RU2337365C1 - Method of differential diagnostics of alcoholic and non-alcoholic steatohepatitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine area, namely, internal illnesses, and can be used for differential diagnostics of alcoholic and non-alcoholic steatohepatitis. Determine concentration of uroporphyrin (UP) and coproporphyrin (CP) in urine, and also content of CP and a protoporphyrin (PP) in feces at the patient with the established steatohepatitis diagnosis. Depending on set of their value, diagnose alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH).

EFFECT: possibility to differentiate steatohepatitis of alcoholic and non-alcoholic etiology.

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Description

The method relates to medicine, more specifically to internal medicine.

The main diagnostic method for steatohepatitis is a histological examination of liver biopsy. Histological changes in the liver are characterized by fatty degeneration of hepatocytes, steatonecrosis, intralobular inflammation and fibrosis (Sherlock Sh., Dooley J. Diseases of the liver and biliary tract. - M., 1999. - S.486-517). Steatohepatitis can also be detected by clinical, biochemical and instrumental (ultrasound) methods.

Strictly specific morphological characters that allow differentiating alcoholic and nonalcoholic steatohepatitis do not exist. The presence of Mallory's corpuscles only suggests that ethanol is a more likely etiological factor.

The well-known publication "Clinical and morphological features of alcoholic steatohepatitis" authors Mansurova H.Kh., Mirodzhova F.Kh. et al. (Clinical Medicine, 2005, No. 4, pp. 37-40). 48 patients with alcoholic steatohepatitis (ASH) were examined. All patients took into account the duration of alcohol abuse, performed ultrasound diagnostics of the liver and spleen, and a morphological study of liver biopsy samples. Among the biochemical parameters, gamma-glutamyl transpeptidase, alkaline phosphatase, nitrosyntetrazrazide, transaminases, bilirubin, cholesterol, triglycerides were analyzed. Also known is the work of Mansurov H.Kh. et al. “Some indicators of carbohydrate and lipid metabolism in non-alcoholic steatohepatitis” (Clinical Medicine, 2005, No. 6, pp. 47-50). It has been shown that carbohydrate and lipid metabolism disorders are pathogenetic mechanisms leading to the development of hypertension.

The authors conducted biochemical studies and registration of disorders (dysfunction of carbohydrate, lipid metabolism, increased enzyme activity, etc.) did not lead to the identification of disorders that would be specific for alcoholic or non-alcoholic steatohepatitis and would allow for their differential diagnosis.

Disclosure of invention

The essence of the proposed method for the differential diagnosis of alcoholic and nonalcoholic steatohepatitis is that in a patient with a diagnosed steatohepatitis, the concentration of uroporphyrin (UP), coproporphyrin (CP) in the urine, as well as the content of coproporphyrin and protoporphyrin (PP) in the feces and when:

- the content of KP in feces exceeding 16 nmol / g of dry weight, and / or the content of PP in feces exceeding 36 nmol / g of dry weight, against the background of normal or increased concentration of UP and KP in urine, ASH is diagnosed;

- the concentration of KP in urine exceeding 125 nmol / day against the background of normal concentration of UE in urine (≤45 nmol / day), normal content of KP (≤16 nmol / g dry weight) and PP (≤36 nmol / g dry weight ) in feces diagnosed with NASH.

If the patient’s analyzes do not fit into the specified criteria, then differential diagnosis with this method cannot be carried out.

We examined 24 patients (18 men and 6 women) aged 34 to 68 years (average age 52.4 years). In 19 patients, the diagnosis of steatohepatitis was made on the basis of histological examination of the liver, in 5 patients - by clinical, biochemical and instrumental (ultrasound) methods. The development did not include patients with blood diseases, viral liver lesions, as well as cirrhosis of the liver of various etiologies, chronic lead intoxication, in which porphyrin metabolism disorders can occur.

The diagnosis of ASH was made by identifying signs of chronic alcohol intoxication using rapid diagnosis using:

- modified test "Lego Grid",

- CAGE questionnaire (Congress on Alcohol and Healft, 1994),

- PAS profiles (Post-Intoxication Alcohol Syndrome),

- a test to detect latent alcohol dependence.

The habit of drinking alcohol was evaluated according to the recommendations of Kalinina A.M. et al. (Kalinina A.M., Pavlova L.I., Korolkov A.E. et al. // Therapeutic Archive. - 1988. - No. 10. - P.106-110).

All patients were divided into 2 groups. Group 1 included 5 patients with NASH. Group 2 consisted of 19 patients with ASH.

In all patients, bilirubin level, aminotransferase activity, serum concentration of total cholesterol and triglycerides, fasting glucose in capillary blood were determined.

The excretion of UP and CP in the daily urine volume was determined by chromatographic-spectrophotometric method using the Bio-systems test kit (Spain). The content of KP and PP in feces was determined by elution spectrophotometric method (Porfiry / Kuznetsova N.P., Pankov B.S., Chubarova A.S. et al. - M., 1981. - 192 p.). Quantitative calculation of the KP and PP fractions in the feces was carried out by spectrophotometric measurement of optical density on a domestic SF-24 spectrophotometer, followed by the use of the Rimington correlation coefficient formulas.

The data obtained were evaluated differentially and compared with the results of a survey of 22 healthy individuals.

The following data from a biochemical study of patients indicate disorders recorded in hypertension.

AlAT activity from 0.8 to 3.4 μmol / L (average 2.6 ± 0.3 μmol / L, normal 0.4 ± 0.2 μmol / L; p <0.001) was recorded in 21 patients (87, 5%), AcAT from 0.6 to 2.3 μmol / L (average 1.2 ± 0.4 μmol / L, normal 0.3 ± 0.1 μmol / L; p <0.001) - in 13 people (54.2%). Hyperbilirubinemia from 36.6 to 52.2 mmol / L (average 41.8 ± 2.2 μmol / L, normal 11.1 ± 0.4 μmol / L; p <0.001) was observed in 5 patients (20.8 %). Hypertriglyceridemia from 2.2 to 10.6 mmol / L (average 3.8 ± 0.4 mmol / L, normal 1.1 ± 0.1 mmol / L; p <0.001) was detected in 19 patients (79.2 %). The level of total cholesterol ranged from 5.8 to 8.9 mmol / L (average 6.8 ± 0.2 mmol / L, normal 4.3 ± 0.3 mmol / L; p <0.001). In general, in the group of examined hypercholesterolemia was detected in 12 patients (50%). Carbohydrate disorders (type 2 diabetes mellitus, impaired glucose tolerance) were observed in 11 patients (45.8%).

A differentiated assessment of porphyrin metabolism in 5 patients with NASH and 19 patients with ASH showed the following picture (see table).

Excretion of porphyrins with urine and their content in feces in patients with NASH and ASH Groups examined The content of porphyrins in urine, nmol / day The content of porphyrins in feces, nmol / g dry weight UP KP KP PP Norm (n = 22) 13 ± 2.9 57 ± 7.7 4.6 ± 0.6 10.5 ± 4.3 NASH (n = 5) 17.6 ± 6.7 336.8 ± 68.5 5.7 ± 2.4 17.6 ± 5.2 ASG (n = 19) 150 ± 43.8 * 126 ± 22.9 * 32.4 ± 5.8 * 69.7 ± 9.4 * Note. Legend: UP - uroporphyrin, KP - coproporphyrin, PP - protoporphyrin. * - differences between the NASH and ASH groups are statistically significant (p <0.05-0.001).

The scatter in the concentrations of porphyrin fractions in the healthy group was as follows:

- in urine: UP - from 0 to 45 nmol / day, KP - from 1.5 to 125 nmol / day;

- in feces: KP - from 0.2 to 16 nmol / g dry weight; PP - from 6 to 36 nmol / g dry weight.

The upper values of the normal concentration of porphyrin fractions were taken as criteria for the differential diagnosis of ASH and NASH.

In the group of patients with NASH, in all 5 patients the values of UE concentration in urine, the content of KP and PP in feces did not exceed the upper limit of the norm, i.e. amounted to: UE in urine ≤45 nmol / day; KP in feces ≤16 nmol / g dry weight; PP in feces ≤36 nmol / g dry weight. As for the concentration of KP in urine, in all 5 patients it exceeded the upper limit, i.e. was higher than 125 nmol / day.

In the group of patients with ASH in 13 patients out of 19, the content of KP in feces exceeded 16 nmol / g of dry weight, in 17 patients out of 19, the content of PP in feces exceeded 36 nmol / g of dry weight, and exceeding the upper limit of the norm in the content of KP or PP in feces were observed in all 19 patients. As for the concentration of UP and CP in the urine, in about half of the patients these indicators were within normal limits, and in the other half they exceeded the upper limit of the norm.

We give our observations as an illustration.

Observation 1. Patient R. (45 years old, medical history No. 86263) was admitted to the department complaining of weakness, dry mouth, frequent urination mainly at night, weight loss of 3 kg, lack of appetite, blood pressure lability, discomfort in the right hypochondrium , a feeling of heaviness and intermittent short-term pain.

Sick for about a year. An outpatient examination diagnosed arterial hypertension and revealed carbohydrate metabolism disorders. Family history data indicated maternal hyperlipidemia.

Alcohol is not abused. There are no clinical signs of chronic alcohol intoxication. The data from the modified Lego Grid test, CAGE questionnaire, PAS questionnaire and test for revealing latent alcohol dependence gave a negative result.

Condition upon receipt of satisfactory. The physique is correct, flesh-colored skin, pink mucous membranes, sclera of usual color. Height 174 cm, body weight 86 kg, BMI 28.4 kg / m ² , waist circumference 108 cm. In the lungs vesicular breathing, no wheezing. Heart sounds are muffled, rhythmic, II tone accent above the aorta, heart rate - 78 per minute. HELL - 140/100 mm Hg The abdomen is regular in shape, symmetrical, soft, painless on palpation. The lower edge of the liver is smooth, rounded, protrudes 3 cm from the edge of the costal arch, the liver is densely elastic, its surface is even, according to Kurlov 16 × 10 × 9 cm. The spleen is not palpable.

Instrumental studies: ultrasonography - hepatomegaly, signs of fatty hepatosis; ECG - sinus rhythm 72 per minute, diffuse changes in the myocardium. Bicycle ergometry: the test with physical activity is positive, the ST offset is 1 mm below the contour line. Daily monitoring of blood pressure: maximum SBP - 172 mm Hg, DBP - 104 mm Hg; minimum GARDEN - 93 mm Hg, DBP - 63 mm Hg

Laboratory research data: general analysis of blood and urine without pathology; total bilirubin - 17.4 μmol / l, direct - 2.1 μmol / l; AsAT - 0.7 μmol / l, AlAT - 0.8 μmol / l; total cholesterol - 8.9 mmol / l, triglycerides - 8.4 mmol / l; fibrinogen - 5.2 g / l; fasting blood sugar - 11.8 mmol / L. 2 hours after eating, blood sugar -14.8 mmol / L. Markers of viral hepatitis B and C are negative.

A puncture biopsy of the liver was performed. Histological examination data: in the liver tissue, pronounced large-droplet fatty degeneration, sclerosis and usual inflammatory infiltration along the portal tracts are observed.

In the study of porphyrin metabolism, secondary coproporphyrinuria was detected. Excretion of porphyrins with urine: UP - 12 nmol / day, KP 244 nmol / day. The content of porphyrins in feces: KP 1.8 nmol / g dry weight, PP 11.4 nmol / g dry weight.

Based on the clinic and examination data, the diagnosis was made: coronary heart disease, angina pectoris of FC _II , arterial hypertension of degree II risk class 4, diabetes mellitus type 2, non-alcoholic steatohepatitis.

Observation 2. Patient B., 54 years old, was hospitalized in the clinic with complaints of dry mouth, thirst, weakness. Since 1998, he suffers from arterial hypertension, and in 2000 diabetes was diagnosed.

The data from the modified Lego Grid test, the CAGE questionnaire, the PAS questionnaire and the test for revealing latent alcohol addiction gave a positive result. Consumes alcohol systematically (up to 4-5 times a week).

The condition is satisfactory. The physique is correct. Signs of chronic alcohol intoxication were revealed: facial skin hyperemia, hypertrophy of the parotid salivary glands and Dipuytren's contracture of the 4 phalanges of the left hand. The subcutaneous fat layer is overdeveloped, waist circumference 112 cm, body mass index 29.7 kg / m ² . In the lungs, vesicular breathing, no wheezing. Heart sounds are muffled, rhythmic, pulse - 76 per minute. HELL - 160/100 mm Hg The abdomen is soft, painless. The liver protrudes 2 cm from the edge of the costal arch.

ECG: sinus rhythm, signs of left ventricular hypertrophy. Ultrasonography - hepatomegaly, signs of fatty hepatosis.

Laboratory data: a general blood test is within normal limits. Proteinuria was detected in the urine - 0.009 g / day. Total bilirubin - 20 mmol / L, AcAT - 0.8 μmol / L, AlAT - 0.3 μmol / L, blood sugar from 7.2 to 15.2 mmol / L during the day; triglycerides - 3.3 mmol / l; total cholesterol - 7.4 mmol / l; fibrinogen - 5.3 g / l.

In the study of porphyrin metabolism, increased excretion with urine of UE (172 nmol / day) and KP (225 nmol / day) were noted, in the feces, the content of KP (50.5 nmol / g dry weight) and PP (141.9 nmol / g dry weight).

Diagnosed with grade II arterial hypertension, risk 4; type 2 diabetes mellitus, moderate severity, decompensation phase; alcoholic steatohepatitis.

Claims (1)

A method for the differential diagnosis of alcoholic and nonalcoholic steatohepatitis, characterized in that in a patient with a diagnosed steatohepatitis, urroporphyrin (UP) and coproporphyrin (CP) in the urine are determined, as well as the content of coproporphyrin and protoporphyrin (PP) in the feces and when the content of CP in the feces in excess of 16 nmol / g dry weight and / or the content of PP in feces in excess of 36 nmol / g dry weight against the background of normal or elevated concentrations of UP and KP in urine, ASH is diagnosed; and at a concentration of KP in urine exceeding 125 nmol / day. against the background of normal concentration of UE in urine (≤45 nmol / day), normal content of KP (≤16 nmol / g dry weight) and PP (≤36 nmol / g dry weight) in the feces, NASH is diagnosed.