Alkaline phosphatase: can it be considered as an indicator of liver fibrosis in non-alcoholic steatohepatitis with type 2 diabetes?

OBJECTIVE: While isolated hepatosteatosis is a benign disease, in minority of cases non-alcoholic steatohepatitis (NASH) may even lead to cirrhosis in long-term. In order to find the stage of the disease and determine the prognosis, a liver biopsy is indicated. In this study, we studied the relationship of liver histopathological findings with serum levels of hepatic enzymes. METHODS: We recruited 52 cases of NASH with Type 2 diabetes mellitus. Diagnosis of NASH was made based on biochemical tests, ultrasound images and liver biopsy. RESULTS: Steatosis was mild in 57.7%, moderate in 30.8%, and severe in 11.6% of patients. While no infiltration was found in 78.8% of cases, there was a grade-1 infiltration in 15.4% and a grade-2 infiltration in 5.8% of cases. Similarly, no fibrosis was found in 42.3% of patients, but there was a stage-1 fibrosis in 50%, and a stage-2 fibrosis in 7.7% of cases. In patients with severe steatosis, serum levels of AST were higher than mild or moderate stage steatosis. Accordingly, in patients with no inflammation, serum levels of ALT were higher than in patients with inflammation. However, in patients with fibrosis, triglycerides levels were significantly lower and ALP was significantly higher than in patients without fibrosis. The correlation analysis indicated a positive association between serum levels of ALP and C-peptide. CONCLUSION: In addition to conventional risk factors such as age, presence of diabetes, female sex; higher levels of ALP may be considered as a risk factor linked to hepatic fibrosis in patients with NASH and type 2 diabetes (Tab. 6, Ref. 8).

Value of copper-associated protein in diagnostic assessment of liver biopsy.

Of 1361 consecutive liver biopsy specimens, 24% contained orcein-positive granules. The highest incidence of positivity was found in biliary disease (90.9%), long before cirrhosis had developed, whereas in chronic non-primarily biliary disease, positive results were almost exclusively in patients with well established cirrhosis. Orcein-positive granules were never found in acute liver disease. These granules were also demonstrated in tumour cells of primary hepatocellular tumours (benign 4 of 4 cases; malignant 9 of 37 cases), while all the secondary tumour deposits were negative. In our view the additional information obtained by this technique warrants its adoption as a routine procedure.

Tuberculous peritonitis--reports of 26 cases, detailing diagnostic and therapeutic problems.

OBJECTIVE: To evaluate the clinical presentation, biochemical (ascites and serum) and laparoscopic findings, and to assess the efficacy of triple antituberculous therapy without rifampicin for 6 months in patients with tuberculous peritonitis. METHODS: Twenty-six tuberculous peritonitis patients (11 male, 15 female) with a mean age of 34.8 +/- 3.4 years (range 14-77) were assessed with regard to diagnostic and therapeutic features. RESULTS: The most common symptoms and signs were abdominal pain (92.3%) and ascites (96.2%), respectively. Tuberculin skin test (TST) was positive in all patients. An abnormal chest radiography suggestive of previous tuberculosis was present in five patients (19.2%), and two patients (7.7%) had extra-peritoneal (cerebral, pericardial) active tuberculous involvement. In 24 of the 25 patients who underwent laparoscopy with directed biopsy, whitish nodules suggested tuberculous peritonitis; 76% of the biopsy specimens revealed caseating, 20% non-caseating granulomatous inflammation, and 4% non-specific findings. The ascitic fluid of one patient (3.8%) was positive for acid-resistant bacilli, and culture was positive in two patients (7.7%). Twenty-four of the patients were treated for 6 months with isoniazid, streptomycin (total dose 40 g) and pyrazinamide (for the first 2 months and then substituted with ethambutol). Eighteen patients also received methyl prednisolone, initially 20 mg/day, for 1 month. The follow-up period was 19 +/- 1.7 months after the end of therapy (range 6-36). Ascites and abdominal pain abated earlier in patients on steroid therapy. All but two of the 24 patients responded to treatment. CONCLUSION: Non-invasive tests such as acid-fast stain and culture of the ascitic fluid are usually insufficient, hence invasive laparoscopy and peritoneal biopsy are necessary for the diagnosis of tuberculous peritonitis if non-invasive tests such as ascites adenosine deaminase activity measurement are not easily available. Triple therapy without rifampicin for 6 months is sufficient to treat tuberculous peritonitis.

Phantom steatosis of the liver: report of a case.

A patient, referred under a diagnosis of metastatic liver tumors, was found to have multiple areas of focal fatty change (FFC) which, during follow-up, exhibited discordant evolutions. To our knowledge, this phenomenon-regression of a FFC lesion with concurrent appearance or progression of other similar lesions in the same patient, has been reported in only one previous case. FFC can be strongly suggested by clinical, biochemical and radiologic criteria. However, an exact diagnosis can only be made with biopsy. To avoid misdiagnosing a malignancy as FFC and vice versa, biopsy should be performed without hesitation in all patients in whom a change in approach is possible.

Granulomatous hepatitis: MRI findings.

The purpose of this study was to describe the magnetic resonance imaging findings of granulomatous hepatitis on T1-weighted, T2-weighted and postgadolinium images. Eight patients with histopathological diagnosis of granulomatous hepatitis were evaluated in this study. MRI examinations included precontrast T1-weighted breath-hold spoiled gradient echo, breathing independent STIR sequences, and T1-weighted breath-hold spoiled gradient-echo sequence following after i.v. gadolinium administration in arterial, intermediate and late phases. Diffuse nodular liver involvement was visualized in all patients. Nodules were consistent with granulomas and were 0.5-4.5 cm in diameter. Caseating granulomas were intermediate and high signal on T2-weighted, low signal on T1-weighted images. They revealed no enhancement in two patients, and enhanced in one patient. Noncaseating granulomas revealed intermediate signal on T1, and T2-weighted images and increased enhancement on arterial phase images with persisting enhancement in late phase images. Portal lymph nodes were visible in five patients. Splenomegaly was present in five patients. Granulomatous hepatitis has spectrum of MRI features, to be considered in differential diagnosis with other diffuse nodular liver pathologies.

Helicobacter pylori eradication lowers esophageal sphincter pressures in functional dyspepsia patients.

BACKGROUND/AIMS: Helicobacter pylori infection is the most common cause of gastroduodenal diseases. The role H. pylori eradication in functional dyspepsia patients is contradictory. We performed this study to determine the effects of H. pylori eradication in functional dyspepsia patients with respect to physiological and histological parameters including esophageal sphincter functions. METHODOLOGY: We studied 20 functional dyspepsia patients, whose H. pylori infection was confirmed by histology and urease test. We also confirmed eradication using the same methods after three months. We performed 24-hour esophageal pH monitoring, esophageal manometry, meal stimulated gastrin release test and measured dyspepsia severity score and gastric emptying time before and three months after eradication. Eradication regimen consisted of omeprazol 20 mg b.i.d., clarithromycin 500 mg b.i.d. and metranidazol 500 mg b.i.d., for two weeks. Gastric inflammation and H. pylori density within biopsy samples from the antrum (n = 4), corpus (n = 4), cardia (n = 2), fundus (n = 2), duodenum (n = 2) and distal esophagus (n = 1) were assessed. RESULTS: Dyspepsia severity score (P < 0.001), meal stimulated gastrin levels, upper (P = 0.01) and lower (P = 0.06) sphincter pressures were decreased after eradication irrespective of gastric histology; but gastric emptying times (P = 0.87) and pH < 4.5% reflux (P = 0.91) were not changed significantly. CONCLUSIONS: H. pylori eradication results in decreased esophageal sphincter pressures irrespective of gastric histology in functional dyspepsia patients. These decreases are not associated with increased objective reflux or reflux symptomatology. The clinical significance of these finding deserves further evaluations.

Persistently normal alanine transaminase levels in chronic C hepatitis: what does it tell us?

BACKGROUND/AIMS: We evaluated the demographic, clinical, histological and serological characteristics of chronic hepatitis C infection with persistently normal serum alanine transaminase levels and compared the results with those obtained in a group of chronic hepatitis C infection with serum alanine transaminase levels above normal. METHODOLOGY: Twenty-one patients who had chronic hepatitis C infection with normal alanine transaminase during the follow-up period and 34 patients who had chronic C infection with serum alanine transaminase levels above normal were included in this study. Demographic, clinical, histological and serological parameters of these two groups were evaluated. RESULTS: There were no significant differences in age, gender, known route of infection, viral load and genotype distribution between the two groups (P > 0.05). The gamma-glutamyltransferase and gamma-globulin levels were significantly higher in the serum alanine transaminase levels above normal group (P < 0.01 and P < 0.05). Among the patients with normal alanine transaminase, liver biopsy findings were normal in eight patients (38%). None of the patients with serum alanine transaminase levels above normal had normal liver biopsy findings. Histologic activity index was significantly higher in serum alanine transaminase levels above normal group (9.7 +/- 2.2 vs. 6.4 +/- 1.9; P < 0.001). Histologic activity index and alanine transaminase levels correlate with the stage of the disease (P < 0.05). CONCLUSIONS: For a definite diagnosis in patients with HCV-RNA+ and normal alanine transaminase liver biopsy is necessary and significant liver disease may be present in such patients irrespective of viral load, genotype and alanine transaminase levels.

Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress.

Thioacetamide (TAA) administration (0.3 g/l of tap water for a period of 3 months) to rats resulted in hepatic cirrhosis as assessed by biochemical and histopathological findings. This treatment caused an increase in the levels of malondialdehyde (MDA) and diene conjugates (DCs) and a decrease in the levels of glutathione (GSH), vitamin E, vitamin C and the activities of glutathione peroxidase (GSH-Px) in the liver of rats. Superoxide dismutase (SOD) activities were unchanged. Taurine (2% w/w, added to the chow diet) was administered together with TAA (0.3 g/l of drinking water) for 3 months. Taurine was found to decrease TAA-induced hepatic lipid peroxidation and to increase TAA-depleted vitamin E levels and GSH-Px activities. Histopathological findings also suggested that taurine has an inhibitive effect on TAA-induced hepatic cirrhosis. These results indicate that taurine treatment has a protective effect against TAA-induced liver cirrhosis by decreasing oxidative stress.

The protective effect of taurine against thioacetamide hepatotoxicity of rats.

Thioacetamide (TAA) administration (three consecutive intraperitoneal injections of 400 mg/kg at 24-h interval) to rats resulted in hepatic injury as assessed by the measurement of serum transaminase activities and histopathological findings. This treatment caused an increase in the levels of malondialdehyde (MDA), diene conjugates (DCs) and glutathione (GSH) and the activity of superoxide dismutase SOD ), and a decrease in the levels of vitamins E and C and the activity of glutathione peroxidase (GSH-Px) in the liver of rats. Taurine administration (400 mg/kg, i.p., every 12 h and started 24 h prior to the first TAA injection) was found to decrease serum transaminase activities and hepatic lipid peroxidation without any significant change in hepatic antioxidant system. Histopathological findings also suggested that taurine has ameliorated effect on TAA-induced hepatic necrosis. These results indicate that taurine treatment, together with TAA administration, diminished the severity of the liver injury by decreasing oxidative stress due to its possible scavenger effect.

Aminoguanidine, an inducible nitric oxide synthase inhibitor, plus N-acetylcysteine treatment reduce the lipopolysaccharide-augmented hepatotoxicity in rats with cirrhosis.

Hepatic cirrhosis is produced in rats by administration of thioacetamide (TAA) (0.3 g/L tap water for a period of three months). This treatment caused an increase in oxidative stress in the liver. Lipopolysaccharide (LPS) administration (5 mg/kg) to rats with cirrhosis was observed to increase hepatotoxicity as well as oxidative stress according to biochemical and histopathological findings. However, aminoguanidine (AG), an inducible nitric oxide synthase (iNOS) inhibitor, plus N-acetylcysteine (NAC) treatment reduced the LPS-augmented hepatotoxicity in rats with cirrhosis without making any changes in oxidative stress in the liver.

Tuberculosis of the parotid gland.

The presentation of tuberculosis as an isolated parotid lump is rare. In this paper, six cases with tuberculous parotitis are reported which were evaluated as a benign parotid neoplasm in 216 specimens pre-operatively. All but one of them had no previous history of tuberculosis and all had a parotid lump as a sole symptom for at least one year. The diagnosis of tuberculosis was made, after superficial parotidectomy, by histopathology. Parenchymal involvement and intraparotid lymph node involvement with tuberculosis were seen in five and three patients, respectively. Two of the patients had lymph node involvement outside the parotid area. One of six patients had a coincidental Warthin tumour. A surgical approach is not only therapeutic but also diagnostic when other diagnostic tools fail.

The effect of carnosine pretreatment on oxidative stress and hepatotoxicity in binge ethanol administered rats.

Carnosine is a dipeptide having strong antioxidant effects. Oxidative stress plays an important role in pathogenesis of alcohol-induced liver injury. In this study, we investigated the effect of carnosine pretreatment on ethanol-induced oxidative stress and hepatotoxicity. Rats were given carnosine (2 g/L in drinking water) for 4 weeks and then ethanol was administered orally to rats at a dose of 5 g/kg every 12 hours for 3 doses totally (binge model). All rats were killed 6 hours after last ethanol injection. Plasma alanine (ALT) and aspartate (AST) transaminase activities and liver triglyceride, malondialdehyde (MDA), diene conjugate (DC), glutathione (GSH), vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. Binge ethanol administration resulted in significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. However, GSH, vitamin E, vitamin C levels and GSH-Px and GST activities were found to be decreased following ethanol administration. Macromicrovesicular steatosis was also seen. Carnosine pretreatment appeared to prevent the increase of plasma ALT and AST activities and hepatic MDA and DC levels following ethanol treatment. In addition, hepatic GSH levels increased, but there were no changes in triglyceride, vitamin E, vitamin C levels and SOD, GSH-Px and GST activities, following ethanol treatment in carnosine-pretreated rats. There was also no change in liver histopathological appearance. In conclusion, carnosine prevented the increases in serum transaminase activities and lipid peroxides in liver of ethanol-treated rats, without any change on steatosis in liver.

Inflammatory pseudotumor of the liver. Report of two cases.

Inflammatory pseudotumor (IPT) is a rare lesion of the liver. We report two cases of IPT of the liver. Patients were a 32-year-old man and a 45-year-old female. Preoperative clinical diagnoses were respectively amebic abscess and metastatic tumor. Fine needle aspirations were performed and cytopathologic findings were compatible with an inflammatory process in both cases. Simple excision was performed in the first case and left lobectomy in the second one. Gross examination revealed expansive solid tumoral masses which measured 3 x 2 x 2 cm and 7 x 5 x 5 cm, respectively. Both lesions were yellow and firm. On microscopic examination, lesions were composed of fascicles of plump spindle cells intermingled with a varying number of plasma cells, lymphocytes and histiocytes. The spindle cell fascicles also contained a moderate amount of intercellular collagen. No microorganism was found on PAS, Giemsa, Grocott and Ziehl Nielsen stained sections. Plasma cells were immunoreactive for both kappa and lambda light chains, revealing their polyclonal nature. Since hepatocellular carcinoma is concerned in differential diagnosis, IPT is of particular clinical importance. Despite the limited experience with fine needle aspiration cytology, histopathologic diagnosis of IPT does not pose great difficulty.

The effect of intraoperative mebendazole-albendazole applications on the hepatobiliary system.

Caustic sclerosing cholangitis occurs with the use of scolicidal solutions in liver hydatid disease draining into the biliary system. In this study, we investigated the effectiveness of benzimidazole solutions, their in vitro scolicidal effects and the histopathological changes in the hepatobiliary system due to their intraoperative use. It was found that 5 mg% mebendazole and 1 mg% albendazole have strong scolicidal effects. In an in vivo study, under general anesthesia, 5% mebendazole in group I, 1% albendazole in group II and normal saline in group III were injected into the biliary system of rabbits. Liver biochemical tests showed no significant changes. More elaborate ductal mucosal proliferation, ductal dilatation and periductal fibrosis were found in group I compared with group II in biopsies taken on the 60th day. The biopsies of group III were normal.

Primary solitary tuberculosis of the liver.

Primary solitary tuberculous involvement of the liver is a rare condition. We present the case of a patient who was operated on with a preoperative diagnosis of hepatocellular carcinoma. Liver resection was performed and antituberculous therapy was started. It is difficult to make the correct diagnosis preoperatively except when a successful needle biopsy can be performed. Despite the rarity of the condition primary solitary tuberculosis should be considered among the space occupying lesions of the liver.

Betaine or taurine administration prevents fibrosis and lipid peroxidation induced by rat liver by ethanol plus carbon tetrachloride intoxication.

The aim of this study was to investigate the effect of betaine or taurine on liver fibrogenesis and lipid peroxidation in rats. Fibrosis was induced by treatment of rats with drinking water containing 5% ethanol and CCl(4) (2 x weekly, 0.2 ml/kg, i.p.) for 4 weeks. Ethanol plus CCl(4) treatment caused increased lipid peroxidation and disturbed antioxidant system in the liver. Histopathological findings suggested that the development of liver fibrosis was prevented in rats treated with betaine or taurine (1% v/v in drinking water) together with ethanol plus CCl(4) for 4 weeks. When hepatic taurine content was depleted with beta-alanine (3% v/v in drinking water), portal-central fibrosis induced by ethanol + CCl(4) treatment was observed to proceed cirrhotic structure. Betaine or taurine was also found to decrease serum transaminase activities and hepatic lipid peroxidation without any change in hepatic antioxidant system in rats with hepatic fibrosis. In conclusion, the administration of betaine or taurine prevented the development of liver fibrosis probably associated with decreased oxidative stress.

Celiac disease and glycogenic acanthosis: a new association?

UNLABELLED: A 6-y-old boy and an 8-y-old girl were admitted to our clinic with anaemia and failure to thrive. Laboratory tests revealed iron deficiency anaemia and positive antigliadin antibodies in both of the patients. Slightly raised grey-white plaques were observed on oesophageal mucosa during endoscopical investigation of the patients. While intestinal mucosal samples confirmed diagnosis of celiac disease histologically, histopathological assessment of oesophageal lesions demonstrated glycogenic acanthosis. Since glycogenic acanthosis associated with celiac disease hasn't been reported in the literature previously to our knowledge, case reports of our patients were presented. CONCLUSION: We suggest that glycogenic acanthosis needs to be investigated as a possible new association of celiac disease in greater paediatric series.

Adenocarcinoma of the gallbladder associated with congenital choledochal cyst and anomalous pancreaticobiliary ductal junction. Case report.

In a 61-year-old woman, villous adenocarcinoma of the gallbladder was associated with a congenital choledochal cyst and anomalous pancreaticobiliary ductal junction. The patient had a history of congenital choledochal cyst treated by cystoduodenostomy 27 years previously. The condition was demonstrated by intraoperative cholangiography and histologically confirmed. Extended cholecystectomy, regional lymph node dissection, excision of the cyst and hepaticojejunostomy were performed successfully.

The impact of various suture materials on experimental colorectal carcinogenesis.

Local tumor recurrence following restorative surgery for colorectal cancer may occasionally result from the promotion of a neoplastic lesion in a zone of proliferative instability adjacent to the anastomosis. This study was designed to determine the influence of various suture materials on experimental colorectal carcinogenesis. A total of 72 rats were divided into six groups, four of which were subjected to colotomy and repair using catgut, silk, polyglactin (PG), or stainless steel. The fifth group was given a sham procedure and the sixth group served as a control. Methylnitrosourea was administered rectally to all the animals, at a dose of 4 mg/kg/week for 20 weeks. The mean number of tumors per rat was significantly higher in the PG group than in the other groups. The mean tumor size was found to be significantly larger in each of the suture material groups than in the sham group. A tendency for tumor occurrence to develop at the anastomosis rather than at the other colon sites was seen in the PG group. These results indicate that PG has an adverse effect on local tumor occurrence in experimental colorectal carcinogenesis.

Primary lymphoma of the liver: report of a case.

We describe herein a female patient with non-Hodgkin's lymphoma of the liver and present a review of the related literature. The patient was referred with the diagnosis of malignant hemangiopericytoma (with an open biopsy). The physical examination, standard laboratory test results and tumor marker levels were all normal. A nonstandard left lobectomy was performed. Histopathological and immunohistochemical examinations revealed non-Hodgkin's lymphoma of B-cell type. The findings of a peripheral blood smear and bone marrow biopsy were normal. There was no other site of involvement based on physical or radiological examinations. These findings established the diagnosis of primary hepatic lymphoma. Fewer than 100 cases have been reported in the world literature. The best treatment results have been obtained by a resection followed by chemotherapy when feasible.