Vol. 11 Issue 4
On the cover: A. Axial phase. B. Saggital, PV phase. C. Coronal, PV phase. D. 3D reformat.
Noninvasive markers of fibrosis have emerged as an alternative to the staging of fibrosis by means of liver biopsy. Apart from being noninvasive and thus lacking the adverse effects of liver biopsy, they offer some advantages such as reduced risk of sampling error, objectiveness in the interpretation of the result, appropriateness for repeated measurements and lower cost. Many studies have validated different panels of blood markers and imaging/transient elastography for the estimation of fibrosis with acceptable accuracy. Clinical scenarios leading to inacurate or failed estimation must be acknowledged, as well as the fact that performance of blood markers and transient elastography, and their diagnostic cut-off values vary among specific liver diseases. The combination of two blood markers or of a blood marker and transient elastography has been shown to increase accuracy of the estimation. Further, unlike liver biopsy the noninvasive markers of fibrosis are not associated with a ceiling effect after cirrhosis is identified, but can discriminate early from advanced stages of cirrhosis. Longitudinal studies have shown their utility as predictors of complications from portal hypertension and mortality, outperforming liver biopsy. In conclusion, noninvasive markers of fibrosis provide major advantages over liver biopsy. The reported performance of some of the available tests -particularly when used in combination- make them a reliable tool, very attractive for daily clinical practice.
Recent evidence has linked obesity and the metabolic syndrome with gut dysbiota. The precise mechanisms underlying that association are not entirely understood; however, microbiota can enhance the extraction of energy from diet and regulate whole-body metabolism towards increased fatty acids uptake from adipose tissue and shift lipids metabolism from oxidation to de novo production. Obesity and high fat diet relate to a specific gut microbiota, which is enriched in Firmicutes and with less Bacterioidetes. Microbiota can also play a role in the development of hepatic steatosis, necroinflammation and fibrosis. In fact, some studies have shown an association between small intestinal bacterial overgrowth, increased intestinal permeability and nonalcoholic steatohepatitis (NASH). That association is, in part, due to increased endotoxinaemia and activation of the Toll-like receptor-4 signaling cascade. Preliminary data on probiotics suggest a potential role in NASH treatment, however randomized controlled clinical trials are still lacking.
Introduction. Response to hepatitis C treatment is known to differ by race; and, limited data suggests by ethnicity as well. A lower efficacy of HCV therapy in Latinos has been observed; whether higher doses may improve the response is unknown. Material and methods. This study used the available data from the patients enrolled in the PROGRESS study and stratified it by race and ethnicity. The primary objectives were to evaluate the early viral kinetic pattern in Latino patients and to assess whether it was improved by higher doses of Peg-IFN alfa-2a and/or RBV, as compared to Caucasian and African American patients. Results. From a total of 1145 patients, 51 (4%) were classified Latino, 886 (77%) Caucasian, 124 (11%) African American and 84 (7%) other. Latinos had a similar virological response between the treatment groups at week 4; but by week 12, achieved a greater response with the higher intensified dose of peginterferon alfa-2a, and remained so at week 72. Caucasians had a greater response at week 4 and week 12 with the intensified dose; but by week 72, the response became similar between the treatment groups. The virological responses for African Americans were unaffected by the doses; and by week 12, were lower than both Latinos and Caucasians. In conclusion, this retrospective analysis provides further evidence for racial/ethnic differences in the response to peginterferon alfa-2a (40KD) plus ribavirin therapy in patients with HCV. Although the sample sizes in this analysis are small for generalized conclusions, the findings are of importance to physicians treating Latinos.
Introduction. The inactive hepatitis B surface antigen (HBsAg) carrier state is usually characterized by minimal or absent liver pathology. However, in developing countries, owing to the very early age of infection with hepatitis B virus (HBV), this state is reached after a very prolonged immune tolerant and immune reactive phase, during which considerable liver damage may have occurred. The extent of liver damage in inactive HBsAg carriers has not been thoroughly assessed in developing countries. We thus sought to characterize liver pathology among Egyptian inactive HBsAg carriers. Material and methods. Liver biopsy was conducted on 30 inactive HBsAg carriers [positive for HBsAg; negative for HBeAg; positive for antibody to HBeAg (anti-HBe); HBV-DNA levels < 2,000 IU/mL; persistently normal serum alanine aminotransferase (ALT)]. Liver histopathology was assessed according to the Ishak scoring system. Results. Among the studied carriers, 6.7% had no hepatic fibrosis, 73.3% had stage 1 fibrosis, and 20% had stage 2 fibrosis. The majority (80%) of carriers had minimal hepatic necroinflammation (grades 2-4), while 20% had mild hepatic necroinflammation (grade 5). All patients with stage 2 fibrosis were males, while no gender predilection was observed for necroinflammation. Age, ALT and HBV-DNA levels did not differ significantly according to fibrosis or necroinflammatory scores. Conclusion. Our study findings do not support the presence of significant hepatic fibrosis or necroinflammation among Egyptian inactive HBsAg carriers. However, follow-up studies on these carriers may be required to monitor any further pathological progress of the disease.
Background. Living donor liver transplantation (LDLT) for patients with high model for end-stage liver disease (MELD) scores is controversial due to its poor outcome. However, there is little information regarding which factor would negatively impact the outcome of patients with high MELD scores. The aim of this study was to identify factors associated with the in-hospital mortality of patients with high MELD scores after LDLT. Material and methods. All patients with an MELD scores ≥ 20 who received LDLT from 2005 to 2011 were recruited for the present study. Pre- and intra-operative variables were retrospectively and statistically analyzed. Results. A total of 61 patients were included in the current study. The overall 3-month survival rate was 82% for patients with high MELD scores. Preoperative renal dysfunction, hyponatremia, starting albumin level < 2.8 g/dL, preoperative renal replacement for severe renal failure, anhepatic period > 100 minutes and intraoperative red blood cell (RBC) transfusion ≥ 10 units were identified as potential risk factors by univariate analysis. However, only hyponatremia, preoperative dialysis and massive RBC transfusion were independent risk factors in a multivariate analysis. The 3-month survival rates of patients with two or more independent risk factors and patients with none or one risk factor were 91 and 25%, respectively. A significant difference was observed (P < 0.001). Conclusion. Hyponatremia, preoperative dialysis and massive RBC transfusion were related to poor outcome for sicker patients. Patients with two or more of the above-mentioned risk factors and high MELD scores may exhibit extremely poor short-term survival.
Background. There is sparse literature on the association of adipose tissue with liver histology in patients with nonalcoholic fatty liver disease (NAFLD). Aim. To study the correlation of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) with liver histology in Indian patients with NAFLD. Material and methods. A single slice CT scan at the level of L4-L5 vertebrae was done to assess the abdominal VAT and SAT volumes in 21 patients with histological diagnosis of NAFLD. Adult treatment panel III criteria with modified abnormal waist were used to define metabolic syndrome (MS). Histological grading was done according to the NAFLD activity score (NAS). Results. Twenty-one patients with NAFLD [13 males, median age: 35 years, median BMI: 25.97 kg/m2] were included prospectively. Even though overweight/obese patients had severe liver disease, there was no difference in the volume of VAT adjusted for BMI between 6 (28.5%) lean and 15 (71.5%) overweight/obese patients. Patients with NASH and borderline NASH were older, obese with higher VAT and SAT volumes than no-NASH group. SAT volume (SATV) correlated significantly with hepatic steatosis but none of the adipose tissue volumes had any correlation with other histological variables. Both SATV and TAT volume (TATV) correlated significantly with severity of liver disease as determined by NAS score whereas presence of MS or insulin resistance had no correlation with histological severity. Conclusion. Both subcutaneous and total adipose tissue volume are related to the disease severity as determined by NAFLD activity score in Indian patients with NAFLD.
Background and aim. Metabolic syndrome is recognised as a potential risk factor for the development of hepatocellular carcinoma (HCC). The association between metabolic factors and hepatitis C (HCV)-related HCC has not yet been well clarified. This study was conducted to elucidate the role of metabolic factors in HCV-related HCC. Material and methods. We recruited 147 HCC patients and compared them with 147 matched CHC patients and 320 controls. The plasma levels of homeostasis model assessment-IR (HOMA-IR), adiponectin and lipids for all participants were assessed. Results. The HCC group showed significantly higher levels of insulin, glucose, HOMA-IR and adiponectin as well as lower levels of total cholesterol, HDL-C, LDL-C, and triglycerides compared with the matched CHC patients and controls. HOMA-IR did not correlate with pathologic features of HCC, whereas serum adiponectin levels correlated positively with the size of tumour nodules (P = 0.009). Based on stepwise logistic regression analysis, age (OR: 1.456, 95% CI: 1.072- 1.979, P < 0.01), HOMA-IR (OR: 2.50, 95% CI: 1.70-3.69, P = 0.001), and adiponectin (OR: 1.585, 95% CI: 1.269- 1.980, P = 0.001) were independently associated with HCC. Conclusions. Metabolic abnormalities are closely associated with the occurrence and development of HCV-related HCC. Patients with CHC and high serum adiponectin levels face a higher risk of developing liver cancer. Insulin resistance, as measured by HOMA-IR, is significantly associated with HCV-related HCC.
Background. Transforming growth factor alpha (TGFα) is an important mitogen that binds to epidermal growth factor receptor and is associated with the development of several tumors. Aims. Assessment of the immunoexpression of TGFα in hepatocellular carcinoma (HCC) and in non-neoplastic liver tissue and its relationship to morphological patterns of HCC. Material and methods. The immunohistochemical expression of TGFα was studied in 47 cases of HCC (27 multinodular, 20 nodular lesions). Five lesions measured up to 5 cm and 15 lesions above 5 cm. Thirty-two cases were graded as I or II and 15 as III or IV. The non-neoplastic tissue was examined in 40 cases, of which 22 had cirrhosis. HBsAg and anti-HCV were positive in 5/38 and 15/37 patients, respectively. The statistical analysis for possible association of immunostaining of TGFα and pathological features was performed through chi-square test. Results. TGFα was detected in 31.9% of the HCC and in 42.5% of the non-neoplastic. There was a statistically significant association between the expression of TGFα and cirrhosis (OR = 8.75, 95% CI = [1.93, 39.75]). The TGFα was detected more frequently in patients anti-HCV(+) than in those HBsAg(+). The immunoexpression of TGFα was not found related to tumor size or differentiation. In conclusion the TGFα is present in hepatocarcinogenesis in HBV negative patients. Further analysis is needed to examine the involvement of TGFα in the carcinogenesis associated with HCV and other possible agents. In addition, TGFα has an higher expression in hepatocyte regeneration and proliferation in cirrhotic livers than in HCC.
Background. Spontaneous reports of herb induced liver injury (HILI) represent a major regulatory issue, and it is in the interest of pharmacovigilance to identify and quantify previously unrecognized adverse reactions and to confirm or refute false positive signals of safety concerns. In a total of 13 spontaneous cases, liver disease has initially been attributed to the use of Pelargonium sidoides (PS), a plant from the South African region. Water/ethanol extracts derived from its roots are available as registered herbal drugs for the treatment of upper respiratory tract infections including acute bronchitis. Objectives. The present study examines whether and to what extent treatment by PS was associated with the risk of liver injury in these spontaneous cases. Study design: Overall, 13 spontaneous cases with primarily suspected PS hepatotoxicity were included in the study. Their data were submitted to a thorough clinical evaluation that included the use of the original and updated scale of CIOMS (Council for International Organizations of Medical Sciences) to assess causality levels. These scales are liver specific, validated for liver toxicity, structured and quantitative. Results. None of the 13 spontaneous cases of liver disease generated a positive signal of safety concern, since causality for PS could not be established on the basis of the applied CIOMS scales in any of the assessed patients. Confounding variables included comedication with synthetic drugs, major comorbidities, low data quality, lack of appropriate consideration of differential diagnoses, and multiple alternative diagnoses. Among these were liver injury due to comedication, acute pancreatitis and cholangitis, acute cholecystitis, hepatic involvement following lung contusion, hepatitis in the course of virus and bacterial infections, ANA positive autoimmune hepatitis, and other preexisting liver diseases. In the course of the case assessments and under pharmacovigilance aspects, data and interpretation deficits became evident. Possible improvements include appropriate data quality of cases in spontaneous reports, case assessment by skilled specialists, use of a validated liver specific causality assessment method, and inclusion only of confirmed cases into the final regulatory case database. Conclusions. This study shows lack of hepatotoxicity by PS in all 13 spontaneous cases as opposed to initial judgment that suggested a toxic potential of PS. Major shortcomings emerged in the pharmacovigilance section that require urgent improvements.
Introduction. The use of prognostic models for cirrhotic patients admitted to the medical intensive care unit (ICU) is of great importance, since they provide an objective evaluation for a group of patients with high mortality rates and high resource utilization. Objective. To evaluate the validity and to compare the prognostic predictive value of the CTP, MELD, SOFA and APACHE II scoring systems in cirrhotic patients admitted to the ICU, the CTP and MELD models being exclusive for patients with liver disease. Material and methods. Commonly used predictors of mortality such as age, sex, CTP, MELD, APACHE II and SOFA were evaluated, and their prognostic value was investigated. Results. A total of 201 patients were included in this study. Patients who survived had mean CTP score of 9.5 ± 2.4, MELD score 18.1 ± 7.1, APACHE II score of 13.4 ± 4.8 and SOFA score of 4.2 ± 2.6, compared to respective scores of 11.4 ± 2.8, 28.0 ± 11.2, 24.6 ± 10.4 and 8.7 ± 4.0 in patients who died. The difference between groups was statistically significant for each of one of the scoring systems (p < 0.001). Conclusion. In this study, SOFA was found to be the most powerful predictor of prognosis for cirrhotic patients admitted to the ICU. This was followed by APACHE II, MELD and CTP models, in descending order of strength (AUROC values of 0.847, 0.821, 0.790 and 0.724, respectively).
Aim. To establish an algorithm which includes the liver stiffness (LS) and/or spleen stiffness (SS) assessed by ARFI for the prediction of significant esophageal varices-EV (at least grade 2). Material and methods. Our study included 145 newly diagnosed cirrhotic patients admitted in our Department between September 2009-August 2011. 62 patients (42.7%) had significant EV. We performed 10 ARFI measurements in each patient, both in the liver and in the spleen; median values were calculated, expressed in meters/second. In 24 consecutive newly diagnosed cirrhotic patients admitted between September 2011-December 2011, we prospectively analyzed the value of the new score for predicting significant EV. Results. The LS and SS assessed by ARFI elastography, and the percentage of patients with ascites were stastically significant higher in patients with significant EV as compared with those without EV or grade 1 EV. By multiple regression analysis we obtained the following formula for predicting significant EV: prediction of significant EV (Pred EV2-3) score: -0.572 + 0.041 x LS (m/s) + 0.122 x SS (m/s) + 0.325 x ascites (1-absent, 2-present). The best Pred EV2-3 cut-off value for predicting significant EV was > 0.395 (AUROC = 0.721, accuracy = 69.6%). The accuracy in the group of patients in which the value of this score was prospectively analyzed was similar with that obtained in the first cohort of patients (70.8 vs. 69.6%). In conclusion, the proposed Pred EV2-3 score had a enough good value for predicting significant EV.
Background. Hospital outcome report cards are used to judge provider performance, including for liver transplantation. We aimed to determine the impact of the choice of risk adjustment method on hospital rankings based on mortality rates in cirrhotic patients. Material and methods. We identified 68,426 cirrhotic patients hospitalized in the Nationwide Inpatient Sample database. Four risk adjustment methods (the Charlson/Deyo and Elixhauser algorithms, Disease Staging, and All Patient Refined Diagnosis Related Groups) were used in logistic regression models for mortality. Observed to expected (O/E) death rates were calculated for each method and hospital. Statistical outliers with higher or lower than expected mortality were identified and rankings compared across methods. Results. Unadjusted mortality rates for the 553 hospitals ranged from 1.4 to 30% (overall, 10.6%). For 163 hospitals (29.5%), observed mortality differed significantly from expected when judged by one or more, but not all four, risk adjustment methods (25.9% higher than expected mortality and 3.6% lower than expected mortality). Only 28% of poor performers and 10% of superior performers were consistently ranked as such by all methods. Agreement between methods as to whether hospitals were flagged as outliers was moderate (kappa 0.51-0.59), except the Charlson/Deyo and Elixhauser algorithms which demonstrated excellent agreement (kappa 0.75). Conclusions. Hospital performance reports for patients with cirrhosis require sensitivity to the method of risk adjustment. Depending upon the method, up to 30% of hospitals may be flagged as outliers by one, but not all methods. These discrepancies could have important implications for centers erroneously labeled as high mortality outliers.
Background. Type I and type IV-A choledochal cysts (CC) in Todani's classification are the most frequent types of CC. Unlike type I cyst, in which the dilatation is confined to the extrahepatic bile duct, type IV-A affects both extra and intrahepatic ducts. Aim. To review our experience of complete cyst excision with Roux-en-Y hepaticojejunostomy for the treatment of type I and type IV-A CC in childhood, in order to better characterize these entities. Material and methods. Data was collected retrospectively from a cohort of children who underwent cyst resection for CC from 1989 to 2011 in our institution. Results. Twelve patients were submitted to surgical excision of extrahepatic cyst and hepaticojejunostomy for treatment of type I (n = 6) and type IV-A (n = 6) cysts, with a complication rate of 25% (n = 3) and no mortality. Long term follow-up was available in 92% of patients, with a median of 10 years (2-22 years). Morbidities consisted of bile leak (2 patients) and late-onset cholestasis (1 patient); two of these required anastomotic revision. The results did not reveal any significant differences between the groups regarding postoperative outcomes (P > 0.05). Preoperative intrahepatic dilatation was found to permanently vanish in 83% of patients diagnosed with type IV-A cyst after operative repair. Conclusions. Intrahepatic dilatation of type IV-A cyst in children did not adversely affect the postoperative outcome after conventional surgical repair. This operative approach was effective in the management of type I and type IV-A cysts.
We present an unusual case of extensive avascular malformations (AVMs) causing non-cirrhotic portal hypertension. This phenomenon, though previously described, is a rare clinical entity which, in the setting of life threatening portal hypertension, may require vascular decompression either by surgery or a transjugular intrahepatic portosystemic shunt.
Aminotransferase elevation is a frequent cause of consultation for the Hepatologist, in both the outpatient and inpatient settings, but identifying the origin of these biochemical alterations may be challenging. Here we report a case where acute elevation of aminotransferases, associated with abdominal symptoms, was the cause of two hospitalizations in a short period of time. As the patient suffered from type 1 diabetes, celiac disease, and autoimmune thyroiditis, several potential causes of damage could be hypothesized, including celiac hepatitis, fatty liver, and autoimmune hepatitis. A liver biopsy performed in the occasion of the second hospitalization allowed to rule out autoimmune hepatitis and celiac hepatitis, showing mild signs of fatty infiltration. Staining with periodic acid-Schiff with or without diastase showed a marked accumulation of glycogen, indicating the presence of a glycogenic hepatopathy associated with poorly controlled type 1 diabetes. This condition may be a cause of liver damage in patients with type 1 and occasionally type 2 diabetes, but its occurrence is often overlooked. This case report illustrates the fact that glycogenic hepatopathy may relapse, and prompts the clinician to take into account this condition in the differential diagnosis of causes of liver injury.
Peripheral blood eosinophilia has been described in a broad variety of allergic, infectious, neoplastic and autoimmune diseases. To the best of our knowledge blood eosinophilia has never previously been reported in association with isolated autoimmune hepatitis (AIH) in the absence of other autoimmune conditions. Herein we report an interesting case of an 18 year old man who presented to our hospital with an acute autoimmune hepatitis diagnosed on the basis of clinical features, serology and histopathology. He was noted to have a moderate peripheral eosinophilia at diagnosis which resolved within days of initiation of corticosteroids for treatment of the AIH. Given the absence of other systemic conditions or drugs which may have produced the eosinophilia and its rapid resolution with treatment of the underlying liver disease, we wished to highlight this rather novel presentation of AIH.
In recent years there has been a significant increase in the consumption of dietary energy supplements (DES) associated with the parallel advertising against obesity and favoring high physical performance. We present the case and outcome of a young patient who developed acute mixed liver injury (hepatocellular and cholestatic) after ingestion of various "over the counter" products to increase muscle mass and physical performance (NO Xplode®, creatine, L-carnitine, and Growth Factor ATN®). The diagnosis was based on the exclusion of other diseases and liver biopsy findings. The dietary supplement and herbal multivitamins industry is one with the highest growth rates in the market, with annual revenues amounting to billions and constantly lacking scientific or reproducible evidence about the efficacy and/or safety of the offered products. Furthermore, and contrary to popular belief, different forms of injury associated with these natural substances have been documented particularly in the liver, supporting the need of a more strict regulation.