RU2386134C1 - Differential diagnostic technique for intrahepatic cholestasis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention can be applied as a differential diagnostic technique for intrahepatic choloestasis (IHC) in chronic liver diseases. Substance of the technique consists in evaluating the ratio of gamma glutamyl transpeptidase to alkaline phosphatase (GGTP/AP), gamma glutamyl transpeptidase to leucine aminopeptidase (GGTP/LAP), alkaline phosphatase to leucine aminopeptidase (AP/LAP) in blood serum. Intrahepatic cholestasis is diagnosed for the patients with drug-induced hepatitis in case GGTP/AP is more than 1, GGTP/LAP is less than 4, AP/LAP is less than 4. In patients with alcoholic liver disease, IHC is detected by GGTP/AP more than 1, GGTP/LAP less than 2.5, AP/LAP less than 2.5. IHC is diagnosed for patients with primary sclerosing cholangitis with GGTP/LAP more than 4, GGTP/AP more than 1, AP/LAP less than 3. If GGTP/AP is less 0.5, GGTP/LAP is more than 4, AP/LAP is more than 5, IHC is diagnosed for the patients with primary biliary cirrhosis.

EFFECT: application of the technique allows improving accuracy of differential diagnostics for intrahepatic cholestasis in chronic liver diseases.

5 ex, 5 tbl

Description

The invention relates to medicine, namely to hepatology, and can be used as a method of differential diagnosis of intrahepatic cholestasis.

A known method for the diagnosis and differential diagnosis of intrahepatic cholestasis by puncture biopsy of the liver and subsequent histological examination (1 - Podymova S.D. Liver diseases. M., 1984). This method is taken as an analog.

A known method for the differential diagnosis of intrahepatic cholestasis by evaluating clinical symptoms, namely jaundice, the presence of xanthelasma, skin itching, hepato- and splenomegaly (2 - Podymova SD, Diseases of the liver. M., 1984). This method is adopted as a prototype.

However, the prototype method provides only a rough estimate of the development of various types of hepatic cholestasis.

The aim of the present invention is to improve the accuracy of the differential diagnosis of intrahepatic cholestasis.

The technical result is achieved by the fact that in the method for diagnosing intrahepatic cholestasis in chronic liver diseases, the ratios of gamma-glutamyl transpeptidase to alkaline phosphatase (GGTP / ALP), gamma-glutamyl transpeptidase to leucine aminopeptidase (GGTP / LAP), and alkaline phosphatase to serum / leptinopept are determined intrahepatic cholestasis in patients with drug hepatitis with GGTP / ALP is greater than 1, GGTP / LAP is less than 4, ALP / LAP is less than 4; in patients with alcoholic liver disease with GGTP / ALP more than 1, GGTP / LAP less than 2.5, ALP / LAP less than 2.5; in patients with primary sclerosing cholangitis with GGTP / LAP more than 4, GGTP / ALP more than 1, ALP / LAP less than 3; in patients with primary biliary cirrhosis with GGTP / ALP less than 0.5, GGTP / LAP more than 4, ALP / LAP more than 5.

The method is implemented as follows.

Patients come with the presence of skin itching, yellowness of the skin and sclera, the presence of telangiectosis and hepatic palms. From the anamnesis it is known that patients suffered from drug-induced hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, and also alcoholic liver disease.

On palpation, compaction and tenderness of the edge of the liver are noted. With ultrasound, the liver and spleen are enlarged. An endoscopic examination revealed varicose veins of the esophagus. Biochemical studies show an increase in the level of liver enzymes - gamma glutamyl transpeptidase, leucine aminopeptidase, silk phosphatase, as well as changes in cholesterol, bilirubin, platelet count, prothrombin and protein fractions.

Ultrasound and computer studies show an increase in the size of the liver, an increase in its echogenicity, dilatation of the portal and splenic veins, dilatation of the veins of the anterior abdominal wall.

Further, intrahepatic cholestasis is diagnosed for chronic liver diseases, determining the ratios of gamma-glutamyl transpeptidase to alkaline phosphatase (GGTP / ALP), gamma-glutamyl transpeptidase to leucine aminopeptidase (GGTP / LAP), and patients with alkaline phosphatase to leucine amine peptidase and with drug hepatitis with GGTP / ALP greater than 1, GGTP / LAP less than 4, ALP / LAP less than 4; in patients with alcoholic liver disease with GGTP / ALP more than 1, GGTP / LAP less than 2.5, ALP / LAP less than 2.5; in patients with primary sclerosing cholangitis with GGTP / LAP more than 4, GGTP / ALP more than 1, ALP / LAP less than 3; in patients with primary biliary cirrhosis with GGTP / ALP less than 0.5, GGTP / LAP more than 4, ALP / LAP more than 5.

The method is confirmed by the following examples.

Example 1

Patient Xn, 78 years old, was admitted with a diagnosis of primary biliary cirrhosis. From the anamnesis it is known that the patient has been using proton pump inhibitors, non-steroidal anti-inflammatory drugs, and drugs that lower blood pressure over the past 20 years.

Upon admission, general weakness, bloating, swelling of the legs, loose stools up to 3-4 times a day are noted. Appetite is reduced. Over the past 3 months, he lost 4 kg. Considers herself ill since February 2004, when bitterness in the mouth and weakness appeared. With CT, diffuse changes in the liver, splenomegaly. Virological examination is negative.

Upon admission: satisfactory condition. The skin is pale. In the lungs, vesicular breathing, no wheezing. BH 18 in minutes Heart sounds of normal sonority, rhythmic, heart rate 76 per min. HELL 130/80 mm Hg The abdomen is soft, painless. The liver +2 cm from the edge of the costal arch, the spleen is not palpable. There is no dysuria.

Ultrasound There is no free fluid in the abdominal cavity. The size of the liver is slightly increased (thickness of the right lobe 134 mm, left lobe - 60 mm), unevenly increased echogenicity. Visibility of vascular structures is significantly impaired. Gall bladder -7 × 2 cm, uniform thickening of the walls of the gall bladder up to 3 mm. The caliber of the common bile duct is normal (3 mm). The pancreas is within normal limits (head - 23 mm, body - 14 mm, tail - 24 mm). Echogenicity is unevenly increased. The size of the spleen is increased (area 101 sq. Cm). Expansion of the splenic (1.1 cm) and portal (1.6 cm). The kidneys are within normal limits.

Conclusion Diffuse liver damage. Portal hypertension.

ECG. Normal position of the electrical axis of the heart. Sinus rhythm, correct. Heart rate 81.

The mucous membrane of the stomach is thinned, in the antrum it has a mottled appearance. The gatekeeper is going through. On the front wall of the duodenal bulb, a post-ulcerous scar is visible. Conclusion: chronic gastroduodenitis, varicose veins of the esophagus of the first degree, moderately pronounced cicatricial ulcer deformation of the duodenal bulb.

The conclusion of the neurologist. Encephalopathy II degree.

Irrigoscopy. The colon is retrograde filled, the pelvic location of the rectum. The contours of the colon are clear, even, the haustra are well defined. Conclusion: dyskinesia of the colon.

CT scan. The liver is not enlarged, with clear even contours, pronounced vascular pattern. Hepatic parenchyma 50+ units. The gallbladder is of normal shape. The pancreas is of normal size, the outline is clear, even, the parenchyma is homogeneous. The spleen is huge, homogeneous. The right kidney is usually located, the left is pushed to the right by an enlarged spleen. HR is not increased. Conclusion on CT data: splenomegaly with dislocation of the left kidney, diffuse changes in the liver.

Scintigraphy. The accumulation of fluoropharmaceutical in the anterior-middle liver projection is up to 65%, spleen - 35%. The spleen is usually located, the location of the radiopharmaceutical in the liver is uneven. Conclusion: scintigraphic signs of diffuse changes in the liver.

LABORATORY DATA

General urine analysis: beats. weight -1019, protein, sugar - no, white blood cells - units. in s / sp.

The ratios of gamma-glutamyl transpeptidase to alkaline phosphatase (GGTP / ALP), gamma-glutamyl transpeptidase to leucine aminopeptidase (GGTP / LAP), alkaline phosphatase to leucine aminopeptidase (ALP / LAP) in the blood serum are determined; in patients with primary biliary cirrhosis with GGTP / ALP less than 0.5, GGTP / LAP more than 4, ALP / LAP more than 5 diagnosed with primary biliary cirrhosis.

Example 2

Patient B-in, 48 years old, was admitted with a diagnosis of primary sclerosing cholangitis. Portal hypertension. Varicose veins of the esophagus I degree. Thrombocytopenia. Encephalopathy of mixed origin. Chronic gastritis. Biliary pancreatitis in the stage of subsiding exacerbation.

Upon receipt of a complaint about an increase in the volume of the abdomen, weakness, nausea, loss of appetite, pain in the right iliac region. The state of moderate severity. The skin is icteric, large telangiectasias, and sclera are icteric. In the lungs, harsh breathing, X-ray pneumosclerosis. Heart sounds are sonorous, rhythmic, heart rate of 100 per min. HELL 110/70 mm Hg Palpation of the liver is painful.

Ultrasound The size of the liver is increased (thickness of the right lobe 146 mm, left 82 mm), a pronounced uneven increase in the echogenicity of the echo signals with a predominance of high-intensity signals, the visibility of the vascular structures is weakened. The gallbladder is 3.2 × 2.1 cm, the wall is thickened to 4 mm, the contents are uniform in the cavity. The common bile duct is within normal limits. The pancreas is not visualized. The size of the spleen increased 174 × 82 mm (area 118 cm ² ). Portal vein gauge 1.6 cm, splenic - 1.2 cm, enlarged. Sound properties of the kidneys are within normal limits. Conclusion: diffuse liver damage. Portal hypertension.

ECG. The horizontal position of the electrical axis of the heart. Sinus rhythm, correct. Heart rate 97 per minute. Moderately pronounced diffuse changes in the myocardium.

Endoscopic endoscopy: Conclusion: Varicose veins of the esophagus I degree. Chronic gastritis.

Chest x-ray: Diffuse pneumosclerosis. The shadow of the heart is slightly widened to the left.

General urine analysis: beats. weight - 1014, protein, sugar - no, white blood cells - 3-4 in s / sp. Urine diastasis: 236 U / L (Norm up to 450).

Diagnosis of intrahepatic cholestasis in chronic liver diseases is carried out by determining the ratios of gamma-glutamyl transpeptidase to alkaline phosphatase (GGTP / ALP), gamma-glutamyl transpeptidase to leucine aminopeptidase (GGTP / LAP), and alkaline phosphatase to leukin amine peptiditis and / LAP more than 4, GGTP / ALF more than 1, ALF / LAP less than 3.

Example 3

Patient Bn, 19 years old, was admitted with a diagnosis of primary sclerosing cholangitis. Portal hypertension: expansion of the portal and splenic veins. Splenomegaly. Received complaints of skin itching, aggravated by night, episodes of severity in the right hypochondrium, severe flatulence. According to the mother, the cause of the disease was poor vaccination.

Objectively: the condition is satisfactory. The skin and visible mucous membranes are icteric, of moderate humidity. In the lungs, vesicular breathing, no wheezing, BH 17 in min. Heart sounds are sonorous, the rhythm is correct, systolic murmur at the apex, heart rate of 80 per minute. HELL 110/70 mm Hg The tongue is coated with white plaque. The abdomen is not enlarged, painless on palpation. Palpation of the liver is difficult due to well-defined abdominal pressure, percussion the lower edge of the liver protrudes 4 cm from under the edge of the costal arch. The spleen is not palpable. Stroke syndrome is negative on both sides. Ascites, no edema.

Ultrasound The liver is enlarged (the thickness of the right lobe is 138 mm, the thickness of the left lobe is 88 mm), the structure is heterogeneous, and the echogenicity of the liver tissue is increased. The vascular pattern is depleted. The portal vein gauge is 12 mm (normal). The gallbladder is 54 × 23 mm, the walls of the bladder are thickened to 3 mm, their echogenicity is increased, the structure is homogeneous. Caliber of the common bile duct 3 mm. The pancreas is not enlarged (head 22 mm, body 12 mm, tail 18 mm), the contours are even, clear, the echogenicity of the tissue is not changed, the structure is homogeneous, the Wirsung duct is 1 mm. The spleen is enlarged (area 74 sq.cm, 161 mm × 66 mm). The splenic vein gauge is 7 mm (not expanded). The kidneys are typically located, the contours are even, clear. The right kidney is 109 × 48 mm, the left kidney is 109 × 48 mm. The corticomedullary differentiation is preserved, the pyelocaliceal system is not expanded. There are no calculi, additional formations. Paranephric fiber is not changed. The adrenal gland is not changed. There is no free liquid. Loops of the intestines are not expanded. Conclusion: signs of diffuse liver damage.

Endoscopy: upon examination of the esophagus, the mucous membrane of it is light pink. The cardia socket closes. The mucous membrane of the stomach in the antrum is somewhat hyperemic, erosive-ulcerative changes were not detected. Folds straighten out with air. Peristalsis is normal. The gatekeeper is free to pass. The mucous membrane of the duodenal bulb is light pink, elastic folds. Conclusion: chronic, slightly pronounced gastritis of the antrum.

ECG: deviation of the electrical axis of the heart to the right, sinus rhythm, correct heart rate of 60 per min.

Puncture biopsy of the liver. The portal tracts are dilated, infiltrated by lymphocytes and severely fibrosed. Hyperplasia of the ducts, proliferation of epithelial cells of the bile ducts and severe periductural fibrosis are noted. Cells of proliferating epithelium violate the integrity of the border plate and penetrate deep into the lobules. Connective tissue cords with the formation of perihepatocellular fibrosis and false lobules extend from some portal tracts deep into the lobules. Pathological conclusion: primary sclerosing cholangitis 2-3 stages.

Computed tomography of the abdominal organs (with intravenous contrast): on a series of consecutive CT sections in axial projection, an image of the abdominal organs and retroperitoneal space is obtained. In the projection of the pleural sinuses and abdominal cavity, free fluid is not determined. The liver is enlarged due to the left and caudate lobes, with clear even contours, structurally homogeneous. The density of the hepatic parenchyma is 48-50 units of N before contrast and 67 units of N after. Portal vein expanded to 16.5 mm. The gallbladder is not enlarged, the walls are not thickened, the contents are homogeneous. The cystic duct, common hepatic and common bile ducts are not dilated, their walls are thickened, densified: cystic and common hepatic with a diameter of 2.5 mm, walls 2.5-3 mm, choledoch in the terminal section with a diameter of 5.4 mm with walls 4 mm thick . The pancreas is not enlarged in size, the contours of the gland are even, clear, its parenchyma is homogeneous, the density is 54-57 units N before contrast and 65 units N after. Wirsung duct is not expanded. Parapancreatic fiber is not changed. The spleen was enlarged in size - 113 × 80 × 140 mm, in the parenchyma of its foci of pathological density was not detected. Splenic vein 10 mm. The adrenal glands are usually located, structurally and unchanged in size. The kidneys are usually located, their shape and size are not changed. Kidney parenchyma without foci of pathological density. HR is not changed. Rg-contrast calculi in renal heart disease are not determined. Paranephric fiber is not changed. At the investigated level, retroperitoneal lymph nodes are not enlarged. Conclusion: CT scan signs of cirrhosis. CT signs of cholangitis. CT signs of portal hypertension.

LABORATORY DATA

General urine analysis: beats. weight - 1013, protein - 0.02, sugar - no, bilirubin +, urobilinoids +, white blood cells - 2-3-4 in n / a. Analysis of daily urine for copper 14.1 mcg / day (0.0-60.0).

Diagnosis of intrahepatic cholestasis in chronic liver diseases is carried out by determining the ratios of gamma-glutamyl transpeptidase to alkaline phosphatase (GGTP / ALP), gamma-glutamyl transpeptidase to leucine aminopeptidase (GGTP / LAP), and alkaline phosphatase to leukin amine peptiditis and / LAP more than 4, GGTP / ALF more than 1, ALF / LAP less than 3.

Example 4

Patient Z-na, 64 years old, was admitted with a diagnosis of drug hepatitis, chronic cholecystitis in remission, chronic pancreatitis in old remission. On admission, she complained of general weakness, skin itching, and periodic nausea after eating. In August of this year, she consulted a doctor about a troubling skin itch.

Upon receipt, the general condition is satisfactory. The color of the skin is not changed. Palmar erythema, xanthomas in the face. In the lungs, vesicular breathing, wheezing is not heard. BH 17. Rhythmic heart sounds, heart rate 80, blood pressure 160/90. The abdomen is enlarged due to the pronounced subcutaneous fat, palpation is soft, painless. The liver does not protrude from under the costal arch. The spleen is not palpable.

Ultrasound Liver - the size of the liver is increased due to the left lobe, the structure of the parenchyma is homogeneous, echogenicity is significantly increased, the vascular pattern is preserved. The portal vein is not dilated. Gall bladder - dimensions are not changed, sludge. The walls are thickened unevenly to 3.3 mm, echogenicity is increased, the structure is heterogeneous. Pancreas - dimensions are not changed: head - 26 mm, body - 8 mm, tail - 25 mm, parenchyma structure is homogeneous, fine-grained, increased echogenicity. Wirsung duct is not expanded. Spleen - dimensions not changed, area 36 cm ² . The splenic vein is not dilated. Conclusion: diffuse liver damage, chronic cholecystitis, chronic pancreatitis in remission.

Endoscopy. An examination of the esophagus revealed no pathology. The mucous membrane of the stomach is thinned in places, and in the antrum in some places it is fine-grained. Peristalsis is normal. The mucous membrane of the duodenum is light pink, elastic folds. Conclusion: chronic focal gastritis.

ECG: Normal position of the electrical axis of the heart. Sinus rhythm, correct. Heart rate 74 per minute. Moderately pronounced diffuse changes in the myocardium.

LABORATORY DATA

Upon enrolment At discharge Upon enrolment At discharge Hemoglobin 140 133 Bilirubin 14.5 15.0 Red blood cells 48 4.83 Cholesterol 5.8 8.5 White blood cells 5,4 6.0 Alkaline phosphatase 193.4 218.0 Eosinophils 2.0 one GGTP 73.1 55.3 PO Box one 2 AcT 47.5 41.9 s / i 54 58 Alt 47.5 42 Lymphocytes 38 34 Glucose 6.3 7.2 Monocytes 5,0 5,0 Amylase ESR 7.0 12 Total protein 65,4 74 Prothrombin one hundred one hundred Albumin 42.3 47 Platelets 123 152 Paw 55

General urine analysis: beats. weight 1017, protein, sugar - no, white blood cells - 4-5 in s / sp.

Diagnosis of intrahepatic cholestasis in chronic liver diseases is carried out by determining the ratios of gamma-glugamyl transpeptidase to alkaline phosphatase (GGTP / ALP), gamma-glutamyl transpeptidase to leucine aminopeptidase (GGTP / LAP), and patients with alkaline phosphatase to leucine amine peptidase and hepatitis HGTP / ALP is greater than 1, GGTP / LAP is less than 4, ALP / LAP is less than 4.

Example 5

A 48-year-old patient M was admitted with a diagnosis of liver cirrhosis of alcoholic etiology of active subcompensated, Child-Pu A. Portal hypertension, ascites, splenomegaly. Varicose veins of the esophagus I degree. Chronic pacreatitis, remission. Arterial hypertension. Upon receipt, the condition is satisfactory, complaints of heaviness in the right hypochondrium.

The skin is of normal color. In the lungs, vesicular breathing, no wheezing. BH 18 in minutes Heart sounds of normal sonority, heart rate 74 per min. HELL 130/90 mm Hg The abdomen is soft, painless. The liver is increased by 2 cm due to the right lobe, with palpation is dense, the spleen is not palpable. There is no dysuria.

Ultrasound A small amount of free fluid in the abdominal cavity; liver - liver sizes are increased (thickness of the right lobe 139 mm, left 78 mm), uneven increase in echogenicity, the visibility of the vascular structures is weakened. Gall bladder 6.6 × 2.3 cm. The common bile duct (3 mm) and pancreas (24-16-12 mm) are within normal limits. Echogenicity is unevenly increased. Roughness of the contour. The size of the spleen is increased (area 79 cm ² ). The portal vein gauge 1.4 cm, splenic 1.0 cm. Conclusion: diffuse liver damage. Portal hypertension. Ascites. Chronic pancreatitis.

Liver scintigraphy. The position of the liver relative to the costal arch is normal. The shape of the liver is not changed. The contours of the image are smooth. The distribution of the radiopharmaceutical in the liver is diffusely uneven. The spleen is visualized, the location is normal. Conclusion: Scintigraphic signs of diffuse liver damage.

LABORATORY DATA

Upon enrolment At discharge Upon enrolment At discharge Hemoglobin 16.1 14.8 Bilirubin 22.3 21.3 Red blood cells 5.2 4.92 Cholesterol 4.8 4.9 White blood cells 7.6 4.8 Alkaline phosphatase 115 109 Eosinophils 2.0 2.0 GGTP 123 113 PO Box 2 one AcT eighteen 26 s / i 53 56 Alt 33.6 42 Lymphocytes 36 36 Glucose 5,4 5.89 Monocytes 7.0 5,0 ESR 23.0 16,0 Total protein 86 81 Prothrombin 83 92 Albumin 47 49 Platelets 196 254 Paw 52

General urine analysis: beats. weight - 1017, protein, sugar - no, white blood cells - 4-5 in s / sp.

Diagnosis of intrahepatic cholestasis in chronic liver diseases is carried out by determining the ratios of gamma-glutamyl transpeptidase to alkaline phosphatase (GGTP / ALP), gamma-glutamyl transpeptidase to leucine aminopeptidase (GGTP / LAP), and alkaline phosphatase to hepatic leukin amine peptidase and / Alkaline phosphatase greater than 1, GGTP / LAP less than 2.5, alkaline phosphatase / LAP less than 2.5.

According to the stated criteria, 115 patients were examined, high diagnostic reliability of the identified criteria for differential diagnosis was revealed. intrahepatic cholestasis in various etiological forms of liver disease.

Claims (1)

A method for the diagnosis of intrahepatic cholestasis in chronic liver diseases by determining the ratio of gamma-glutamyl transpeptidase to alkaline phosphatase (GGTP / ALP), gamma-glutamyl transpeptidase to leucine aminopeptidase (GGTP / LAP), alkaline phosphatase to leukin aminopeptidase (ALF) drug hepatitis with GGTP / ALP is greater than 1, GGTP / LAP is less than 4, ALP / LAP is less than 4; in patients with alcoholic liver disease with GGTP / ALP more than 1, GGTP / LAP less than 2.5, ALP / LAP less than 2.5; in patients with primary sclerosing cholangitis with GGTP / LAP more than 4, GGTP / ALP more than 1, ALP / LAP less than 3; in patients with primary biliary cirrhosis with GGTP / ALP less than 0.5, GGTP / LAP more than 4, ALP / LAP more than 5.