Ajay Duseja

Diagnosis and Prognostic Significance of Minimal Hepatic Encephalopathy in Patients with Cirrhosis of Liver

Background and AimsMinimal hepatic encephalopathy is the mildest form of the spectrum of hepatic encephalopathy (HE) that impairs health-related quality of life. We assessed (1) the usefulness of psychometric hepatic encephalopathy score and critical flicker frequency for the diagnosis of minimal hepatic encephalopathy, and (2) prognostic significance of minimal hepatic encephalopathy.MethodsOne hundred patients with liver cirrhosis without overt HE were subjected to psychometric hepatic encephalopathy score and critical flicker frequency evaluation. Eighty-three age- and sex-matched healthy volunteers served as controls. Minimal hepatic encephalopathy was diagnosed when the psychometric hepatic encephalopathy score was ≤−5. An age-adjusted Z score <−2 on the critical flicker frequency was considered abnormal.ResultsForty-eight (48%) patients had minimal hepatic encephalopathy as indicated by altered psychometric hepatic encephalopathy score. Critical flicker frequency was altered in 21 patients; 17 also showed impaired psychometric hepatic encephalopathy score thus providing additional information in only 4 patients. Forty-six of 48 patients with minimal hepatic encephalopathy and 48 of 52 patients without minimal hepatic encephalopathy completed the follow-up. Eighteen (39.1%) patients died among those who had minimal hepatic encephalopathy compared to 11 (22.9%) patients who did not have minimal hepatic encephalopathy. Among the several variables analyzed in this study, univariate analyses showed that age, serum bilirubin level, Child-Turcotte-Pugh score and psychometric hepatic encephalopathy score were associated with a poor prognosis. The multivariate analysis identified two variables as significant independent prognostic factors; psychometric hepatic encephalopathy score ≤−6 [hazard ratio 2.419 (95% CI, 1.014–5.769)] and Child-Turcotte-Pugh score ≥8 [hazard ratio 2.466 (95% CI, 1.010–6.023)] predicted poor survival.ConclusionsPsychometric hepatic encephalopathy score is a useful tool for the diagnosis of minimal hepatic encephalopathy in an outpatient setting. Both psychometric hepatic encephalopathy score and Child-Turcotte-Pugh score have prognostic value on survival.

Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy

BACKGROUND & AIMS Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encephalopathy. This cross-sectional study was carried out to elucidate the role of bacterial overgrowth of the small intestine and delayed intestinal transit among patients with MHE. METHODS Two-hundred-thirty patients with cirrhosis were screened; 102 patients (44.4%) who met the eligibility criteria were included in the study. MHE was diagnosed when the psychometric hepatic encephalopathy score was ≤-5. All patients underwent a glucose breath test for small intestinal bacterial overgrowth (SIBO) and lactulose breath test for oro-cecal transit time (OCTT). RESULTS Fifty-seven (55.9%) patients with cirrhosis had MHE. Among these patients with MHE, 22 (38.6%) had SIBO, while 4 (8.9%) without MHE had SIBO (p = 0.001). The prevalence of SIBO was higher in patients with CTP classes B and C (69.2%) compared to those in CTP class A (30.8%); p = 0.054. OCTT was significantly prolonged in patients who had SIBO than in those who did not have SIBO (p<0.0001). Univariate analysis demonstrated that increased age, female gender, low educational status, low albumin, presence of SIBO, and prolonged OCTT were associated with the presence of MHE. Multivariate analysis demonstrated SIBO as the only factor associated with MHE. CONCLUSIONS Our study conclusively demonstrates high prevalence of SIBO in patients with cirrhosis with MHE. This study gives the rationale of treatment directed against SIBO and gut dysmotility, which may include non-absorbable antibiotics such as rifaximin, probiotics, and prokinetics.

Early indicators of prognosis in fulminant hepatic failure: An assessment of the Model for End‐Stage Liver Disease (MELD) and King's College Hospital Criteria

While Kings Hospital Criteria (KCH) criteria are used worldwide, the Model for End‐Stage Liver Disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in conditions for liver transplantation (LT). The aim of the present study was to compare MELD and KCH criteria with other early clinical prognostic indicators (CPI) in a cohort of patients with fulminant hepatic failure (FHF). A total of 144 patients (mean age 31.7 ± 14.7 yr; range 12–82 yr; 62 males) with FHF due to acute viral hepatitis were included into the study. Variables found significant on univariate analysis were entered into a multivariate logistic regression analysis. A total of 52 (36.1%) patients survived, the remaining 92 (63.9%) died. Univariate analysis showed that age, duration of jaundice, jaundice‐encephalopathy interval (JEI), grade of encephalopathy, presence of cerebral edema, bilirubin, prothrombin time, creatinine, and MELD score were significantly different between survivors and nonsurvivors. Multivariate logistic regression identified 6 independent CPI of adverse outcome on admission: age ≥50 yr, JEI >7 days, grade 3 or 4 encephalopathy, presence of cerebral edema, prothrombin time ≥35 seconds, and creatinine ≥1.5 mg/dL. Presence of any 3 of 6 CPI was optimum in identifying survivors and nonsurvivors. A MELD score of ≥33 was found to be best discriminant between survivors and nonsurvivors by the construction of receiver operating characteristic (ROC) curves. Any 3 CPI were superior to MELD and KCH criteria in predicting the outcome (c‐statistic [95% confidence interval]: CPI 0.802 [0.726–0.878], MELD 0.717 [0.636–0.789], and KCH criteria 0.676 (0.588–0.764); P values: CPI vs. MELD 0.045, CPI vs. KCH criteria 0.019, and MELD vs. KCH criteria 0.472). In conclusion, MELD and KCH criteria are not as useful as a combination of other early CPI in predicting adverse outcome in patients with FHF due to acute viral hepatitis. Liver Transpl, 2007.

Probiotic VSL#3 Reduces Liver Disease Severity and Hospitalization in Patients With Cirrhosis: A Randomized, Controlled Trial

BACKGROUND & AIMS Little is known about whether probiotics can affect outcomes of patients with cirrhosis and hepatic encephalopathy (HE). We assessed the efficacy of a probiotic preparation in preventing the recurrence of HE (primary outcome) and reducing the number of hospitalizations and severity of liver disease in patients with cirrhosis. METHODS We performed a double-blind trial at a tertiary care hospital in India. Patients with cirrhosis who had recovered from an episode of HE during the previous month were assigned randomly (using computer-generated allocation) to groups given a probiotic preparation (VSL#3, 9 × 10(11) bacteria; CD Pharma India Private Limited, New Delhi, India) (n = 66) or placebo (n = 64) daily for 6 months. RESULTS There was a trend toward a reduction in the development of breakthrough HE among patients receiving the probiotic (34.8% in the probiotic group vs 51.6% in the placebo group; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.38-1.11; P = .12). Fewer patients in the probiotic group were hospitalized for HE (19.7% vs 42.2%, respectively; HR, 0.45; 95% CI, 0.23-0.87; P = .02) or for complications of cirrhosis (24.2%) than in the placebo group (45.3%) (HR, 0.52; 95% CI, 0.28-0.95; P = .034). Child-Turcotte-Pugh and model for end-stage liver disease scores improved significantly from baseline to 6 months in the probiotic group, but not in the placebo group. There were no adverse events related to VSL#3. CONCLUSIONS Over a 6-month period, daily intake of VSL#3 significantly reduced the risk of hospitalization for HE, as well as Child-Turcotte-Pugh and model for end-stage liver disease scores, in patients with cirrhosis. ClinicalTrials.gov number: NCT01110447.

Review article: the modern management of portal vein thrombosis.

Background  Portal vein thrombosis (PVT) is an important cause of portal hypertension. It may occur as such with or without associated cirrhosis and hepatocellular carcinoma. Information on its management is scanty.

Minimal hepatic encephalopathy: Consensus statement of a working party of the Indian National Association for Study of the Liver

Hepatic encephalopathy (HE) is a major complication that develops in some form and at some stage in a majority of patients with liver cirrhosis. Overt HE occurs in approximately 30–45% of cirrhotic patients. Minimal HE (MHE), the mildest form of HE, is characterized by subtle motor and cognitive deficits and impairs health‐related quality of life. The Indian National Association for Study of the Liver (INASL) set up a Working Party on MHE in 2008 with a mandate to develop consensus guidelines on various aspects of MHE relevant to clinical practice. Questions related to the definition of MHE, its prevalence, diagnosis, clinical characteristics, pathogenesis, natural history and treatment were addressed by the members of the Working Party.

The Clinicopathological Profile of Indian Patients with Nonalcoholic Fatty Liver Disease (NAFLD) is Different from That in the West

There are limited data on nonalcoholic fatty liver disease (NAFLD) from India. The clinicopathological profile of Indian patients with NAFLD may be different from that of Western patients. One hundred NAFLD patients with increased liver enzymes were prospectively evaluated for clinical presentation, associated diseases, overweight/obesity, central obesity (n=54), presence of diabetes mellitus, lipid abnormalities, insulin resistance (n=39), metabolic syndrome (n=54), serum iron, serum ferritin, and transferrin saturation (n=60), and HFE gene mutations (n=30). Risk factors for the grade and stage of the disease on histology were studied in 38 biopsy-proven patients. Patients were treated with lifestyle modifications and ursodeoxycholic acid (UDCA). Seventeen nonresponder patients were treated with metformin. The majority of patients were males (n=70). Twenty percent of patients were overweight, 68% had obesity, and 78% had central obesity. Abnormal cholesterol, HDL, and triglycerides were present in 36%, 66%, and 53% of patients, respectively. Twelve percent of patients had diabetes mellitus and 16% patients had various associated diseases. All 22 (100%) patients studied by ITT and all but 1 (98%) studied by HOMA-IR were found to have reduced insulin sensitivity and 50% were found to have metabolic syndrome by the modified ATP III criteria. Two (3%) patients were found to have high serum iron, 4 (7%) patients had high ferritin, 5 (8%) patients had increased transferrin saturation, and 4 (13%) patients were found to be heterozygotes for H63D HFE gene mutation. Twenty patients of 38 (53%) had histological evidence of NASH (class 3=6, class 4=14). The other 18 (47%) qualified for class I (n=1) or class II (n=17) NAFLD. Four (10.5%) patients had bridging fibrosis and none had evidence of cirrhosis liver. Seventy-four (74%) patients achieved a biochemical response to lifestyle modification and UDCA. All 17 patients treated with metformin had a reduction in ALT level and 10 (59%) of them had normalization of their enzymes. We conclude that the clinicopathological profile of NAFLD in Indian patients is different from that in the West.

APACHE II score is superior to SOFA, CTP and MELD in predicting the short‐term mortality in patients with acute‐on‐chronic liver failure (ACLF)

The aim of the study was to assess the performance of various prognostic scores including the acute physiology and chronic health evaluation (APACHE II), sequential organ failure assessment (SOFA), Child–Turcotte–Pugh (CTP) and model for end‐stage liver disease (MELD) scores in predicting short‐term mortality in patients with acute‐on‐chronic liver failure (ACLF).

Obesity and NAFLD: The Role of Bacteria and Microbiota

There are trillions of microorganisms in the human intestine collectively called gut microbiota. Obesity may be affected by the gut microbiota through energy harvesting and fat storage by the bacteria. Small intestinal bacterial overgrowth is also responsible for endotoxemia, systemic inflammation, and its consequences including obesity and nonalcoholic fatty liver disease (NAFLD). Relationship between gut microbiota and NAFLD is also dependent on altered choline and bile acid metabolism and endogenous alcohol production by gut bacteria. Further evidence linking gut microbiota with obesity and NAFLD comes from studies showing usefulness of probiotics in animals and patients with NAFLD. This article reviews the relationship among gut microbiota, obesity, and NAFLD.

Nonalcoholic fatty liver disease in India – a lot done, yet more required!

Nonalcoholic fatty liver disease (NAFLD) is emerging as an important cause of liver disease in India. Epidemiological studies suggest prevalence of NAFLD in around 9% to 32% of general population in India with higher prevalence in those with overweight or obesity and those with diabetes or prediabetes. Clinicopathological studies show that NAFLD is an important cause of unexplained rise in hepatic transaminases, cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma in Indian patients. There is high prevalence of insulin resistance and nearly half of Indian patients with NAFLD have evidence of full-blown metabolic syndrome. Though oxidative stress is involved in the pathogenesis of NAFLD/nonalcoholic steatohepatitis, serum or liver iron and HFE gene mutations appear not to play a role in the pathogenesis of NAFLD in Indian patients. Imaging modalities are not useful in differentiating simple steatosis from NASH and liver biopsy may be useful in those with risk factors for significant liver disease. Pilot studies on treatment strategies have shown that weight reduction and exercise, ursodeoxycholic acid, metformin, vitamin E and pentoxyfylline are effective in normalizing transaminases and or in improving hepatic steatosis and inflammation in Indian patients with NAFLD. Randomized controlled treatment trials involving large number of patients with histological end point are required to assess the efficacy of different modalities. In conclusion, a lot has been done, yet more is required to understand various aspects of NAFLD in India.