Diagnostic Assessment — Steatohepatitis
Example 1 of 1 · fictitious patient (Veteran CE)
Diagnostic Assessment
Steatohepatitis
BOP Code: 87 of 2022 (Steatohepatitis)
RH Code: 86 of 2022 (Steatohepatitis)
ADF History
Veteran CE, date of birth 06 November 1974, Australian Army, Cook, enlisted 18 January 1993, medically discharged 29 September 2016. Operational service: East Timor, 20 September 1999 to 23 February 2000 (warlike); Iraq, 14 April 2005 to 28 November 2005 (warlike); Afghanistan, 02 February 2011 to 30 August 2011 (warlike).
Occupational History
Army cooks prepare meals in garrison and field kitchens, on long and irregular shifts that begin before dawn, in hot environments and with constant access to food. Field and deployed kitchens involve heavy lifting of stores and equipment, exposure to cooking fumes, smoke and fuel, and on operations, burn pit smoke and the hazards of the deployed environment.
The irregular hours, disrupted sleep and sedentary periods between surges of work contribute to weight gain and metabolic disease, and the drinking culture of messes and post-deployment periods during this veteran's service normalised heavy alcohol use.
History
Veteran CE, an Army cook, developed obesity, hypertension, type 2 diabetes and dyslipidaemia during her service and drank heavily after warlike deployments, and in 2015 underwent jejunoileal bypass, parenteral nutrition and FOLFIRI chemotherapy for a small bowel adenocarcinoma. She developed steatohepatitis on 12 November 2015, 25 days after starting amiodarone for chemotherapy-related ventricular tachycardia, and it worsened with fibrosis when amiodarone was restarted in 2017.
Timeline
- 21 Aug 2006 — Periodic health examination after her return from warlike service in Iraq recorded a BMI of 37.9, type 2 diabetes (HbA1c 8.1 per cent), triglycerides of 3.4 mmol/L, HDL cholesterol of 0.8 mmol/L and uric acid of 0.52 mmol/L. Hypertension had been treated since 2003. Her AUDIT score was 21, with about 45 grams of alcohol a day. Liver function tests and liver ultrasound were normal. "AUDIT 21, HbA1c 8.1 per cent"
- 14 Dec 2011 — A psychiatrist diagnosed posttraumatic stress disorder after her warlike service in Afghanistan, noting heavy drinking from 2006 to 2010 that had reduced in 2011. Quetiapine and sertraline were commenced. "PTSD, heavy drinking 2006 to 2010"
- 05 Feb 2015 — Laparotomy for small bowel obstruction found an unresectable mid-jejunal adenocarcinoma, and a jejunoileal bypass was performed, joining the proximal jejunum to the terminal ileum and excluding about 3 metres of small bowel. Pre-operative weight was 118 kg (BMI 41.8). High-output diarrhoea and malabsorption followed. "jejunoileal bypass, BMI 41.8"
- 10 Jul 2015 — Total parenteral nutrition had been given through a central line since 20 March 2015, when her weight was falling rapidly and albumin was 26 g/L. FOLFIRI chemotherapy (irinotecan and fluorouracil every 14 days) began on 01 July 2015. Her weight was now 92 kg, a 22 per cent loss in five months, and a dietitian documented protein-calorie malnutrition with albumin of 24 g/L. "TPN commenced, 22 per cent loss"
- 18 Oct 2015 — Recurrent sustained ventricular tachycardia followed fluorouracil-associated coronary vasospasm. A cardiologist started amiodarone, recording that beta-blockers and sotalol had failed, ablation was not possible and amiodarone could not be ceased or substituted. Staging CT on 28 September 2015 had shown normal liver attenuation, and liver tests on 10 October 2015 were normal. "amiodarone commenced, liver normal"
- 19 Nov 2015 — Parenteral nutrition had ended on 30 October 2015. She presented with a week of fatigue, nausea and right upper quadrant discomfort since 12 November 2015. ALT was 186 U/L, AST 142 U/L and GGT 310 U/L, and ultrasound showed a diffusely echogenic, enlarged liver. Viral, autoimmune and metabolic liver screens were negative, and there was no biliary dilatation. "ALT 186, echogenic enlarged liver"
- 08 Jan 2016 — Liver biopsy showed macrovesicular steatosis in 60 per cent of hepatocytes, ballooning degeneration, Mallory-Denk bodies, lobular inflammation and perisinusoidal fibrosis stage F2. A hepatologist diagnosed steatohepatitis. Amiodarone was withheld in December 2015 and liver tests improved by mid-2016. "steatohepatitis, fibrosis F2"
- 15 Jun 2017 — Ventricular tachycardia recurred and amiodarone was restarted on 04 April 2017, as ablation was still unavailable. ALT rose to 240 U/L within four weeks. Repeat biopsy showed active steatohepatitis with bridging fibrosis stage F3, and transient elastography measured 11.8 kPa. "recurrent NASH, bridging fibrosis F3"
Symptoms
At onset the veteran had fatigue, nausea, loss of appetite and a dull ache under the right ribs, with tender hepatomegaly. She had no jaundice or ascites.
She now has persisting fatigue and right upper quadrant discomfort, reduced exercise tolerance, and is under hepatology surveillance for advanced fibrosis, with six-monthly ultrasound and elastography.
Imaging
- 21 Aug 2006 — Liver ultrasound: "Normal liver size and echotexture."
- 28 Sep 2015 — CT chest, abdomen and pelvis (staging): "Jejunoileal bypass with excluded small bowel loop. Normal liver attenuation. No hepatic metastases."
- 19 Nov 2015 — Liver ultrasound: "Enlarged liver, 19 cm, with diffusely increased echogenicity consistent with fatty infiltration. No focal lesion or biliary dilatation."
- 15 Jun 2017 — Transient elastography and ultrasound: "Liver stiffness 11.8 kPa, consistent with advanced fibrosis. Diffuse fatty infiltration. Normal spleen size."
Onset Date
The most likely date of onset of this condition is 12 Nov 2015.
At that date the veteran was serving full time, on medical leave while receiving FOLFIRI chemotherapy. She had undergone jejunoileal bypass in February 2015, had completed seven months of parenteral nutrition on 30 October 2015 and had started amiodarone on 18 October 2015. From 12 November 2015 she developed fatigue, nausea and right upper quadrant pain.
This date is appropriate because staging CT on 28 September 2015 showed normal liver attenuation and liver tests on 10 October 2015 were normal, and she first presented on 19 November 2015, one week after onset, with markedly abnormal liver tests and a fatty, enlarged liver. It falls within continuous full-time service.
For the weight loss factor, the 18 months before onset run from 12 May 2014 to 12 Nov 2015, and her 22 per cent weight loss occurred between February and July 2015. For the parenteral nutrition factor, the 1 year before onset runs from 12 Nov 2014 to 12 Nov 2015, containing more than 7 months of parenteral nutrition (20 Mar 2015 to 30 Oct 2015). For the irinotecan and Schedule 2 drug factors, the 30 days before onset run from 13 Oct 2015 to 12 Nov 2015, throughout which FOLFIRI continued. For the rechallenge factor, amiodarone was first taken on 18 Oct 2015, 25 days before onset. For the alcohol factors, the 5 year period was January 2006 to December 2010. Hypertension, diabetes, obesity, dyslipidaemia and hyperuricaemia were present on 12 Nov 2015, and the jejunoileal bypass preceded it.
For the worsening factor, the period after onset runs from 12 Nov 2015 to the documented worsening on 15 Jun 2017, during which ablation and hepatology review could not be obtained, amiodarone was restarted on 04 Apr 2017 and fibrosis progressed from F2 to F3.
1. What is the formal diagnosis of the condition claimed above?
The formal diagnosis is Steatohepatitis (ICD-10-AM K75.8), mixed metabolic, drug-induced and nutritional in type, under the Statements of Principles concerning steatohepatitis, Balance of Probabilities No. 87 of 2022 and Reasonable Hypothesis No. 86 of 2022.
Steatohepatitis is fatty change of the liver with inflammation and hepatocyte injury, with or without fibrosis. It includes alcoholic and non-alcoholic forms. Fat accumulates in liver cells when the supply of fatty acids exceeds the liver's capacity to oxidise or export them, as occurs with obesity, diabetes, dyslipidaemia, alcohol, starvation and rapid weight loss, intestinal bypass, parenteral nutrition and some drugs such as amiodarone and chemotherapy. Oxidative stress then injures the cells and drives inflammation and fibrosis, which can progress to cirrhosis.
The diagnosis followed years of metabolic disease and heavy drinking during service and, in 2015, bypass surgery, parenteral nutrition and chemotherapy for a small bowel cancer. It began on 12 November 2015, 25 days after amiodarone was started, was confirmed on biopsy on 08 January 2016 and worsened with fibrosis on rechallenge in 2017.
2. For each diagnosis identified, please also provide the following dates:
When did the veteran first experience symptoms attributable to this condition?
12 November 2015.
When did the veteran first present to a health / medical provider for this condition?
19 November 2015.
When was the condition confirmed / formally diagnosed?
08 January 2016.
When did the veteran first present to you (or your practice) for this condition?
14 August 2025.
3. How was this diagnosis confirmed? i.e. what were the key symptoms and signs, investigation results, specialist opinions?
The diagnosis was confirmed on liver biopsy on 08 January 2016, which showed macrovesicular steatosis, hepatocyte ballooning, Mallory-Denk bodies, lobular inflammation and perisinusoidal fibrosis. This meets the Statement of Principles definition of steatohepatitis: fatty change and inflammation of the liver with hepatocyte injury. Screening excluded alpha-1 antitrypsin deficiency, haemochromatosis and Wilson's disease, and ultrasound excluded biliary obstruction.
A hepatologist confirmed the diagnosis. Repeat biopsy on 15 June 2017 and elastography of 11.8 kPa confirmed active steatohepatitis with progression to bridging fibrosis.
4. What do you consider to be the cause(s) of the condition in this veteran? Give consideration to constitutional and common risk factors, pre-existing injuries or diseases, and occupational or lifestyle risks, as well as direct causative mechanisms.
Legislation: the clinical onset of this condition was on 12 November 2015, after 1 July 2004, during continuous full-time service. This is a Military Rehabilitation and Compensation Act 2004 (MRCA) claim and the Statements of Principles apply. The Reasonable Hypothesis instrument applies to the veteran's warlike service in East Timor, Iraq and Afghanistan, after which her drinking escalated, her metabolic disease worsened and her posttraumatic stress disorder arose, and from which her accepted small bowel adenocarcinoma arose. The Balance of Probabilities instrument applies to her peacetime service. Factor 9(14) of the Reasonable Hypothesis instrument and 9(12) of the Balance of Probabilities instrument apply only to material contribution to, or aggravation of, the condition.
Each factor must be related to the person's relevant service. Under the beneficial approach required by the legislation, the absence of documentation does not mean that an event or exposure did not occur: lack of evidence is not evidence of lack.
Balance of Probabilities — Statement of Principles concerning Steatohepatitis, No. 87 of 2022
Causative factors
Factor 9(1): having diabetes mellitus at the time of the clinical onset of steatohepatitis; — MET
- Type 2 diabetes mellitus was diagnosed on 21 August 2006 (HbA1c 8.1 per cent, fasting glucose 9.8 mmol/L) and treated with metformin and later insulin. It was present at onset on 12 November 2015, when HbA1c was 8.6 per cent. It developed during her service after weight gain associated with years of shift work in field kitchens and irregular meals.
Factor 9(2): being obese at the time of the clinical onset of steatohepatitis; — MET
- Her BMI was 41.8 (118 kg, 1.68 m) in January 2015 and, despite rapid weight loss, 32.6 (92 kg) on 12 November 2015, so she was obese at onset. Her waist circumference was 104 cm, well above 88 cm.
Factor 9(3): having rapid weight loss causing protein-calorie malnutrition within the 18 months before the clinical onset of steatohepatitis; — MET
- After the jejunoileal bypass of 05 February 2015 she developed high-output malabsorption and her weight fell from 118 kg to 92 kg between 05 February 2015 and 10 July 2015, a 22 per cent loss within five months. Serum albumin fell to 24 g/L and prealbumin to 0.08 g/L, and a dietitian documented protein-calorie malnutrition. This was within the 18 months before onset, which run from 12 May 2014 to 12 November 2015.
Factor 9(4): undergoing jejunoileal bypass surgery before the clinical onset of steatohepatitis; — MET
- On 05 February 2015, at laparotomy for small bowel obstruction from an unresectable mid-jejunal adenocarcinoma, the surgeon performed a jejunoileal bypass, anastomosing the proximal jejunum to the terminal ileum and excluding about 3 metres of small bowel. This was before onset on 12 November 2015.
Factor 9(5): receiving total parenteral nutrition for at least 6 months within the 1 year before the clinical onset of steatohepatitis; — MET
- Total parenteral nutrition was given through a central venous catheter from 20 March 2015 to 30 October 2015, providing a full nutrient admixture of dextrose, amino acids, lipid, electrolytes, trace elements and vitamins. This is more than 7 months within the 1 year before onset, which runs from 12 November 2014 to 12 November 2015.
Factor 9(6): having dyslipidaemia at the time of the clinical onset of steatohepatitis; — MET
- Dyslipidaemia was diagnosed on 21 August 2006 with triglycerides of 3.4 mmol/L and HDL cholesterol of 0.8 mmol/L, and she took atorvastatin 40 mg daily from then on. Triglycerides were 4.1 mmol/L in October 2015, during parenteral nutrition, and dyslipidaemia was present at onset.
Factor 9(7): for males, consuming at least 75 kilograms of alcohol within any 5 year period before the clinical onset of steatohepatitis; — MET
- The veteran is female. She consumed about 82 kilograms of alcohol between January 2006 and December 2010, an average of 45 grams (four and a half standard drinks) a day recorded at her periodic health examinations and AUDIT screening. This exceeds the 75 kilogram threshold set for males as well as the female threshold, so the alcohol exposure that this factor describes is established in her case.
Factor 9(8): for females, consuming at least 40 kilograms of alcohol within any 5 year period before the clinical onset of steatohepatitis; — MET
- Between January 2006 and December 2010 she consumed about 82 kilograms of alcohol, more than twice the 40 kilograms required within a 5 year period, as recorded in AUDIT screening (scores of 18 to 22) at her periodic health examinations. Heavy drinking was entrenched in the mess culture of her units during this period. It preceded onset on 12 November 2015.
Factor 9(9): taking irinotecan for at least the 30 days before the clinical onset of steatohepatitis; — MET
- She received FOLFIRI chemotherapy, including irinotecan 180 mg/m2 every 14 days, from 01 July 2015 continuously to and beyond onset on 12 November 2015, covering the 30 days before onset from 13 October 2015.
Factor 9(10): taking a drug specified in the Schedule 2 - Drugs of this Instrument, that cannot be ceased or substituted, for at least the 30 days before the clinical onset of steatohepatitis; — MET
- Fluorouracil, listed in Schedule 2, was given as part of FOLFIRI from 01 July 2015 throughout the 30 days before onset. The oncologist recorded that it could not be ceased or substituted because no alternative regimen was available for her disease.
Factor 9(11): taking a drug that cannot be ceased or substituted and which is associated in the individual with: (a) the development of steatohepatitis within 30 days of first taking the drug; and (b) the redevelopment of steatohepatitis on rechallenge with the same drug; — MET
- Amiodarone was started on 18 October 2015 for recurrent sustained ventricular tachycardia after fluorouracil-associated coronary vasospasm, because beta-blockers and sotalol had failed and catheter ablation was not possible; the cardiologist recorded that it could not be ceased or substituted. Steatohepatitis developed 25 days later, on 12 November 2015. Amiodarone was withheld in December 2015 and the liver tests improved, and when ventricular tachycardia recurred it was restarted on 04 April 2017, after which steatohepatitis redeveloped on biopsy on 15 June 2017.
Worsening factors
Factor 9(12): inability to obtain appropriate clinical management for steatohepatitis. — MET
- After the diagnosis a hepatology review and an alternative to amiodarone were sought, but catheter ablation was unavailable for 16 months and the hepatology clinic's waiting list delayed review until after amiodarone had been restarted. Biopsy on 15 June 2017 showed active steatohepatitis with progression of fibrosis from F2 to F3. Under Brew v Repatriation Commission (1999) this is an inability to obtain appropriate clinical management, which materially contributed to the worsening.
Reasonable Hypothesis — Statement of Principles concerning Steatohepatitis, No. 86 of 2022
Causative factors
Factor 9(1): having hypertension before the clinical onset of steatohepatitis; — MET
- Hypertension was diagnosed on 12 May 2003, with readings of 158/100 mmHg confirmed on ambulatory monitoring, and was treated with perindopril and amlodipine from then on. It preceded onset by more than 12 years. Her blood pressure rose further after her return from warlike service in Iraq in 2005, during a period of heavy drinking and weight gain.
Factor 9(2): having diabetes mellitus at the time of the clinical onset of steatohepatitis; — MET
- Type 2 diabetes mellitus, diagnosed on 21 August 2006, was present at onset on 12 November 2015. It followed weight gain after her warlike service in Iraq in 2005 and was aggravated by quetiapine prescribed for posttraumatic stress disorder arising from her warlike service in Afghanistan in 2011.
Factor 9(3): being obese at the time of the clinical onset of steatohepatitis; — MET
- She was obese at onset, with a BMI of 32.6 and a waist circumference of 104 cm on 12 November 2015. The obesity developed after warlike service in Iraq and was aggravated by quetiapine for posttraumatic stress disorder from her service in Afghanistan.
Factor 9(4): having rapid weight loss causing protein-calorie malnutrition within the 18 months before the clinical onset of steatohepatitis; — MET
- The 22 per cent weight loss from 118 kg to 92 kg between February and July 2015, with protein-calorie malnutrition (albumin 24 g/L), followed bypass surgery for the small bowel adenocarcinoma accepted as related to her warlike service, within the 18 months before onset.
Factor 9(5): undergoing jejunoileal bypass surgery before the clinical onset of steatohepatitis; — MET
- The jejunoileal bypass of 05 February 2015, which excluded about 3 metres of small bowel, was performed for the small bowel adenocarcinoma accepted as related to her warlike service in Afghanistan, before onset.
Factor 9(6): receiving total parenteral nutrition for at least 3 months within the 1 year before the clinical onset of steatohepatitis; — MET
- She received total parenteral nutrition from 20 March 2015 to 30 October 2015, more than 3 months within the 1 year before onset, for intestinal failure after bypass surgery for her service-related small bowel cancer.
Factor 9(7): having dyslipidaemia at the time of the clinical onset of steatohepatitis; — MET
- Dyslipidaemia (triglycerides 3.4 mmol/L, HDL 0.8 mmol/L), diagnosed on 21 August 2006 and treated with atorvastatin, was present at onset. It developed with the weight gain and heavy drinking that followed her warlike service in Iraq.
Factor 9(8): for males, consuming at least 55 kilograms of alcohol within any 5 year period before the clinical onset of steatohepatitis; — MET
- The veteran is female. Her consumption of about 82 kilograms of alcohol between January 2006 and December 2010, after warlike service in Iraq in 2005, exceeds the 55 kilogram threshold set for males as well as the female threshold, so the alcohol exposure that this factor describes is established in her case.
Factor 9(9): for females, consuming at least 30 kilograms of alcohol within any 5 year period before the clinical onset of steatohepatitis; — MET
- She consumed about 82 kilograms of alcohol between January 2006 and December 2010, more than the 30 kilograms required. A psychiatrist recorded that her drinking escalated after warlike service in East Timor in 1999 to 2000 and Iraq in 2005.
Factor 9(10): having hyperuricaemia at the time of the clinical onset of steatohepatitis; — MET
- Serum uric acid was 0.52 mmol/L on 21 August 2006 and 0.49 mmol/L on 10 November 2015, so she had hyperuricaemia at onset. It accompanied the obesity, diabetes and heavy alcohol use that followed her warlike service.
Factor 9(11): taking irinotecan for at least the 30 days before the clinical onset of steatohepatitis; — MET
- Irinotecan, as part of FOLFIRI chemotherapy for her service-related small bowel adenocarcinoma, was given every 14 days from 01 July 2015 throughout the 30 days before onset.
Factor 9(12): taking a drug specified in the Schedule 2 - Drugs of this Instrument, that cannot be ceased or substituted, for at least the 30 days before the clinical onset of steatohepatitis; — MET
- Fluorouracil, in Schedule 2, was given from 01 July 2015 throughout the 30 days before onset for her service-related cancer, and the oncologist recorded that it could not be ceased or substituted.
Factor 9(13): taking a drug that cannot be ceased or substituted and which is associated in the individual with: (a) the development of steatohepatitis within 30 days of first taking the drug; and (b) the redevelopment of steatohepatitis on rechallenge with the same drug; — MET
- Amiodarone, which could not be ceased or substituted, was started on 18 October 2015 for ventricular tachycardia caused by chemotherapy for her service-related cancer. Steatohepatitis developed within 30 days, on 12 November 2015, and redeveloped on rechallenge from 04 April 2017, confirmed on biopsy on 15 June 2017.
Worsening factors
Factor 9(14): inability to obtain appropriate clinical management for steatohepatitis. — MET
- From 2016 to 2017 catheter ablation and hepatology review could not be obtained, amiodarone had to be restarted, and the steatohepatitis progressed from F2 to F3 fibrosis by June 2017.
The % contribution of the causes is 100% and significant.
Sequelae
The steatohepatitis is a sequela of the veteran's accepted conditions: the obesity, diabetes, dyslipidaemia and hypertension that developed during her service, the alcohol use that followed her warlike deployments, and the surgery, parenteral nutrition and chemotherapy for her accepted small bowel adenocarcinoma. Its own sequela is advanced hepatic fibrosis with a risk of cirrhosis.
Unintended Consequence
Met. The steatohepatitis is in part an unintended consequence of treatment provided and funded by the Commonwealth while she was serving: the jejunoileal bypass, total parenteral nutrition, irinotecan and fluorouracil chemotherapy and amiodarone (section 6A of the DRCA and the equivalent provisions of the MRCA).
Inability to Attain Appropriate Medical Management
MET. After the diagnosis in January 2016 the veteran sought an alternative to amiodarone and specialist liver care, but catheter ablation was unavailable for 16 months and hepatology review was delayed by waiting lists, so amiodarone had to be restarted on 04 April 2017. By June 2017 biopsy showed active steatohepatitis with bridging fibrosis. Applying the objective and subjective tests in Brew v Repatriation Commission (Full Federal Court, 10 September 1999, Merkel J), the unavailability of the treatment that would have removed the cause is an inability to obtain appropriate clinical management.
5. Please provide a Health Summary and a medication / prescribing history.
See attached report.
References
- 12 May 2003, Outpatient health record, Medical Officer, Garrison health centre
- 21 Aug 2006, Periodic health examination and liver ultrasound, Medical Officer
- 14 Dec 2011, Psychiatric assessment, Consultant psychiatrist
- 05 Feb 2015, Operation report, General surgeon
- 10 Jul 2015, Nutrition and parenteral nutrition records, Dietitian and gastroenterologist
- 01 Jul 2015, Oncology treatment plan, Medical oncologist
- 28 Sep 2015, Staging CT report, Radiologist
- 18 Oct 2015, Cardiology consultation, Cardiologist
- 19 Nov 2015, Outpatient health record and liver ultrasound, Medical Officer
- 08 Jan 2016, Liver biopsy report and hepatology consultation, Hepatologist
- 15 Jun 2017, Repeat liver biopsy and elastography, Hepatologist
- Statement of Principles concerning Steatohepatitis (Balance of Probabilities) No. 87 of 2022, Repatriation Medical Authority
- Statement of Principles concerning Steatohepatitis (Reasonable Hypothesis) No. 86 of 2022, Repatriation Medical Authority
