Krzysztof Gutkowski

Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension

Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH.

Kidneys in chronic liver diseases

Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support.

Coagulopathy in liver diseases

Liver cirrhosis is associated with number of hematological complications and coagulation disturbances. In view of various haemostatic abnormalities it is surprising that many patients do not bleed spontaneously. Severe coagulopathy of liver disease is more frequently seen in acute liver failure, but still remains important complication of liver cirrhosis and chronic liver failure. Decreased production of blood coagulation factors by the liver plays a key role in altered haemostasis in liver diseases. Altered fragile balance of blood coagulation proteins and infection are associated with both worsening coagulopathy and bleeding risk. Additional haemostatic abnormalities in patients with severe liver diseases are thrombocytopenia, chronic disseminated intravascular coagulation, accelerated fibrinolysis, hypofibrinogenemia and dysfibrinogenemia. In this review we discuss a complicated issue of multiple coagulopathies in patients with advanced liver dysfunction.

Procalcitonin and macrophage inflammatory protein-1 beta (MIP-1β) in serum and peritoneal fluid of patients with decompensated cirrhosis and spontaneous bacterial peritonitis.

PURPOSE Spontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis causing significant mortality which requires rapid recognition for effective antibiotic therapy, whereas ascitic fluid cultures are frequently negative. The aim of this study was to evaluate the SBP diagnostic efficacy of procalcitonin (PCT) and macrophage inflammatory protein-1 beta (MIP-1β) measured in serum and peritoneal fluid. MATERIAL/METHODS Thirty-two participants with liver cirrhosis and ascites were included into the study (11 females and 21 males, mean age 49.5 ± 11.9 years). The peritoneal fluid and venous blood were collected for routine laboratory examinations and measurements of PCT and MIP-1β. Patients were divided into two groups according to the ascitic absolute polymorphonuclear leukocytes count (≥250 mm(-3) and <250 mm(-3)). RESULTS Ascites was sterile in 22 participants and SBP was diagnosed in 10 patients. Serum and ascitic levels of PCT and MIP-1β did not correlate with clinical and routine laboratory parameters. MIP-1β in the ascitic fluid was significantly higher in patients with SBP (213 ± 279 pg/ml vs. 66.3 ± 49.8 pg/ml; p=0.01). The sensitivity and specificity for diagnosis of SBP with ascitic MIP-1β were 80% and 72.7%, respectively (cut-off value 69.4 pg/ml) with AUROC 0.77 (95%CI 0.58-0.96). Serum levels of MIP-1β showed lower diagnostic yield. Serum and ascitic PCT levels were not different in patients with and without SBP. CONCLUSIONS MIP-1β concentration in ascitic fluid may distinguish patients with and without SBP with satisfactory sensitivity and specificity. Chemokines should be further explored for diagnostic use.

Liver injury induced by high-dose methylprednisolone therapy: a case report and brief review of the literature.

Corticosteroids are used widely to treat many types of disease. In general, these drugs are considered safe for the liver; however, recent reports have demonstrated that high-dose methylprednisolone (MT) may cause severe liver injury. Here, we report a case of a 24-year-old female who was given pulsed MT therapy for multiple sclerosis. MT induced icteric hepatitis and impaired liver synthetic function. Hepatotoxicity developed several weeks after drug exposure, and the causal association with MT was confirmed by unintentional rechallenge test. A brief review of the literature on corticosteroid-induced hepatotoxicity is presented.

Serological prevalence of hepatitis B virus and hepatitis C virus infection in the elderly population: Polish nationwide survey--PolSenior.

Background The hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may seriously affect survival rate. The median length of life in developed countries is increasing and the elderly may be considered as an epidemiologically distinct group due to higher whole-life risk of blood-borne viral infections. Aim To determine the seroprevalence of HBV and HCV infections in elderly individuals participating in a Polish nationwide survey – PolSenior. Methods A total of 4979 individuals aged 65 years and older were asked about past or present viral hepatitis, and a blood test was carried out for HBsAg and anti-HCV antibodies in 3826 individuals. The respondents were divided into six age groups of equal size: 65–69, 70–74, 75–79, 80–84, 85–89, and 90+ years. Results Past or present diagnosis of viral hepatitis was reported by 176 individuals (3.58%) and its prevalence was significantly most common in urban than in rural residents (4.02 vs. 2.92%; P=0.04). In multivariate analysis, only the job category was a significant variable (P=0.01) for the occurrence of viral hepatitis [most frequently in white-collar workers (3.56%) and least frequently in agricultural workers (1.47%)]. The overall prevalence of a positive HBsAg test was 1.12% (n=43) and that of an anti-HCV test was 2.93% (n=112). Only 12 anti-HCV-positive patients (10.7%) were aware of infection. Multivariate analyses did not indicate significant effects of age, sex, alcohol consumption, nutrition, marital or economic status, educational level, and site of residence on the incidence of HBV and HCV infections. HBsAg was associated with higher serum levels of aspartate aminotransferase, and anti-HCV with higher levels of aspartate aminotransferase and alanine aminotransferase. Conclusions In elderly individuals, the seroprevalence of HBsAg is lower and the seroprevalence of anti-HCV is considerably higher than that in the general Polish population. The former may have been because of increased mortality from HBV-related complications and the latter of increased whole-life risk of infection. Programs for screening of elderly individuals for occult HCV infection should be considered.

Laboratory-based scoring system for prediction of hepatic inflammatory activity in patients with autoimmune hepatitis

In autoimmune hepatitis (AIH), inflammation is closely related to fibrosis. Although transaminase levels are commonly used to assess hepatic inflammation, they may not relate directly to the histology. We developed a noninvasive diagnostic score as an alternative to liver biopsy to help optimize treatment for AIH and monitor disease progress.

Critical flicker frequency fails to disclose brain dysfunction in patients with primary biliary cirrhosis

BACKGROUND Recent studies suggest that stage-independent symptoms of primary biliary cirrhosis (PBC) such as chronic fatigue are a consequence of structural and functional abnormalities of the brain. Critical flicker frequency (CFF) is a psychophysiological modality analysing function of cerebral cortex. AIM To analyse the usefulness of CFF in detection of brain dysfunction in patients with PBC. METHODS Fifty-one (37 non-cirrhotic/14 cirrhotic) patients with PBC were included. Control group consisted of 31 matched healthy individuals. Fatigue and health-related quality of life (HRQoL) were assessed using Fatigue Impact Scale (FIS) and questionnaire PBC-40. CFF was analysed with HEPAtonorm Analyzer(®). RESULTS When compared to healthy controls all patients with PBC showed significantly impaired HRQoL in majority of PBC-40 domains and increased fatigue level in physical domain of FIS. No differences in HRQoL and PBC-40 domains were seen, when patients with and without cirrhosis where compared. CFF analysis showed no difference between healthy controls and patients with PBC. CFF did not correlate with PBC-40 and FIS domains. CONCLUSION CFF fails to determine brain dysfunction in non-encephalopatic patients with PBC, suggesting that functional efficiency of their cerebral cortex remains unaffected and other central mechanisms are responsible for chronic fatigue in these patients.

Comment on Hepatitis C Virus-Specific Th17 Cells Are Suppressed by Virus-Induced TGF-β

We have read with interest the article published by Rowan et al. in the October 1, 2008 issue of The Journal of Immunology ([1][1]). The authors reported for the first time that Ag-specific Th17 cells were induced in patients infected by the hepatitis C virus (HCV). They also indicated that TGF- β

A rare cause of chylous ascites.

In a 60-year-old man, a plastic stent was inserted into the common bile duct because of icterus caused by a biliary stricture at the level of the hilum. The patient’s medical history before the jaundice was unremarkable and an epithelial smear taken from the stenosed biliary duct showed no atypical cells. Four months later, the patient was referred to our department because of ascites. No mass on abdominal computed tomography or digestive tract cancer at panendoscopy and colonoscopy were found. The serum level of CA 19-9 was not elevated. An ascitic tap revealed a milky fluid with a triglyceride level of 556 mg/dl (the serum triglyceride level was 109 mg/dl) and a negative cytology for malignant cells. Laparoscopy showed white flat plaques covering the parietal peritoneum (Fig. 1), from which histopathology revealed the diagnosis of cholangiocarcinoma (Fig. 2) (co-expression of CK7, CK17 and CD7). Chylous ascites is rare (one per 20 000 hospital admissions), and characterized by appearance in the abdominal cavity of a milky fluid rich in triglycerides. Obstruction of lymphatic channels leading to the formation of lymphatic fistulas communicating with the peritoneal cavity is a key mechanism underlying chylous ascites. Intra-abdominal malignancies including lymphomas and adenocarcinomas of the digestive tract are the most common causes of this pathology. Non-malignant causes of chylous ascites include blunt abdominal trauma, vascular surgery, irradiation, cirrhosis, abdominal tuberculosis and filariasis (1, 2). In the differential diagnosis of this disorder, cholangiocarcinoma is rarely considered as only two such cases have been reported in PubMed (3, 4).