Metabolic Dysfunction-Associated Fatty Liver Disease and Fibrosis Status in Patients with Type 2 Diabetes Treated at Internal Medicine Clinics: Türkiye DAHUDER Awareness of Fatty Liver Disease (TR-DAFLD) Study.

This awareness study aimed to determine the ultrasound (US) examination rates in relation to US-confirmed metabolic dysfunction-associated fatty liver disease (MAFLD) diagnosis in internal medicine outpatients with type 2 diabetes (T2D) across Türkiye. A total of 6283 T2D patients were included in this multicenter retrospective cohort study conducted at 17 internal medicine clinics across Türkiye. The presence and indications for US performed within the last 3 years were recorded along with US-confirmed MAFLD rates, laboratory findings on the day of US, and referral rates. Fibrosis-4 (FIB-4) index was calculated to estimate the risk of advanced liver fibrosis (FIB-4 index ≥ 1.3). Overall, 1731 (27.6%) of 6283 patients had US examination, which revealed MAFLD diagnosis in 69.9% of cases. In addition, 24.4% of patients with US-confirmed MAFLD were at risk of advanced fibrosis (FIB-4 index ≥ 1.3), and the referral rate was 15.5%. In conclusion, our findings emphasize an insufficient MAFLD awareness among clinicians and the likelihood of most of T2D patients to be at risk of living with an unknown status regarding their MAFLD and advanced fibrosis risk.

Uterine Serosal Inclusion Cysts with Greater Omentum Involvement in a Cat.

A 7-year-old nulliparous Chinchilla queen was admitted to a veterinary clinic for routine ovariohysterectomy. Examination of the uterus, greater omentum and varicose ovarian veins revealed multiple thin-walled cysts filled with a transparent fluid over the serosal surfaces of these organs. Histologically, the cysts were of variable size, filled with a small amount of mucinous fluid, and had thin walls that contained hypocellular collagen and a few small calibre vessels. The inner and outer epithelium of the cyst walls and the cells that lined the uterine serosa were immunopositive for cytokeratin and vimentin, suggesting a mesothelial origin. Alpha-smooth muscle actin immunolabelling was patchy or continuous in smooth muscle in the wall of many of the cysts.

Validity and reliability of the Turkish version of brief diabetic foot ulceration risk checklist.

OBJECTIVE: This study aims to determine the validity and reliability of the Turkish translation of brief diabetic foot ulceration risk checklist (BDURC). METHODS: This methodological study was conducted at the diabetes clinic of a state hospital in Istanbul, Turkey. The data were collected with the BDURC developed by Zhou et al. in 2018. A study was conducted with 430 patients with Type 2 diabetes. The scale was retested after 4 weeks by 60 participants. Language equivalence of the scale was provided. Experts' opinions were taken about the content validity of the scale. Reliability of the scale was determined with the test-retest reliability, item-total correlation, and internal consistency analysis. RESULTS: Confirmatory factor analysis revealed a two-factor structure with good model suitability. Cronbach's alpha coefficient for the scale and its subscales was 0.79. Test-retest scores showed no statistically significant difference between the items (p>0.05). The reliability index was higher than 0.80. CONCLUSION: The BDURC-TR is a valid and reliable tool that can be used in clinics to identify the risk factors for diabetic foot ulcers in patients with Type 2 diabetes in Turkey.

Is daytime insulin more physiologic and less atherogenic than bedtime insulin?

The question is whether bedtime insulin, one of the standard therapy regimens of type 2 diabetes, can be more atherogenic than daytime insulin. There is no study to answer this question. However, pharmacokinetics of drugs and physiopathology of type 2 diabetes are considered, we can assume that daytime OAD plus bedtime insulin therapy might be more atherogenic than daytime insulin plus bedtime OAD therapy. The rationale for combination therapy is based on the assumption that, if evening insulin lowers the fasting glucose concentration to normal, then daytime oral agents will be more effective in controlling postprandial hyperglycemia. However, exogenous insulin administration is not a convenient way to inhibit hepatic glucose production which determines fasting plasma glucose because in post absorptive period, hepatic glucose production is determined by high glucagon and low insulin levels. In postprandial period, beta cell-originated insulin inhibits glucagon synthesis by paracrine effect and also inhibits hepatic glucose production by using half of its concentration that administered to portal system. Since half of insulin that found in portal system is exposed to hepatic clearance to inhibit hepatic glucose production, portal insulin concentration is 2-4-folds higher than peripheral insulin concentration. But, exogenous insulin neither inhibits glucagon synthesis via paracrine effect, nor reaches desired portal concentrations because it has a short half-life and in opposition to physiologic states it is not administered to the portal system. On the contrary, its peripheral concentration is higher than portal one. Thus, exogenous insulin that is used to inhibit hepatic glucose production requires higher concentrations than physiologic values. Eventually, peripheral hyperinsulinemic state which is a risk factor of CVD is created iatrogenically. Bearing in mind that PI3K pathway, working synchronously with the diurnal rhythm of other metabolic hormones, is more active during daytime especially in postprandial period when aminoacids and glucose exist in the environment, and that decreased insulin response in PI3K pathway in diabetics, we may propose iatrogenically created hyperinsulinemia can cause more atherogenic effects via MAPK pathway. For that reason, using OAD instead of bedtime insulin may be a more convenient way to inhibit hepatic glucose production. Thus, glucagon synthesis inhibition can be achieved via paracrine effect of OAD-induced insulin secretion, as well as required portal insulin concentration can be reached by the direct secretion of insulin to the portal system. Moreover, lower peripheral hyperinsulinemia state can be provided.

Is lipid lowering treatment aiming for very low LDL levels safe in terms of the synthesis of steroid hormones?

Today atherosclerotic diseases are among the most important causes of death in the world. Epidemiological, clinical, genetic, experimental and pathological studies have clearly shown the role of lipoproteins in atherosclerosis. LDL is the major atherogenic lipoprotein and has been defined as the primary target of lipid lowering treatment by NCEP. Although the level of LDL, the primary target in the treatment of dyslipidemia, has been set as below 100 mg/dl in coronary heart diseases (CHD) and CHD risk equivalents, this level has been pulled down to below 70 mg/dl for the group defined as very high risk group by the ATP (Adult Treatment Panel) guide that has been updated following the new clinical studies. As we already know, cholesterol is the precursor of glucocorticoids, mineralocorticoids and sex steroids, besides being a structural component of the cell membrane. Both adrenal and non-adrenal (ovarian+testicular) all steroid hormones are primarily synthesized using the LDL-cholesterol in the circulation. In addition to this, there is 'de novo' cholesterol synthesis in both the adrenals and gonads controlled by the HMG-CoA reductase enzyme. A third pathway, which under normal circumstances has little contribution as compared to the first two, is the use of circulatory HDL-cholesterol by the adrenal and gonadal tissues for the synthesis of steroids. Our knowledge on extremely lowered LDL levels is quite limited. However, since statins both decrease circulatory LDL and inhibit de novo cholesterol synthesis, they are likely to affect the synthesis of steroid hormones.

Treatment of prediabetes.

Progression of normal glucose tolerance (NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance (IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diabetes mellitus (type 2 DM) and even normoglycemic IGT patients manifest these defects. Beta cell dysfunction and insulin resistance also contribute to the progression of IGT to type 2 DM. Improving insulin sensitivity and/or preserving functions of beta-cells can be a rational way to normalize the GT and to control transition of IGT to type 2 DM. Loosing weight, for example, improves whole body insulin sensitivity and preserves beta-cell function and its inhibitory effect on progression of IGT to type 2 DM had been proven. But interventions aiming weight loss usually not applicable in real life. Pharmacotherapy is another option to gain better insulin sensitivity and to maintain beta-cell function. In this review, two potential treatment options (lifestyle modification and pharmacologic agents) that limits the IGT-type 2 DM conversion in prediabetic subjects are discussed.

Strong association between insulin-mediated glucose uptake and the 2-hour, not the fasting plasma glucose concentration, in the normal glucose tolerance range.

AIM: The aim of this study was to examine the relationship between whole-body insulin-mediated glucose disposal and the fasting plasma glucose concentration in nondiabetic individuals. RESEARCH DESIGN AND METHODS: Two hundred fifty-three nondiabetic subjects with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance received a 75-g oral glucose tolerance test and euglycemic hyperinsulinemic clamp. Total glucose disposal (TGD) during the insulin clamp was compared in IFG and NGT individuals and was related to fasting and 2-hour plasma glucose concentrations in each group. RESULTS: TGD varied considerably between NGT and IFG individuals and displayed a strong inverse relationship with the 2-hour plasma glucose (PG; r = 0.40, P < .0001) but not with the fasting PG. When IFG and NGT individuals were stratified based on their 2-hour PG concentration, the increase in 2-hour PG was associated with a progressive decrease in TGD in both groups, and the TGD was comparable among NGT and IFG individuals. CONCLUSION: The present results indicate the following: 1) as in NGT, insulin-stimulated TGD varies considerably in IFG individuals; 2) the large variability in TGD in IFG and NGT individuals is related to the 2-hour PG concentration; and 3) after adjustment for the 2-hour proglucagon concentration, IFG subjects have comparable TGD with NGT individuals.

Effect of vildagliptin add-on treatment to metformin on plasma asymmetric dimethylarginine in type 2 diabetes mellitus patients.

AIMS: A close association has been demonstrated between increased cardiovascular risk and high asymmetric dimethylarginine (ADMA) levels in type 2 diabetes mellitus (DM) patients. We planned to measure serum ADMA levels in type 2 DM patients using vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. MATERIALS AND METHODS: A total of 68 type 2 DM patients who were on metformin were enrolled in the study. Based on the glycemic levels of patients, vildagliptin was added on to treatment in 33 patients. Patients were followed for 6 months. Serum ADMA, C-reactive protein, and fibrinogen levels were compared in groups of patients using metformin or metformin + vildagliptin, after 6 months. RESULTS: Serum ADMA levels were found to be significantly lower in the group using vildagliptin compared to the group using metformin + vildagliptin (P<0.001). However, serum C-reactive protein and fibrinogen levels were statistically similar in the two study groups (P=0.34 and P=0.23, respectively). CONCLUSION: Metformin + vildagliptin treatment was observed to lower serum ADMA levels in type 2 DM patients. Our findings notwithstanding, large-scale prospective randomized controlled studies are warranted to conclude that vildagliptin provides cardiovascular protection along with diabetes regulation.

Evaluation of cardiac functions with tissue Doppler imaging in prediabetic subjects.

BACKGROUND AND OBJECTIVES: The aim of the present study was to evaluate left ventricle systolic and diastolic function, using tissue Doppler echocardiography (TDE), in relation to blood glucose status in prediabetic patients who had no evidence of heart disease by conventional echocardiography (CE). SUBJECTS AND METHODS: We included 60 patients (30 female, 30 male) and 20 healthy controls (10 male, 10 female). All participants were randomised into four groups according to their oral glucose tolerance test. Group-I consisted of those patients who had only impaired fasting glucose (IFG). group-II consisted of patients who had only impaired glucose tolerance (IGT) and group-III consisted of patients who had both IFG and IGT, that is so-called combined glucose intolerance. Group-IV included the healthy controls. All subjects underwent both CE and TDE. RESULTS: No significant differences were found among the four groups in terms of CE. There was no significant difference between group-IV and group-I with respect to the early peak diastolic velocity (Ea) of medial mitral annulus (11.65±0.66 vs. 9.72±1.58, p>0.05), whereas a statistically significant difference was found between group-IV and group-II (11.65±0.66 vs. 9.06±1.07, p<0.001) and between group-IV and group-III (11.65±0.66 vs. 9.74±1.09, p<0.05). CONCLUSION: Diastolic myocardial dysfunction in prediabetic patients may be identified by quantitative TDE before the appearance of CE indices of myocardial dysfunction.

Distinct ß-cell defects in impaired fasting glucose and impaired glucose tolerance.

To characterize the defects in ß-cell function in subjects with impaired fasting glucose (IFG) and compare the results to impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) subjects, ß-cell glucose sensitivity and rate sensitivity during the oral glucose tolerance test were measured with the model by Mari in 172 Mexican Americans. A subgroup (n=70) received a 2-h hyperglycemic clamp (+125 mg/dL), and first- and second-phase insulin secretion were quantitated. Compared with NGT, subjects with IFG and IGT manifested a decrease in ß-cell glucose sensitivity; IFG subjects, but not IGT subjects, had decreased ß-cell rate sensitivity. In IFG subjects, the defect in ß-cell glucose sensitivity was time dependent, began to improve after 60 min, and was comparable to NGT after 90 min. The incremental area under the plasma C-peptide concentration curve during the first 12 min of the hyperglycemic clamp (ΔC-pep[AUC]0-12) was inversely related with the increase in FPG concentration (r=-36, r=0.001), whereas ΔC-pep[AUC]15-120 positively correlated with FPG concentration (r=0.29, r<0.05). When adjusted for the prevailing level of insulin resistance, first-phase insulin secretion was markedly decreased in both IFG and IGT, whereas second-phase insulin secretion was decreased only in IGT. These results demonstrate distinct defects in ß-cell function in IFG and IGT.

Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose.

Subjects with impaired fasting glucose (IFG) are at increased risk for type 2 diabetes. We recently demonstrated that IFG subjects have increased hepatic insulin resistance with normal insulin sensitivity in skeletal muscle. In this study, we quantitated the insulin secretion rate from deconvolution analysis of the plasma C-peptide concentration during an oral glucose tolerance test (OGTT) and compared the results in IFG subjects with those in subjects with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). One hundred and one NGT subjects, 64 subjects with isolated IGT, 24 subjects with isolated IFG, and 48 subjects with combined (IFG + IGT) glucose intolerance (CGI) received an OGTT. Plasma glucose, insulin, and C-peptide concentrations were measured before and every 15 min after glucose ingestion. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide concentration. Inverse of the Matsuda index of whole body insulin sensitivity was used as a measure of insulin resistance; 56 subjects also received a euglycemic hyperinsulinemic clamp. The insulin secretion/insulin resistance (disposition) index was calculated as the ratio between incremental area under the ISR curve (∆ISR[AUC]) to incremental area under the glucose curve (∆G[AUC]) factored by the severity of insulin resistance (measured by Matsuda index during OGTT or glucose disposal during insulin clamp). Compared to NGT, the insulin secretion/insulin resistance index during first 30 min of OGTT was reduced by 47, 49, and 74% in IFG, IGT, and CGI, respectively (all < 0.0001). The insulin secretion/insulin resistance index during the second hour (60-120 min) of the OGTT in subjects with IFG was similar to that in NGT (0.79 ± 0.6 vs. 0.72 ± 0.5, respectively, P = NS), but was profoundly reduced in subjects with IGT and CGI (0.31 ± 0.2 and 0.19 ± 0.11, respectively; P < 0.0001 vs. both NGT and IFG). Early-phase insulin secretion is impaired in both IFG and IGT, while the late-phase insulin secretion is impaired only in subjects with IGT.

The relationship between {beta}-cell function and glycated hemoglobin: results from the veterans administration genetic epidemiology study.

OBJECTIVE: The study objective was to assess the relationship between ß-cell function and HbA(1c). RESEARCH DESIGN AND METHODS: A total of 522 Mexican American subjects participated in this study. Each subject received a 75-g oral glucose tolerance test (OGTT) after a 10- to 12-h overnight fast. Insulin sensitivity was assessed with the Matsuda index. Insulin secretory rate was quantitated from deconvolution of the plasma C-peptide concentration. ß-Cell function was assessed with the insulin secretion/insulin resistance (IS/IR) (disposition) index and was related to the level of HbA(1c). RESULTS: At HbA(1c) levels <5.5%, both the Matsuda index of insulin sensitivity and IS/IR index were constant. However, as the HbA(1c) increased >5.5%, there was a precipitous decrease in both the Matsuda index and the IS/IR index. Subjects with HbA(1c) = 6.0-6.4% had a 44 and 74% decrease in the Matsuda index and the IS/IR index, respectively, compared with subjects with HbA(1c) <5.5% (P < 0.01 for both indices). Subjects with normal glucose tolerance and HbA(1c) <5.7% had ß-cell function comparable to that of subjects with normal glucose tolerance with HbA(1c) = 5.7-6.4%. However, subjects with impaired fasting glucose or impaired glucose tolerance had a marked decrease in ß-cell function independent of their HbA(1c) level. CONCLUSIONS: The results of the current study demonstrate that in Mexican Americans, as HbA(1c) increases >6.0%, both insulin sensitivity and ß-cell function decrease markedly. Performing an OGTT is pivotal for accurate identification of subjects with impaired ß-cell function.

Heart rate variability and heart rate turbulence in patients with chronic obstructive pulmonary disease.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) patients, functional and structural changes of the respiratory system greatly influence cardiovascular autonomic functions. Determining autonomic balance may be important in understanding the pathophysiology of COPD and useful clinically in the treatment of COPD patients. Heart rate variability (HRV) and heart rate turbulence (HRT) are useful tools in assessing the autonomic neurovegetative function. Our aim in this study was to evaluate the HRV and HRT variables in COPD patients. Twenty five moderate to severe COPD patients and 25 healthy subjects were included in this study. METHODS: Pulmonary function tests and echocardiographic examination, arterial blood gases analysis were performed, HRV and HRT analysis were assessed from a 24-hour Holter recording. RESULTS: When HRV and HRT parameters were compared, COPD patients had significantly decreased sNN50 total, pNN50, SDANN, SDNN, SDNNI, rMSDD in time domain HRV parameters, and the values of the HRT onset was significantly less negative in COPD patients. Although the values of the HRT slope were lower in COPD patients, there was no significant difference between the two groups. We also found a correlation between HRT and HRV parameters. CONCLUSIONS: In addition to HRV parameters, HRT onset was significantly different in COPD patients. In our opinion, the combination of HRV variables and HRT onset may be simple and elegant ways of evaluating cardiac autonomic functions. New investigations of HRT and HRV in COPD patients have a potential importance for improving risk stratification and therapeutic approaches, and understanding the autonomic outcomes of the disease process.

Tissue Doppler echocardiography in evaluation of cardiac effects of subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism (SH) is a mild form of thyroid failure, associated with initial signs of cardiovascular hypothyroidism. Tissue Doppler echocardiography (TDE) is a new and powerful method in evaluation of both regional and global systolic or diastolic ventricular function. We aimed to investigate the use of TDE in evaluation of cardiac effects of SH and affect of thyroid hormone replacement therapy (TRT) on tissue Doppler parameters of SH patients. METHODS: Twenty-two patients who were diagnosed as SH and 22 healthy, age and sex-matched cases were included in the study. Conventional echocardiography and TDE were performed in all individuals. TRT was started in SH group. On the achievement of euthyroid state echocardiography were repeated. RESULTS: Septal annulus relaxation time was significantly higher in SH group (82+/-21, 98+/-11 ms, p=0.024). Lateral annulus and myocardial relaxation times, precontraction/contraction ratios and precontraction times were also slightly higher. Septal lateral annulus and lateral myocardial relaxation times were decreased after TRT (98+/-11 vs. 81+/-12, p<0.001, 89+/-14 vs. 78+/-11, p=0.022, 90+/-16 vs. 80+/-14 ms, p=0.008, respectively). Precontraction times and precontraction/contraction ratios decreased after TRT but did not reach the significance level. There was a positive correlation between TSH and TDE relaxation times. CONCLUSIONS: TDE is a powerful tool in diagnosis and follow-up of SH patients and TRT inhibits adverse affects of SH on myocardium. Septal myocardium is the most affected region of left ventricle in SH. The relaxation time is the best criteria of cardiac involvement and monitoring the effect of TRT.

A case of hypothyroidism mimicking acute coronary syndrome.

Hypothyroid patients have increased concentrations of creatinine kinase that is mostly due to increased CK-MM. However, CK-MB has also been reported to increase above reference values in hypothyroid patients without apparent myocardial damage. This may create confusion during the evaluation of myocardial injury in a hypothyroid patient presenting with chest pain. Troponin I is considered as a superior marker for the diagnosis of myocardial infarction in hypothyroid patients. However, there are some reports showing an increase in the level of troponin I without any myocardial damage in hypothyroid patients as in our case. In this report, we present a 47 years old male hypothyroid patient who had chest pain, abnormal electrocardiographic findings and increased cardiac enzymes suggesting acute coronary syndrome although he had normal coronary arteriogram.

The prevalence of neuropathy and relationship with risk factors in diabetic patients: a single-center experience.

OBJECTIVE: To determine the rate of distal symmetrical polyneuropathy (DSP) in patients with type 2 diabetes mellitus, to evaluate the role of history, neurological examination and the electrodiagnostic methods in the diagnosis of DSP, and to determine the association between electromyography-supported neuropathy (ESN), neuropathic complaints (NCs) and risk factors. SUBJECTS AND METHODS: A total of 191 type 2 DM patients (109 female, 82 male; mean age 58.7 +/- 10 years) were recruited. The NCs were recorded. All patients had electromyographic (EMG) examinations. The relationship between ESN, NCs and risk factors were evaluated. RESULTS: Of the 191 patients, 83 (43.5%) had DSP on EMG examinations and 92 (48.2%) patients suffered from NCs. Among the ESN patients, a significant relationship existed with HbA1(c) level, illness duration, smoking, male gender or insulin usage (p < 0.05) but not with age, hypertension, hypercholesterolemia or hypertriglyceridemia. The frequency of NCs was higher in patients with ESN. There was also a significant association between NCs and ESN (p < 0.05). The presence of NCs was not related to age, gender, smoking, hypertension, hypercholesterolemia and hypertriglyceridemia (p > 0.05) but NCs were correlated to HbA1(c) level, illness duration and insulin usage (p < 0.05). CONCLUSION: Our data show that a strong association exists between the presence of DSP and illness duration, HbA1(c), smoking, thereby indicating that cessation of smoking and near normal glycemic control would be additional precautions to delay the beginning or progression of polyneuropathy.

Evaluation of right ventricular function in patients with thyroid dysfunction.

BACKGROUND: Thyroid gland dysfunction affects the structure and function of the heart. Tissue Doppler echocardiography is a new technique, and it has been used frequently in the evaluation of ventricular function. In the present study, right ventricular function was assessed in patients with overt or subclinical hypothyroidism and hyperthyroidism and in healthy subjects using the tissue Doppler method, and results were compared. PATIENTS AND METHODS: 20 healthy subjects and 63 patients diagnosed with overt and subclinical hypothyroidism and hyperthyroidism were included in the study. Annular and myocardial systolic peak velocities, early and late diastolic peak velocities, precontraction, total contraction and relaxation times of the right ventricle were recorded by tissue Doppler echocardiography. The results of the patients were compared to those of the controls. RESULTS: Myocardial systolic velocity was significantly higher in patients with hyperthyroidism. Annular and myocardial late diastolic velocities were found to be significantly lower in patients with overt hypothyroidism. Annular precontraction time was increased in patients with overt and subclinical hypothyroidism. Myocardial precontraction time was decreased in patients with hyperthyroidism, and increased in patients with overt hypothyroidism patients. Annular relaxation time was increased in patients with overt hypothyroidism. CONCLUSIONS: Right ventricular function is affected in patients with thyroid diseases. The tissue Doppler technique is a suitable tool to detect impairments in right ventricular function. There is a significant correlation between serum thyroid hormone levels and right ventricular velocities and time intervals.

The prevalence of hepatic granulomas in chronic hepatitis C.

OBJECTIVES: Hepatic granulomas are not usual findings in chronic hepatitis C. A few studies addressing the frequency of hepatic granulomas in chronic hepatitis C reported it as less than 10%. The presence of it has been suggested to predict a favorable response to interferon treatment. Also, case reports described the development of hepatic granulomas after interferon treatment. In this study, we aimed to detect the prevalence of hepatic granulomas in chronic hepatitis C and to identify the causes other than chronic hepatitis C, if present, to search whether there is an association between the presence of granuloma and response to interferon treatment and also to see whether interferon leads to the formation of hepatic granulomas. METHODS: Patients from 3 university clinics were included. All patients with chronic hepatitis C were determined. All patients with hepatic granulomas were screened for the other causes of hepatic granuloma with tuberculin skin test, chest X-ray and computed tomography, Venereal Disease Research Laboratory, and Brucella agglutination tests. The histologic assessment of liver biopsies was done by the same pathologist in each center. RESULTS: A total of 725 liver biopsies of 605 patients with chronic hepatitis C were screened. In 8 patients, hepatic granulomas were detected in the initial liver biopsies. Four patients had repeat biopsies, and all had hepatic granulomas again. The prevalence of hepatic granulomas in patients with chronic hepatitis C was calculated as 1.3% (8 of 605) in reference to patient population. Presence or absence of hepatic granulomas was seemingly stable. All patients with hepatic granulomas had negative results of tuberculin skin test, Venereal Disease Research Laboratory, chest X-ray and computed tomography, and Brucella agglutination tests. All repeat biopsies were obtained after interferon (+/- ribavirin) in varying doses and duration. Four of 8 patients with hepatic granulomas were found to respond interferon therapy. No patient was found to develop hepatic granulomas after interferon therapy. CONCLUSION: Hepatic granulomas are a rare finding in HCV infection. The presence of it does not seem to predict the response to interferon therapy. The development of hepatic granulomas during interferon therapy is not usual.