-alcoholic fatty liver disease as a result of additional determination of the ratio of AlT/AsT, RUCAM scale assessment and microscopic examination of biopsy materials.

1 cl, 2 ex

Description

The invention relates to medicine, and in particular to methods of diagnosis of drug-induced liver damage in patients with non-alcoholic fatty liver disease.

A known method for the diagnosis of drug-induced liver damage in children, characterized in that they diagnose the presence of cytolytic syndrome and the level of ALT is 5 to 10 times higher than normal (1 - Borzakov S.N. and others. Viral and drug-induced liver damage in children, patients with tuberculosis: prevalence, clinical features., Expert. Clin., 2013; 1: 38-43). This method is adopted for analog.

A known method for the diagnosis of drug-induced liver damage by examining biochemical blood parameters (2 - http://viferon.su/lekarstvennyj-gepatit; Found Google, 06/03/2018). The method adopted for the prototype. However, this method is not sufficiently accurate in patients with non-alcoholic fatty liver disease (NAFAB).

The goal is to improve the accuracy of diagnosis of drug-induced liver damage in patients with non-alcoholic fatty liver disease.

The technical result is achieved by additionally determining the AlT / AST ratio, evaluating the RUCAM scale, conducting microscopic examination of biopsy specimens, and in the presence of hepatitis necrosis, intralobular and portal infiltration, and extralobular cholestasis, with an AlT / AST ratio of 5 or more, in the study of scale RUCAM 6 and more diagnose drug-induced liver damage in patients with non-alcoholic fatty liver disease

The method is implemented as follows.

Patients at admission complain of general weakness, discomfort in the right hypochondrium, jaundice of the sclera, skin and visible mucous membranes, pain in all parts of the abdomen.

Medical history of the disease: They consider themselves to be sick for several years, when aHCV was first identified. Received antiviral therapy with interferon for 12 months, at the end of therapy, the HCV virus was not detected. 2 months after the end of therapy, RNA HCV +. After several years, antiviral therapy with interferon was repeated (12 months). Over the next year, for the first time, an abdominal growth in the volume was detected, and therefore the patients were hospitalized.

Respiratory: A palpation painless, elastic. When topographic percussion - the boundaries of the lungs in the normal range. With auscultation - vesicular breathing. NPV 16-18 per min.

Circulatory system. The region of the heart and large vessels of the neck is not visually altered. The apical impulse is palpable in the V intercostal space, localized. Borders of relative cardiac dullness: the top 3 edge, left along the left mid-clavicular line, right at the level of the right edge of the sternum. Muffled heart sounds, correct rhythm. HELL: 110 / 70-130 / 80 mm Hg. Art. Pulse: 80-84 beats / min.

Digestive System: Oral mucosa is pink, clean. Tongue dry, white coated. The abdomen is enlarged due to ascites, participates in the act of breathing, with superficial palpation - painful in the right hypochondrium. Liver + 3-6 cm from the edge of the costal arch. Palpation thick, painless. Spleen - not palpable.

Urogenital system: The kidney area is not changed, the kidneys are not palpable. The symptom of "tapping" is negative on both sides. Diuresis is adequate.

The examination diagnosed - cirrhosis of drug etiology, class C in patients with non-alcoholic fatty liver disease. When examined by ultrasound: hepatosplenomegaly, portal hypertension, ascites. According to EGDS-GRVP 2 degrees.

Clinical blood test

Hemoglobin 13.5-14.0 (13.0-16.0) g / dL; Red blood cells 3.40-3.50 (4.00-5.00) 10 * 6 / μl; Hematocrit 35-38 (40.0-48.0) g / l; Platelets 110-115 (180-320) 10 ³ / µl; Leukocytes 7,5-8,2 (4,00-9.00) 10 ⁹ / l; Neutrophils 75-76 (48.00-78.00)%: Lymphocytes 18-18.9 (19.00-37.00)%; Basophils 1.5-1.6 (0.0-1.0)%; Monocytes 1.4-1.8 (3.0-11.0)%: Eosinophils 2.5-3.0 (0.5-5.0)%.

In b / chemical analysis of blood, markers of cholestatic syndrome (total bilirubin 450-500 µmol / l, straight line - 315-330 µmol / l, GGTP - 105-120 U / l, alkaline membrane - 200-230 U / l cytolytic syndrome (AlT - 220-240 U / l, AST - 38-40 U / l), creatinine - 320-350 μmol / l, urea - 9.2-9.6 mmol / l According to a coagological study - prothrombin - 25-30 % INR-2.55-2.62 sec.

A morphological study, a study on the RUCAM scale, the determination of the ratio AlT / AsT. The RUCAM scale includes the following criteria: the time interval from the start of taking or discontinuing the drug to the onset of manifestations of LPP, risk factors, the dynamics of the patient’s condition after discontinuation of the drug, risk factors, taking other drugs, excluding other etiological factors of liver damage, the likelihood of a drug reaction with the indication in the instructions for the drug and the response to reappointment.

A morphological study reveals hepatocyte necrosis, a large droplet and a small droplet of hepatocyte dystrophy, intralobular and portal infiltration and extralobular cholestasis. The RUCAM score is 6 or more. Alt / AsT ratio is 5 or more. The combination of these signs allows you to make a diagnosis - drug-induced liver damage in patients with non-alcoholic fatty liver disease. Portal hypertension: VRVP 2 st. Expansion of the portal and splenic, splenomegaly. Ascites 2-3 tbsp. Background - cirrhosis of the liver HCV etiology.

Against the background of the treatment (hepatoprotectors, diuretics), patients are discharged with improvement in the form of a decrease in the severity of ascites. Recommended intake of hepatoprotectors (phosphogliv) courses. The therapy was carried out with phosphoglive, beta-blockers with positive dynamics in the form of a decrease in the severity of cholestatic syndrome.

Drug hepatitis develops when taking chemotherapeutic drugs (cisplatin, gemcitabine), diclofenac and its derivatives, paracetamol, antibiotics (doxycycline) and other drugs and dietary supplements.

Recommendations

Compliance with the diet and diet, 5-6 meals a day, in small portions, completely eliminate alcohol intake, as well as fatty, fried, spicy, smoked. Limit salt intake. The use of hepatotoxic drugs and psychotropic drugs, NSAIDs, aminoglycosides, semi-synthetic penicillins, phytopreparations, dietary supplements is strictly prohibited.

Example 1

Patient K. On admission complains of general weakness, discomfort in the right hypochondrium, yellowing of the skin and sclera, darkening of the urine, discoloration of feces, aversion to food, loss of appetite.

Medical history of the disease: A patient has been taking psychotropic drugs for depression for 30 years (amitriptyline 20 mg / day, sonapax 20 mg / day, clonazepam 500 mcg / day). Since October 2017, for the first time, she noted the gradual yellowing of the skin, sclera. Turned to the clinic for m / f. The examination revealed mechanical jaundice, signs of biliary hypertension, laboratory hyperbilirubinemia up to 50 µmol / l. Subsequently, due to deterioration in the form of an increase in general weakness, a decrease in appetite, she independently applied to the hospital. ERCP, papillosphincterotomy, revision of the common bile duct, the cause of acute incomplete obstructive obstructive jaundice, biliary hypertension was stenosis of the terminal section of the common bile duct, and the bile ducts were drained using EPST. The patient was discharged with recommendations for taking UDCA 750 mg per day, antispasmodics, Heptral 400 mg × 2 p / d - without positive dynamics. Due to the increasing yellowness of the skin, the lack of positive dynamics against the background of the therapy, the patient was referred to ICB No. 2 to exclude viral damage to the liver. When additional data for viral liver damage was not detected; picture of obstructive jaundice. Transferred to the surgical department. According to MRI-mechanical jaundice was not detected, the picture of sclerosing cholangitis. Ascites Fibroelastometry of the liver, stage of liver fibrosis F4 on the METAV1R scale. The clinical picture of parenchymal jaundice, most likely, is due to a hit with cirrhosis of the liver. The patient was discharged with a diagnosis of cirrhosis of the liver (of unknown etiology). She was further consulted at the Sklifosovsky Research Institute - liver transplantation is not indicated. According to the results of recent studies, laboratory-pronounced cytolytic syndrome, minimal cholestasis, severe hyperbilirubinemia, hypokalemia, increased IgG levels to 2 norms, alpha-fetoprotein to 10 norms. LKM, ANA, AMA-M2 - negative. Due to the deterioration of the condition, the lack of positive dynamics of hospitalization again.

The general condition is severe. General inspection of BMI 22.6 (norm). Normostenic physique. Skin and visible mucous icteric staining. Palmar erythema. Peripheral lymph nodes are not enlarged. Bone and muscular system without features. Peripheral edema no. Height 156 cm. Weight 55 kg, Temperature 36 ° С.

The phenomena of encephalopathy persist as lethargy, lethargy. Skin and visible mucous icteric staining. Palmar erythema. There pastoznost legs and feet. Breathing weakened in n / o, no wheezing. NPV 16. Muffled heart sounds, regular rhythm. HR 84 beats / min. HELL 130/65 mm Hg. The abdomen is soft, palpation sensitive in the right hypochondrium. The liver and spleen are not palpable. The chair was once. Diuresis is sufficient.

Morphological examination of the liver reveals hepatocyte necrosis, a large droplet and a small droplet of hepatocyte dystrophy, intralobular and portal infiltration, and extralobular cholestasis. The RUCAM score is 6. The ratio of AlT / AsT is 5.5. The combination of these signs allows you to make a diagnosis - drug-induced hepatitis in patients with non-alcoholic fatty liver disease of the severe course with the transformation into liver cirrhosis. (K74.6)

Complication. Portal hypertension esophageal varicose veins 1 st. Portal gastropathy, portal vein expansion. Hypersplenism syndrome latent thrombocytopenia. Hepatocellular failure. Ascites 1 tbsp. Encephalopathy of mixed genesis (hepatic + vascular) 2-3 St with severe cognitive impairment in neurodynamic type in patients with NAFLD.

The main diagnosis is drug-induced hepatitis.

Treatment

Drug treatment. Survey and treatment of UDCA, lactulose, IPP, ademetionin / cap, prokinetics / m, ornithine / cap, correction of electrolyte disorders, diuretics, nutritive support in / in ka, GCS 120/90 mg / cap, cephalosporins in / in the page, antioxidants in / in the page, beta-blockers.

In the totality of the research conducted, the patient has a severe drug-induced lesion of the liver against the background of uncontrolled intake of psychotropic drugs. The phenomena of hepatocellular insufficiency are noted, it is impossible to exclude the transformation into cirrhosis of the liver. It is shown to continue therapy of GKS.

On the background of the therapy, positive dynamics in the form of improved blood laboratory parameters - increase in albumin, prothrombin, reduction of cytolytic syndrome and bilirubin.

Recommendations

Compliance with the diet and diet, 5-6 meals a day, in small portions, completely eliminate alcohol intake, as well as fatty, fried, spicy, smoked. Limit salt intake. The use of hepatotoxic drugs and psychotropic drugs, NSAIDs, aminoglycosides, semi-synthetic penicillins, phytopreparations, dietary supplements is strictly prohibited.

Pantoprazole 40 mg on 1 tab in the morning 15 minutes before a meal - 4 weeks, then 20 mg in the morning - 2 weeks. Lactulose 30 ml × 3 r / d to soft stool 2-3 times a day.

Spironolactone 25 mg 2 -1 - 1 tab + furosemide 40 mg 1 tab in the morning, under the control of weight, diuresis, abdominal volume, blood electrolytes (sodium, potassium) and nitrogen slags (creatinine) every 15 days, ultrasound control of ascites after 30 days and consultation of the gastroenterologist on m /. Ursodeoxycholic acid 250 mg 2 drops 2 times a day after meals - 6 months. Ciprofloxacin 750 mg 1 time per week for a long time.

Methylprednisolone 32 mg in the morning for 2 weeks, followed by a dose reduction of 4 mg 1 time in 3 days until completely discontinued.

L-ornithine L-aspartate 5 g for 1 pack × 3 p / d after meals for a month, then with courses 4 times a year. Metoprolol 25 mg × 2 p / d under the control of blood pressure (at least 90/60 mm Hg) and heart rate (at least 55). Preparations of potassium - magnesium 1-2 tab × 3 r / d for 3 weeks.

When follow-up observation for 1 year - a positive trend.

Example 2

Patient M., 46 years old, complains of yellowness of the skin and visible mucous membranes, weakness, discomfort in the right hypochondrium, pain in all parts of the abdomen.

Anamnesis. The patient received antiviral therapy in combination with paracetamol for a respiratory viral infection with high fever.

On the 3rd day of treatment, the appearance of ikterichnost sclera, frequent, pasty stools up to 8-10 times, accompanied by pain in all parts of the abdomen. There was a pronounced yellowness of the skin and visible mucous membranes, the pain syndrome persisted.

Clinical blood test

Hemoglobin 14.0 (13.0-16.0) g / dl; Red blood cells 3.50 (4.00-5.00) 10 * 6 / μl; Hematocrit 38 (40.0-48.0) g / l; Platelets 115 (180-320) 10 ³ / µl; Leukocytes 8.2 (4.00-9.00) 10 ⁹ / l; Neutrophils 76 (48.00-78.00)%; Lymphocytes 18.9 (19.00-37.00)%; Basophils 1.6 (0.0-1.0)%; Monocytes 1.8 (3.0-11.0)%: Eosinophils 1.6 (0.5-5.0)%.

In b / chemical analysis of blood - markers of cholestatic syndrome: total bilirubin 500 µmol / l, straight line - 330 µmol / l, GGTP - 120 U / l, ALP - 230 U / l cytolytic syndrome (AlT - 240 U / l, AcT - 31 U / l), creatinine - 350 µmol / l, urea - 9.6 mmol / l. According to the coagulogram - prothrombin - 30%, MHO - 2.62 seconds.

Survey data (cytolytic syndrome, cholestatic syndrome, hyperbilirubinemia, hepatodepression syndrome, portal hypertension). Inspection data (yellowness of the skin and visible mucous membranes, sensitivity to palpation in the right right hypochondrium, enlarged liver, increased abdominal volume, positive Shchetkin-Blumberg symptom). Put os: Cirrhosis

A morphological study, a study on the RUCAM scale, the determination of the ratio AlT / AsT.

A morphological study reveals hepatocyte necrosis, a large droplet and a small droplet of hepatocyte dystrophy, intralobular and portal infiltration and extralobular cholestasis. The RUCAM rating is 8. The ratio of AlT / AsT is 7.8. The combination of these signs allows you to make a diagnosis of drug-induced liver damage in patients with non-alcoholic fatty liver disease.

Diagnosed. Main. Fulminant drug hepatitis / toxic kidney damage on the background of antiviral therapy and paracetamol administration.

Complications: Hepatic renal failure. Portal hypertension: VRVP 2 tbsp., Expansion of the portal and splenic, splenomegaly. Ascites 2-3 tbsp. Hypersplenism: mild thrombocytopenia. Encephalopathy 2 tbsp.

Concomitant disease: Concomitant: Occlusive thrombosis of the superficial veins of the right shoulder. JCB: Chronic calculous cholecystitis.

Treatment

Drug treatment: Drug therapy was carried out by the following groups of drugs: Analgesics: Metamizole sodium + Pitofenon + Fenpiverinium bromide. Antibiotics: Imipenem + Cilastatin; Ceftriaxone. Hepatoprotectors: Ademethionine. Diuretics: Furosemide. Plasma substitutes: human albumin.

The patient is discharged. Gastroenterologist control. Treatment of drug-induced hepatitis was performed in 26 patients with NAFLD. Positive dynamics of treatment confirms the achievement of the goal of the invention - improving the accuracy of diagnosis of drug-induced liver lesions in patients with non-alcoholic fatty liver disease.

Information sources:

1. Borzakova S.N. Virus and drug-induced liver damage in children with tuberculosis: prevalence, clinical features. An expert. Wedge. Gastro 2013; 1: 38-43).

2. http://viferon.su/lekarstvennyj-gepatit; Found Google, 06/03/2018

Claims (1)

A method for diagnosing a drug-induced liver injury in patients with non-alcoholic fatty liver disease, including data from the history and clinical picture, characterized in that the AlT / AST ratio is additionally determined, the RUCAM score is evaluated, microscopic examination of biopsy specimens is performed, and in the presence of hepatocyte necrosis, intralobular and portal infiltration and extralobular cholestasis, the ratio of AlT / AST 5 and more, a study on the scale RUCAM 6 and more diagnose a drug induced lesion liver in patients with non-alcoholic fatty liver disease.